Regeneration of lost tail is of great importance to lizards. Anolis carolinensis, a green lizard, is capable of regenerating its tail efficiently after autotomy. Hence, it is considered as a model organism in regeneration study. A. carolinensis shed its tail in order to distract the predator’s attention and thus makes a way to escape. Restoring of the amputated tail takes several days and the mechanism is currently clearly understood. Although save its life, tail regeneration is associated with the impairment of several vital functions in Anoles. In addition, various differences have been observed between original and regenerated tail in terms of mechanism and structure. To date, very little work has been conducted on tail autotomy and regeneration at molecular and genetic level. The genes responsible for regeneration in anoles are identified recently. These genes are evolutionarily conserved through all tetrapod vertebrates. They are, however, in a state of ‘switched-off’ in other vertebrates including humans. Consequently, a throughout study of these so called ‘switched-off’ genes may provide a way of restoring lost organs in human, and thus could revolutionize the modern medical science.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

Mink astrovirus infection remains a poorly understood disease entity, and the aetiological agent itself causes disease with a heterogeneous course, including gastrointestinal and neurological symptoms. This paper presents cases of astrovirus infection in mink from continental Europe. RNA was isolated from the brains and intestines of animals showing symptoms typical of shaking mink syndrome (n = 6). RT-PCR was used to detect astrovirus genetic material, and the reaction products were separated on a 1% agarose gel. The specificity of the reaction was confirmed by sequencing all samples. The presence of astrovirus RNA was detected in each of the samples tested. Sequencing and bioinformatic analysis indicated the presence of the same variant of the virus in all samples. Comparison of the variant with the sequences available in bioinformatics databases confirmed that the Polish isolates form a separate clade, closely related to Danish isolates. The similarity of the Polish variant to those isolated in other countries ranged from 2.4% (in relation to Danish isolates) to 7.1% (in relation to Canadian isolates). Phylogenetic relationships between variants appear to be associated with the geographic distances between them. To our knowledge, this work describes the first results on the molecular epidemiology of MAstV in continental Europe. The detection of MAstV in Central Europe indicates the need for further research to broaden our understanding of the molecular epidemiology of MAstV in Europe.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

Abstract: A. baumannii exhibits resilience in harsh environments and progressively develops resistance to diverse antibacterial agents over time. This adaptability poses a significant challenge in treating an infection caused by this bacterium within healthcare settings. The presence of peptidoglycan, a crucial precursor for cell wall synthesis, contributes to this challenge. Peptidoglycan serves not only as a structural support in bacterial cells but also provides protection against adverse environmental conditions. The synthesis of the peptidoglycan layer involves a group of substrates such as N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), within a three-partitioned process occurring in the membrane, periplasmic space, and cytoplasm of each bacterium. Initiated in the cytoplasm and extending to the inner cell membrane, this synthesis starts with the production of nucleotide precursors. The first step involves the synthesis of UDP-GlcNAc, orchestrated by Glm (GlmS, GlmM, and GlmU) enzymes using fructose-6-phosphate. Subsequently, enzymes from the Mur family, namely MurB, MurA, MurD, MurC, MurI, MurF, and MurE, synthesize UDP-N-acetylmuramyl-pentapeptide (UDP-Mpp) from UDP-GlcNAc. Concurrently, on the cytosolic side, the production of membrane-surrounded undecaprenyl phosphate occurs, involving membrane-side proteins MraY and MurG in the biosynthesis of peptidoglycan. This review emphasizes updated information on Mur family proteins, encompassing physicochemical properties, nature of binding site, number and type of binding site residues, functional domain details, three-dimensional structural aspects, and their functions within bacterial cells. Special attention is directed towards their enzymatic role in peptidoglycan biosynthesis due to the limited availability of precursors in the market. Additionally, the review provides a comprehensive summary of existing inhibitors and ongoing efforts in identifying new targeted inhibitors, recognizing these enzymes as potential candidates for antibacterial drug design and discovery.

Many types of banana (Musa spp.)—one of the most economically important horticultural crops—exist, and their ploidy (diploid, triploid, and tetraploid, usually) and genome types (containing A or/and B genome in most cases) differ. At present, observation and genome type detection are commonly used to identify banana germplasm resources. However, the former is tedious, while the latter cannot distinguish categories below genome types. It is therefore urgent that a simple and effective method for identifying banana germplasm resources is established. We sequenced and analyzed the ribosomal DNA internal transcribed spacer (ITS) sequences of 62 banana germplasm and found that the sequencing peaks, especially the 20 bp region near the 420 bp position (referred to as the “420 bp region”), exhibited relatively recognizable and repeatable polymorphism characteristics. Using the “420 bp region” as a marker, we were able to quickly distinguish bananas belonging to different genome type groups (comprising the AA, AB, AAA, ABB, AAB, ABBB, AAAB, and AAAA groups) or different subgroups in the same genome type group (for example, the Cavendish, Gros Michel, Red, Lakatan, and Ibota Bota subgroups in the AAA group; and the Pisang Raja, Plantain, Pome and Silk subgroups in the AAB group). Moreover, it appeared that Sanger sequencing of ITS could be used for identifying banana hybrid offspring. These results demonstrated that the banana ITS region contains rich genetic information that is useful for genotyping. In general, ITS sequencing simplifies the classification of banana germplasm resources and has potential application in several areas of Musa improvement.

Climate change, growing world population and increasing food demand require higher yields and adaptability of crops, including spring bread wheat. Modern plant breeding based on achievements of genetics has a significant impact on plant resistance to diseases, climate variability and other factors. Genome wide association studies (GWAS) is one of genetics tools for mining of genome loci associated with economically important traits. In the current study, we applied GWAS to reveal QTL for spike productivity and grain quality using a panel of spring varieties of Triticum aestivum L. bred in different decades of the last century in Russia and Germany. The study has enabled to find new genetic markers associated with grain yield and quality. Studying genetic basis of grain yield and quality by comparison of wheat varieties from different breeding periods, including landraces preserved as the source of valuable genetic diversity for breeding and genetic studies, makes it possible not only to understand selection processes in the past, but also to develop strategies for future breeding work.

This study aimed to investigate the appearance and frequencies of the booroola polymorphism of the bone morphogenetic protein receptor 1b (BMPR1B) gene (FecB) and the embrapa polymorphism of the growth differentiation factor 9 (GDF9) gene (FecGE) in sheep in Thailand. A total of 454 cross-bred sheep blood samples were collected from four provinces in Thailand during August 2022 to July 2023. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the FecB and FecGE genotype. The history of ewe birth types was collected from the owners to analyze the association between Fecundity (Fec) genotypes and the history of birth types. The genotypic frequencies of FecB for homozygous genotype (B/B), heterozygous genotype (+/B) and wild-type (+/+) were 0.22%, 1.54%, and 98.24%, respectively. Meanwhile, the genotypic frequencies of FecGE for homozygous genotype (E/E), heterozygous genotype (+/E), and wildtype (+/+) were 0.00%, 2.42%, and 97.58%, respectively. Furthermore, three ewes exhibited both FecB and FecGE genotypes. Fisher’s exact test revealed that the possessor of FecB genotype was associated with multiple births (p<0.01). Both FecB and FecGE mutations were identified in crossbred sheep in Thailand. Sheep containing FecB allele is a better candidate to be selected to improve the prolificacy of crossbred sheep in Thailand.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI) resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects.

Glioblastoma (GBM) is the most common primary brain tumor in adults, with few available therapies and a 5-year survival rate of 7.2%. Hence, strategies for improving GBM prognosis are urgently needed. The translocator protein 18kDa (TSPO) plays crucial roles in essential mito-chondria-based physiological processes and is a validated biomarker of neuroinflammation, which is implicated in GBM progression. The TSPO gene has a germline single nucleotide pol-ymorphism, rs6971, which is the most common SNP in the Caucasian population. High TSPO gene expression is associated with reduced survival in GBM patients; however, the relation between the most frequent TSPO genetic variant and GBM pathogenesis is not known. The present study ret-rospectively analyzed the correlation of the TSPO polymorphic variant rs6971 with overall and progression-free survival in GBM patients using three independent cohorts. TSPO rs6971 poly-morphism was significantly associated with shorter overall survival and progression-free survival in male GBM patients but not in females in one large cohort of 441 patients. We observed similar trends in two other independent cohorts. These observations suggest that the TSPO rs6971 pol-ymorphism could be a significant predictor of poor prognosis in GBM, with a potential for use as a prognosis biomarker in GBM patients. These results reveal for the first time a biological sex-specific relation between rs6971 TSPO polymorphism and GBM.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

Drosophila melanogaster serves as a important research model both for genetic investigations and for the study of metal toxicity, facilitating the elucidation of physiological mechanisms comparable to those of human organisms. In our research, we evaluated the toxicity effect resulting from exposure to various concentrations of lead and copper on the prolificity rates throughout the life cycle (egg-adult) of four genotypes of Drosophila melanogaster: wild-type (control), white, brown, and white-vestigial. During our study, the prolificity rates were examined across three repetitions under the impact of exposure to concentrations of 0.50, 1.00, 2.00, and 4.00 mM of copper (CuSO₄) and lead (Pb(C₂H₃O₂₎₂). Prolificity rates throughout the life cycle exhibited variations as a direct consequence of genetic factors, the concentration of exposure, and the specific type of metal, either copper or lead. The mutant white-vestigial genotype revealed an IC₅₀ concentration for prolificity inhibition at lower doses of 2.00 mM for copper and 4.00 mM for lead, in contrast to the control genotype (wild-type), which exhibited an inhibition concentration rate >IC₅₀ of 4.00 mM only in the case of copper. Our results concluded that the (i) dose influences the prolificity rate in a directly proportional manner, (ii) comparative analyses between copper and lead revealed that copper displayed toxicity across all genotypes within the concentration range of 0.50 mM to 2.00 mM. In contrast, lead exhibited toxicity within the concentration range of 1.00 mM to 4.00 mM, highlighting a (iii) more acute toxicity characteristic in the case of copper. Thus, the results of this research reflect the importance of using Drosophila melanogaster as a genetic model in the comparative study of the interaction between genetic factors and the toxicity of metals, offering significant insights into monitoring their impact and defining the maximum permissible doses on organisms.

Fourteen Russian potato cultivars (cvs.) grown for three years in field plots of VIR (Northwestern region of the Russian Federation) were evaluated for productivity and a number of biochemical parameters of tubers. The 12 parameters that have been evaluated in tubers annually one month after harvesting and after cold storage (at 2 - 4°C) include the content of dry matter, starch, protein, ascorbic acid, carotenoids and β-carotene, anthocyanins, total sugars and monosaccharides (reducing sugars), phenolic compounds, as well as total acidity, and antioxidant activity. The cultivars differed significantly in productivity and biochemical composition of tubers. Dry matter content ranged from 16.40% in cv. ʻKumachʼ to 27.28% in ʻNayadaʼ, starch content ranged from 8.96 % in cvs. ʻFioletovyjʼ, ʻKumachʼ to 20.08% in ‘Sokur’, the total sugar content reached 2.46% in cv. ʻSiverskij’ whereas ‘Sokur’ has the smallest content of reducing sugars in post-harvest tubers. Protein content ranged from 1.02% to 2.77% with the highest accumulation in cv. ʻSokurʼ. Content of ascorbic acid (vitamin C) ranged from 6.3 mg/100 g FW in ʻKrasa Meŝeryʼ to 26.6 mg/100 g FW in cv. ʻKrasavchikʼ. Carotenoids content ranged from 0.157 mg/100 g FW in cv. ‘Nayada’ to 0.645 mg/100 g FW in cv. ʻGrandʼ. Content of anthocyanins in potato ranged from 1.04 mg/100g FW (not colored tubers of cv. ʻKrasa Meŝeryʼ) to 283.04 mg/100g FW (colored tubers of cv. ʻFioletovyiʼ). The nutritional value of tubers (content of dry matter, sugars, starch and protein) was determined to a greater extent (38-49%) by varietal characteristics, rather than by meteorological conditions in vegetation period. The content of vitamin C, carotenoids, protein and anthocyanins varied depending on the year. The highest content of dry matter, starch and carotenoids was noted in tubers harvested in 2019, marked by low temperatures and precipitation deficit in growing season. The conditions of 2020 with low temperatures and excess precipitation were the most favorable for anthocyanin’s accumulation in potato tubers while not for other biochemical parameters. Of the cultivars, ʻSokurʼ had the highest content of dry matter, protein and starch. Cv. ʻFioletovyiʼ had small starch content and high level of anthocyanins. Cv. ʻPlamyaʼ can be recommended for potato products manufacturing due to dry matter content above 20% and reducing sugars content 0.24%..

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G>A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G>A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G>A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: χ2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).

Morphological features and composition of ISSR DNA fragments were studied in species of the genus Tulipa L. A comparative analysis of the data obtained was carried out and an attempt was made to clarify the species belonging of plants. Plants obtained from various sources were studied. It was found that representatives of the genus Tulipa L. from the two subgenera Tulipa and Eriostemones are well separated not only morphologically, but also by the composition of ISSR fragments. At the intra- and interspecific level, the results for morphological traits and molecular data differed. Interspecific and intraspecific differences were more clearly traced in the complex analysis of morphological features and ISSR PCR data. All samples obtained in the form of bulbs and renewed vegetatively had an identical set of ISSR fragments. Plants grown from seeds were characterized by a significant variety of molecular markers and had both species-specific and in-dividual genetic variability. It was found that the samples obtained and registered as the Tulipa urumiensis Stapf are the yellow-flowered form of the Tulipa tarda Stapf, and a sample received as the Tulipa turkestanika Regel is the Tulipa bifloriformis Vved. Thus, a comprehensive study of both the data of fragmentary DNA analysis and morphological features, provided a sufficient number of DNA samples, makes it possible to clarify the species of tulip plants, and also allows us to assess the genetic diversity of the genus Tulipa.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite advancements in treatment, the prognosis for patients with GBM remains poor due to its aggressive nature and resistance to therapy. CRISPR-based genetic screening has emerged as a powerful tool for identifying genes crucial for tumor progression and treatment resistance, offering promising targets for tumor therapy. In this review, we provide an overview of the recent advancements in CRISPR-based genetic screening approaches and their applications in GBM. We highlight how these approaches have been used to uncover genetic determinants of GBM progression and susceptibility to various therapies. Furthermore, we discuss ongoing challenges and future directions of CRISPR-based screening methods in advancing GBM research.

Transferrin (TF) is a key iron carrier protein. Studies in human cohorts and in cultured adipocytes suggested that decreased transferrin expression and intracellular iron in adipocytes leads to impaired insulin responsiveness and causes differential expression of genes involved in metabolism, insulin action, and obesity. While suggestive, these studies did not definitively prove in an intact organism that altering TF expression in adipocytes is sufficient to affect glucose homeostasis and insulin resistance. In this study we created a mouse model of decreased transferrin expression only in adipocytes (Trf+/-Cre+/-) to test the hypothesis that iron trafficking in adipose tissue is sufficient to affect insulin sensitivity. Area under the glucose curve (AUCg) after intraperitoneal glucose administration was increased in the Trf+/-Cre+/- mice compared to wild type (WT) mice on a normal chow diet, and the mice were slightly heavier (p=0.02 for both). Homeostasis Model of Insulin Resistance (HOMA-IR) values were also significantly higher in the Trf+/- Cre+/- mice (p<0.05). Thus, supporting our hypothesis, analysis of mice with decreased expression of TF restricted to adipocytes showed that a decrease in adipocyte TF is sufficient to affect insulin resistance, weight, and glucose homeostasis.

Sulfotransferases (SULTs) family plays a significant role in the biotransformation of a variety of xenobiotics and endogenous compounds by which carcinogenesis and mutagenicity of different malignancies are increasingly affected. Recent data identified various genetically polymorphic SULTs enzymes with significant variations in the enzyme activity. This study aimed to investigate the impact of SULT1A1 gene polymorphism and and its potential risk on females with breast cancer in Jordan using a PCR-RFLP and Sanger Sequencing methods. The analysis showed that 24.7% of the patients and 25.3% of the controls were homozygous for the SULT1A1*1 allele (SULT1A1*1/SULT1A1*1) compared to 8.8% and 5.7% homozygous for the SULT1A1*2 allele (SULT1A1*2/SULT1A1*2) for patients and controls respectively. Most of the patients and controls were heterozygous for SULT1A1*1 allele (SULT1A1*1/SULT1A1*2) with rates of 66.5% and 69.0% in patients and controls respectively. In addition, the frequencies of the mutant SULT1A1*2 allele were 0.42 and 0.4 in the patient and control groups respectively. No significant difference in genotype and allele distribution was noted between the breast cancer and control groups. The risk of breast cancer in individuals carrying the SULT1A1*2 allele was determined by combining the SULT1A1*1/SULT1A1*2 and ULT1A1*2/SULT1A1*2 genotypes. No association was observed between SULT1A1 polymorphism and breast cancer incidence (P = 0.63; OR, 0.93; 95% CI, 0.68–1.26). However, SULT1A1*2 allele was found to increase the risk of breast cancer by 1.26-fold.

Apis cerana and Apis mellifera, are very important honey species for agriculture in Asian countries. In recent decades, A. cerana populations have sharply declined in all Asian countries as a result of Sacbrood Virus infection and have now recovered to their original size. It can change the genetic structure of local populations of A. cerana. We used the nuclear gene Vitellogenin VG to assess the genetic structure of local populations of A. cerana and the signature of adaptive selection. We performed a population genetic analysis of the honey bees A. cerana from South Korea in comparison with A. cerana samples from Russia, Japan, Nepal, and China. The sequences of the gene VG of a closely related honey bee species, A. mellifera, from India and Poland were used as outgroup samples. A comparative analysis of northern and southern A. cerana populations was performed. The signatures of positive adaptive selection were found in the local population of A. cerana. We performed the Tajima's neutrality D test for A. cerana populations from different local populations based on the gene VG exon sequences. All A. cerana populations showed signs of population size expansion following the possible recent decline in population sizes. The local populations of A. c. koreana were subdivided according to their geographical distribution into southern, northern, and central Korean clusters. The gene VG exon sequences can be used as informative markers for monitoring the changes in genetic structure and adaptation to the environment processes in A. cerana populations.

This paper investigates pseudo-polymorphism in 2-pyridylmethoxy derivatives of p-tert-butylcalix[4]arene (PyC4), p-tert-butyldihomooxa-calix[4]arenes (PyHOC4), and p-tert-butylhexahomotrioxacalix[3]arenes (PyHO3C3), presenting 11 crystal structures with 15 crystallographically independent molecules. The macrocycle of PyC4 is smaller and less flexible with respect to those of PyHOC4 and PyHO3C3 and in solution, the cone conformation of these three molecules exhibit different point symmetries: C4, Cs and C3, respectively. A correlation is observed between the macrocycle's structural rigidity and the number of pseudo-polymorphs formed. The more rigid PyC4 displays a higher number (6) of pseudo-polymorphs compared to PyHOC4 and PyHO3C3, which exhibit a smaller number of crystalline forms (3 and 2, respectively). The X-ray structures obtained show that the conformation of the macrorings is primarily influenced by the presence of an acetonitrile guest molecule within the cavity, with limited impact from crystal packing and intermolecular cocrystallized solvent molecules. Notably, both calix[4]arene derivatives produce host-guest complex with acetonitrile, while the most flexible and less aromatic PyHO3C3 do not give crystals with acetonitrile as guest. Intertwined 1D and 2D solvent channel networks were observed in the PyHOC4-hexane and in the PyHO3C3-H2O-MeOH crystal structures, respectively, while the other pseudopolymorphs of PyHOC4 and PyHO3C3 and all PyC4 crystal forms exhibit a closely packed crystal structures without open channels.

MicroRNAs are tissue-specifically expressed short RNAs that serve post-transcriptional gene reg-ulation. A specific microRNA can bind to mRNAs of different genes and thereby suppress their protein production. In the context of the complex phenotype of fibromyalgia, we used the Axiom miRNA Target Site Genotyping Array to search genome-wide for DNA variations in microRNA genes, their regulatory regions and in the 3'UTR of protein-coding genes. To identify dis-ease-relevant DNA polymorphisms, a cohort of 176 female fibromyalgia patients was studied in comparison to a cohort of 162 healthy women. The association between 48.329 markers and fibromyalgia was investigated using logistic regression adjusted for population stratification. 29 markers had p-values < 1 × 10-3 and the strongest asso-ciation was observed for rs758459 (p-value of 0.0001), located in the Neurogenin 1 gene, targeted by hsa-miR-130a-3p. Furthermore, we identified a gene locus (rs2295963) predicted to disrupt binding of hsa-miR-1-3p. Both microRNAs were previously reported to be differentially expressed in fi-bromyalgia patients. Despite its limited statistical power, this study reports two microRNA-related polymorphisms which may play a functional role in the pathogenesis of fibromyalgia. For a better understanding of the disease pattern, further functional analyses on the biological significance of microRNAs and microRNA-related polymorphisms are required.

The increased prevalence of obesity worldwide has been implicated for the alarming rise of the incidence of gestational diabetes and preeclampsia as well, both considered as threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF and VEGF-receptor all known to be involved in pregnancy complications aiming to identify possible predisposing risk factors in pregnancies with obesity. G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and to those developed preeclampsia it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptor. We conclude that the genetic profile of the obese pregnant woman shares a common background with that of a pre-existing type 2 diabetes mellitus and therefore predisposes to complications in pregnancy.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

The conventional well placement was done manually by using a numerical reservoir simulator, and it required a lengthy trial-and-error process. It required great experience and expertise to manipulate the variables and uncertainties that lie on the reservoir to determine the best placement of the well. In addition, the traditional gradient-based methods such as Line-search and Trust-region were not viable in terms of maximum results obtained. Gradient-based methods were too dependent on the surface gradient of the solution and may only converge to local optima instead of global optima. Complex reservoirs have rough surfaces with high uncertainties, which hinders the traditional gradient-based method from converging to global optima. Thus, genetic algorithms were utilized to automate the manual trial-and-error process and to overcome the limitations of the traditional gradient-based method. The objectives of this study were to analyse the effect of different initial well placement distributions, the number of random solution sizes, and the crossover rate on cumulative oil production. A synthetic reservoir model built using CMG Builder was used as the testing platform for the optimization problems. Well-placement parameterization and optimization set-up were carried out using the CMG CMOST optimization tool. The integration of CMG IMEX and CMOST optimized cumulative oil production based on the objectives of the study. The results obtained showed that the higher number of random solutions used resulted in higher cumulative oil production, with more generations needed to reach the optimum solution. It can be concluded that the larger number of random solutions used increased the probability of reaching the optimum solution, but will take more generations.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

We present results on the spontaneous crystallization of freely-jointed polymers of hard spheres obtained in an unprecedentedly long Monte Carlo (MC) simulation on a system of 54 chains of 1000 monomers. Starting from a purely amorphous configuration and after a transitory dominance of the hexagonal closed packed (HCP) polymorph, the system crystallizes in a final, stable, face centered cubic (FCC) crystal of very high perfection. Through refined metrics we gauge the degree of ordering and identify the regions of the phase transition and the corresponding morphologies. An analysis of chain conformational characteristics, of the spatial distribution of monomers and of the volume accessible to them shows that the phase transition is caused by an increase in translational entropy that is larger than the loss of conformational entropy of the chains in the crystal compared to the amorphous state. Polymer chains in the crystal adopt ideal random walk statistics as their great length renders local conformational details, imposed by the geometry of the FCC crystal, irrelevant.

Dysferlinopathies comprise a spectrum of muscular dystrophies characterized by progressive muscle weakness and degeneration due to mutations in the DYSF gene, which encodes the dysferlin protein critical for muscle membrane repair. This review delves into the clinical spectra of dysferlinopathies, their molecular mechanisms, and the spectrum of emerging therapeutic strategies. We explore the phenotypic heterogeneity of dysferlinopathies, highlight the incomplete understanding of genotype-phenotype correlations, and discuss the implications of various DYSF mutations. Furthermore, we examine the utility of animal models in elucidating disease mechanisms and the potential of symptomatic, pharmacological, molecular, and genetic therapies in mitigating the disease's progression. We also consider the roles of diet and metabolism in managing dysferlinopathies, as well as the impact of clinical trials on treatment paradigms. By culminating the complexities inherent in dysferlinopathies, this article emphasizes the need for multidisciplinary approaches, precision medicine, and extensive collaboration in research and clinical trial design to advance our understanding and treatment of these challenging disorders.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Preventive Maintenance (PM) is a periodic maintenance strategy, which has great results for devices in extending their life, increasing productivity, and most importantly, help avoid unexpected breakdowns and their costly consequence. A preventive maintenance scheduling (PMS) is determining the time for carrying out PM, and it represents a sensitive issue in terms of impact on production if the time for the PM process is not optimally distributed. In this study, hybrid heuristic methods were used to solve the PMS problem, as genetic algorithm and Tabu research were adopted. The optimal solution was reached in a short time compared to previous studies in which optimal methods were used, integer programming and nonlinear integer programming. Also, sensitivity analysis was applied to measure the robustness and strength of the method used, where an optimal solution was obtained for all experiments and in record time. This method can be used for power plants in privet or public sectors, to generate an optimal PMS, to save money, and to avoid water or electricity cuts.

Background: The COMT gene polymorphism is associated with neurological and psychiatric disorders and pain perception. This study aimed to determine the relationship between the COMT (catechol-O-methyltransferase) gene polymorphism, pain perception in parturients with inhaled nitrous oxide during labour, and anxiety as a personality trait. Methods: A total number of 181 woman who chose vaginal birth were enrolled in this study. To present the difference in pain perception, the parturients were divided into one group (n=80) that chose labour analgesia with inhaled nitrous oxide (50% nitrous oxide and 50% oxygen) and one group without analgesia. The blood samples were taken during the pregnancy as a part of routine pregnancy controls in the hospital. The COMT gene polymorphism was detected with the PCR technique. Pain perception of labouring women was self-evaluated two times according to the VAS (Visual Analogue Scale) and anxiety as a personality trait was determined with STAI-T (State Trait Anxiety Inventory). Pain perception as well as anxiety were compared according to COMT genotypes. Results: In the 181 pregnant women there were 40 women (22%) of wild homozygotes (GG) of COMT, 95 women (53%) of mutant heterozygotes (GA), and 46 women (25%) of mutant homozygote (AA). A negative association of pain perception with the GA (mutant heterozigote) polymorphism of the COMT gene versus the wild type (GG polymorphism) was observed. The GA polymorphism of the COMT gene was associated with 0.46 units lower pain perception compared to the wild type (GG). The anxiety trait score in group AA was lower than in groups GA and AA. The difference reached statistical significance only when comparing AA versus GA (P&gt;0.042). Analgesic efficacy of nitrous oxide was noticed in 22% of labouring women who reported moderate pain (VAS score 4-7). Conclusions: The COMT gene polymorphism was associated with pain perception and anxiety among labouring women. The COMT gene polymorphism GA was associated with negative pain perception among labouring women. Nitrous oxide showed statistical significance in anxiolytic efficacy during labour in women with mild anxiety as a personality trait. Anxiolytic efficacy of nitrous oxide has shown better efficacy in labouring women with the COMT gene polymorphism AA.

MiRNAs are 20-22 nucleotide long single-stranded non-coding RNA sequences, which can regulate post transcriptional activity of mRNA by binding with it at 3’UTR region (untranslated region). Thus deregulation of miRNA expression is responsible for dysregulating mRNA function which contributes in developing various diseases as well as cancerous phenotypes. Alteration of single nucleotide in miRNA sequence is one of the reasons behind deregulation of miRNA expression. The most frequent carcinoma in current day is breast cancer which causes a high mortality among women around the world as well as India. Despite of the advancement of diagnostic tools, strategies and treatment, the cases of breast cancer is increasing every year. There are plenty of biomarkers like ER, PR, Her2, Ki-67, etc available which are frequently used in diagnosis and treatment of breast cancer. After the discovery of MiRNA in 1993 in Caenorhabiditis elegans, it is attracting all the limelight in diagnosis and treatment of different carcinomas as well as breast cancer. In this review we will discuss on involvement of different types of MiRNAs and miR SNPs in breast cancer occurrence and susceptibility in a detailed manner.

Bacillus anthracis, the causative agent of anthrax, has two virulence plasmids: pXO1 and pXO2. Plasmid pXO2 carries the genes of an antiphagocytic capsule synthesis. Plasmid pXO1 carries the genes pagA, lef, and cya encoding anthrax toxins, as well as atxA, which encodes the main regulator of pathogenicity factor expression. In the present paper, we evaluated the polymorphism of the pagA, lef, cya, and atxA genes for 85 B. anthracis strains belonging to different evolutionary lineages and canSNP groups and three B. cereus strains possessing pXO1-like plasmids. We found 19 genotypes (GT) strongly correlated with the main evolutionary lineages; they were mainly correlated with the canSNP group within these lines. In some cases, one GT combined the strains of several canSNP groups, and some canSNP groups were divided into several GTs. The most interesting of such cases were 1) the formation of a separate GT by strains of the A.Br.008/009 group isolated in the former USSR; 2) the presence of a unique GT in some American strains of the A.Br.Aust94 group; 3) the division of the A.Br.001/002 group into two subgroups, one of which may be a transitional link to the group A.Br.Ames; 4) the fact that European isolates of the B.Br.CNEVA group and Arctic strains of the B.Br.001/002 group have a common GT.

Amid the swift progression of the global automobile industry, the aspiration for lightweight vehicle design has surfaced as a crucial approach to boost fuel efficiency and curtail environmental impact. The objective of this study revolves around achieving holistic optimization of vehicle structure via detailed scrutiny of vehicle process characteristics, amalgamated with a Back Propagation neural network (BPNN) optimized by a genetic algorithm (GA) and a topology optimization (TO) method.The process initiates with an examination of the vehicle's technical characteristics, succeeded by an optimization protocol that couples GA with BPNN. This exhaustive optimization procedure derives the best-fit values of design parameters and identifies the globally optimal lightweight design approach. Subsequently, a comprehensive structural optimization is actualized by modifying the topological distribution of the structure.A simulation experiment of the conceptual car body beam skeleton is conducted as a conclusive step, and the anti-collision capacity of the car body beam skeleton is assessed by measuring deformation intrusion. The findings reveal that in the vehicle topology optimization, a comparative analysis of pre and post-optimization results indicates an improved topological density across diverse sections. The topological density of the vehicle's frontal structure escalates from 0.75 to 0.8. Following optimization, the stiffness assessment records a marginal increase (within the range of 0.02–0.05), implying that the lightweight design does not compromise the general rigidity of the structure.The optimized body structure manifests superior crashworthiness in the crash test: the deformation intrusion diminishes by 27% in front-end collisions. In side impacts, the deformation and intrusion at critical points are reduced by 13.15% to 10% respectively. The comprehensive method proposed herein proves to be an efficient strategy to actualize the lightweight design of vehicles.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C&gt;T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations of bone metabolism leading to a defective skeleton, associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, being TP53 one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in the humanized Tp53 Arg72Pro knock-in mice. This work reported on the influence of TP53 Arg72Pro polymorphism in bone microarchitecture, OPG gene expression and apoptosis bone status. The results showed that the proline variant of TP53 Arg72Pro polymorphism (Pro72-p53) was associated with deteriorated bone tissue, lower OPG/RANK ratio and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker to identify individuals with an increased risk of suffering metabolic bone alterations

Cassava (Manihot esculenta Crantz), domesticated in the Amazonian region of South America, presents an important diversity in Ecuador, where it is a main staple food; however, only few Ecuadorian cassava accessions have been included in international molecular assessments. The purpose of this study was to apply suitable cassava mi-crosatellites to characterize the genetic variability of the Ecuadorian cassava collection composed mainly of local landraces from the Coast, Andes and Amazonia regions. The use of microsatellite markers allowed the determination of the genetic diversity of the collection. Seven selected SSR primers, permitted to identify homozygous and hetero-zygous materials within the cassava collection of 133 accessions. The loci presented an average genetic diversity value of 0.7 and an average PIC value of 0.67, which is con-sidered high. Low number of duplicates (8.8%) were identified in the Ecuadorian col-lection which is not fully duplicated at CIAT. Currently, a wide range of cassava diver-sity is still cultivated in multi-crop agro-ecosystem, mainly in the Coast and Amazo-nian regions. Especially in the Amazonian region, due to important cultural uses of cassava by local ethnic communities, more in depth studies in the region could unveil the genetic diversity present in situ today.

The weight coefficients of the diaphragm spring depend on experiences in the traditional optimization. However, this method not only cannot guarantee the optimal solution but it is also not universal. Therefore, a new optimization target function is proposed. The new function takes the minimum of average compress force changing of the spring and the minimum force of the separation as total objectives. Based on the optimization function, the result of the clutch diaphragm spring in a car is analyzed by the non-dominated sorting genetic algorithm (NSGA-II) and the solution set of Pareto is obtained. The results show that the pressing force of the diaphragm spring is improved by 4.09%by the new algorithmand the steering separation force is improved by 6.55%, which has better stability and steering portability. The problem of the weight coefficient in the traditional empirical design is solved. The pressing force of the optimized diaphragm spring varied slightly during the abrasion range of the friction film, and the manipulation became remarkably light.

Atopic dermatitis (AD) is a chronic inflammatory disorder presenting a dysregulated immune response and derangement of the epidermal barrier lipids. The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signal axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D-epidermal equivalents. We used tofacitinib, a low-molecular-mass JAK inhibitor, to screen for the JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4, and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase, and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitate and caused a depletion of triglycerides. This depletion was associated with altered PC profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very long chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by halted homeostasis of FA metabolism.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

A literature review was conducted to summarize the frequency of the D-allele of the angiotensin-converting enzyme-1 in all countries with available data. Using an ecological study design limited to high income countries, we found that the country-level frequency of the D-allele was associated with increased COVID-19 incidence and mortality.

Background: COPD is characterized by dyspnea, chronic cough, sputum production and extra pulmonary multimorbidity including depression, anxiety and cognitive problems. Methods: Cognitive and psychological clinical alterations/disorders; QoL/Health-related QoL; and Coping strategies were evaluated in 71 COPD patients characterized for FKBP5 gene (rs4713916). Instruments: MMSE, MoCA, ROCF, BDI-II, CES-D, SAS, SF-36, ADL, IADL, SGRQ, MRF 26, CIRS, Brief COPE. Results: Carriers of the rs4713916 polymorphisms (G:A) show better cognitive performances, higher degree of independence in the ADL and IADL, better QoL before and after rehabilitation, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorder, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant anti-psychotic, hypnotic-sedative drugs. On the other hand, no difference was found as regards the number of comorbidities. Conclusions: Our study shows that rs4713916 is positively associated with better outcome for COPD. These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical and behavioral features of COPD patients.. Our data may be used as initial benchmark for future clinical studies.

In this work we looked for a stable and accurate procedure to perform feature selection in datasets with a much higher number of predictors than individuals, as in Genome-Wide Association Studies. Due to the instability in feature selection when many potential predictors are measured, a variable selection procedure is proposed that combines several replications of shrinkage regression models. A weighted formulation is used to define the final predictors. The procedure is applied to investigate Single Nucleotide Polymorphisms (SNPs) predictors associated to Alzheimer’s disease in the Alzheimer’s disease Neuroimaging Initiative (ADNI) dataset. Two data scenarios are investigated: one considering only the set of SNPs and another with the covariates age, sex, educational level and APOE4 genotype. The SNP rs2075650 and the APOE4 genotype are given as risk factors for AD, which is in line with the literature, and other four new SNPs are pointed, opening new hypotheses for in vivo analyses. These experiments demonstrate the potential of the new method for stable feature selection.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups, as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (P < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (P < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5 – 7 years (P < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (P < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (P < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (P < 0.05). Interestingly, the skin antioxidant capacity and oxidative damage exhibited significant positive and negative correlations, respectively, with the population of active secondary hair follicles (P < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

USP21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of USP21 dysfunction have yet to be fully understood. Here, we generated Usp21 knockout (KO) mice and conducted microarray to identify genes that Usp21 regulates. Its results raised several genes based on their biological characteristics, and RT-qPCR confirmed their expression. KO mice exhibited significant elevations in the expression of the genes Fabp7 and Nlrc5, which play a role in lipid metabolisms, compared to wild-type mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol and free fatty acids in KO mice compared to wild-type mice. These data suggest that Usp21 may play roles in lipid metabolism associated with Fabp7 and Nlrc5. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was associated with hypercholesterolemia. These data suggest that USP21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia.

The aim of the study is to develop a population pharmacokinetic (PopPK) model and to investigate the influence of CYP3A5/CYP3A4 and ABCB1 single nucleotide polymorphisms (SNPs) on the Tacrolimus PK parameters after LCP-Tac formulation in stable adult renal transplant patients. The model was developed using NONMEM v7.5, from full PK profiles from a clinical study (n=30) and trough concentrations (C0) from patient follow-up (n=68). The PK profile of the LCP-Tac formulation was best described by a two-compartment model with linear elimination, parameterised in elimination (CL/F) and distributional (CLD/F) clearances and central compartment (Vc/F) and peripheral compartment (Vp/F) distribution volumes. A time lagged first order absorption process was characterized using transit compartment models. According to the structural part of the base model, the LCP-Tac showed an absorption profile characterized by 2 transit compartments and a mean transit time of 3.02 hours. Inter-individual variability was associated with CL/F, Vc/F and Vp/F. Adding inter-occasion variability (IOV) on CL/F caused a statistically significant reduction in the model minimum objective function MOFV (p<0.001). Genetic polymorphism of CYP3A5 and cluster of CYP3A4/A5 SNPs statistically significantly influenced Tac CL/F. In conclusion a PopPK model was successfully developed for LCP-Tac formulation in stable renal transplant patients. CYP3A4/A5 SNPs as a combined cluster including three different phenotypes (high, intermediate, and poor metabolizers) was the most powerful covariate to describe part of inter-individual variability associated with apparent elimination clearance. Incorporating this covariate in the initial dose calculation and during the therapeutic drug monitoring (TDM) would probably optimize Tac exposure attainments.

The geographic variability of the dorsal pattern (DP) of the Italian wall lizard, Podarcis siculus, across its native range was studied with the aim to understand whether the distributions of this phenotypic trait were more shaped by allopatric differentiation rather than adaptive processes. A total of 1298 georeferenced observations scattered across the Italian peninsula and the main islands (Sicily, Corsica and Sardinia) were obtained from citizen science databases and five DPs were characterized by different shapes of the dark pattern (“reticulated”, “campestris”, “reticulated/campestris” and “striped”) or by absence of it (“concolor”). Frequencies of different DP phenotypes differ between the two main mtDNA lineages settled in central-northern and in southern Italy respectively. This pattern may be indicative of a role of long-term allopatric historical processes in determining the observed pattern. The analysis also identified a putative wide area of secondary contact, in central southern Italy, characterized by high diversity of the DP. Generalized Linear Models (GLMs), used to estimate a possible association between bioclimatic variables and the observed phenotypic variation, showed that each of the five DPs is correlated to different environmental factors and show different distribution of areas with high probability of occurrence. However, for all but one of the DPs, the area with the greatest probability does not correspond exactly to the real distribution of the DP. Conversely, the “concolor” phenotype does not seem related to any particular mtDNA lineage and it shows a preference for areas with high temperature and low rainfall. This is in agreement with the expectation of low amount of melanin of the dorsal pattern that, in the study areas, is characterized by a light uniform coloration which could confer a better thermoregulation ability in high temperatures environments avoiding overheating.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

Udder diseases (mastitis) are a serious cause of economic losses in sheep breeding as they have a negative impact on lamb rearing and the quality of dairy products. So far the progress in treatment and prevention of these diseases has been insufficient, giving ground for searching possibilities of using natural immunity to combat mastitis. The aim of the study was to assess the relationship between the microsatellite polymorphism of selected Ovar-MHC genes and the health status of the mammary gland of sheep. The research was carried out on sheep of the Polish Heath and Polish Lowland breeds. In ovine milk the number of somatic cells (SCC) and the percentage of the lymphocyte subpopulation were assessed. On the basis of genomic DNA, molecular analysis of the Ovar-MHC gene fragments (OLADRB1, OLADRB2, OMHC1) polymorphism was performed. Significant differences were found in SCC and the percentage of lymphocytes (CD4, CD8, CD19) in the milk depending on the alleles of the Ovar-MHC genes. Alleles of 488 bp (DRB1) and 284 bp (DRB2) were found more frequently in sheep with healthy udders, while carriers of the 508 bp (DRB1) and 272 bp (DRB2) alleles were more prone to subclinical mastitis. The obtained results justify the need for further research in order to better understanding the genetic basis of mastistis and to search for effective molecular markers that can be used in breeding practice.

Acne vulgaris is one of the most common skin diseases and genetic relationships have been documented. The aim was to evaluate the association of CYP17 (T-34C) polymorphism related to the risk of acne in a meta-analysis study. The databases (Scopus, Web of Science, PubMed, and Cochrane Library) were searched until September 2018 to check the relationship between acne risk and CYP17 (T-34C) polymorphism and impact of this polymorphism on severity of acne. We used Review Manager 5.3 software to analyze the data using OR and 95% CI to check this relationship. Four studies were included and analyzed in the meta-analysis. The OR in analysis of C versus T in acne patients compared to the healthy controls was 1.42 (P=0.02), in CC vs. TT was 1.54 (P=0.04), in TC vs. TT was 1.46 (P=0.12), in TC + CC vs. TT was 1.55 (P=0.04), and in CC vs. TT + TC was 1.39 (P=0.06). There was no acne risk related to CYP17 (T-34C) in none of genetic models in Caucasian ethnicity, whereas in Asian ethnicity, there was higher acne risk related to CYP17 (T-34C) without heterogeneity. The results of the present meta-analysis showed the presence of C allele and CC genotype of CYP17 polymorphism can be risk factors for acne, mainly in the Asian ethnicity.

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

Recent technological advancements in conservation genetics and genomics have resulted in diverse tools for aiding conservation of species. The precision and resolution of high throughput sequencing technologies provide valuable insights to aid conservation decisions, but these technologies are often financially unfeasible or unavailable in resource constrained countries. Inter-Simple Sequence Repeat (ISSR) markers, when combined with sensitive automated detection systems, provide a simple, cheap means to investigate genetic diversity and discriminate closely related species. Here we apply this technology to assess genetic diversity and taxonomic delimitation in the Encephalartos eugene-maraisii species complex, a highly threatened, taxonomically dubious group of cycads in South Africa. Silica dried cycad leaflets were extracted using the Oktopure robot employing Sbeadex chemistry and amplified with fluorescently tagged ISSR primers. Band presence was scored with an ABI 3130 genetic sequencer under three different fluorescence cut-off values. Phenetic analyses were performed in NTSYS software while Bayesian analysis was performed in STRUCTURE, and haplotype network analysis, AMOVA and Tajima’s D statistic was computed with PopART. Our analyses support taxonomic singularity of E. dyerianus, E. dolomiticus and E. eugene-maraisii. Relationships between E. nubimontanus and E. cupidus remain uncertain. E. middelburgensis samples showed no clustering but had poor amplification success. This study demonstrated the suitability of automated ISSR fingerprinting as a method for plant conservation studies, especially in resource-constrained countries.

Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent an-timicrobial activity toward uropathogenic bacteria. The RNASE6 gene is heterogeneous in hu-mans due to the presence of single nucleotide polymorphisms (SNPs). RNASE6 rs1045922 is the most common non-synonymous SNP, resulting in a G to A substitution that determines an ar-ginine (R) to glutamine (Q) transversion at position 66 in the protein sequence. By structural analysis we observed that R66Q substitution significantly reduces the positive electrostatic charge at the protein surface. Here, we generated both recombinant RNase 6 -R66 and -Q66 protein variants and determined their antimicrobial activity toward uropathogenic Escherichia coli (UPEC), the most common cause of UTI. We found that the R66 variant, encoded by the major SNP rs1045922 allele, exhibited superior bactericidal activity in comparison to the Q66 variant. The higher bactericidal activity of R66 variant correlated with an increase in the protein lipopolysac-charide binding and bacterial agglutination abilities, while retaining the same enzymatic effi-ciency. These findings encourage further work to evaluate RNASE6 SNP distribution and its impact in UTI susceptibility.

The potential to affect gene expression via G-quadruplex stabilization has been extended to all domains of life, including viruses. Here, we investigate the polymorphism and structures of G-quadruplexes of the human papillomavirus type 52 with UV, CD and NMR spectroscopy and gel electrophoresis. We show that oligonucleotide with five G-tracts folds into several structures and that naturally occurring single nucleotide polymorphisms (SNPs) have profound effects on the structural polymorphism in the context of G-quadruplex forming propensity, conformational heterogeneity and folding stability. With help of SNP analysis, we were able to select one of the predominant forms, formed by G-rich sequence d(G3TAG3CAG4ACACAG3T). This oligonucleotide termed HPV52(1-4) adopts a three G-quartet snap back (3+1) type scaffold with four syn guanine residues, two edgewise loops spanning the same groove, a no-residue V loop and a propeller type loop. The first guanine residue is incorporated in the central G-quartet and all four-guanine residues from G4 stretch are included in the three quartet G-quadruplex core. Modification studies identified several structural elements that are important for stabilization of the described G-quadruplex fold. Our results expand set of G-rich targets in viral genomes and address the fundamental questions regarding folding of G-rich sequences.

Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p &lt; 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.

Genetic engineering has become an essential element in developing climate-resilient crops and environmental sustainable solutions to respond to the increasing need for global food security. Genome editing using CRISPR/Cas [Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated protein (Cas)] technology is being applied to a variety of organisms, including plants. This technique has become popular because of its high specificity, effectiveness, and low production cost. Therefore, this technology has the potential to revolutionize agriculture and contribute to global food security. Over the past few years, increasing efforts have been seen in its application in developing higher-yielding, nutrition rich, disease resistant, stress-tolerant “crops” fruits and vegetables. Cas proteins such as Cas9, Cas12, Cas13, and Cas14, among others, have distinct architectures and have been used to create new genetic tools that improve features that are important for agriculture. The versatility of Cas has accelerated genomic analysis and facilitated the use of CRISPR/Cas to manipulate and alter nucleic acid sequences in cells of different organisms. This review provides the evolution of CRISPR technology exploring its mechanisms and contrasting it with traditional breeding and transgenic approaches to improve different stress tolerance. We have also discussed the CRISPR/Cas system and explored three Cas proteins that are currently known to exist: Cas12, Cas13, and Cas14 and their potential to generate foreign DNA free or non-transgenic crops that could be easily regulated for commercialization in most countries.

Psoriasis is considered an immune-mediated disease involving the innate and adaptative immune system triggered by environmental risk factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, specially genome and epigenome-wide studies, have allowed a more sensitive study of the genetic and epigenetic mechanisms, allowing an enhanced understanding of its physiopathology and facilitating the development of new drugs. In this review, we aim to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.

This document summarizes the evidence currently available about the effects of the anesthetic agents and techniques used in primary cancer surgery and long-term oncologic outcomes, and the biomolecular mechanisms involved in their interaction..

Nowadays genetic algorithm (GA) is greatly used in engineering pedagogy as an adaptive technique to learn and solve complex problems and issues. It is a meta-heuristic approach that is used to solve hybrid computation challenges. GA utilizes selection, crossover, and mutation operators to effectively manage the searching system strategy. This algorithm is derived from natural selection and genetics concepts. GA is an intelligent use of random search supported with historical data to contribute the search in an area of the improved outcome within a coverage framework. Such algorithms are widely used for maintaining high-quality reactions to optimize issues and problems investigation. These techniques are recognized to be somewhat of a statistical investigation process to search for a suitable solution or prevent an accurate strategy for challenges in optimization or searches. These techniques have been produced from natural selection or genetics principles. For random testing, historical information is provided with intelligent enslavement to continue moving the search out from the area of improved features for processing of the outcomes. It is a category of heuristics of evolutionary history using behavioral science-influenced methods like an annuity, gene, preference, or combination (sometimes refers to as hybridization). This method seemed to be a valuable tool to find solutions for problems optimization. In this paper, the author has explored the GAs, its role in engineering pedagogies, and the emerging areas where it is using, and its implementation.

Combating viral disease outbreaks has doubtlessly been one of the major public health challenges for the 21^st century. Here, the host entry machinery required for COVID-19 (SARS-CoV-2) infection was examined for the gene expression profiles and polymorphism. The four human population groups of Europeans, Africans, Asians, and Americans had specific and also a shared pool of variants for the X-linked locus of ACE2 receptor. Several specific and common ACE2 variants were of the utmost importance to the viral entry and infection. In the absence of gender bias for the gene expression profiles, the hemizygous rare variants of ACE2 describe the observed higher mortality rate in males. Finally, a personalized medicine strategy is conceived for isolating high-risk individuals in epidemic circumstances.

Resistance against amitraz in varroa mite populations has become a subject of interest in recent years due to increasing reports of reduced field efficacy of amitraz treatments, especially from some beekeepers in France and the United States. The loss of amitraz as a reliable tool to effectively reduce varroa mite infestation in the field could severely worsen the position of beekeepers in the fight to keep varroa infestation rates in their colonies at low levels. In this publication, we present data from French apiaries, collected in the years 2020 and 2021. These data include field efficacy of an authorized amitraz-based varroa treatment (Apivar®) and results of laboratory sensitivity assays of varroa mites exposed towards the reference LC90 concentration of amitraz. In addition, a total of 240 varroa mites from Eastern, Central, and Southern regions in France that were previously classified as either “sensitive” or “resistant” towards amitraz in a laboratory sensitivity assay were genotyped. The genetic analyses of mite samples are focused on the β−adrenergic-like octopamine receptor, which is considered as the main target site for amitraz in varroa mites. Special attention was given to a single nucleotide polymorphism (SNP) at position 260 of the ORβ-2R-L gene that had previously been described by Hernández Rodríguez et al. (2021) as associated to the resistance to amitraz in French varroa mites. Our findings confirm that amitraz resistance occurs in patches or “islands of resistance” with a less severe reduction in treatment efficacy compared to pyrethroid resistance or coumaphos resistance in varroa mites. The results of our genetic analyses of varroa mites call into question the hypothesis of the SNP at position 260 of the ORβ-2R-L gene being directly responsible for amitraz resistance development.

Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/ or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here we review current knowledge of tauopathies listing known genetic and important sporadic forms of this disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tool and usage of epigenetic therapy strategies for these diseases.

The medicinal plant Abrus precatorius L. was traditionally used in Siddha and Ayurvedic systems of medicine in India. The Indian centre of origin holds vast variability for its seed color. The objective of this study was to assess the total monomeric anthocyanin, flavonol, antioxidative potential, protein content and ash content among the accessions. A total of 99 accessions conserved in the Indian National Genebank were used in this study. The method used for the estimation of total monomeric anthocyanin, flavonol, antioxidative potential, protein content and ash content was pH differential method, Oomah method, Ferric Reducing Antioxidant Potential, Dumas method and gravimetric method respectively. The completely black colored accession was recorded with highest total monomeric anthocyanin (51.95 mg / 100 g of cyanidin 3-glucoside equivalent) and flavonol content (66.41 mg/g of quercetin equivalent). Red + black colored accessions have recorded the maximum value with respect to antioxidants (14.18 mg/g of gallic acid equivalent). Highest amount of protein content was found in a completely white colored accession (20.67%) and maximum ash content was recorded in red + black seed colored accession (4.01%). The promising accessions identified can be used by pharmaceutical companies in drug development and in curing degenerative diseases.

Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.

Background: Currently, completed suicide, suicide ideation, suicide behavior, and suicide attempts are major public health problems worldwide. Major Depressive Disorder (MDD) is one of the most common mental disorders associated with an increased risk of suicide. Since the relationship between suicide and cholesterol levels is still controversial, in this study, we explore the association between SNPs rs754203 and rs4900442 of CYP46A1 with suicide risk in Mexican patients with major depressive disorder. Methods: We evaluated 188 unrelated suicide completers and compared them to 144 non-suicidal individuals (controls) and 126 MDD patients. Genotypes were analyzed using the Real Time-polymerase chain reaction method and two allele-specific probes to detect specific SNP targets. A chi-square test was used to identify a possible risk genotype or allele type for suicide. Results: Statistical analysis showed significant differences between completed suicide and controls in their allelic and genotypic frequencies in rs754203 SNP. The genotype G/G of CYP46A1 rs754203 was significantly associated with suicide. Also, the G allele was associated with an increased risk of suicide (OR= 1.370, 95% CI= 1.002-1.873). No differences in either genotype distribution or allele frequencies of CYP46A1 rs4900442 were observed. Conclusions: The results of the current study report the first association between G allele carriers (A/G + G/G) of rs754203 and increased risk for suicide, especially in males.

The experiments described in this research article were designed to test the effect of rare variants into genomic prediction in dairy cattle. Common polymorphisms are able to explain only a small proportion of the underlying genetic variation of complex phenotypes. Variants representing functional mutations with large effects on complex phenotypes are expected to be rare due to natural (humans) or artificial (livestock) selection pressure. Therefore, it is important to check whether the use of rare variants could increase the accuracy of ranking of animals by providing the tool for more precise differentiation among the bulls with high additive genetic merit. The goal of our study was to verify whether including rare variants in a genomic selection model allows for a more accurate description of the additive genetic background of traits under selection in dairy cattle. We used the linear mixed model for comparison SNP estimates for Holstein-Friesian cattle of the two data sets – a set containing only single nucleotide polymorphisms defined by minor allele frequency ≥ 0.01, which is routinely used in the Polish genomic evaluation system (46,216 SNPs), and a set containing SNPs selected based only on the call rate (54,378 SNPs). Based on the SNP estimates we also calculated DGV and GEBV and compared them between both data sets. In all the analyses we used production, fertility, conformation and udder health traits. We also assessed the time required for the two most computationally demanding components of genomic selection: preparing genotype data, and estimation of SNP effects between those two data sets. The results of our study indicated that the analysis including rare variants resulted in changes in the individual ranking of the top 100 male and female candidates, but had no effect on the outcome of the quality of EBV prediction as expressed by the Interbull validation test.

Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed by transient elastography No patient had cirrhosis at baseline (LSM≥12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected by HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR)=1.14; p=0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM≥5 kPa) [adjusted odds ratio (aOR)=2.37; p=0.029], and greater than 7 kPa (ΔLSM≥7 kPa) [aOR=3.24; p=0.032], after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR=2.18; p=0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Skin cancer is a prevalent and heterogenous disease with several subtypes, such as melanoma, basal cell carcinoma, and squamous cell carcinoma. Among them, melanoma is the most aggressive subtype, with a higher propensity to spread compared to most solid tumors. The application of OMICS approaches has revolutionized the field of melanoma research by providing comprehensive insights into the molecular alterations and biological processes underlying melanoma development and progression. This review aims to offer an overview of melanoma biology, covering its transition from primary to malignant melanoma, as well as the key genes and pathways involved in the initiation and progression of this disease. Utilizing online databases, we extensively explored the general expression profile of genes, identified the most frequently altered genes, and gene mutations, and examined genetic alterations responsible for drug resistance. Additionally, we studied the mechanisms responsible for immune checkpoint inhibitors resistance in melanoma.

Information molecules of DNA and RNA should obey principles of quantum mechanics where unitary operators in form of unitary matrices have key meanings. Unitary matrices are the basis of calculations in quantum computers. This article presents some author's results, which show that matrix forms of the representation of structured systems of molecular-genetic alphabets can be considered as sets of sparse unitary matrices related with phenomenologic features of the degeneracy of the genetic code. These sparse unitary matrices have orthogonal systems of functions in their rows and columns. A complementarity exists among some unitary genetic matrices in relation each other. Decompositions of numeric genetic matrices into sets of sparse unitary matrices are connected with the logical operation of modulo-2 addition used in quantum computers as well. Tensor (or Kronecker) families of unitary genetic matrices with their fractal-like properties are also considered. The described results are discussed in the frame of development of quantum-information approaches for modeling genetic systems.

Determining genetic and non-genetic sources of variation in a breed is vital for the formulation of strategies for its conservation and improvement. The present study was aimed at estimating the (co)variance components and genetic parameters of Mecheri sheep by fitting six different animal models in the restricted maximum likelihood method, with a preliminary investigation on the performance of animals for non-genetic sources of variation. A total of 2616 lambs were studied, and varying levels of significance were found for the effect of period, season, parity of dam and birth type on different body weight traits. Direct heritability estimates derived from the best animal model for body weight at birth, 3 months, 6 months, 9 months and 12 months were 0.21, 0.24, 0.10, 0.15 and 0.09, respectively, and maternal heritabilities of the corresponding traits were 0.12, 0.05, 0.04, 0.04 and 0.04, respectively. The genetic correlations between body weight traits were all positive and moderate to strong except for birth weight with the other body weight traits. The significance of non-genetic factors studied in this work demanded a correction to improve the accuracy of the direct selection of lambs for body weight traits. The estimated genetic parameters identified the weaning weight as a selection criterion for the improvement in body weight of Mecheri lambs at different ages. Inbred individuals accounted for approximately 13% of the total population in the Mecheri sheep population studied. There were 877 founders in the population, and the actual effective size of the population was 128.48. The population's mean generation interval was 3.26. The mean inbreeding values ranged from 0.005 to 0.010 across generations. The population's average relatedness ranged from 0.001 to 0.014 across generations. Individual inbreeding was found to be 0.45 per cent for the entire population and 3.4 per cent for the inbred population.

The grooved carpet-shell clam is one of the most economically relevant shellfish species living in the Mediterranean and nearby Atlantic coasts. Previous studies using different types of genetic markers showed a remarkable genetic divergence of the Eastern Mediterranean, Western Mediterranean and Atlantic populations, but important details remained unclear. Here, data from six nuclear introns scored for restriction fragment size polymorphisms in eight populations that have not been studied before have been pooled for the analysis with data scattered through three previous studies, totaling 32 samples from 29 locations. The results show lower levels of heterozygosity, higher mean number of alleles, and alleles with restricted distribution in the Mediterranean populations, suggesting the existence of a large isolated population in the eastern Mediterranean at the middle Pleistocene. The data also confirm the similarity of populations from Tunisia to western Mediterranean populations. Finally, a genetic mosaic is apparent in the Atlantic coasts of the Iberian Peninsula, with a divergence of Rias Baixas populations from more northern populations and Central Portugal populations. The effects of oceanic fronts, seasonal upwellings, river plumes and/or fishery management operations could explain this and other features of the Atlantic populations.

Polymorphism of vitamin D3 receptor (VDR), has been associated with low bone mineral density and other immune and metabolic disorders; however, its impact on mortality of female dialysis patients is not well studied. This study aimed to identify bone mass-related factors, VDR gene polymorphism, and their interaction with morbid conditions that could influence all-cause mortality. In 246 female dialysis patients, age 43±11 years on continuous ambulatory dialysis peritoneal; 48%, haemodialysis; 23% and automated peritoneal dialysis; 29%. Tscore, Ca, PO4, albumin, hs-CRP, osteoprotegerin, fetuin, osteocalcin, iPTH, PINP and β-CTx were measured. PCR products were digested with Bsml to analyze VDR polymorphisms. Patients n=229; were followed for a median of 17 (15-31) months; 42 patients died. Bsml polymorphism, bb=64% and BB+Bb=36%. Hs-CRP was the risk of death in multivariate Cox Analysis. Patients with bb and inflammation had a higher risk of death (HR 2.48, 95% CI 1.08-5.68) persisted after adjustment for age, diabetes and iPTH (HR 2.33; 95% CI, 1.01-8.33) and after further adjustment for vintage, albumin, osteoprotegerin and vitamin D therapy (HR 3.49; 95% CI, 1.20-10.9). We may conclude that the presences of the bb genotype of VDR and inflammation have additive effects on all cause-mortality in females in CAPD, APD, and HD patients.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

TSPO-PET tracers are sensitive to a single-nucleotide-polymorphism (rs6971-SNP) resulting in low (LAB), medium (MAB) and high (HAB) affinity binders, but the clinical relevance for [18F]GE-180 is still unclear. We evaluate the impact of rs6971-SNP on in vivo [18F]GE-180 binding in healthy brain and in pseudo-reference tissue in neurooncological and neurodegenerative diseases. Standardized uptake values (SUV) of [18F]GE-180-PET were assessed using a manually drawn region of interest in the fronto-parietal and cerebellar hemisphere. SUVs were compared between LAB, MAB and HAB in controls, glioma, 4-repeat tauopathies (4RT) and Alzheimer’s disease (AD) subjects. Second, SUVs were compared between patients and controls within their rs6971-subgroup. After exclusion of patients with prior therapy, n=24 LABs (n=7 controls, n=5 glioma, n=6 4RT, n=6 AD) were analysed. Age- and sex-matched MABs (n=38) and HABs (n=50) were selected. LABs had lower fronto-parietal and cerebellar SUVs when compared to MABs and HABs, but no significant difference was observed between MABs and HABs. Within each rs6971 group no SUV difference between patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [18F]GE-180 quantification, revealing lower binding in LABs when compared to MABs/HABs. Fronto-parietal and cerebellar ROIs were successfully validated as pseudo-reference regions.

Acanthamoeba keratitis (AK) is a severe, rare protozoal infection of the cornea. Acanthamoeba can survive in diverse habitats and at extreme temperatures. AK is mostly seen in contact lens wearers, whose lenses have become contaminated, or a history of water exposure, and in those without contact lens wear, who have experienced recent eye trauma involving contaminated soil or water. Infection usually results in severe eye pain, photophobia, inflammation, and corneal epithelial defects. The pathophysiology of this infection is multifactorial, including the production of cytotoxic proteases by Acanthamoeba that degrades the corneal epithelial basement membrane and induce the death of ocular surface cells, resulting in degradation of the collagen-rich corneal stroma. AK can be prevented by avoiding the risk factors, which include avoiding water contact such as swimming or showering in contact lenses, and wearing protective goggles when working on the land. AK is mostly treated with an antimicrobial therapy of biguanides alone or in combination with diaminidines, although the commercial availability of these medicines is variable. Other than anti-amoeba therapies, targeting host immune pathways in Acanthamoeba disease may lead to the development of vaccines or antibody therapeutics which could transform the management of AK.

The article shows materials to the question about algebraic features of the genetic code and about the dictatorial influence of the DNA and RNA molecules on the whole organism. Presented results testify in favor that the genetic code is an algebraic code related with a wide class of algebraic codes, which are a basis of noise-immune coding of information in communication technologies. Structural features of the genetic systems are associated with hypercomplex double (or hyperbolic) numbers and with bisymmetric doubly stochastic matrices. The received results confirm that represented matrix approaches are effective for modeling genetic phenomena and revealing the interconnections of structures of biological bodies at various levels of their organization. This allows one to think that living organisms are algebraically encoded entities where structures of genetic molecules have the dictatorial influence on inherited structures of the whole organism. New described algebraic approaches and results are discussed.

Impressing discoveries in the field of the genetic code have been described by its researchers by means of the terminology borrowed from linguistics and the theory of communications. Leading experts on structural linguistics believe for a long time already that languages of human dialogue were formed not from an empty place, but they are continuation of genetic language or, anyhow, are closely connected with it, confirming the idea of information commonality of organisms. The aticle continues the theme about a connection of linquistic languages with the genetic language. It describes results of comparative study of long Russian literary texts (novels by L.Tolstoy, F.Dostoevsky, A.Pushkin, etc.) and long sequences of hydrogen bonds in double helixes of DNA of different organisms. Formalisms of quantum informatics are used in modeling some of these results taking into account thoughts of many researches about possible using principles of quantum informatics in organisation of living bodies.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR) gene, which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR variant, which has recently been related to longevity, is associated with enhanced signal transduction and higher receptor function. Many of these studies indicated that the growth response to GH treatment may be affected. Individuals carrying the d3GHR isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the WT isoform. Further, studies performed in patients with acromegaly, Prader-Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR variant may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.

Human tuberculosis (TB) is caused mainly by Mycobacterium tuberculosis (MTB) and M. africanum (MAF) remains a major global health threat. The varying response of different host to contact with the TB bacteria, indicates the importance of host genetics in susceptibility to TB disease. We explored the association among selected human/host genomic variants and disease caused by the two causative pathogens in Ghana through a case control study. MTBC isolates (323) recovered from pulmonary TB patients recruited between 2016 and 2018 were genotyped using spoligotyping. A selection of 29 SNPs from MTB-related genes with high frequency among African populations were genotyped using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Associations between MTBC lineages and host variables were assessed using univariate and multivariate logistic regression. The prevalence of MTB and Maf among the participants were 79% and 21% respectively. Association analysis between the controls and MAF showed that rs2695342 variant on the SIC11A1 gene have the propensity to confer susceptibility to MAF infections (P = 0.093, OR = 8.35, 95% CI = 0.70 – 99.24) whilst the rs17048476 (P = 0.088, OR = 1.57, 95% CI = 0.93 – 2.63) and rs1482868 (P = 0.095, OR = 0.60, 95% CI = 0.33 – 1.09) were observed to be only suggestive. Our findings implicate SLC11A1 as a potential susceptibility gene of substantial interest for TB caused by MAF which is an important pathogen in West Africa and highlight the need for in-depth host pathogen studies in West Africa.

The aim of this study is to have an idea on the molecular mechanisms of C. albicans resistance to fluconazole in Burkina Faso, by studying the polymorphism of the ERG11 gene, and its implication in the C. albicans virulence and resistance in vivo according to the Galleria mellonella model; (2) Methods: Ten (10) clinical strains including, 5 resistant and 5 susceptible and 1 virulent and susceptible reference strain SC5314 are used. For the estimation of virulence, the larvae were inoculated with 10 μL of C. albicans cell suspension at variable concentrations: 2,5.105, 5.105, 1.106, and 5.106 CFU/larva of each strain. For the in vivo efficacy study, fluconazole was administered at 1, 4 and 16 mg/kg respectively to G. mellonella larvae, after infection by inoculum 5.106 CFU / larvae of each strain; (3) Results: Six (6) non-silent mutations in the ERG11 gene (K143R, F145L, G307S, S405F, G448E, V456I on ERG11p) were found in 4 resistant isolates. Larval mortality depended on fungal burden and strain. The inoculum 5.106 CFU caused 100% mortality in 2 days for the 2 CAAL-1 and CAAL-2 strains carrying the F145L mutation, in 3 days for the reference strain SC5314, in 4 days for the ensemble of resistant strains, and in 5 days for the ensemble of susceptible strains. The comparison of the mortality due to the reference strain SC5314 CFU / larva and the average mortality due to the two mutant F145L strains, shows a significant difference (P <0.05).Fluconazole significantly protected (P> 0.05) the larvae from infection by susceptible strains and the reference strain. However, 100% mortality in 6 days after injection of the resistant strains, was observed (4) Conclusions: Certain mutations in the ERG11 gene such as the F145L mutation are thought to be a source of increased virulence in Candida albicans. Fluconazole effectively protected larvae from infection by susceptible strains in vivo, unlike resistant strain

Cotton fiber, a crucial and sustainable resource for global textile production, undergoes a complex five-stage developmental process, encompassing initiation, elongation, transition, secondary cell wall biosynthesis, and maturation. These elongated single-cell fibers originate from the outer ovule epidermis. The development of cotton fibers involves intricate changes in gene expression and physiological processes, resulting in a nearly pure cellulose product vital for the global cotton industry. Decoding genes associated with fiber development enhances our understanding of cotton fiber mechanisms and facilitates the cultivation of varieties with enhanced quality. In recent decades, advanced omics approaches, including genomics, transcriptomics, and proteomics, have played a pivotal role in identifying genes and gene products linked to cotton fiber development, including the MYB transcription factor family which coordinates cotton fiber development. Molecular studies have revealed transcription factors like MYB, WRKY, Homeodomain Leucine Zipper (HD-ZIP) and basic Helix-Loop-Helix (bHLH) influencing fiber initiation and elongation. The intricate interplay of phytohormones like auxin, gibberellic acid (GA), brassinosteroid (BR), jasmonic acid (JA), ethylene, abscisic acid (ABA), and cytokinin is explored, providing a comprehensive perspective on shaping cotton fibers. Numerous candidate genes and cellular processes affecting various aspects of fiber development hold promise for genetic engineering or marker-assisted breeding to improve fiber quality. This review presents a comprehensive overview of key achievements in cotton molecular biology, with a specific emphasis on recent advancements in understanding transcription factors and phytohormones involved in cotton fiber initiation and elongation.

Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is limited due to its high interindividual and interpopulation variability. The lipid ratios: atherogenic index of plasma (AIP=log TG/HDL-C) and the Castelli risk index 2 (CI2=LDL-C/HDL-C) have been proposed as better predictors of cardiovascular risk, but the genetic variability associated to these ratios has not been investigated. This study aimed to identify genetic associations with these indexes. The study population (n=426) included males (40%) and females (60%) aged 18-52 years (mean 39 years), the Infinium GSA array was used for genotyping. Regression models were developed using R and PLINK. AIP was associated with variation on APOC3, KCND3, CYBA, CCDC141/TTN, and ARRB1 (p-value < 2.1E-6) the three former previously associated to blood lipids, while CI2 was associated with variants on DIPK2B, LIPC, and 10q21.3 rs11251177 (p-value 1.1E-7) the latter previously linked to coronary atherosclerosis and hypertension. KCND3 rs6703437 was associated with both indexes. This study is the first to characterize the potential link between genetic variation and atherogenic indexes, AIP and CI2, highlighting the relation between genetic variation and dyslipidemia predictors. These results also contribute to consolidating the genetics of blood lipid and lipid indexes.

Background: Exposure to chronic low levels of aflatoxin B1 (AFB1) contamination can lead to immune suppression and nutritional consequences that might greatly contributed in the increase of hepatocellular carcinoma (HCC). The toxicity of AFB1 is greatly vary between different population, affected by age, gender, and environmental factors. Material and subjects: Aflatoxin B1 (AFB1) was measured in 50 blood samples collected from non B, C hepatitis viruses and non CMV-Ab liver disease patients from different general hospitals and polyclinic in KSA during period 01-2013 to 06-2014. All Patients demonstrate elevation of ALT and AST with unknown etiology. Serum samples were obtained and kept at −20 °C for AFB1detection. Results: Out of the 50 blood samples, 38 demonstrate a detectable serum level of AFB1 while the remaining 12 patients were AFB1 negative and used as control participants. While AST was non-significantly different in AFB1 exposed patients, ALT was significantly higher in AFB1 positive samples compared to control AFB1-negative. AFB1 was positively correlated with AST and ALT as liver function enzymes and with age as a risk factor of long duration of AFB1 chronic exposure. Multiple linear regression analysis ascertained the association between AFB1 chronic exposure and ALT increase in liver dysfunction Saudi patients. Conclusion: Measurement of elevated ALT as marker of liver injury in AFB1 chronically exposed Saudi patients can help to avoid the future development of HCC. Moreover, early detection of AFB1 exposure, together with early vaccination against HBV and HCV can remove the synergistic effects of these two etiological factors and thus decrease the risk of developing liver cancer.

This paper introduces the implementation of a genetic programming (GP)-based procedure to the automatic design and tuning of process controllers. The proposed approach makes a significant contribution to the field of artificial intelligence (AI) in control engineering. Unlike other controller design methods, the GP-based program handles the entire design in the time domain, including differential operations like derivatives and integrals, without the need for intermediate inverse Laplace transformation. This approach not only simplifies the design process but also ensures that all generated controllers are implementable in physical systems. Furthermore, GP’s functions set includes various mathematical operations beyond basic arithmetic operators, such as trigonometric, exponential, and logarithmic operators. The performance and validity of the resulting controllers generated by the proposed GP-based approach are evaluated by verifying whether the generator can replicate the structure and performance of those produced by traditional controller design methods and, in some cases, achieve even better results. As a result, the GP-based approach presents a promising solution for automating the controller design process and addressing control problems in various engineering applications.

Ovarian cancers are curable by surgical resection when discovered early enough. Unfortunately, most ovarian cancers are diagnosed in the later stages. One strategy to identify early ovarian tumors is to screen women who have the highest risk scores. This mini review summarizes the accuracy of different methods used to assess the risk of developing ovarian cancer, including family history, BRCA genetic tests, and polygenic risk scores. The accuracy of these is compared to the maximum theoretical accuracy, revealing a substantial gap. We suggest that this gap, or missing heritability, could be caused by epistatic interactions between genes. An alternative approach to computing genetic risk scores, using chromosomal-scale length variation should incorporate epistatic interactions. Future research in this area should focus on this and other alternative methods of characterizing genomes.

Missense mutations in the LRRK2 gene were first identified as a pathogenic cause of Parkinson’s disease (PD) in 2004. Soon thereafter, a founder mutation in LRRK2, p.Gly2019Ser (rs34637584), was described, and it is now estimated that there are approximately 100,000 people worldwide that carry this risk variant. While the clinical presentation of LRRK2 parkinsonism has been largely indistinguishable from sporadic PD, disease penetrance and age at onset can be quite variable. In addition, its neuropathological features span a wide range from nigrostriatal loss with Lewy body pathology, lack thereof, or atypical neuropathology including a large proportion of cases with concomitant Alzheimer’s pathology, hailing LRRK2 parkinsonism as the "Rosetta stone" of parkinsonian disorders. These differences may result from interactions between LRRK2 mutant protein and other proteins or environmental factors that modify LRRK2 function, and thereby influence pathobiology. This review explores how potential genetic and biochemical modifiers of LRRK2 function may contribute to the onset and clinical presentation of LRRK2 parkinsonism. We review, which genetic modifiers of LRRK2 influence clinical symptoms, age at onset, and penetrance, what LRRK2 mutations are associated with pleomorphic LRRK2 neuropathology, and which environmental modifiers can augment LRRK2 mutant pathophysiology. Understanding how LRRK2 function is influenced and modulated by other interactors and environmental factors –either increasing toxicity or providing resilience- will inform targeted therapeutic development in the years to come. This will allow developing disease-modifying therapies for PD and LRRK2-related neurodegeneration.

Biological systems often need to operate in complex environments where conditions can rapidly change. This is possible due to their inherent ability to sense changes and adapt their behavior in response. Here, we detail recent advances in the creation of synthetic genetic parts and circuits whose behaviors can be dynamically tuned through a variety of intra- and extra-cellular signals. We show how this capability lays the foundation for implementing control engineering schemes in living cells and allows for the creation of biological systems that are able to self-adapt, ensuring their functionality is maintained in the face of varying environmental and physiological conditions. We end by discussing some of the broader implications of this technology for the safe deployment of synthetic biology.

Dispersal represents a key life-history trait with several implications for the fitness of organisms, population dynamics and resilience, local adaptation, meta-population dynamics, range shifting and biological invasions. Plastic and evolutionary changes of dispersal traits have been intensively studied over the past decades in entomology, in particular in wing-dimorphic insects for which literature reviews are available. Importantly, dispersal polymorphism also exists in wing-monomorphic and wingless insects, and except for butterflies, fewer syntheses are available. In this perspective, by integrating the very last research in the fast moving field of insect dispersal ecology, this review article provides an overview of our current knowledge of dispersal polymorphism in insects. After having provided a definition of the main terms characterising insects’ movements, some of the most often used experimental methodologies for the separation of dispersers and residents in wing-monomorphic and wingless insects are presented. The existing knowledge on the morphological and life-history trait differences between resident and disperser phenotypes is then synthetized. The fourth part examines the effects of range expansion on dispersal traits and performance, in particular for insects from range edges and invasion fronts. Finally, some research perspectives are proposed in the last part of the review.

The Populus L. genus unites tree species, which are botanically grouped into several sections. The species successfully hybridize both in the same section and between some sections. The poplar hybridization widely occurs in nature and in variety breeding. Therefore, the development of poplar species specific molecular markers is very actual. The effective markers for trees of the Aigeiros Daby section have been recently developed using the polymorphism of the 5S rDNA non-transcribed spacers (NTSs). In this article, the 5S rDNA NTS based markers were designed for several species of the Leuce Daby section. The alb9 marker amplifies one fragment with DNA matrix of P. alba and P. × canescens (natural hybrid P. alba × P. tremula). The alb2 marker works the same way except the case with P. bolleana. In this case, the amplification of three fragments was observed. The tremu1 marker amplification is detected with DNA matrix of P. tremula and P. × canescens. Thus, the developed markers may be applied as useful tool for the P. alba, P. tremula, P. × canescens and P. bolleana identification in such areas of plant science as botany, dendrology, genetics of populations, variety breeding etc.