At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

Cellular Integrated Stress Response (ISR), the mitochondrial Unfolded Protein Response (UP-Rmt) and the IFN signaling are associated with viral infections. The Activating transcription fac-tor 4 (ATF4) plays a pivotal role in these pathways and controls the expression of many genes involved in redox processes, amino acid metabolism, protein misfolding, autophagy and apop-tosis. The precise role of ATF4 during viral infection is unclear and depends on cell hosts, viral agents and models. Furthermore, ATF4 signaling can be hijacked by pathogens to favor viral in-fection and replication. In this review, we summarize the ATF4-mediated signaling pathways in response to viral infections, focusing on human immunodeficiency virus (HIV). We examine the consequences of ATF4 activation for HIV replication and reactivation. The role of ATF4 in au-tophagy and apoptosis is explored as in the context of HIV infection programmed cell deaths contribute to the depletion of CD4 T cells. Furthermore, ATF4 can also participate in the estab-lishment of innate and adaptive immunity that are essential for the host to control viral infec-tions. We finally discuss the putative role of the ATF4 paralogue, named ATF5, in HIV infection. This review underlines the role of ATF4 at the crossroads of multiple processes reflecting host-pathogen interactions.

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exist e.g. in Parkinson’s disease or Alzheimer’s disease, there are only few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disorder characterized by progressive motor neuron degeneration. Initial studies, however, highlight that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, mitochondrial and dysfunction alterations in mitochondrial morphology, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2 and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc- and GPX4 activity, respectively, yielding in lipid peroxidation and cellular demise. Mutations in Fused in Sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as putative cell death pathway in motor neuron demise. However, mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated ferroptosis vulnerability in a FUS-ALS cell model, revealing mitochondrial disturbance and increased susceptibility for ferroptosis in cells harboring the mutant FUS variant. This was accompanied by altered expression of ferroptosis-associated proteins, particularly by dramatic reduction of xCT expression, leading to cellular imbalance of the redox system and increased lipid peroxidation. Iron chelation with deferoxamine as well as inhibition of the mitochondrial calcium uniporter (MCU) significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential therapeutic targets.

In this paper, a low-power Injection-Locked Clock and Data Recovery (ILCDR) using 28nm FDSOI technology is presented. The back-gate auto-biasing of UTBB-FDSOI transistors allows us to create a QRO (Quadrature Ring Oscillator) reducing both size and power consumption. By injecting a digital signal into this circuit, we realize an Injection-Locked Oscillator (ILO) with low jitter. Thanks to the good performance of this oscillator, we propose a low power ILCDR with fast locking time and low jitter for burst-mode applications. The main novelty consists in the implementation of a complementary QRO based on back-gate control using FDSOI technology to realize a simple and efficient ILCDR circuit. With a Pseudo-Random Binary Sequence (PRBS7) at 868Mbps, the recovered clock jitter is 26.7ps (2.3%UIp-p) and the recovered data jitter is 11.9ps (1%UIp-p). With a 0.6V power supply, the power consumption is 318μW. The estimated Chip area is around 6600μm².

Plant growth regulators (PGRs) and deficit irrigation (DI) play a crucial strategic role in sustaining agricultural yield and reducing water stress in drought prone areas. The study was carried out in 2021-2022 to assess the impact of various PGRs (SA & NAA) & irrigation levels (60% Epan, 80 % Epan, and 100 % Epan) with DI & partial root drying (PRD) irrigation strategies. PGR application boosted fruit yields and demonstrated its significance in reducing water stress by lowering canopy temperature, maintaining higher relative water content in the leaves, modifying stomatal opening, and increasing photosynthetic rate. PGRs were used to assess the increased accumulation of total phenols, flavonoids, and improved antioxidant activity. Results indicated that exogenous use of PGRs like SA+NAA in conjunction with 80% irrigation levels increased fruit yield (31.97 and 40.38%) and water productivity (64.92 and 75.39%) for DI and PRD treatments, respectively. Thus standardizing irrigation and crop management practices including PGR application can be recommended to boost pomegranate productivity particularly in water-scarce environments.

Stress Granules formation is a pro-survival mechanism helping cells to cope with environmental challenges. Stress Granules have been studied for two decades in fundamental research, and are now being examined in the context of human pathogenesis. Here, we review studies highlighting stress granules’ involvement in cancer development through translational pattern modification.

Aging is associated with an increasing dysfunction of key brain homeostasis mechanisms and represents the main risk factor across most neurodegenerative disorders. However, the degree of dysregulation and the affectation of specific pathways set apart normal aging from neurodegenerative disorders. In particular, the neuronal metabolism of catecholaminergic neurotransmitters appears to be a specifically sensitive pathway that is affected in different neurodegenerations. In humans, catecholaminergic neurons are characterized by an age-related accumulation of neuromelanin (NM), rendering the soma of the neurons black. This intracellular NM appears to serve as a very efficient quencher for toxic molecules. However, when a neuron degenerates, NM is released together with its load (many undegraded cellular components, transition metals, lipids, antibiotics) contributing to initiate and worsen an eventual immune response, exacerbating the oxidative stress, ultimately leading to the neurodegenerative process. This review focuses on the analysis of the role of NM in normal aging and catecholaminergic metabolism due to its capability as a pro-oxidant and other harmful molecules, versus its involvement in oxidative stress and aberrant immune response, which it is highly dependent on NM saturation state and its extracellular release.

Sustainable development and education in sustainable development (ESD) are crucial and interconnected topics under wide discussion today. Young adults need to be educated in how to help bring about change. Thus, the dynamic relationship between school and home is important. In education, use could be made of English language classes, especially since English is a global language that enables access to the sustainability literature and facilitates discussion in global conferences and meetings. Consequently, English as a foreign language (EFL) students could gain confidence from being able to understand and use the terminology of, for example, sustainability. In this paper, the use of competence-based language teaching (CBLT) is proposed as a means of introducing sustainability topics into EFL writing classes at a university in Saudi Arabia. Students’ competence in sustainable development is therefore considered based on their ability to write about suggested sustainable development topics, measured on a scale for five dimensions of ESD proposed by Michelsen and Fischer (2017). The results demonstrate that the students possessed competence in sustainable development and intended to participate in its implementation. Thus, recommendations are made for the stakeholders in the education sector to include sustainable development topics as an initial offering in the curricula of various specialties using the CBLT approach.

Phosphite (Phi) has gained attention in agriculture due to its biostimulant effect on crops. This molecule has been found to benefit plant performance by providing protection against pathogens, improving yield and fruit quality, and improving nutrient and water use efficiency. It is still unclear how Phi enhances plant growth and protects against multiple stresses. It has been hypothesized that Phi acts by directly affecting the pathogens and interacting with the plant cellular components and molecular machinery to elicit defense responses. This study delves into elucidating the mechanisms underlying Phi’s beneficial effects on plants, revealing a complex interplay with fundamental signaling pathways. A RNA-seq study of Arabidopsis seedlings under optimal and limiting phosphate conditions helped us unveil Phi’s role in promoting plant growth by activating the expression of genes involved in the biosynthesis and signaling pathways associated with abscisic acid (ABA), salicylic acid (SA), and jasmonic acid (JA). Expression of ABA-related genes, known for their involvement in stress response and development regulation, is triggered by Phi treatment, contributing to enhanced resilience and growth. Simultaneously, the activation of the SA pathway, associated with defense responses, suggests Phi’s potential in bolstering plant immunity. Moreover, Phi influences JA biosynthesis and signaling, which are crucial for defense against herbivores and pathogens, thereby strengthening plants’ defenses. Our findings reveal a multifaceted mechanism through which Phi benefits Arabidopsis development. Understanding its intricate interplay with key signaling pathways opens avenues for leveraging Phi as a strategic tool to enhance plant resilience, immunity, and growth in agricultural and ecological contexts.

Neurodegenerative diseases like Alzheimer’s disease (AD) are poised to become a global health crisis, and therefore understanding the mechanisms underlying the pathogenesis is critical for the development of therapeutic strategies. Mutations in genes encoding presenilin occur in most familial Alzheimer’s disease but the role of PSEN in AD is not fully understood. In this review, the potential modes of pathogenesis of AD are discussed, focusing on calcium homeostasis and mitochondrial function. Moreover, research using Caenorhabditis elegans to explore the effects of calcium dysregulation due to presenilin mutations on mitochondrial function, oxidative stress and neurodegeneration is explored.

To enhance pomegranate production on marginal gravelly lands, standardized planting techniques were evaluated in an 8-year-old orchard. Trenching, wider pit excavation, pit digging, and auger digs with dimensions of 1 and 2 m were employed. Utilizing native soil from barren land, with or without spent wash, and mixing it with black soil up to 1 m deep, growth parameters, leaf nutrients, fruit production, and fruit quality were assessed. The trench and wider pit methods outperformed others, yielding greater above-ground biomass (>70.3 kg tree⁻¹), root biomass (>24.5 kg, tree⁻¹), and cross-sectional area (>3.30 m² tree⁻¹). These methods also produced longer roots (>4.0 m tree⁻¹) and higher leaf phosphorus (>0.28%) and potassium (>1.81%) levels, fruit juice content (>48.50%), and total soluble solids (>16.05°) compared to other planting methods. This resulted in higher and more sustainable fruit yield production under the trench and wider pit planting methods (>7.21 t ha⁻¹). Similarly, the native and black soil mixture produced healthy fruit trees, improved fruit quality, and sustainably higher fruit yield over the native soil alone. In summary, the trench and wider pit methods (2–3 m³), combined with a soil mixture, are recommended for sustainable, high-quality fruit production in shallow gravelly terrains, thereby improving food security and the livelihoods of farmers in arid regions.

The intricacies of translational strategies make this stage of the implementation of genetic information one of the most difficult to understand and, at the same time, perhaps the most interesting. It also becomes clear that all this variety of strategies is not just a consequence of a long evolutionary history but is of paramount importance for fine-tuning gene expression and metabolic modulation. This is especially true for those organisms that demonstrate predominantly biochemical and physiological reactions with a lack of behavioural ones. Plants are just such a group of organisms. Overcoming unfavourable environmental conditions occupies a key place in plant physiology. This is especially true with the changing conditions of global warming and the irretrievable loss or depletion of natural ecosystems. Conceptually, the response of plants to abiotic stress is a set of complex and intricate strategies. This is dictated both by a variety of abiotic factors that provoke stressful conditions and by a variety of molecular genetic mechanisms that make it possible to fine-tune the metabolic pathways through which the plant organism overcomes non-standard and non-optimal conditions. In the presented review, we tried to focus on the state-of-the-art in the field of translational regulation in plants under abiotic stress conditions. Various regulatory elements and patterns are considered in relative chronological order. We also considered it necessary to pay attention to key high-performance methods for studying the dynamics of genetic information at the stage of translation.

Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that occurs following exposure to traumatic events. The prevalence of PTSD is estimated to be 5-10% worldwide, and it is associated with significant distress and disability. Recent evidence suggests that PTSD may be a risk factor for the development of subsequent neurodegenerative disorders, including Alzheimer’s dementia and Parkinson’s disease. Identification of biomarkers known to be associated with neurodegeneration in patients with PTSD would shed light on the pathophysiological mechanisms linking these disorders, and would also help in the development of preventive approaches aimed at reducing the risk of neurodegenerative disorders in PTSD. In the current review, the PubMed and Scopus databases were searched for studies aimed at identifying genetic, biochemical, neuroimaging or behavioral markers associated with neurodegeneration in patients with PTSD. Out of a total of 342 citations retrieved, 29 relevant studies were identified for inclusion in the review. The results of these studies suggest that several potentially relevant biological markers, including cerebral cortical thinning, disrupted white matter integrity, specific genetic polymorphisms, immune-inflammatory alterations, vitamin D deficiency, metabolic syndrome and parasomnias, may be associated with an increased risk of neurodegeneration in patients with PTSD. Though many of these results need replication, they highlight a number of biological pathways that plausibly link PTSD with neurodegenerative disorders, and suggest potentially valuable avenues for prevention and early intervention in this patient population.

We are currently facing a potential ‘polycrisis’, a critical inflection point that requires a whole-of-society response aimed at building collective foresight and preparedness for short-, medium-, and long-term risks. The role of higher education institutions and social stakeholders is decisive to make an impact. This paper depicts the alignment of academia, governance, and industry with the aim to challenge, inspire, and encourage universities to go beyond commodified courses and mere employability, enhance student growth and bind macro-scale measures that lead to a sustainable future. A modest teaching innovation project has served as a transforming lever, with the private sector joining in, to create a platform that reaches more than 50 000 undergraduate students and teaching staff. The resulting structure, rooted in the University’s strategic plan, has served to channel local and regional initiatives, establish effective partnerships with broad social members, raise awareness and promote actions to advance in the pursuit of Sustainable Development Goals. Chronology, materials and methodology, together with a description of the different courses, programmes and actions are provided. The paper concludes with some recommendations for future research, policy and cooperation among stakeholders. Research methodology posted on clinicaltrials.gov under ID NCT04392869, NCT05598944, and NCT05775978.

We are currently facing a potential ‘polycrisis’, a critical inflection point that requires a whole-of-society response aimed at building collective foresight and preparedness for short-, medium-, and long-term risks. The role of higher education institutions and social stakeholders is decisive to make an impact. This paper depicts the alignment of academia, governance, and industry with the aim to challenge, inspire, and encourage universities to go beyond commodified courses and mere employability, enhance student growth and bind macro-scale measures that lead to a sustainable future. A modest teaching innovation project has served as a transforming lever, with the private sector joining in, to create a platform that reaches more than 50 000 undergraduate students and teaching staff. The resulting structure, rooted in the University’s strategic plan, has served to channel local and regional initiatives, establish effective partnerships with broad social members, raise awareness and promote actions to advance in the pursuit of Sustainable Development Goals. Chronology, materials and methodology, together with a description of the different courses, programmes and actions are provided. The paper concludes with some recommendations for future research, policy and cooperation among stakeholders. Research methodology posted on clinicaltrials.gov under ID NCT04392869, NCT05598944, and NCT05775978.

Stress is one of the important factors affecting the growth and development of plants. In recent years, a large body of data on transcriptional changes in response to stress in plants has been obtained. Despite the fact that the important role of the regulation of translation in response to stress has been proven in plants, knowledge in this area remains extremely scarce. In this review, we focused on mRNA translation in the cytoplasm of higher plants. Most of the current research on the effects of translation has been done in yeast and mammalian systems. Translation factors and mechanisms are mostly conserved among eukaryotes; however, some differences are known to exist among plants. A comprehensive understanding of the complex apparatus of translation and its regulation in plants is required. In this work, we have tried to update modern ideas about the regulation of translation under conditions of abiotic stress.

In the ongoing transition from fossil fuels to renewable energies, advances are particularly expected regarding safe and cost-effective solutions. Publicising instances of such advances and emphasising safety considerations constitute the rationale for this communication. Knowing that high-strength steels can prove economically relevant for transporting hydrogen in pipelines by limiting the pipe wall thickness required to withstand high pressure, one advance relates to a bench designed for contributing to study the safety of the gaseous transport or renewable-energy-related buffer storage of hydrogen. That bench has been specifically implemented at technology readiness level TRL 6 for testing initially intact, damaged, or pre-notched DN 300/NPS 12, DN 600/NPS 24, and DN 900/NPS 36 pipe sections in order to provide data allowing for the possible validation of fully satisfactory predictive models in terms of hydrogen embrittlement and potential corollary ruin. The other advance relates to the reactivation of a previously fruitful applied research into mass solid-state hydrogen storage through a new public-private partnership. This latest development comes at a time when markets have started driving the hydrogen economy, bearing in mind that phase-change materials decisively allow levelling the heat transfers during the absorption/melting and solidification/desorption cycles and attaining an overall energy efficiency of up to 80% for MgH₂-based compacts doped with expanded natural graphite.

Many neurodegenerative diseases are characterised by impairment of protein quality control mechanisms in neuronal cells. Ineffective clearance of misfolded proteins by the proteasome, autophagy pathways and exocytosis leads to accumulation of toxic protein oligomers and aggregates in neurons. Toxic protein species affect various cellular functions resulting in the development of a spectrum of different neurodegenerative proteinopathies, including Huntington’s disease (HD). Playing an integral role in proteostasis, dysfunction of the ubiquitylation system in HD is progressive and multi-faceted with numerous biochemical pathways affected, in particular the ubiquitin proteasome system and autophagy routes for protein aggregate degradation. Unravelling the molecular mechanisms involved in HD pathogenesis of proteostasis provides insight in disease progression in HD as well as possible therapeutic avenues. Recent developments of potential therapeutics are discussed in this review.

In recent years, the chiral biological effects of nanomedicines have become a subject of widespread interest. The research focus has been on understanding the influence of material chirality on cellular transcription and metabolism. Stress granules are membraneless organelles formed through liquid-liquid phase separation of G3BP1 proteins and related compartments. They have been extensively studied and proven to be closely associated with cellular damage repair and metabolism. However, the role and mechanism of chiral nanomaterials in modulating stress granules remain unknown. The aim of this study was to investigate the expression and structural characteristics of stress granules under the individual influence of chiral nanomaterials and in combination with chemotherapy. To achieve this, we constructed a library of chiral ligand-modified materials and employed immunofluorescence, live-cell imaging, and fluorescence recovery after photobleaching assays. We also used proximity labeling techniques combined with proteomics analysis to identify the protein corona adsorbed on the surface of the nanomaterials and explore their relationship with nanomaterial chirality. Our results demonstrate that the assembly of stress granules is chiral-dependent and can be regulated by chiral nanomaterials. Furthermore, we achieved enhanced chemotherapy sensitivity in cancer cells and protected normal cells by exploiting the chiral-dependent modulation of material assembly in stress granules. This study provides important insights into the regulation of membraneless cellular structures based on chiral biological effects.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

Neurological disorders, such as amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease, are commonly associated with persistent neuro-inflammation, and there is an urgent need to discover new therapeutic agents that may target the various pathways involved in neurodegeneration. In this study, we investigated the therapeutic potential of folecitin, a flavonoid isolated from Hypericum oblongifolium, against lipopolysaccharide (LPS)-induced oxidative stress associated with neurodegeneration, amyloidogenic Aβ production pathway, and memory dysfunction in mice. LPS was administered i.p. at 250 µg/kg/day for 3 weeks, followed by the administration of folecitin at a dose of 30 mg/kg/day for the last two weeks. A Western blot technique was used to assess the expression of different proteins involved in oxidative stress, neurodegeneration, and neuronal synapse. Results indicated that folecitin significantly reduced LPS-induced apoptotic neurodegeneration, including the expression of BAX, Caspase-3, and PARP-1 proteins, inhibited BACE1, and the amyloidogenic Aβ production pathway. Folecitin improved both pre- and post-neuronal synapse, as well as memory dysfunction. Furthermore, folecitin significantly activated endogenous antioxidant proteins such as Nrf-2 and HO-1 via stimulating the phosphorylation of Akt proteins. These findings suggest that folecitin may be a suitable lead to design new drugs for neurotoxin-triggered neurodegenerative disorders.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

Ectopic expression of the MYB transcription factor of AmROSEA1 from Antirrhinum majus has been reported to change anthocyanin and other metabolites in several species. In this study, we found that overexpression of AmRosea1 significantly improved the tolerance of transgenic rice to drought and salinity stress. Transcriptome analysis revealed that a considerable amount of stress-related genes were affected by exogenous AmRosea1 during both drought and salinity stress treatments. These affected genes are involved in stress signal transduction, the hormone signal pathway, ion homeostasis and the enzymes that remove peroxides. This work suggests that the AmRosea1 gene is a potential candidate for genetic engineering of crops.

In this work SiC-Ti3AlC2 and TiC-Ti3AlC2 composites produced by additive manufacturing are investigated. The fused granules fabrication (FGF) method as one of the material extrusion additive manufacturing (MEAM) technology is used to obtain composite samples. Composites with different ratios between components and different powder:polymer ratios are investigated. The technological features of the additive formation of composites are investigated, as well as their structure and properties. The optimal sintering temperature to form the best mechanical properties for both composites is 1300 °C. The composites have a regulatable porosity. Ti3AlC2 content, sintering temperature, and polymer content in the feedstock are the main parameters that regulates the porosity of FGF samples.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

Mitochondria are dynamic organelles that can adjust and respond to different stimuli within a cell. This plastic ability allows them to effectively coordinate several cellular functions in cells and becomes particularly relevant in highly complex cells such as neurons. An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular function and ultimately to a range of diseases, including neurodegenerative disorders. Regulation of mRNA transport and local translation inside neurons is crucial for maintaining the proteome of distal mitochondria, which is vital for energy production and synaptic function. A significant portion of the axonal transcriptome is dedicated to mRNAs for mitochondrial proteins, emphasizing the importance of local translation in sustaining mitochondrial function in areas far from the cell body. In neurons, local translation and the regulation of mRNAs encoding mitochondrial-shaping proteins could be essential for synaptic plasticity and neuronal health. The dynamics of these mRNAs, including their transport and local translation, may influence the morphology and function of mitochondria, thereby affecting the overall energy status and responsiveness of synapses. Comprehending the mitochondria-related mRNAs regulation and local translation, as well as its influence on mitochondrial morphology near the synapses will help to better understand neuronal physiology and neurological diseases where mitochondrial dysfunction and impaired synaptic plasticity play a central role.

As the global population ages, the prevalence of neurodegenerative diseases has become a major public health concern. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks—such as genomic instability, telomere attrition, and neuroinflammation—and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.

Neurodegenerative protein conformational diseases are characterized by misfolding and aggregation of metastable proteins encoded within the host genome. The host is also home to thousands of proteins encoded within exogenous genomes harbored by bacteria, fungi, and viruses. Yet, their contributions to host protein-folding homeostasis, or proteostasis, remain elusive. Recent studies, including our previous work, suggest that bacterial products contribute to toxic aggregation of endogenous host proteins. We refer to these products as bacteria-derived protein aggregates (BDPAs). Furthermore, antibiotics were recently associated with increased risk for neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis  possibly by virtue of altering the composition of the human gut microbiota. Other studies have shown a negative correlation between disease progression and antibiotic administration, supporting their protective effect against neurodegenerative diseases. These contradicting studies emphasize the complexity of the human gut microbiota, the gut-brain axis, and the effect of antibiotics. Here, we further our understanding of bacteria’s effect on host protein folding using the model Caenorhabditis elegans. We employed genetic and chemical methods to demonstrate that the proteotoxic effect of bacteria on host protein folding correlates with the presence of BDPAs. Furthermore, the abundance and proteotoxicity of BDPAs are influenced by gentamicin, an aminoglycoside antibiotic that induces protein misfolding, and by butyrate, a short-chain fatty acid that we previously found to affect host protein aggregation and the associated toxicity. Collectively, these results increase our understanding of host-bacteria interactions in the context of protein conformational diseases.

Two decades after the antiretroviral therapy (ART) introduction, several challenges still prevail in maintaining people living with HIV (PLHIV), even with "Test and Treat" and/or "Rapid Start of ART" initiatives, as well as the scale-up of ART worldwide to promote access and adherence to treatment. This review examined articles on ART adherence in Africa between 2016 and 2023, published in English and indexed in PubMed. A total of 16 articles out of 2415 were eligible and included for analyses. Overall, ART adherence rates in SSA regions ranged from 43% to 84%. Rates in the centre of the SSA region ranged from 58% to 80%, in the north from 50% to 83%, in the south from 77% to 84%, in the west from 43% to 60% and in the east from 69% to 73%. Most African countries use the self-report to assess treatment adherence, although unreliable. The main factors with negative influence on ART adherence were comorbidities, lack of motivation, socioeconomic difficulties or side effects. Conclusion: Adherence to ART is a good indicator for controlling the spread of HIV. It is important to overcome the barriers that make it difficult to comply with ART and reinforce the factors that facilitate the accession of medication.

To investigate the differences in cadium (Cd) uptake and translocation among edible rapes and select suitable rape varieties for safe production, a field experiment was carried out with 25 varieties of edible rapes on a farmland polluted with Cd in the central souothern part of Hunan Province. The growing characteristics and Cd contents in rape tissues were measured, and the amount of Cd removed was calculated. The results showed that the growth of 25 rape varieties was not inhibited without withering or inconsistent changes in leaf and so on. The Cd contents in stem-leaf and root of rapes were in the range 0.05-0.26mg·kg-1 and 0.04-0.26mg·kg-1, respectively. Basing on BCF, the stem-leaf showed a greater capacity for Cd transport than root. And the total Cd removed by rape were 0.002-0.016 mg·plant-1. Except for plant height, BCF of soil available Cd from soil to stem-leaf, TCF of Cd from root to stem-leaf and Cd taken away by rape, there was no significant difference among edible rape varieties. Although Cd contents in stem-leaf of 25 rape varieties does not exceed the national safety standards, planting “Lvjin 1”, “Guanyou Qingjing” and “Guanyou brassica” not only reduced soil pollution but also allowed the production of safe leafy rape.

Elevation of the intermediate amino acid metabolite Homocysteine (Hcy) causes Hyperhomocysteinemia (HHcy), a metabolic disorder frequently associated with mutations in the methionine-cysteine metabolic cycle as well as with nutritional deficiency and aging. Previous literature suggest that HHcy is a strong risk factor for cardiovascular diseases. Severe HHcy is well established to correlate with vascular pathologies primarily via endothelial cell death. Though moderate HHcy is more prevalent and associated with an increased risk of cardiovascular abnormalities in later part of life, its precise role in endothelial physiology is largely unknown. In this study, we report that moderate elevation of Hcy causes endothelial dysfunction through impairment of their migration and proliferation. We established that unlike severe elevation of Hcy, moderate HHcy is not associated with suppressed endothelial VEGF/VEGFR signaling and oxidative stress induction. We further showed that moderate HHcy induces a sub-lethal ER stress that causes defective endothelial migration through abnormal actin cytoskeletal remodeling. We also found that sub-lethal increase of Hcy causes endothelial proliferation defect by suppressing mitochondrial respiration and concomitantly increases glycolysis to compensate the consequential ATP loss and maintain overall energy homeostasis. Finally, analyzing an available microarray dataset, we confirmed that these hallmarks of moderate HHcy are conserved in adult endothelial cells as well. Thus, we identified adaptive UPR and metabolic rewiring as two key mechanistic signatures in moderate HHcy-associated endothelial dysfunction. As HHcy is clinically associated with enhanced vascular inflammation and hypercoagulability, identifying these mechanistic pathways may serve as future targets to regulate endothelial function and health.

Localized protein translation occurs through trafficking of mRNAs and protein translation machineries to different compartments of the cell, leading to rapid on-site synthesis of proteins in response to signaling cues. The spatiotemporally precise nature of the local translation process necessitates continual developments of technologies reviewed herein to visualize and map biomolecular components and the translation process with better spatial and temporal resolution, and with fewer artifacts. We also discuss approaches to control local translation, which can serve as a design paradigm for subcellular genetic devices for eukaryotic synthetic biology.

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, increasing evidence indicates that Pdcd4 enhances the chemosensitivity of several chemotherapeutic drugs. To date, several translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may enhance chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

The retinal pigment epithelium (RPE), which ensures the normal functioning of the neural retina, is a pigmented single-cell layer that separates the retina from the Bruch's membrane and the choroid. There are three main types of pigment granules in the RPE cells of the human eye: lipofuscin granules (LG) containing the fluorescent “age pigment” lipofuscin, melanoprotein granules (melanosomes, melanolysosomes) containing the screening pigment melanin and complex melanolipofuscin granules (MLG) containing simultaneously both types of pigments - melanin and lipofuscin. This review examines the functional role of pigment granules in the aging process and in the development of oxidative stress and associated pathologies in RPE cells. The focus is on the process of light-induced oxidative degradation of pigment granules caused by reactive oxygen species. The reasons leading to increased oxidative stress in RPE cells as a result of oxidative degradation of pigment granules are considered. A mechanism has been proposed to explain the phenomenon of age-related decline in melanin content in RPE cells. The essence of the mechanism is that when the lipofuscin part of the melanolipofuscin granule is exposed to light, reactive oxygen species are formed, which destroy its melanin part. As more melanolipofuscin granules are formed with age and the development of degenerative diseases, the melanin in pigmented epithelial cells ultimately disappears.

The dynamic equilibrium of iron homeostasis has an important role in sustaining metabolic and neurological functions during human life. Iron excretion is modest and unregulated hence this overall equilibrium is tightly regulated in normal conditions by increasing deficient or limiting excessive iron assimilation. Here we focus on neural tissue overload, dyshomeostasis that is preceded by excessive assimilation, disturbances in internal homeostasis or both. Normal steps in iron homeostasis include its uptake across the apical membrane of the enterocytes in a mildly acidic duodenal milieu by the major importer of ferrous iron, Divalent Metal Transporter 1 (DMT1) (Nramp2/DCT1/SLC11A2, solute carrier family 11 member 2) [1, 2], responsible for the uptake of Non-Transferrin Bound Iron (NTBI) and divalent metals [3], passage through enterocytes bound to a chaperone and crossing the basal membrane via the only known cellular ferrous iron exporter, ferroportin [4] with the iron bound to transferrin (Tf) as it exits. Cells in peripheral tissues largely utilize circulating iron after uptake by receptor-mediated endocytosis of Tf-bound Iron [5]. Derangement of duodenal NTBI absorption of iron and heavy metals is influenced by systemic iron metabolism associated with inflammation that leads to iron accumulation into peripheral tissues and potential development of neurodegenerative diseases, involving distribution and fine regulation of DMT1 also in the central nervous system, where inflammatory-related acidosis influences DMT1 uptake, via its action as a proton cotransporter. Pharmacological strategies to inhibit NTBI transport selectively will be illustrated in relationship to protection, particularly neuroprotection, against iron overload associated with acidosis, inflammation, neuroinflammation and subsequent neurodegeneration.

Background: The COVID-19 pandemic led to rapid growth in telemental health services and investment in digital mental health technologies. Digital mental health technologies could expand access to mental health care amid increasing provider deficit by providing tools for expedited psychiatric symptom assessment and treatment augmentation. This systematic review explores the recent evidence for the use of scalable digital tools, including virtual reality, neurofeedback training, wearables, mobile apps, digital phenotyping, and machine learning for PTSD symptom assessment, diagnosis, and treatment. Methods: A PubMed search identified studies on digital technologies with current or future potential for scalability (accessible through a small, digital device without the virtual or in-person presence of a mental health care provider)–and PTSD diagnosis, symptom assessment, or symptom treatment as the primary outcome. Thirty-five studies inform this review. Results: Virtual reality exposure therapy is efficacious for combat-related PTSD treatment. Conclusions of studies investigating apps and neurofeedback training are limited by low sample size and methodological heterogeneity. Machine learning models demonstrate capability in detecting PTSD symptoms via passively collected data from smartphones, wearables, and actively collected data from patient speech, writing, and videos, but standardization of data collection and modeling are needed before application to clinical settings. Conclusions: Advancements in scalable digital tools could address barriers in healthcare access and improve patient engagement by providing asynchronous assessment and treatment augmentation. Future research utilizing diverse patient populations in standardized controlled trials is needed to determine evidence-based protocols for implementation.

Different bacterial species have dramatically different generation times, from 20-30 minutes in Escherichia coli to about two weeks in Mycobacterium leprae. The translation machinery in a cell needs to synthesize all proteins for a new cell in each generation. The three subprocesses of translation, i.e., initiation, elongation, and termination, are expected to be under stronger selection pressure to optimize in short-generation bacteria (SGB) such as Vibrio natriegens than in the long-generation Mycobacterium leprae. The initiation efficiency depends on the start codon decoded by the initiation tRNA, the optimal Shine-Dalgarno (SD) decoded by the anti-SD (aSD) sequence on small subunit rRNA, and the secondary structure that may embed the initiation signals and prevent them from being decoded. The elongation efficiency depends on the tRNA pool and codon usage. The termination efficiency in bacteria depends mainly on the nature of the stop codon and the nucleotide immediately downstream of the stop codon. By contrasting SGB with long-generation bacteria (LGB), we predict that 1) SGB to have more ribosome RNA operons to produce ribosomes, and more tRNA genes for carrying amino acid to ribosomes, 2) SGB to have a higher percentage of genes using AUG as start codon and UAA as stop codon than LGB, 3) SGB to exhibit better codon and anticodon adaptation than LGB, and 4) SGB to have weaker secondary structure near translation initiation signals than LGB. These differences between SGB and LGB should be more pronounced in highly expressed genes than lowly expressed genes. We present empirical evidence in support of these predictions.

For its microtubule-binding properties, the expression level of the neurodegeneration-associated protein Tau is pondered as a potential modifier of cancer resistance to chemotherapy since decades. Indeed, Tau binds microtubules at the same site as taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network in order to stall cell division and to induce tumor cell death. Whilst independent studies report the association between low Tau expression and superior taxane response, the data were refused by a meta-analysis, suggesting interference of other parameters. Unpredictably, Tau expression level was identified as a prognostic cancer marker, whereby its positive or negative predictive value for survival depended on the cancer type. With recent experimental evidence linking Tau to P53 signaling, DNA stability and protection and to the implication of Tau in cancer is strengthened. The identification of a role of Tau at the interface between two major aging-related disorder families, neurodegeneration and cancer, offers clues for the epidemiological observation inversely correlating these disorders. Elucidating how Tau is mechanistically implicated in cellular pathways common to these devastating illnesses may extend the Tau-targeting therapeutic opportunities to cancer.

Traditional African vegetables (TAV) are an important component of an ecologically sustainable approach to addressing food and nutrition security in Africa (countries?). This review aims to identify the scope of the knowledge translation literature that exists across multiple aspects of the TAV value chain and to identify gaps in knowledge translation research. A scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was conducted. The Population, Concept, and Context (PCC) framework was used to guide the development of inclusion and exclusion criteria for this review. Web of Science, Scopus, Science direct and ABI/Inform databases were searched to identify relevant studies which were then screened using the Covidence online software to select studies and extract information for analysis and reporting. A total of 182 studies/articles were selected and examined. The most significant knowledge documented about TAVs is their vast genetic diversity contributing to their rich nutritional and medicinal properties, their ability to withstand harsh environmental conditions such as drought, pests, and diseases as well as the effects of various post-handling techniques on nutrient content of TAVs with the production phase of TAVs value chain being the most studied. This review found that although there is a breadth of knowledge created about TAVs, there is still little documentation of transferring and utilizing of this knowledge across the TAVs value chain. This review identified that more research is needed to document strategies and practices for the transfer and utilisation of knowledge to ensure it is utilized to enhance nutritional outcomes across Africa.

Traumatic brain injury (TBI) is a devastating event with severe long-term complications. TBI and its sequelae are one of the leading causes of death and disability in those under 50 years old. The full extent of secondary brain injury is still being intensely investigated; however, it is now clear that neurotrauma can incite chronic neurodegenerative processes. Chronic traumatic encephalopathy, Parkinson’s disease, and many other neurodegenerative syndromes have all been associated with a history of traumatic brain injury. The complex nature of these pathologies can make clinical assessment, diagnosis, and treatment challenging. The goal of this review is to provide a concise appraisal of the literature with focus on emerging strategies to improve clinical outcomes. First, we review the pathways involved in the pathogenesis of neurotrauma-related neurodegeneration and discuss the clinical implications of this rapidly evolving field. Next, because clinical evaluation and neuroimaging are essential to the diagnosis and management of neurodegenerative diseases, we analyze the clinical investigations that are transforming these areas of research. Finally, we briefly review some of the preclinical therapies that have shown the most promise in improving outcomes after neurotrauma.

Circular RNAs (circRNAs) are covalently closed RNAs that are present in all eukaryotes tested. CircRNAs are less abundantly expressed than mRNAs. Recent RNAseq analyses indicate that more than 800,000 circRNA isoforms exist in humans, which is more than twice the number of currently known mRNA isoforms. CircRNAs are generated through backsplicing that depends on pre-mRNA structures, which are influenced by intronic elements, for example primate-specific Alu elements, leading to species-specific circRNAs. CircRNAs are mostly cytosolic, stable and influence cells by sequestering miRNAs and RNA-binding proteins. We review the increasing evidence that circRNAs are translated into proteins using several cap-independent translational mechanisms, that include internal ribosomal entry sites, N6-methyladenosine RNA modification, adenosine to inosine RNA editing and interaction with the eIF4A3 component of the exon junction complex. CircRNA are translated under conditions that favor cap-independent translation, notably in cancer. CircRNA-encoded proteins are shorter than mRNA-encoded proteins and overall have a high propensity for phase separation. In summary, circRNA encoded proteins are translated under particular cellular conditions and contribute to proteome diversity and pathophysiology.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-regulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression, and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation up-regulates SOX2OT expression. This up-regulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ER stress reprogramming of breast cancer cells.

Proteolysis Targeting Chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD) with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focusses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.

Recent advancements in brain stimulation and nanomedicine have ushered in a new era of therapeutic interventions for psychiatric and neurodegenerative disorders. This review explores the cutting-edge innovations in brain stimulation techniques, including their applications in alleviating symptoms of main neurodegenerative disorders and addiction. Emphasis is placed on the underlying main neurotransmitter modifications and their specific brain area location, particularly focusing on the dopaminergic system, which plays a critical role in these conditions. Furthermore, the review delves into the groundbreaking developments in nanomedicine, highlighting how nanotechnology can be utilized to target aberrant signaling in neurodegenerative diseases, with a specific focus on the dopaminergic system. The discussion extends to emerging technologies such as magnetoelectric nanoparticles (MENPs), which represent a novel intersection between nanoformulation and brain stimulation approaches. These innovative technologies offer promising avenues for enhancing the precision and effectiveness of treatments by enabling non-invasive, targeted delivery of therapeutic agents as well as on site, on-demand stimulation. By integrating insights from recent research and technological advances, this review aims to provide a comprehensive understanding of how brain stimulation and nanomedicine can be synergistically applied to address complex neuropsychiatric and neurodegenerative disorders, paving the way for future therapeutic strategies.

Neuronal cells are believed to rely on autophagy to maintain cellular homeostasis. Nevertheless, autophagy may be a therapeutic target for neurodegenerative diseases because of the role it plays in neuronal cell death. Despite Beclin 1 association with autophagy and apoptosis, the molecular mechanisms that underlie Tau-induced vesicular pathology and Tau protein aggregates in humans remain poorly understood. Here, we set out to examine the role of three genes-ATG14L, Beclin 1 and VPS34- in autophagy nucleation failure-associated Tau disorders in fruit fly models. We found that either reduced ATG14L levels improve neuronal outcomes, or transgenic expression of ATG6/Beclin 1 greatly reduced age-dependent neurodegeneration and Tau pathology; whereas, the loss of Beclin 1 exacerbated these effects. Prior to p-Tau accumulation, the neuronal Beclin 1 network is critical for reducing p-Tau accumulation, indicating that the loss of Beclin 1 causes Tau pathology and neurodegeneration. As neurodegeneration progressed, glial cells showed an upregulation of vesicular Beclin 1 immunoreactivities. The reduced VPS34 also resulted in p-Tau accumulation, suggesting that neurons require both Beclin 1 and VPS34 to reduce p-Tau accumulation. Our results provide mechanistic insight into the molecular pathways that cause age-dependent Tau pathology and neurodegeneration due to an excess of autophagy nucleation processes and autophagy activity, and we derive novel inferences on the therapeutic possibilities of rebalanced Beclin 1 network by reducing autophagic specific nucleation component of ATG14L.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs) including Alzheimer’s Disease (AD). Both amyloid β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to that of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms are largely focusing on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and how this knowledge could contribute to diagnoses and treatments for the given NDs.

Background: Aging rate is affected by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle and environmental factors. In accelerated aging (AA), biological age exceeds the chronological one. Objective: To undertake a critical reappraisal of the AA concept and to reveal its weaknesses and limitations. Methods: We reviewed over 300 recent articles dealing with physiology of brain aging and pathophysiology of neurodegeneration. Results: (1) Organ systems age at different rates, which interferes with application of the AA concept to individual organs. (2) Aging rate can be decelerated due to individual structure–functional reserves built with cognitive, physical training or pharmacological interventions. (3) The AA concept lacks standardised terminology and methodology. (4) Specific molecular biomarkers (MBM) reflect aging. To consolidate the AA theory, researchers should validate numerous MBM candidates. (5) Aging factors, mechanisms and the exact nature of their biological outcomes are not well understood. Conclusion: Although considered as a perspective theory, the AA concept has serious limitations and it requires an update.

Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are caused by a combination of multiple events that damage neuronal function. A well-characterized biomarker of neurodegeneration is proteinaceous aggregates accumulation in the brain. However, the gradually worsening symptoms of neurodegenerative diseases are unlikely to be solely due to the result of a mutation in a single gene, but rather a multi-step process involving epigenetic changes. Multiple epigenetic studies have revealed that modification of histones accompanied by both the local and global remodeling of the chromatin structure and alternations in transcriptional patterns are closely associated with the pathogenesis of neurodegenerative diseases. Unlike DNA mutations, epigenetic alterations are reversible, and therefore raise the possibilities for therapeutic intervention including dietary modifications. Additionally, reactive oxygen species may contribute to the pathogenesis of Alzheimer’s disease and Parkinson’s disease. Given that the antioxidant properties of plant-derived phytochemicals are likely to exhibit pleiotropic effects against ROS-mediated epigenetic alternation, dietary intervention may be promising for the management of neurodegeneration in these diseases. In this review, the state-of-the-art applications using single-cell multi-modal omics approaches including genetics, and epigenetics, and dietary approaches for the identification of novel biomarkers and therapeutic approaches for the treatment of neurodegenerative diseases are discussed.

Developing prolonged antigen delivery systems that mimick the long-term exposure to pathogens appears as a promising, still poorly explored approach to reach durable immunities. In this study, we have used a simple technology by which his-tagged proteins can be assembled, assisted by divalent cations, as supramolecular complexes with progressive complexity, namely protein-only nanoparticles and microparticles. Microparticles produced out of nanoparticles are biomimetics of secretory granules from the mammalian hormonal system. Upon subcutaneous administration, they slowly disintegrate, acting as an endocrine-like secretory system, and rendering the building block nanoparticles progressively bioavailable. The performance of such materials, previously validated for drug delivery in oncology, has been tested here regarding the potential for time-prolonged antigen release. This has been done by taking, as building blocks, a nanostructured version of p30, a main structural immunogen from the African swine fever virus (ASFV). By challenging the system in both mice and pigs, we have observed unusually potent pro-inflammatory activity in porcine macrophages, and long-lasting humoral and cellular responses in vivo, which might overcome the need for an adjuvant. The robustness of both innate and adaptive responses tag, for the first time, these dynamic depot materials as a novel and valuable instrument with transversal applicability in immune stimulation and vaccinology.

The Transformer architecture, while adept at capturing context through self-attention, falls short in encapsulating complex syntactic structures effectively. Addressing this gap, we introduce the Linguistic Structure through Graphical Interpretation with BERT (LSGIB) approach in Machine Translation (MT) frameworks. Combining the strengths of Graph Attention Network (GAT) and BERT, LSGIB intricately captures syntactic dependencies as explicit knowledge from the source language. This enhances the source language representation and aids in more accurate target language generation. Our empirical analysis leverages gold-standard syntax-annotated sentences and employs a Quality Estimation (QE) model. This approach enables us to assess translation improvements in terms of syntactic accuracy, extending beyond traditional BLEU score metrics. The LSGIB model demonstrates superior translation quality across diverse MT tasks, maintaining robust BLEU scores. Our study delves into the optimal sentence lengths benefiting from LSGIB and identifies which syntactic dependencies are more precisely captured. We observe that GAT's ability to learn specific dependency relations directly influences the translation quality of sentences with those relations. Additionally, we discover that incorporating syntactic structure into BERT's intermediate and lower layers offers a novel approach to modeling linguistic structure in source sentences.

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m⁶A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of so-called “non-coding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m⁶A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and non-invasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected sub-cutaneously with Matrigel™ to generate so called pseudo tumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 hours after heating. We showed that dextran-coated magnetic iron oxide nanoparticles dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as non-invasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

Abstract The relationship between cancer and neurodegeneration has spurred extensive scientific discourse, challenging their historical classification as distinct disorders. While cancer signifies uncontrolled cellular proliferation and neurodegeneration marks progressive neuronal loss, recent insights highlight intriguing interconnections between these seemingly disparate conditions. Cancer entails perpetual signaling for growth, evasion of growth inhibitors, resistance to cell death, acquisition of replicative immortality, stimulation of blood vessel growth (angiogenesis), and initiation of invasion and metastasis. Conversely, investigations emphasize disrupted cellular energy regulation and evasion of immune surveillance as key traits arising from genome instability, mutations, and inflammation driving tumorigenesis. Neurodegeneration involves neuronal malfunction and depletion, synaptic impairment, and protein abnormalities aggregations contributing to muscle atrophy and cognitive deficits. Varied clinical studies underscore contrasting correlations between cancer and neurodegeneration, hinting at mirrored molecular pathways that foster cell resilience or vulnerability. Research explores cellular signaling in tumorigenesis, shared with neurodegenerative disorders. Aberrant expression or mutations in crucial genes implicated in neurodegeneration also surface in cancer contexts. Debates persist on the nature of the relationship between cancer and neurodegeneration, contemplating inverse associations or shared pathways. Understanding their complex interplay, encompassing genetics, cellular mechanisms, and environmental influences, remains pivotal in unraveling their connections. This review explores the intriguing perspective that neurodegeneration and cancer might share fundamental genetic links, delving into potential implications for their onset and progression.

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by TUNEL staining and PARP and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, inverted screen test, and climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI.

Autophagy was initially recognized as a bulk degradation process that randomly sequesters and degrades cytoplasmic material in lysosomes (vacuoles in yeast). In recent years, various selective autophagy pathways have been discovered. Glycophagy, the selective autophagy of glycogen granules, is one of them. It is an important contributor to Pompe disease, a type of lysosomal storage disorder with lysosomal accumulation of glycogen. Here, we developed the Komagataella phaffii yeast as a simple model of glycogen autophagy under nitrogen starvation conditions. For this, we turned the self-glucosylating initiator of glycogen synthesis, Glg1, which is covalently bound to glycogen, into the Glg1-GFP autophagic reporter. Our results revealed that vacuolar delivery of Glg1-GFP and its processing to free GFP were strictly dependent on autophagic machinery and vacuolar proteolysis. Notably, this process was independent of Atg11, the scaffold protein common for many selective autophagy pathways. Importantly, the non-mutated Glg1-GFP (which synthesizes and marks glycogen) and mutated Glg1Y212F-GFP (which does not synthesize glycogen and is degraded by non-selective autophagy as cytosolic Pgk1-GFP) were equally well delivered to the vacuole and had similar levels of released GFP. Therefore, we concluded that glycogen autophagy is a non-selective process in K. phaffii yeast under nitrogen starvation conditions.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

Large Language Models (LLMs) have proved significant proficiency when comes to code generation especially in Structured Query Language (SQL) for databases and recent successful Text-to-SQL method involves fine-tuning pre-trained LLMs for SQL generation tasks. Transforming natural language text into SQL queries, has been attempted to solve with various learning techniques including Few-shot learning[1], fine tuning. In this paper we propose Supervised fine-tuning (SFT) as a better alternative for learning technique for text-to-SQL generation task using Code-Llama that pushes state of art accuracy on spider test suite to 89.6% on dev set which represent first instance of surpassing the earlier best-in-class with 5.5% higher score and 86.8% of exact match accuracy on dev set. Furthermore, we demonstrate that properly prompted LLM along with SFT provides far fewer hallucinations and much more robust LLM that can be used as a general tool for any text-to-SQL generation use case.

Recent advancements in neural language models, particularly attention-based architectures like the Transformer, have substantially surpassed traditional methods in various natural language processing tasks. These models adeptly generate nuanced token representations by considering contextual relations within a sequence. However, augmenting these models with explicit syntactic knowledge, such as part of speech tags, has been found to remarkably bolster their effectiveness, especially under constrained data scenarios. This study introduces the Linguistic Enhanced Transformer (LET), which integrates multiple syntactic features, showing a notable increase in translation accuracy, evidenced by an improvement of up to 1.99 BLEU points on subsets of the WMT '14 English-German dataset. Furthermore, this paper demonstrates that enriching BERT models with syntax-aware embeddings enhances their performance on several GLUE benchmark tasks.

When using computer-aided translation systems in a typical, professional translation workflow, there are several stages at which there is room for improvement. The SCATE (Smart Computer-Aided Translation Environment) project investigated several of these aspects, both from a human-computer interaction point of view, as well as from a purely technological side. This paper describes the SCATE research with respect to improved fuzzy matching, parallel treebanks, the integration of translation memories with machine translation, quality estimation, terminology extraction from comparable texts, the use of speech recognition in the translation process, and human computer interaction and interface design for the professional translation environment. For each of these topics, we describe the experiments we performed and the conclusions drawn, providing an overview of the highlights of the entire SCATE project.

Severe malaria is a major public health concern in Angola, particularly among adults, with limited data on clinical outcomes and manifestations. The study therefore assessed the clinical manifestations and outcome of severe Plasmodium falciparum malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango, Angola. The study retrospectively reviewed the individual records of patients over 14 years old, admitted for severe malaria during the first trimester of 2021 and 2022. World Health Organization (WHO) criteria were used to define severity. A total of 640 patients were recorded into the study, 167 in 2021 and 473 in 2022, distributed across the departments; Intensive Care Unit (ICU; n=81), Medicine (MED; n=458) and Infectiology (INF; n=101). The median age was 26 years and 59.4% were males. The most common manifestation of severe malaria was renal impairment (37.4%). The overall mortality rate was 7% and decreased considerably from 10.2% in 2021 to 5.9% in 2022. The increase in malaria cases during 2022 with increased in prevalence of life-threatening signs like renal impairment, jaundice and impaired conscience, underscores the urgent need for enhanced malaria control and surveillance strategies to mitigate morbidity and mortality, highlighting the potential for antimalarial drug resistance.

This paper investigates the application of blended learning in undergraduate translation classes to enhance the effective incorporation of technology in teaching. Blended learning is the combination of face-to-face instruction with online learning, which provides students with a flexible and diverse learning environment for developing technological proficiency. Using a case study methodology, this research examines the translation undergraduate program at the University of Jeddah, which implemented blended learning as its primary instructional framework starting in 2021. The study aims to explore the advantages and challenges associated with the adoption of blended learning in translation classes while offering practical suggestions that could help in its implementation. The findings show several advantages of integrating blended learning into undergraduate translation classes. Firstly, the students could benefit from a flexible learning environment that accommodates their individual learning preferences and schedules. Secondly, It also helps to promote active engagement and interaction which nurture collaborative learning opportunities among students. Thirdly and lastly, blended learning provides a platform for students to develop their technological skills, which become crucial in today's digital age. Despite this, the study also points out significant challenges that need to be addressed. These important challenges include the required planning and preparation involved in creating effective online components, ensuring equitable access to technology and the internet, and adapting teaching and learning approaches to optimise the blended learning experience.To sum up, this paper contributes to the understanding of blended learning in the context of undergraduate translation classes.

Polyphenols represent a group of secondary metabolites of plants which have been analyzed as potent regulators of multiple biological processes, including cell proliferation, apoptosis and autophagy, among others. These natural compounds exhibit beneficial effects and protection against inflammation, oxidative stress and related injuries including metabolic diseases, such as cardiovascular damage, obesity and diabetes and neurodegeneration. In the present review, we report the main biological effects in relationship to autophagy regulation in response to different dietary polyphenols and its impact on metabolic and neurodegenerative diseases

Mitochondrial dysfunction plays a pivotal role in numerous complex diseases. Understanding the molecular mechanisms by which the “powerhouse of the cell” turns into the “factory of death” is an exciting yet challenging task that can unveil new therapeutic targets. The mitochondrial matrix protein CyPD is a peptidylprolyl cis-trans isomerase involved in the regulation of the permeability transition pore (mPTP). The mPTP is a multi-conductance channel in the inner mitochondrial membrane whose dysregulated opening can ultimately lead to cell death and whose involvement in pathology has been extensively documented over the past few decades. Moreover, several mPTP-independent CyPD interactions have been identified, indicating that CyPD could be involved in the fine regulation of several biochemical pathways. To further enrich the picture, CyPD undergoes several post-translational modifications that regulate both its activity and interaction to its clients. Here, we will dissect what is currently known about CyPD and critically review the most recent literature about its involvement in neurodegenerative disorders, focusing on Alzheimer’s Disease and Parkinson’s Disease, supporting the notion that CyPD could serve as a promising therapeutic target for the treatment of such conditions. Notably, significant efforts have been made to develop CyPD-specific inhibitors, which hold promise for the treatment of such complex disorders.

Musyakalah is one of the Arabic linguistic styles included under the category of majaz. This style is commonly used in Al-Quran. The Indonesian translation of Al-Quran is a case where many of the figures of speech are translated literally, thereby causing serious semantic problems. Thus, the research problem of this is formulated with the following questions: 1) How many musyakalah ayahs are there in Al-Quran?; 2) How are the musyakalah ayahs translated, literally (harfiyya) or interpretatively (tafsiriyya)?; 3) How many ayahs are translated literally and how many are translated interpretatively?; and 4) Which translated musyakalah ayahs have the potential to raise semantic and theological problems? The corpus in this research consists of all musyakalah ayahs in Al-Quran and their translation to Indonesian published by the Department of Religious Affairs of Indonesia. The research adopted a descriptive-semantic method. The findings of this research are: 1) There are only eleven ayahs in Al-Quran using musyakalah style, namely: Alhasyr ayah 19, Ali Imran ayah 54, Annaml ayah 50, Alanfal ayah 30, Asysyura ayah 40, Albaqarah ayah 15, Almaidah 116, Aljatsiah ayah 34, Attaubah ayah 79, Annisa ayah 142, and Albaqarah 194; 2) The musyakalah ayahs translated literally are: Aljatsiah 34, Almaidah 116, Asysura 40, Annaml 50, and Alhasyr 19, whereas the musyakalah ayahs translated interpretatively are Albaqarah 194, Annisa 142, Attaubah 79, Albaqarah 15, Alanfal 30, and Ali Imran 54; 3) Of the eleven musyakalah ayahs, only Alhasyr ayah 19 that is translated correctly and does not have the potential of creating misinterpretation. Meanwhile, the interpretation of the other four ayahs can potentially cause misinterpretation or are against the basic principles of Islam. The six remaining ayahs are translated interpretatively and thus do not have the potential to be misinterpreted; 4) The findings suggest that musyakalah ayahs are more appropriately translated interpretatively. Therefore, the following is recommended: 1) Considering the different characteristics of Arabic and Indonesian languages, studies on Al-Quran translation into Indonesian should continuously be carried out; 2) In order to avoid misinterpretation, it is better that the translation of musyakalah ayahs uses tafsiriyya (interpretative) approach; 3) The harfiyya (literal) and tafsiriyya (interpretative) approaches should be developed for other styles beside musyakalah..

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetic helps to improve treatment decisions and sometimes also to avoid unnecessary exposure to potentially toxic immunosuppression. New Biomarkers led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is getting wider with a pipeline of promising new therapeutic agents with more sophisticated approaches. This review focuses on all aspects of entities that are associated with nephrotic syndromes with updated information on recent advances in each field. This includes podocytopathies (Focal Segmental Glomerulosclerosis and Minimal-Change Disease), Membranous Nephropathy, Membranoproliferative Glomerulonephritis, IgA-Nephropathy, Fibrillary Glomerulonephritis, Amyloidosis and monoclonal gammopathy of renal significance in the context of the nephrotic syndrome, but also renal involvement in systemic diseases, diabetic nephropathy, and drugs that are associated with nephrotic syndromes.

Microbiome research has gained considerable interest due to the emerging evidence of its impact on human and animal health. Similar to higher organisms, the gut-associated microbiota of mosquitoes affect host fitness and other phenotypes. It is now well established that microbes can alter pathogen transmission in mosquitoes, either positively or negatively, and avenues are being explored to exploit microbes for vector control. However, less attention has been paid to how microbiota affect phenotypes that impact vectorial capacity. Several mosquito and pathogen components, such as vector density, biting rate, survival, vector competence and pathogen extrinsic incubation period all influence pathogen transmission. Interestingly, the mosquito gut-associated microbes can impact each of these components, and therefore ultimately modulate vectorial capacity. Promisingly, this expands the options available to exploit microbes for vector control by also targeting parameters that affect vectorial capacity. However, there are still many knowledge gaps in the biology of the mosquito – microbe symbiosis that need to be addressed in order to understand these interactions more thoroughly and exploit them efficiently. Here, we review current evidence of the impacts of the microbiome on aspects of vectorial capacity highlighting opportunities for novel vector control strategies and areas where further studies are required.

Similarly to his special theory of relativity, Einstein's special principle of relativity extends beyond the limits currently known to it. Up to now, the principle has not been suspected to have the potential to translate laws. However, the principle holds an inherent capacity to translate physical laws and, in so doing, speeds up our understanding and control of physical reality. Such a translation of laws leads to the faster discovery of other laws, such as the Laws of Electronic Motion, characterizing the motion of electrons around the atomic nucleus, and the Third Law of Biological Resistance, facilitating the successful control of drug resistance in medicine. The ability of the special principle of relativity to translate laws shines forth once the said principle is duly interpreted. This interpretation exposes a parallelism between experimental frames of reference and justifies the applicability of the laws of one frame of reference in other parallel frames of reference. This process opens the door to our faster discovery of the laws governing a multiplicity of frames parallel to a frame we already know the laws of. In practice, the interpretation of Einstein's special principle of relativity speeds up our understanding of the workings of physical reality and strengthens our capacity to subdue matter.

The access to cardiac rehabilitation (CR) is contingent upon physician referrals, yet these are often inadequate, particularly in low-resource settings. This multi-method study aimed to translate, culturally adapt, and validate the Portuguese version of the Provider Attitudes toward CR and Referral (PACRR-P) scale, as well as to identify key factors influencing CR referral in a Latin American context for the first time. The PACRR was translated into Brazilian-Portuguese through a rigorous process involving independent translation, back-translation, and expert panel review to ensure face, content, and cross-cultural validity. A total of 44 Brazilian physicians completed the questionnaire, allowing for an assessment of internal consistency, criterion validity, and convergent validity. The findings confirmed the face, content, and cultural validity of the 20 translated items, with a mean item clarity rating of 4.8/5. The final version included 17 of the original 19 PACRR-P items, with a Cronbach’s alpha of 0.73. Referral rates were significantly associated with specific PACRR-P items, supporting the scale's criterion validity, while correlations with ReCaRe scores further supported convergent validity. The most prominent barriers to referral were a lack of familiarity with CR site locations, absence of a standard referral form, and lack of automatic referral processes. The PACRR's validity and reliability among Portuguese-speaking providers are preliminarily supported.

LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, conspicuously during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to human, despite their secondary role for proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules, and CLPX on multi-enzyme condensates, near the inner mitochondrial membrane, as first-aid system. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, in mitochondrial RNA granules and nucleoids, and in D-foci-mediated degradation of toxic double-stranded mtRNA / mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination, and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, like peptidases MPP at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.

Recombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in RGD (arginine-glycine-aspartic acid) sequences, with good processability that is being investigated for regenerative medicine applications. Recently, the biocompatibility and osteogenic ability of β-TCP/RCP (RCP granules combined with β-tricalcium phosphate (TCP) submicron particles) were demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects (three-walled bone defect) created in beagle dogs to investigate tissue responses and subsequent regenerative effects. Micro computed tomography image analysis at 8 weeks postoperatively showed that the amount of new bone after β-TCP/RCP graft was significantly greater (2.2 fold, P<0.05) than that of the control (no graft) group. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including TRAP-positive and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control, and significantly suppressed gingival recession and epithelial downgrowth (P<0.05). These results suggest that β-TCP/RCP is effective as a periodontal tissue regenerative material.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

Worldwide the severity of abiotic stress like heat, drought, salinity, cold, waterlogging, etc. are being increased because of global warming. Wheat crops must adapt to harsh environments through physiological, molecular, and genetic manipulation. Because of abiotic stress, reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced in wheat plants break down DNA and RNA bases, protein, lipid, and other macro- and micromolecules, resulting in stunted growth and yield decline. Abiotic stress also induces the crop's molecular functions, physiological, biological, and cellular processes, and their compositions. Different stressors like high light intensity, heat, drought, and salinity also impair photosynthesis damaging various pigments. Antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX), etc. synthesized in harsh environments can ameliorate ROS/RNS produced in oxidative stress. Under abiotic stress, heat shock proteins (HSPs) heat shock transcription factors (HSFs) in heat stress, and dehydration-responsive element binding proteins (DREBs) in drought stress are activated to synthesize proteins to mitigate the deleterious effects of those stressors. Na⁺ exclusive genes (NAX1, NAX2) and Na⁺/H⁺ (K⁺) antiporter genes (NHX1, NHX2) hinder those ions from uptake into leaf sheaths and blades of wheat resulting in the declination of salinity in plants. Exogenous hormones like gibberellic acid, salicylic acid, and melatonin, etc., and osmoprotectants like proline, and gene manipulation in plants through genetic engineering are being employed to mitigate the toxic effects of abiotic stress on plants, as portrayed in many literatures. The review depicts how abiotic stress affects phenotypic, physiological, and molecular structures and functions of wheat crops, and their mitigation strategies to lessen their noxious effects on wheat.

Drought negatively affects the growth and development of barley. To explore the genetic variation in barley under drought stress, ten breeding genotypes were tested using polyethylene glycol-6000 to simulate drought conditions. We observed that drought stress adversely affected germination-related traits across all barley genotypes and this impact varied between genotypes, suggesting genotype-specific drought tolerance. The drought tolerance index was an ideal criterion for selecting drought-tolerant genotypes as it well characterized the gradient responses of barely genotypes to drought stress. Based on this indicator, genotype OB1878-ON-50 is recommended as a significant germplasm resource for breeding programs under lower precipitation conditions due to its superior tolerance to drought stress.

Numerous investigations have consistently underscored the impact of societal stigma on the well-being of transgender individuals, encompassing both those experiencing gender dysphoria (transgender) and those who have undergone gender-affirming interventions (transsexual). The primary objective of the current research is to translate and adapt the Attitudes Toward Transgendered Individuals Scale into the Greek language. This scale specifically assesses stigma, excluding components such as discreteness and violence, and is tailored to evaluate individuals within the general populace. Employing confirmatory factor analysis (CFA) and assessing gender metric equivalence, the analyses yielded highly favourable outcomes, demonstrating excellent scale fit, reliability, and content validity, reflecting the robustness of the adapted tool for the Greek population.

This literature review provides an in-depth exploration of the research conducted on the investigation and measurement of residual stress (RS) in Wire Arc Additive Manufacturing (WAAM) products, particularly focusing on how process parameters influence the phenomenon. RS plays a crucial role in determining the mechanical behavior and structural integrity of WAAM components. This review article gives an understanding of the relationship between process parameters and RS to optimize the WAAM processes and ensure the durability of the final products. It also summarizes key findings, measurement techniques, challenges, and future directions in this evolving field. The review also analyzes a measurement of RS in the products of WAAM as a function of process parameters depending on examining various research studies, techniques, and methodologies employed in their studies. Experimental measuring techniques and numerical analysis of RS to determine the impacts of RS in mechanical response in products of WAAM were discussed. By offering a comprehensive overview of current research trends and insights, this review serves as a valuable resource to guide future investigations, fostering the advancement of WAAM as a robust and efficient manufacturing technology.

Leishmania species are parasitic protozoans which cause leishmaniasis affecting millions of people worldwide. Sterols are important components of plasma and organellar membranes and serve as precursors for the synthesis of signaling molecules. In contrast to animals, Leishmania do not produce cholesterol but instead synthesize ergostane-based sterols. C14-demethylase is a key enzyme involved in the biosynthesis of sterols in Leishmania parasites and an important drug target. Its inactivation leads to multiple defects including increased plasma membrane fluidity, mitochondrion dysfunction, hypersensitivity to stress and reduced virulence. In this study, we revealed a novel role for sterol synthesis in the maintenance of RNA stability and translation. Sterol alteration in C14-demethylase knockout mutant leads to increased RNA degradation, reduced translation and impaired heat shock response. Thus, sterol biosynthesis plays an unexpected role in global gene regulation in Leishmania parasites.

Papain-like lysosomal cysteine proteases include 11 human cysteine cathepsins which act as endopeptidases and/or exopeptidases. They are involved in numerous physiological and pathological processes. Among them, only cathepsins B, H, C, and X/Z exhibit exopeptidase activity. Their activities are tightly regulated in various ways to prevent potentially hazardous effects on the cell. In this review, we focus on the structural and functional aspects of these four cysteine cathepsins and their role in neurodegeneration and cancer. Neurodegenerative disorders of aging share an endolysosomal dysfunction and accumulation and spread of oligomeric forms of neurotoxic proteins. The accumulation of various protein aggregates activates the microglia, thus inducing the activation and release of cysteine cathepsins and proinflammatory cytokines, leading to neurodegeneration. In cancer, cysteine cathepsins participate in tumor progression and metastasis. Tumor–stromal crosstalk leads to activation of the stroma and overexpression and secretion of proteolytic enzymes, triggering extracellular matrix degradation and the release of soluble factors. Activated stromal cells (i.e., macrophages, fibroblasts, mast cells) secrete additional growth factors, cytokines, and chemokines that are responsible for the regulation of processes leading to tumor progression and metastasis. Therefore, a better understanding of the role of cysteine cathepsins in neurodegeneration and cancer could lead to novel targeted therapeutic approaches.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

The migration from MATLAB to Python (M-to-PY) has gained significant traction in recent computational research. While MATLAB has long served as a linchpin in myriad scientific endeavors, there's an emerging trend to rejuvenate these projects using Python's extensive AI tools and libraries. This study presents a semi-automated process for M-to-PY conversion, using a detailed case study of an image skeletonization project comprising fifteen MATLAB files and a 1404-image dataset. Skeletonization is foundational for ongoing 3D motion detection research using AI transformers, predominantly developed in Python. The utilization of ChatGPT-4, acting as an AI co-programmer, is pivotal in this conversion. By leveraging the public OpenAI API, we developed an M-to-PY converter prototype, evaluated its efficacy using test cases from the Bard bot, and subsequently employed the converted code in an AI application. The dual contributions encompass a well-tested M-to-PY converter and a Skeleton App capable of sketching and skeletonizing any given image, enriching the AI toolset. This study accentuates how AI resources, like ChatGPT-4, can simplify code transitions, opening doors for innovative AI implementations using primarily MATLAB-coded scientific research.

Exploiting the linguistic knowledge of the source language for neural machine translation (NMT) has recently achieved impressive performance on many large-scale language pairs. However, since the Turkish→English machine translation task is low-resource and the source-side Turkish is morphologically-rich, there are limited resources of bilingual corpora and linguistic information available to further improve the NMT performance. Focusing on the above issues, we propose a multi-source NMT approach that models the word feature in parallel to external linguistic features by using two separate encoders to explicitly incorporate linguistic knowledge into the NMT model. We extend the word embedding layer of the knowledge-based encoder to accommodate for each word’s linguistic annotations in the context. Moreover, we share all parameters across encoders to enhance the representation ability of the NMT model on the source language. Experimental results show that our proposed approach achieves substantial improvements of up to 2.4 and 1.1 BLEU scores in Turkish→English and English→Turkish machine translation tasks, respectively, which points to a promising way to utilize the source-side linguistic knowledge for the low-resource NMT.

The arsRBC operon encodes a 3-protein arsenic resistance system. ArsR regulates the transcription of the operon, while ArsB and ArsC are involved in exporting trivalent arsenic and reducing pentavalent arsenic respectively. Previous research in Agrobacterium tumefaciens 5A demonstrated ArsR has regulatory control over a wide range of metal related proteins and metabolic pathways. We hypothesized that ArsR has broad regulatory control in other Gram-negative bacteria and set out to test this. Here, we use differential proteomics to investigate changes caused by the presence of the arsR gene in human microbiome-relevant Escherichia coli during arsenite (AsIII) exposure. We show that ArsR has broad-ranging impacts such as the expression of TCA cycle enzymes during AsIII stress. Additionally, we found that the Isc [Fe-S] cluster and molybdenum cofactor assembly proteins are upregulated regardless of the presence of ArsR under these same conditions. An important finding from this differential proteomics analysis was the identification of response mechanisms that were strain, ArsR, and arsenic specific, providing new clarity to this complex regulon. Given the widespread occurrence of the arsRBC operon, these findings should have broad applicability across microbial genera, including sensitive environments such as the human gastrointestinal tract.

Glycogen, a branched polysaccharide organized into glycogen granules (GGs), is delivered from the cytoplasm to the lysosomes of hepatocytes by the STBD1-driven selective autophagy (glycophagy). Recently, we developed Komagataella phaffii yeast as a simple model of GG autophagy and found that it proceeds non-selectively under nitrogen starvation conditions. However, another group, using Saccharomyces cerevisiae as a model, found that glycogen is a non-preferred cargo of the nitrogen-starvation induced bulk autophagy. To clarify cargo characteristics of K. phaffii GGs, we used the same glycogen synthase-based reporter (Gsy1-GFP) of GG autophagy in K. phaffii, as was used in S. cerevisiae. The K. phaffii Gsy1-GFP marked GGs and reported on their autophagic degradation during nitrogen starvation, as expected. However, unlike in S. cerevisiae, glycogen synthase-marked GGs were delivered to the vacuole and degraded there with the same efficiency as a cytosolic glycogen synthase in glycogen-deficient cells suggesting that glycogen is a neutral cargo of bulk autophagy in K. phaffii. We verified our findings with a new set of reporters based on the glycogen-binding CBM20 domain of human STBD1. The GFP-CBM20 and mCherry-CBM20 fusion proteins tagged GGs, reported about autophagy of GGs and confirmed that GGs in K. phaffii are neither preferred, nor non-preferred substrates of bulk autophagy. They are its neutral substrates.

Stress is a natural yet potentially harmful aspect of human life, necessitating effective management, particularly during overwhelming experiences. This paper presents a scoping review of personalized stress detection models using wearable technology. Employing the PRISMA-ScR framework for rigorous methodological structuring, we systematically analyzed literature from key databases including Scopus, IEEE Xplore, and PubMed. Our focus was on biosignals, AI methodologies, datasets, wearable devices, and real-world implementation challenges. The review presents an overview of stress and its biological mechanisms, details the methodology for the literature search, and synthesizes the findings. It shows that biosignals, especially EDA and PPG, are frequently utilized for stress detection and demonstrate potential reliability in multimodal settings. Evidence for a trend towards deep learning models was found, although the limited comparison with traditional methods calls for further research. Concerns arise regarding the representativeness of datasets and practical challenges in deploying wearable technologies, which include issues related to data quality and privacy. Future research should aim to develop comprehensive datasets and explore AI techniques that are not only accurate but also computationally efficient and user-centric, thereby closing the gap between theoretical models and practical applications to improve the effectiveness of stress detection systems in real scenarios.

According to previous studies the median raphe region (MRR) is known to contribute significantly to social behavior. Beside serotonin, there are reports of a small population of dopaminergic neu-rons in this region. Dopamine is linked to reward and locomotion, but very little has been known about its role in the MRR. To address that, we first confirmed the presence of dopaminergic cells in the MRR of mice (immunohistochemistry, RT-PCR) and humans (RT-PCR). Next, we used chemogenetic technology in mice containing Cre enzyme under the promoter of the dopamine transporter (DAT). With the help of an adeno-associated virus, artificial receptors were expressed in the dopaminergic cells of the MRR (DAT-MRR). Four weeks later, extensive behavioral charac-terization started 30 minutes after the injection of the artificial ligand (Clozapine-N-Oxide). Stimu-lation of DAT-MRR decreased social interest without influencing aggression and with an increase in social discrimination. Additionally, inhibition of the same cells increased the friendly social be-havior during social interaction test. No behavioral changes were detected in anxiety, memory and locomotion. All in all, dopaminergic cells were present both in the mice and human MRR, and manipulation of dopaminergic neurons of the MRR elicited a specific social response.

Microsporidia are intracellular parasites infecting a wide range of vertebrates and invertebrates. In bees, they cause a diarrheal disease called nosematosis, which represents a growing problem contributing to the decline of bee colonies. This parasitic disease infects the gastrointestinal tract of bees, disrupts their immune system, weakens them, and shortens their lifespan. There are two known species of this microsporidial parasite with a global distribution: Vairimorpha apis and Vairimorpha ceranae, with current research indicating that the species V. ceranae is gradually replacing V. apis. In this study, we focused on the detection and occurrence of Vairimorpha spp. in bee colonies kept in different environments, as well as on comparing the impact of hive location on its occurrence. The methods used included sampling from winter bee carcasses, microscopic examination of bee gut contents, and subsequent molecular duplex PCR analysis. Altogether, we examined 82 hives located at 4 different sites and focused on the impact of transportation as an abiotic factor disturbing bees leading to the development of Vairimorpha spp. disease. The results indicate an increased occurrence of this parasite in hives located in urban sites and hives situated in intravillage locations, which may be attributed to transportation and associated vibrations as an abiotic stress factor. Detection revealed that all samples were positive for Vairimorpha ceranae.

This study investigates stress perceptions, somatization, and coping strategies among 271 nursing and dentistry (n=126 and n=145, respectively), undergraduate and postgraduate students. For the study, an e-questionnaire was designed in a two-step process, uploaded in Google Forms and staying open for submissions during February 2024 in the School of Health Sciences, National and Kapodistrian University of Athens. In our sample, predominantly female (68.60%), the majority were undergraduates (80.10%). Females reported higher stress somatization (M=10.22, SD=5.23) compared to males (M=7.94, SD=6.14), with a moderate effect size (Cohen’s d=0.412, p

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 problems of modeling the human bladder and its stress-strain state under external static influence were considered. A method for identification of the anisotropic biomechanical characteristics of bladder tissue was proposed. A FEM model was created, which accepts into regard that the bladder is surrounded by fiber and affected by surrounding organs, and partially protected by pelvic bones. The model considered the presence of constant hydrostatic pressure on the walls of the bladder when it is full. It has been shown that isotropic mechanical characteristics of biological tissue can be used for studying the deformed state of a filled bladder if the filled bladder 300 ml is considered as initial non-deformed stage. This was shown by modeling and verification the effect of the external static force on the bladder. Numerical experiments were conducted based on the constructed model. To validate the results obtained, a series of natural experiments on the effect of external pressure on the bladder under ultrasound control was conducted. In the future, it is planned to use the constructed model to study rupture deformations of the bladder under the influence of static and dynamic loads.

Low-resource languages often face the problem of insufficient data, which leads to poor quality in machine translation. One approach to address this issue is data augmentation. Data augmentation involves creating new data by transforming existing data through methods such as flipping, cropping, rotating, and adding noise. Traditionally, pseudo-parallel corpora are generated by randomly replacing words in low-resource language machine translation. However, this method can introduce ambiguity as the same word may have different meanings in different contexts. This study proposes a new approach for low-resource language machine translation, which involves generating pseudo-parallel corpora by replacing phrases. The performance of this approach is compared with other data augmentation methods, and it is observed that combining it with other data augmentation methods further improves performance. To enhance the robustness of the model, R-Drop regularization is also used. R-Drop is an effective method for improving the quality of machine translation. The proposed method was tested on Chinese-Kazakh (Latin script) translation tasks, resulting in performance improvements of 4.99 and 7.7 for Chinese-to-Kazakh and Kazakh-to-Chinese translations, respectively.

This feature study attempts on setting a granules involving mesoscopic matter-aggregation context as a problem of passing locally by the matter-aggregating system from classical stochastic (mesoscopic limit) to a quantum description (nanoscale quantum-size effect limit). A d-dimensional entropy-production aggregation of the granules-involving matter is considered in terms of a (sub)diffusive realization. It turns out that when taking a full d-dimensional pathway of the aggregation toward the nanoscale, one is capable of disclosing a Heisenberg type (diffusional) relation, setting up an upper uncertainty bound for the (sub)diffusive very slow granules-including environment that matches the quantum limit of h/2pm (m– average mass of a granule; h – the Planck’s constant) for the diffusion coefficient of the aggregation, likely first proposed by Fürth in 1933, and qualitatively foreseen by Schrödinger some years before, both in the context of a diffusing particle cluster. The classical-quantum passage uncovered here, also termed insightfully the quantum-size effect (as borrowed from the quantum dots’ parlance), works properly for the three-dimensional (d=3) case, making use of a substantial physical fact that the (nano)granules interact readily via their surfaces with the also granular surroundings in which they are immersed. This natural observation is embodied in the basic averaging construction of the diffusion coefficient of the aggregation of interest. Certain, possibly biomedical, applications of the model can also be viewed by prospective inspection of tiny inhomogeneities in nanofibrillar and/or lamellar matter for which certain numerical realizations are plausible to prepare based on thorough nanoscale experiments.

Genetic variations at the Apolipoprotein E (ApoE) and microtubule-associated protein tau (MAPT) loci have been implicated in multiple neurogenerative diseases, but their exact molecular mechanisms are unclear. In this study we performed transcript level linear modelling using the blood whole transcriptome data and genotypes of the 570 subjects in the Parkinson’s progression markers initiative (PPMI) cohort. ApoE, MAPT haplotypes and two SNPs at the SNCA locus (rs356181, rs3910105) were used to detect expression quantitative trait loci eQTLs associated with the transcriptome and differential usage of transcript isoforms. As a result, we identified 151 genes associated with the genotypic variations, 29 cis and 122 trans eQTL positions. Profound effect with genome-wide significance of ApoE e4 haplotype on the expression of TOMM40 transcripts was identified. This finding potentially explain in part the frequently established genetic association with the APOE e4 haplotypes in neurodegenerative diseases. Moreover, MAPT haplotypes had significant differential impact on 23 transcripts from the 17q21.31 and 17q24.1 loci. MAPT haplotypes had also the largest (256) and smallest (-178) effect sizes measured as beta values on two different transcripts from the same gene (LRRC37A2). Intronic SNP in the SNCA gene, rs3910105, differentially induces expression of three SNCA isoforms. In conclusion, this study established clear association between well-known haplotypic variance and transcript specific regulation in the blood. APOE e4 and MAPT H1/H2 haplotypic variants are associated with the expression of several genes related to the neurodegeneration.

Neural network regularized learning has garnered significant attention in recent years. We give a systematic investigation on the performance of regularized regression associated zonal translation networks. We propose the concept of Marcinkiewicz-Zygmund inequality Setting (MZIS) for the scattered nodes collected from the unit sphere. We show that, under the MZIS, the corresponding convolutional zonal translation network has reproducing property. Based on these facts,we propose a kind of kernel regularized regression learning framework and provide upper bound estimate for the learning rate with the kernel approach. We also give proof for the density of the zonal translation network with spherical Fourier analysis.We provide the approximation error with a K-functional.

The gene translation system possesses inherent complexity in distinguishing codons with degeneracy through repertoires of aminoacyl-tRNAs in the ribosome. Implementation of inosine nucleoside at the anticodon wobble-position in certain tRNAs, especially in eukaryotes, might be arisen to establish complex decoding systems. This report introduces the novel concept of “decoding tables”, which serve as concise summaries of codon-anticodon pairings provided in codon table-like format. Utilizing tRNA genome database information and a procedure based on compiled tRNA studies, the tRNA repertoire and the use of wobble pairings can be depicted for any organisms. The decoding table sheds light on the use of wobble pairings across diverse organisms.

The Pandemic in 2019 forced a digital adaptation with direct consequences on all educational stakeholders. On behalf of teachers and trainers, while many regarded these changes with some scepticism, others embraced the opportunity to integrate technology into their teaching methods and as learning resources. As translation trainers, it is essential to follow and understand the translation market. Thus, the exponential changes that digital technology has brought to this sector over the years impose constant shifts in teaching and learning methods and resources. In fact, translators require vast competencies, amongst which is the flexibility to adapt. In translation training Project-Based Learning (PBL) has been established as an essential teaching and learning method, as it has proven to foster the development of competencies as it simulates the translator's work environment. Thus, the need to adapt new strategies reinforced PBL and its benefits. PBL, however, similar to a freelance translator, places the student in the centre of the learning process, where self-regulation becomes essential, as it is necessary to analyse the market/situation and be flexible enough to adapt to the context accordingly. As of 2018-2019, technical translation courses at ISCAP have implemented PBL as their main teaching and learning method. At the same time, a study on student self-regulation began. The purpose was to understand student perception on their own self-regulation competence and its development or lack thereof after one year of PBL. Results indicate that PBL is seen as a useful simulation of the translation labour market and that it does enhance many essential competences, amongst which is student self-regulation.

PBRM1, a component of the chromatin remodeller SWI/SNF, is often deleted or mutated in human cancers, most prominently in renal cancers. Core components of the SWI/SNF complex have been shown to be important for the cellular response to hypoxia. Here we investigated how PBRM1 controls HIF-1alpha activity. We find that PBRM1 is required for HIF-1alpha transcriptional activity and protein levels. Mechanistically, PBRM1 is important for HIF-1alpha mRNA translation, as absence of PBRM1 results in reduced activly transalting HIF-1alpha mRNA. Interestingly, we find that PBRM1, but not BRG1, interacts with the m6A reader protein YTHDF2. HIF-1alpha mRNA is m6A modified, bound by PBRM1 and YTHDF2. PBRM1 is necessary for YTHDF2 binding to HIF-1alpha mRNA and reduction of YTHDF2 results in reduced HIF-1alpha protein expression in cells. Our results identify a SWI/SNF independent function for PBRM1, interacting with HIF-1alpha mRNA and the epitranscriptome machinery. Furthermore, our results suggests that the epitranscriptome associated proteins play a role in the control of hypoxia signalling pathways

In this paper, we propose a novel network representation learning model TransPath to encode heterogeneous information networks (HINs). Traditional network representation learning models aim to learn the embeddings of a homogeneous network. TransPath is able to capture the rich semantic and structure information of a HIN via meta-paths. We take advantage of the concept of translation mechanism in knowledge graph which regards a meta-path, instead of an edge, as a translating operation from the first node to the last node. Moreover, we propose a user-guided meta-path sampling strategy which takes users' preference as a guidance, which could explore the semantics of a path more precisely, and meanwhile improve model efficiency via the avoidance of other noisy and meaningless meta-paths. We evaluate our model on two large-scale real-world datasets DBLP and YELP, and two benchmark tasks similarity search and node classification. We observe that TransPath outperforms other state-of-the-art baselines consistently and significantly.

In dentistry, maxillofacial surgery, traumatology, and orthopedics, there is a need to use osteoplastic materials that have not only osteoinductive and osteoconductive properties but are also convenient for use. In the study, compositions based on collagen hydrogel were developed. Polylactide granules (PLA) or a traditional bone graft, a mixture of hydroxyapatite and β-tricalcium phosphate (HAP/β-TCP), were used for gel filling to improve mechanical osteoconductive properties of compositions. The mechanical tests showed that collagen hydrogels filled with 12 wt% highly porous PLA granules (elastic modulus 373 ± 55 kPa) or 35 wt% HAP/β-TCP granules (elastic modulus 451 ± 32 kPa) had optimal manipulative properties. All composite components were cytocompatible. The cell’s viability was above 90%, and the components’ structure facilitated the cell’s surface adhesion. The bone morphogenetic protein-2 (BMP-2) provided osteoinductive composition properties. It was impregnated directly into the collagen hydrogel with the addition of fibronectin or inside porous PLA granules. The implantation of a collagen hydrogel with BMP-2 and PLA granules into a critical-size calvarial defect in rats led to the formation of the most significant volume of bone tissue: 61 ± 15%. It was almost 2.5 times more than in the groups where a collagen-fibronectin hydrogel with a mixture of HAP/β-TCP (25 ± 7%) or a fibronectin-free composition with porous PLA granules impregnated with BMP-2 (23 ± 8%) were used. Subcutaneous implantation of the compositions also showed their high biocompatibility and osteogenic potential in the absence of a bone environment. Thus, the collagen-fibronectin hydrogel with BMP-2 and PLA granules has optimal biocompatibility, osteogenic, and manipulative properties.