Aβ peptides are known to bind neural plasma membranes in a process leading to the deposit of Aβ-enriched plaques. These extracellular structures are characteristic of Alzheimer’s disease, the major cause of late-age dementia. The mechanisms of Aβ plaque formation and deposition are far from being understood. A vast amount of literature describes the efforts to analyze those mechanisms, using a variety of tools. The present review focuses on biophysical studies, mostly carried out with model membranes, or with computational tools. The review starts by describing basic physical aspects of lipid phases, and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The methodological section is followed by the core of the review, a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort in understanding Aβ-bilayer binding. Concepts such as Aβ peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in Aβ-membrane interaction are separately identified and discussed.

We aimed to investigate the relationship between membrane material and development of membrane fouling in a membrane bioreactor (MBR) using membranes with different pore sizes and hydrophilicities. Batch filtration tests were performed using submerged single hollow fiber membrane ultrafiltration (UF) modules with different polymeric membrane materials including cellulose acetate (CA), polyethersulfone (PES), and polyvinylidene fluoride (PVDF) with activated sludge taken from a municipal wastewater treatment plant. The three UF hollow fiber membranes were prepared by a non-solvent-induced phase separation method and had similar water permeabilities and pore sizes. The results revealed that transmembrane pressure (TMP) increased more sharply for the hydrophobic PVDF membrane than for the hydrophilic CA membrane in batch filtration tests, even when membranes with similar permeabilities and pore sizes were used. PVDF hollow fiber membranes with smaller pores had greater fouling propensity than those with larger pores. In contrast, CA hollow fiber membranes showed good mitigation of membrane fouling regardless of pore size. The results obtained in this study suggest that the surface hydrophilicity and pore size of UF membranes clearly affect the fouling properties in MBR operation when using activated sludge.

The processability of conductive polymers such as polyaniline (PANI) still poses a challenge due to their properties. The use of stabilizers, compatible and able to interact with PANI, to obtain dispersible and stable colloids is described in this work. To this aim, potato starch has been used as a steric stabilizer for the preparation of polyaniline (emeraldine salt, ES)/starch biocomposites, by exploiting oxidative polymerization of aniline in aqueous solutions containing different ratios of aniline and starch (% w/w). The polyaniline/starch biocomposites were subjected to structural and spectroscopic analyses, thermal analysis, morphological analysis and electrochemical analysis. The samples were then tested for their dispersibility/solubility in various organic solvents. The results showed the formation of PANI/starch biocomposites with an overall smaller size than starch particles, with improved aqueous dispersion and solubility in organic solvents. Although X-ray diffraction and differential scanning calorimetry analyses indicated a loss of crystallinity in the biocomposites, the cyclic voltammetry tests showed that all PANI ES/starch biocomposites display improved redox exchange properties.

FRAP technique have been used for decades to measure movements of molecules in 2D. Data obtained by FRAP experiments in cell plasma membranes are assumed to be described through means of two parameters, a diffusion coefficient D (as defined in a pure Brownian model) and a mobile fraction M. Nevertheless, it has also been shown that recoveries can be nicely fit using anomalous sub-diffusion. FRAP at variable radii has been developed using the Brownian diffusion model to access geometrical characteristics of the surrounding landscape of the molecule. Here we performed numerical simulations of continuous time random walk (CTRW) anomalous subdiffusion and interpreted them in the context of variable radii FRAP. These simulations were compared to experimental data obtained at variable radii on living cells using the PH domain of the membrane binding protein EFA6 (exchange factor for ARF6, a small G protein). This protein domain is an excellent candidate to explore the structure of the interface between cytosol and plasma membrane in cells. By direct comparison of our numerical simulations to the experiments, we show that this protein does not exhibit anomalous diffusion in BHK cells. The non Brownian PH-EFA6 dynamics observed here is more related to spatial heterogeneities such as cytoskeleton fences effects.

Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.

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Extracorporeal membrane oxygenation (ECMO) is increasingly used in intensive care units; however, ECMO can modify drug pharmacokinetics (PK), leading to underexposure and associated treatment failure. The aim of the present study was to determine the effect of ECMO on the PK of dexmedetomidine (DEX). In vivo rat models were developed, both of which involved a bolus injection of DEX and concentration monitoring. In the in vivo model experiment, rats which underwent ECMO were compared with a control group. PK analysis of in vivo data (noncompartmental analysis and nonlinear mixed-effects modelling) was carried out to determine the effect of ECMO. In vivo PK exploration showed that ECMO induced a decrease in DEX clearance. Because the effect of ECMO on the PK of DEX is not clinically significant, normal DEX dosing for critically ill patients should be effective for patients undergoing ECMO.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu-Aβ4-x] and [Cu-Aβ1-x] complexes toward dopamine and other catechols. The results show that the CuII-ATCUN site is not redox-inert, the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary [CuII-Aβ-catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by re-oxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu-Aβ4-x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site.

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

Neurotoxicity belongs to the leading factors inducing neurodegeneration-related diseases, such as Alzheimer’s (AD) and Parkinson’s disease. In particular, accumulation of β-amyloid proteins in the brain, a hallmark in AD, induces oxidative stress and neurotoxicity. The use of antioxidants in AD is not sufficiently effective and other pharmacological approaches tested failed to cure, prevent or retard the progression of the disease. Clinical studies indicated that several medicinal plants display beneficial effects by improving memory and cognitive functions of patients with mild and moderate AD. In this study, the potential antioxidant and neuroprotective properties of Olea europea, Crocus sativus and Salvia spp extracts, as well as their main active compounds on cell viability was evaluated using an in vitro model of AD, the differentiated human SH-SY5Y neuroblastoma cells to cholinergic neurons. Their effects were assessed against the H2O2- and β-amyloid- induced cell toxicity using the MTS test. Current findings indicated that Salvia fruticosa, S. officinalis, S. argentea leaf extracts and the active compounds, oleuropein, trans-crocin-3 and -4 display significant dose-dependent antioxidant and neuroprotective properties. It is of note though that the total phenolic fragment of Olea europea leaf extract includes several toxic compounds, such as oleocanthal, that markedly reduce cell viability and exacerbate the H2O2- and Aβ-induced cell toxicity. In addition, the Crocus sativus hydrophilic and diethyl ether extracts and all their active compounds tested markedly increased the H2O2-induced cell toxicity. In conclusion, the medicinal plants tested contain several compounds displaying dose-dependent effects against H2O2- and Aβ-induced neurotoxicity and could be used in AD, but they also contain several neurotoxic agents.

Background/Objectives: The aim of this study was to investigate feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and assess thoroughly any potential adverse events. Methods: We conducted a safety and feasibility study including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. Patients underwent a 45-minute NMES session, still on ECMO support, that included a warm up phase of 5 minutes, a main phase of 35 minutes and a recovery phase of 5 minutes. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius and peroneus longus muscle of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with 400 μsec pulse duration, 5 sec on (1,6 sec ramp up and 0,8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of the study were feasibility and safety, evaluated by whether the NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood test, 24 hours after the application of NMES. Results: All patients successfully completed their 45-minute NMES session, without presenting hemodynamic deterioration, adverse events or signs of rhabdomyolysis. The majority of patients achieved type 4 and 5 quality of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology in patients supported with ECMO.

The per capita availability of freshwater resources on a global scale is gradually decreasing due to population growth, rapid urbanization, industrialization, and modern lifestyles. In this situation, wastewater management becomes a major concern. Conventional treatment processes used to treat wastewater discharges are not adequate for the advanced removal of pollutants, especially refractory organic pollutants, which are mainly organic compounds that are not easily biodegradable in the environment. The use of photocatalytic membrane reactors (PMRs) for tertiary wastewater treatment has attracted much interest in recent periods, and various configurations have been investigated. The performance of a PMR using an iron doped titanium photo catalyst and Polysulfone-based polymeric membrane for municipal wastewater treatment was evaluated under natural and simulated solar light. Obtained results proved that solar driven PMRs can remove organic loading (COD) with high efficiencies and may represent a suitable alternative for the tertiary treatment step of municipal wastewater.

As marine traffic is contributing to pollution and mostly have predictable route with repetitive load profiles, to reduce their impact on environment, hybrid system with proton exchange membrane fuel cells (PEMFC-s) and battery pack, is promising replacement. For this purpose, the numerical model of repowered existing vessel that have two diesel engines with 300 kWe is developed. The goal of this paper is to develop numerical model which analyzes and determine equivalent hybrid ship propulsion system for known traveling route. The developed numerical model consists of an interconnected system with PEMFC stack and battery pack as power sources. Numerical model is developed and optimized to meet minimal required power demand for successful route demand, which has variable loads and daily sails six-time same voyage- in total 54 nautical miles. The results have shown that equivalent hybrid power system consists of 300 kWe PEMFC stack and battery pack with 424 kWh battery and state of charge varying between 20 and 87%. To power this new hybrid power system, hydrogen tank of 7200 l holding 284.7 kg at pressure of 700 bar is needed, compared to previous system that spend 1524 kg of diesel and generate 4886 kg of CO2.

Artificial membrane systems can serve as models to investigate molecular mechanisms of different cellular processes, including transport, pore formation, and viral fusion. However, the current simulacrums such as SUVs, GUVs, and the supported lipid bilayers suffer from issues, namely high curvature, heterogeneity, and surface artefacts, respectively. Freestanding membranes provide a facile solution to these issues, but current systems developed by various groups use silicon or aluminium oxide wafers for fabrication that involves access to a dedicated nanolithography facility and high cost while conferring poor membrane stability. Here, we report the development, characterization and applications of an easy-to-fabricate suspended lipid bilayer (SULB) membrane platform leveraging commercial track-etched porous filters (PCTE) with defined microwell size. Our SULB system offers a platform to study the lipid composition-dependent structural and functional properties of membranes with exceptional stability in a high throughput fashion. With dye entrapped in PCTE microwells by SULB, we show that sphingomyelin significantly augments the activity of pore-forming toxin, Cytolysin A (ClyA) and the pore formation induces lipid exchange between the bilayer leaflets. Further, we demonstrate high efficiency and rapid kinetics of membrane fusion by dengue virus in our SULB platform. Our suspended bilayer membrane mimetic offers a novel platform to investigate a large class of biomembrane interactions and processes.

Dye/salt separation has gained increasing attention in recent years, prompting the quest for cost-effective and environmentally-friendly raw materials for synthesis high performance nanofiltration (NF) membrane for effective dye/salt separation. Herein, a high-performance loose structured NF membrane was fabricated by via a simple vacuum filtration method using a green nanomaterial, 2,2,6,6-tetramethylpiperidine-1-oxide radical (TEMPO)-oxidized cellulose nanofiber (TOCNF), by sequentially filtrating larger-size and finer-size TOCNFs on a microporous substrate, followed by cross-linked with trimesoyl chloride. The resultant TCM membrane possesses a separating layer composed entirely of pure TOCNF, eliminating the need for other polymer or nanomaterials additives. TCM membranes exhibits high performance and effective dye/salt selectivity. Scanning Electron Microscope (SEM) analysis shows that the TCM membrane with Fine-TOCNF layer has a tight layered structure. Further characterizations via Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirm the presence of functional groups and chemical bonds of the crosslinked membrane. Notably, the optimized TCM-5 membrane exhibits a rejection rate of over 99% for various dyes (Congo red, orange yellow) and 14.2% for NaCl, showcasing a potential candidate for efficient dye wastewater treatment.

A hybrid material, consisting of commercially available nitrocellulose (NC) membrane non-covalently modified with amino-polyethylene glycol functionalized reduced graphene oxide (NH2-PEG-rGO) nanoparticles, was successfully synthesized for oligonucleotide extraction. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the modification of the NC membrane, revealing characteristic peaks of both compounds NC and NH2-PEG-rGO. Scanning Electron Microscopy (SEM) exhibited morphological changes in the NC/NH2-PEG-rGO hybrid membrane, marked by the introduction of NH2-PEG-rGO particles, resulting in a distinctly smothered surface compared to the porous surface of the NC control membrane. Wettability assays revealed hydrophobic behavior for the NC/NH2-PEG-rGO hybrid membrane, with a water contact angle exceeding 90°, contrasting with the hydrophilic behavior characterized by a 16.7° contact angle in the NC membrane. The performance of the NC/NH2-PEG-rGO hybrid membrane was evaluated for the extraction of ssDNA with fewer than 50 nucleotides from solutions containing various ionic species (MnCl2, MgCl2, and MnCl2/MgCl2). The NC/NH2-PEG-rGO hybrid membrane exhibited optimal performance when incubated in MgCl2, presenting the highest fluorescence emission at 525 relative fluorescence units (r.f.u.). This corresponds to the extraction of approximately 610 pg (≈13%) of the total oligo-DNA, underscoring the efficacy of the pristine material, which extracts 286 pg (≈6%) of oligo-DNA in complex solutions.

Polymer inclusion membranes (PIMs), which contained cellulose tri-acetate used as a polymer base, a plasticizer in the form of o-NPOE, and meso-tetra methyl tetrakis-[methyl-2-(4-acetlphenoxy)] calix[4]pyrrole (KP) used as a carrier, were prepared and tested for the effective purification of aqueous solutions of methylene blue dye. The scanning electron microscope (SEM), thermogravimetric analysis (TGA), and attenuated total reflection Fourier transform infrared (ATR-FTIR) were used to define the microstructure and surface of PIMs. Experimental results showed that with the increased concentration of methylene blue in an aqueous solution, the removal percentage also increased. Further observation also showed that the flux increased with the rise of the source phase pH values from 3 to 10. The carrier and plasticizer content in the membrane significantly influenced the membrane’s transport properties. The optimal composition of the membrane in per cent by weight was for KP: 74% plasticizer; 18% support; 8% carrier. It was shown that the membrane with optimal composition showed good reusability and enabled the easy and spontaneous separation of methylene blue from aqueous solutions.

Ischemic heart disease is the leading cause of mortality worldwide. There is evidence of the participation of Aβ in thrombosis and clinical manifestations of acute coronary syndromes. In this study, we investigated the correlation of Aβ peptides with myocardial injury and inflammation biomarkers in acute coronary syndrome. This is a single-center, cross-sectional, observational, and correlation study that included 65 patients within the first 12 hours after symptom onset (chest pain, shoulder pain, or chest discomfort) with ST-elevation and non-ST elevation myocardial infarction who were admitted in the Coronary Care Unit, biochemical parameters of Aβ peptides levels were evaluated. Our results show that NSTEMI patients had a higher prevalence of hypertension, diabetes, smoking, and prior myocardial infarction when compared to STEMI patients. We observed a higher level of Aβ-42 in NSTEMI, but no difference in Aβ-40 levels. We also found a correlation between age and NT-proBNP with both Aβ peptides (Aβ-40, Aβ-42) in both groups. In this analysis, NSTEMI patients had higher prevalence of cardiovascular risk factors. Considering the toxic properties of Aβ-42 in coronary endothelial cells and cardiomyocytes, this peptide may be useful in risk stratification scores in patients with NSTEMI.

The temporo-spatial theory of consciousness postulates that the brain implements its own inner time and space for conscious processing of outside world. In line with this hypothesis, I present a mechanistic model of mutually connected processes that encode the inner space and time. The model is used to elaborate the binding mechanism between two sets of processes representing the inner space and time, respectively. Further, a stochastic version of the model is developed to investigate the interplay between the binding strength and noise. The spectral entropy is used to characterize the noise effects on the systems of processes when the binding strength is varied. The stochastic modeling results reveal that the spectral entropy values for strongly bound systems have similar entropy values for weakly bound or even decoupled systems. Thus, the analysis performed in this study allows to conclude that the binding mechanism is noise-resilient.

Mandibular critical size defect (CSD) due to pathological conditions, trauma, and congenital disease can not heal spontaneously and predominantly filled with fibrous tissue. Therefore, a Guided Bone Regeneration (GBR) combined with bone grafting can be performed. The researchers considered using Demineralized Dentin Material Membrane (DDMM) from bovine dentine as an alternative GBR. This study aimed to determine the amount of fibroblast and collagen density after DDMM and bone graft implantation on CSD. Thirty-six Rattus norvegicus rats were used as samples. Mandibular bone defect 5x5 mm was made, then filled with bone graft and covered with Bovine Pericardium Collagen Membrane (BPCM) in the control group and DDMM in the treatment group. Six samples were sacrificed on 7, 14, and 21 days post-surgical for histology examination. There were no significant differences in the amount of fibroblast and collagen density (p-value > 0,05). The amount of fibroblast is lower and the collagen density is higher in treatment group. DDMM has microporosity to prevent connective tissue ingrowth and dentine tubules to allow growth factors release. DDMM and bone graft implantation can reduce the amount of fibroblasts and increase collagen density of CSD which potentially being used as a CSD alternative treatment for bone regeneration.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Introduction: IFITM3, an innate immune protein linked to COVID-19 severity, has recently been identified as a novel γ-secretase modulator. Independent research has shown that IFITM3 may facilitate SARS-CoV-2 neurotropism in an ACE2-independent manner. In a previous study, we had detected perturbations in IFITM3 networks in both the CNS and peripheral immune cells donated by AD patients. The purpose of this study is to explore the transcriptomic evidence of the SARS-CoV-2 / IFITM3 / AD interplay, validating previous findings from our group. Methods: Exploratory analyses involved meta-analysis of bulk and single cell RNA data for IFITM3 and FYN differential expression. For confirmatory analyses, we performed gene set enrichment analysis (GSEA) on an AD gene signature from AD Consensus transcriptomics; using the Enrichr platform, we scrutinized COVID-19 datasets for significant, overlapping enriched biological networks. Results: Bulk RNA data analysis revealed that IFITM3 and FYN were differentially expressed in two CNS regions in AD: the temporal cortex (AD vs. Controls, adj.p-value=1.3e^-6) and the parahippocampal cortex (AD vs. controls, adj.p-value=0.012). Correspondingly, single cell RNA analysis of IFITM3 and FYN revealed that it was differentially expressed in neuronal cells donated from AD patients (astrocytes, microglia and oligodendrocyte precursor cells), when compared to controls. Discussion: IFITM3 and by extent FYN were found as interactors within biological networks overlapping between AD and SARS-CoV-2 infection. SARS-CoV-2-mediated FYN/IFITM3 induction would mechanistically result in increased Tau fibrilization and Aβ oligomerization. FYN recruitment by viral processes results in abrogation of both fusion of IFITM3 vesicles with lysosomes; immunoevasion, by FYN-mediated impairment of autophagy would then serve to promote impaired detoxification from Aβ, while propagating Tau pathology in an IFITM3-independent manner.

The purpose of this study was to investigate the effect of circuit training on β-amyloid, BDNF, and cognitive function in untrained obese elderly Korean women. The subjects for the study were aged 65–70 years, composed of the circuit training group(n=12) and control group(n=11). The 60-minute combined exercise was performed 3 times per week for 16 weeks. Exercise intensity was progressively increased from 40% HRR to 70% HRR. The test data were analyzed by paired t-test, independent t-test, and two-way repeated measures ANOVA, and the alpha level of .05 was set for all tests of significance. The findings of this study were as follows: β-amyloid significantly decreased after the exercise group had compared to before the exercise and BDNF and cognitive function significantly increased after the exercise group had compared to before the exercise. However, there were no significant changes in β-amyloid, BDNF, and cognitive function in the control group Therefore, it is suggested that the circuit training used in this study could be an effective exercise method for improving the risk factors of cognitive impairment in obese elderly Korean women.

Biological membranes are fascinating. Santiago Ramón y Cajal, who received the Nobel prize in 1906 together with Camillo Golgi for their work on the nervous system, wrote “[..]in the study of this membrane[..] I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life”[1]. The visualization and conceptualization of these biological objects have profoundly shaped many aspects of modern biology, drawing inspiration from experiments, computer simulations, as well as from the imagination of scientists and artists. The aim of this review is to provide a fresh look on current ideas of biological membrane organization and dynamics by discussing selected examples across fields [1] The full quotation is “I must not conceal the fact that in the study of this membrane I for the first time felt my faith in Darwinism (hypothesis of natural selection) weakened, being amazed and confounded by the supreme constructive ingenuity revealed not only in the retina and in the dioptric apparatus of the vertebrates but even in the meanest insect eye. There, in fine, I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life.” from the autobiography Recollections of My Life.

The most common and taught membrane theory assumes that the membrane behaves as a kind of electrical capacitance that is exposed to an electrical current generated by an ionic flow. If this statement is verifiable, it can be confirmed by the laws of physics, mathematics and in particular electricity. We will demonstrate that this hypothesis is not verified and that it is necessary to modify biophysics according to already established and experimentally verified principles of physics.

Membrane-based sensors (MePSs) exhibit remarkable precision and sensitivity in detecting pressure changes. MePSs are commonly used to monitor catalytic reactions in solution, generating gas products crucial for signal amplification in bioassays. They also allow catalyst quantification by indirectly measuring the pressure generated by the gaseous products. This is particularly interesting to detect enzymes in biofluids associated with disease onset. To enhance the performance of a MePS, various structural factors influence membrane flexibility and response time, ultimately dictating the device's pressure sensitivity. In this study, we fabricated MePSs using polydimethylsiloxane (PDMS) and investigated how structural modifications affect the Young's modulus (E) and residual stress (σ0) of the membranes. These modifications have a direct impact on the sensors' sensitivity to pressure variations, observed as a function of the volume of the chamber (Σ) or of the mechanical properties of the membrane itself (S). MePSs exhibiting the highest sensitivities were then employed to detect catalyst quantities inducing the dismutation of hydrogen peroxide, producing dioxygen as gaseous product. As a result, catalase enzyme was successfully detected using these optimized MePSs, achieving a remarkable sensitivity of (22.7 ± 1.2) µm/nM and a limit of detection (LoD) of 396 pM.

Many studies discuss carbon-based materials because of the versatility of its element. They include different opinions for scientific problems and discuss fairly at convincing and compelling levels within the scope and application. A gas-state carbon atom converts into various states depending on its conditions of processing. The electron transfer mechanism in the gas-state carbon atom is responsible to convert it into various states, namely, graphite, nanotube, fullerene, diamond, lonsdaleite and graphene. The shape of ‘energy trajectory’ enables transferring electrons from the left- and right-sides of an atom is like a parabola. That ‘energy trajectory’ is linked to states (filled state and suitable nearby unfilled state) where force-exertion along the poles of transferring electrons is remained balance. So, the mechanism of originating different states of a gas-state carbon atom is under the involvement of energy first. This is not the case for atoms executing confined inter-state electron-dynamics as the force is involved first. Graphite-, nanotube- and fullerene-state atoms ‘partially evolve partially develop’ (form) their structures. These possess one-dimensional, two-dimensional and four-dimensional ordering of atoms, respectively. Their structural formation also comprises ‘energy curve’ having a shape-like parabola. Transferring suitable filled state electron to suitable nearby unfilled state is under a balance force exerting along the poles. The graphite structure under only attained-dynamics of atoms can also be formed but in two-dimension. Here, binding energy between graphite-state carbon atoms is for a small difference of exerting forces along their opposite poles. Structural formation in diamond, lonsdaleite and graphene atoms involve energy to gain required infinitesimal displacements of electrons through which they maintain orientationally-controlled exerting forces along dedicated poles. In this study, the growth of diamond is found to be south to east-west (ground) where atoms bound ground to south. Thus, diamond atoms merge for a tetra-electron ground to south topological structure. Lonsdaleite atoms merge for a bi-electron ground to just-south topological structure. The growth of graphene is found to be north to ground where atoms bound ground to north. Thus, graphene atoms merge for a tetra-electron ground to north topological structure. Glassy carbon exhibits layered-topological structure where, tri-layers of gas-, graphite- and lonsdaleite-state atoms successively bind in repetitive order. Nanoscale hardness is also sketched based on different force-energy behaviors of different state carbon atoms. Here, structure evolution in each carbon state atom explores its own science.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused bundling of actin filaments in the absence of alpha-actinin and enhanced alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La stabilized the two proteins on actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide–membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

The generation and maintenance of membrane potential is a fundamental part of Membrane Pump Theory. One of the key points of this hypothesis is based on a natural or facilitated molecular diffusion through several types of ion channels and pumps like the Na/K ATPase. Chemistry, physics and especially electrochemistry, however, bring strong contradictions to this theoretical assumption. By respecting the principles of chemistry and electrostatics, it becomes obvious that this theoretical hypothesis cannot work. The ionic diffusion that would be at the origin of this potential cannot take place. Indeed, the topology and the forces involved definitively exclude the current model, which must absolutely be revised according to the current state of our knowledge and allow an advance in the understanding of the phenomena and open new research perspectives.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

In order to alter and adjust the shape of the membrane, cells harness various mechanisms of curvature generation. Many of these curvature generation mechanisms rely on the interactions between peripheral membrane proteins, integral membrane proteins, and lipids in the bilayer membrane. One of the challenges in modeling these processes is identifying the suitable constitutive relationships that describe the membrane free energy that includes protein distribution and curvature generation capability. Here, we review some of the commonly used continuum elastic membrane models that have been developed for this purpose and discuss their applications. Finally, we address some fundamental challenges that future theoretical methods need to overcome in order to push the boundaries of current model applications.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

Abstract: Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin. During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), SEC-HPLC and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX-heme interactions to approximate physiological conditions (from extremely low to more than 2-fold heme excess). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggests more than one binding site in both plasma and rhHPX. Further, our study provides a useful analytical platform for detailed characterization of HPX-heme interactions and potentially, novel HPX fusion constructs.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

In order to achieve the dual carbon goal and simplify the decarbonization process, a CO2 recovery process of the fire-flooding exhaust was designed. The process adopted the two-stage membrane separation method to recover CO2 and obtain high purity CO2 rich flow, and then through the mixed refrigerant liquefaction and rectification column, food grade liquid CO2 was obtained. HYSYS process simulation shows that for the fire-flooding exhaust with a flow rate of 1000 kg/h and a given composition, the process can achieve a CO2 recovery of 69.02%, total product sales S=2086.8 yuan/h, and specific power consumption of 2.818 kW∙h/kg. On this basis, a hybrid simulation platform of HYSYS & Matlab was established. Taking the specific power consumption of the product as the objective function, sequential quadratic programming (SQP) algorithm was adopted to optimize the process, and the optimized specific power consumption was reduced by 18.8%. Finally, by adjusting N2/CO2 components, the adaptability of the optimization condition was analyzed.

The new hybrid composite materials for PEM fuel cell were synthesized by UV-polymerization of acrylic monomers (acrylonitrile (AN), acrylic acid (AA), ethylene glycol dimethacrylate (EGDMA)) and sulfo aromatic monomer – sodium styrene sulfonate (SSS), and tetraethoxysilane/3-methacryloxypropyltrimethoxysilane (TEOS/MAPTMS)-based sol-gel system. By means of X-ray spectroscopy fractal structure of the obtained materials was characterized. Proton conductivity and viscoelastic properties of the materials were investigated depending on the content of inorganic component in nanocomposites. On the basis of impedance studies, an equivalent scheme is proposed that successfully describes the proton conductivity in the synthesized composite electrolyte membranes.

Background/Objectives: An age-associated increase in serum levels of sex hormone binding globulin (SHBG) is considered to be one of the factors leading to the development of male hy-pogonadism. Aim of the study: to study the relationship between the concentration of sex hor-mone-binding globulin in the blood serum and the age of the man, the level of total and free testosterone. A single-center retrospective cross-sectional study was conducted. The results of laboratory tests of 162 male patients aged from 18 to 56 years (median - 34 years) were analyzed. Methods: The level of total testosterone and sex hormone binding globulin (SHBG) was deter-mined by chemiluminescent immunoassay. The level of free testosterone was determined by the calculation method according to Vermeullen. Statistical analysis was performed using SPSS Sta-tistics v23. Results: Correlation analysis did not reveal a significant relationship between age and SHBG levels, as well as between age and total testosterone levels. Serum SHBG concentration showed a significant (p

The selectivity in selective autophagy pathways is achieved via the selective autophagy receptors (SARs) – proteins that bind a ligand on the substrate to be degraded and the Atg8-family protein on the growing autophagic membrane, phagophore, effectively bridging them. In mammals, the most common ligand of SARs is ubiquitin, a small protein modifier that tags substrates for their preferential degradation by autophagy. Consequently, the most common SARs are the ubiquitin-binding SARs, such as SQSTM1/p62 (sequestosome 1). Surprisingly, there is only one SAR of this type in yeast – Cue5, which acts as a receptor for aggrephagy and proteaphagy – pathways that remove the ubiquitinated protein aggregates and proteasomes, respectively. However, recent studies described the ubiquitin-dependent autophagic pathways that do not require Cue5, e.g. stationary phase lipophagy for intracellular lipid droplets and nitrogen starvation-induced mitophagy for mitochondria. What is the role of ubiquitin in these pathways? Here, we propose that the ubiquitinated lipid droplets and mitochondria are recognized by the alternative ubiquitin-binding SARs. Our analysis identifies the proteins that could potentially fulfill this role in yeast. We think that matching of the ubiquitin-dependent (but Cue5-independent) autophagic pathways with the ubiquitin-and-Atg8-binding proteins enlisted here might uncover the novel ubiquitin-binding SARs in yeast.

Abstract: Background: Hemopexin (Hx) is a plasma glycoprotein that scavenges heme (Fe(III) protoporphyrin IX), Hx have important implication in hemolytic disorders and hemorrhagic condition because the release of hemoglobin increase labile heme, which is potentially toxic producing oxidative stress. Hx has been considered for therapeutic use and diagnostics. In this work, we analyzed and mapped interaction sequences of Hx with hemin and hemoglobin (2) Methods: Spot-synthesis technique was used to map human hemopexin (P02790) binding to hemin and human hemoglobin, a library of 15 amino acid peptides with a 10-amino acid overlap was designed to represent the entire coding region (aa 1-462) of hemopexin and synthesized onto cellulose membranes. In silico approach was performed to analyze amino acid frequency in identified interaction regions, and molecular docking was applied for protein-protein interaction (3) Results: Seven linear peptide sequences in Hx were identified to bind hemin (H1-H7), and five were described for Hb (Hb1-Hb5) interaction, with just two sequences shared between hemin and Hb. Amino acid composition of identified sequences demonstrated that Histidine residues are relevant for heme binding, H105, H293, H373, H400, H429, and H462 was distributed in H1-H7 peptide sequences, but other residues may also play an important role. Molecular docking analysis demonstrated Hx association with the β-chain of Hb, with several hot spot amino acids that coordinated interaction. (4) Conclusions: This study highlights new insights on Hx-hemin binding motifs and protein-protein interactions with Hb. Binding sequences and identified specific peptides can be used for therapeutic purposes and diagnostics, as hemopexin is under investigation to treat different diseases, and there is an urgent need for diagnostics of labile heme for monitoring hemolysis.

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands is compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

Adhesive-invasive E. coli have been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to survival inside macrophages, stimulate chronic inflammation and the development of granuloma. In previous reports, we have shown that passage of the СD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates, and with glucose - inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEС in two phenotypes - virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). We showed that, unlike ZvL2-GLU, the ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. Differences in neutrophil NADH-oxidase activation and ζ potential for ZvL2-GLU and ZvL2-PA are associated with changes in the abundance of membrane proteins. Using differential 2D electrophoresis and LC-MS, we identified membrane proteins that may be associated with the activation of the virulence properties of the СD isolate ZvL2.

The generation and maintenance of membrane potential is considered a fundamental element of the cellular machinery. They are based on elements of physics and chemistry. Mathematics is used to validate the equations and evaluate the results. However, this computation process can lead to a misunderstanding of the phenomena involved or to the masking of crucial events. It is even possible that the calculation no longer corresponds to the hypothesis considered. Membrane theory is no exception to these trivial considerations, which are essential for normal theory validation.

Membrane potential generation and maintenance are fundamental parts of membrane theory. However, since its inception, theories and assumptions have remained simple, whereas the amount of knowledge available has only grown. Unfortunately, this simplification and reductionism lead to its loss of validity on both microscopic and macroscopic scales. This article shows that assumptions made outside the context of factual reality lead to contradictions that cannot be compared with science. Membrane theory must be thoroughly revised, taking into account all forgotten and unanswered assumptions and questions to conform to facts and science to maintain credibility.

The membrane potential or resting potential of the neuron has been the subject of many studies. Although this theory explains the generation and maintenance of the membrane potential by direct or even facilitated diffusion, there are too many contradictions to doubt that these forces are sufficient or even at work in a process whose initial conditions are of rare complexity. The aim of this article is to show that already in the past, a competing theory has been developed whose hypothesis seems more scientifically sound. To confirm this last theory, Hirohisa Tamagawa carried out an experiment of great simplicity which makes it possible to invalidate the current theory and to question the teaching and the knowledge in Biology and Biophysics.

There are different treatment options in modern dentistry for the replacement of lost dentition. Of these the most upcoming and acceptable treatment option is Dental implants. The common problem usually with immediate implant placement in the anterior region is the post-operative soft tissue contour as a part of the bone modelling during healing. Hurzeler et al in 2010 introduced a new technique called the “socket shield technique”. This technique has been used as an alternative treatment modality for immediate implant placement in the aesthetic zone.This review articles provides a detailed information regarding the clinical concept of Root membrane technique.

The growing global population and limitations in fish catch production have led to a surge in the demand for aquaculture. Contaminants of emerging concern (CEC) are frequently being detected at low levels in surface water. These CECs, which include previously unidentified or unregulated pollutants, pose potential risks to health and the environment, though their impacts are not yet fully understood. Extensive research studies have been proposed and undertaken to address the issue of aquaculture wastewater, aiming to minimize its impact and implement effective treatment methods. This review provides an analysis of various technologies used for treating aquaculture wastewater using advanced oxidation processes (AOPs) focusing on photocatalysis and ozonation. It examines their advantages and disadvantages, as well as their respective treatment efficacies and discusses their potential applications in sustainable aquaculture practices complying with the Sustainable Development Goals of 1,2 and 6 and the Environmental Social and Governance (ESG) framework.

Endothelial cells are the crucial inner lining of blood vessels, pivotal in vascular homeostasis and integrity. However, these cells are perpetually subjected to a myriad of mechanical, chemical, and biological stresses that can compromise their plasma membranes. A sophisticated repair system involving key molecules, such as calcium, annexins, dysferlin, and MG53, is essential for maintaining endothelial viability. These components orchestrate complex mechanisms, including exocytosis and endocytosis, to repair membrane disruptions. Dysfunctions in this repair machinery, often exacerbated by aging, are linked to endothelial cell death, subsequently contributing to the onset of atherosclerosis and the progression of cardiovascular diseases (CVD) and stroke, major causes of mortality in the United States. Thus, identifying the core machinery for endothelial cell membrane repair is critically important for understanding the pathogenesis of CVD and stroke and developing novel therapeutic strategies for combating CVD and stroke. This review summarizes the recent advances in understanding the mechanisms of endothelial cell membrane repair. The future directions of this research area are also highlighted.

The structure of existing activated models is inherently deficient in reflecting the major role of the membrane filtration. This study developed and proposed a novel model, MASM, for the membrane activated process. The effective filtration size imposed by the membrane module, entrapping larger size particles was adopted as the basis of the proposed model. The model defined a modified COD fractionation, accounting for the captured COD fractions as additional model components and utilizing related mass balance relationships. It was implemented for testing the fate of soluble hydrolysable COD and system performance of super-fast membrane activated sludge based on real data for the characterization and process kinetics of domestic sewage and denim processing effluents. Model evaluation was carried for parallel systems with gravity settling and membrane filtration operated at a sludge age range of 0.5-2.0 d. Results reflected significantly better performance of super-fast membrane activated sludge system for both wastewaters, underlining that it was crucially important to account for the captured COD fractions to provide an accurate evaluation of system behavior and effluent quality. This should also be identified as the major shortcoming of the ASM models for evaluating and predicting system performance of activated sludge configurations with membrane separation.

A simple model is developed for membrane fouling, taking into account two main fouling phenomena: cake formation, due to attached solids onto the membrane surface and pores clogging, due to retained compounds inside the pores. The model is coupled with a simple anaerobic digestion model for describing the dynamics of an Anaerobic Membrane BioReactor (AnMBR). In simulations, we investigate its qualitative behavior: it is shown that the model exhibits satisfying properties in terms of flux decrease due to membrane fouling. Comparing simulation and experimental data, the model is shown to predict quite well the dynamics of an AnMBR. The simulated flux best fits the experimental flux with a correlation coefficient r2=0.968 for the calibration data set and r2=0.938 for the validation data set. General discussions are given on possible control strategies to limit fouling and optimize the flux production. We show in simulations that these strategies allow one to increase the mean production flux to 33 L/(h.m2), whereas without control it was 18 L/(h.m2).

The term neuroinflammation defines the reactions of astrocytes and microglia to alterations in homeostasis in the diseased central nervous system (CNS), the exacerbation of which contributes to the neurodegenerative effects of Alzheimer's disease (AD). Local environmental conditions, such as the presence of proinflammatory molecules, mechanical properties of the extracellular matrix (ECM) and local cell-cell interactions, are determinants of glial cell phenotypes. In AD, the load of the cytotoxic/proinflammatory amyloid β peptide (Aβ) is a microenvironmental component increasingly growing in the CNS, imposing time-evolving challenges on resident cells. This study aimed at investigating the temporal and spatial variations of the effects produced by this process on astrocytes and microglia, either directly or by interfering in their interactions. Ex vivo confocal analyses of hippocampal sections from the mouse model TgCRND8 at different ages have shown that overproduction of Aβ peptide induced early and time persistent disassembly of functional astroglia syncytium and promoted a senile phenotype of reactive microglia, hindering Aβ clearance. In the late stages of disease, these patterns were altered in the presence of Aβ-plaques, surrounded by typically reactive astrocytes and microglia. Morphofunctional characterization of peri-plaque gliosis revealed a direct contribution of astrocytes in plaque buildup that might result in shielding Aβ-peptide cytotoxicity and, as a side effect, in exacerbating neuroinflammation.

In an attempt to correct misunderstandings this article brings together the observations on Calcium, Myosin Binding Protein-C and Hypertrophic Cardiomyopathy in the basic function of cardiac muscle. A finding of many years ago is reiterated in a novel enzyme kinetic format with defined rate limiting step which makes CaATP the apparent substrate of the actomyosin cross-bridge. The relationship of these kinetics to recent observations on disruption of myosin binding protein-C is described along with how this bears on the understanding of the related cardiomyopathies.

At nuclear scale, we present three heuristic relations pertaining to strong and electroweak coupling constants. With these relations, close to beta stability line, it is possible to study nuclear binding energy with a single energy coefficient of magnitude $\left(\frac{1}{{\alpha }_s}\right)\left[\frac{e^2}{4\pi {\epsilon }_0{R}_0}\right]\approx 10.0\text{MeV}\text{.}$ With reference to up and down quark masses, it is also possible to interpret that, nuclear binding energy is proportional to the mean mass of $\left[\left(2m_u+m_d\right)\text{and}\left(m_u+2m_d\right)\right]\approx 10.0\text{MeV}.$

Extracorporeal membrane oxygenation (ECMO) is used for the management of severe respiratory and cardiac failure, as well as bridge to definite treatment or transplantation. ECMO associated coagulopathy (EAC) is a frequent complication leading to high rates of thrombosis or severe haemorrhage, contributing to morbidity and mortality of patients. Understanding the pathophysiology of EAC is substantial for effectively managing patients on ECMO. We analyse the underlying mechanism of EAC and discuss the monitoring of coagulation profile, combining the viscoelastic point of care assays with the conventional coagulation laboratory tests.

Spin Assisted Layer-by-Layer (SA-LbL) assembly is one of the Layer-by-Layer (LbL) assembly variants. It is considered as the fastest LbL assembly, however, the deficiency of layering quality on bigger polymeric support size poses a significant challenge to the application of SA-LbL assembly at a larger or industrial scale. To address the challenge, combined spin-spray assisted Layer-by-Layer (SSA-LbL) is employed to prepare membrane. In this study, nanofiltration (NF) thin film composite membranes were prepared by alternate deposition of branched-polyethyleneimine (PEI) and poly(sodium 4-styrenesulfonate) (PSS) on polyethersulfone (PES) ultrafiltration (UF) membrane support. The resulting membrane was then tested to separate NaCl from water. One of the membranes produced in this work, i.e., (PEI/PSS)10 achieved rejection rate of 76.2 %; permeability of 2.79 l/h·m2·bar tested at pressure of 10 bar, temperature of 24.58 ± 0.51 °C , and NaCl-Feed concentration of 2076.75 ± 40.51 ppm. The membrane fouling resistance was also examined in 5 days-test. The membrane showed stable performance and lost only about 30% flux from the initial flux due to fouling which was comparable to that of commercial NF membrane such as NF90. Hence, this work shows that SSA-LbL can be considered as a promising and innovative membrane fabrication technique as it offers flexibility and applicability for preparing membrane from various materials as well as pertinence to industrial scale.

Substantial studies have focused on early detection of Alzheimer's disease (AD). Cerebral amyloid beta (Aβ), is hallmark of AD, can be observed in vivo via positron emission tomography imaging using amyloid tracer or cerebrospinal fluid assessment, but costly expensive. The current study aims to identify and compared predictability in magnetic resonance imaging (MRI) markers and neuropsychological markers to predict cerebral Aβ status in AD cohort using machine learning (ML) approaches. The predictability in candidate markers for cerebral Aβ status was examined by analyzing 724 participants from the ADNI-2 cohort. Demographic variables, structural MRI markers, and neuropsychological test scores were used as input in several ML algorithms to predict cerebral Aβ positivity. Out of five combination of candidate markers, neuropsychological markers with demographics showed the most cost-efficient result. A feature selection model could distinguish abnormal levels of Aβ with the predictability of 0.85, indicating the same performance with MRI-based models. The result has first to identified the predictability in MRI markers using ML approaches, and secondary to demonstrate the neuropsychological model with demographics could predict Aβ positivity, suggesting a more cost-efficient method for detecting cerebral Aβ status compared to MRI markers.

Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.

The brain’s ability to create a unified conscious representation of an object by integrating information from multiple perception pathways is called perceptual binding. Binding is crucial for normal cognitive function. Some perceptual binding errors and disorders have been linked to certain neurological conditions, brain lesions, and conditions that give rise to illusory conjunctions. However, the mechanism of perceptual binding remains elusive. Here, we present a computational model of binding using two sets of coupled oscillatory processes that are assumed to occur in response to two different percepts. We use the model to study the dynamic behavior of coupled processes to characterize how these processes can modulate each other and reach a temporal synchrony. We identify different oscillatory dynamic regimes that depend on coupling mechanisms and parameter values. The model can also discriminate different combinations of initial inputs that are set by initial states of coupled processes. Decoding brain signals that are formed through perceptual binding is a challenging task, but our modeling results demonstrate how crosstalk between two systems of processes can possibly modulate their outputs. Therefore, our mechanistic model can help one gain a better understanding of how crosstalk between perception pathways can affect the dynamic behavior of the systems that involve perceptual binding.

Ras is the most frequently mutated oncogene and recent drug development efforts have spurred significant new research interest. Here we will review progress toward understanding how Ras functions in nanoscale, proteo-lipid signaling complexes on the plasma membrane, called nanocluster. We will discuss how G-domain reorientation is plausibly linked to Ras-nanoclustering and -dimerization. We will then look at how these mechanistic features could cooperate in the engagement and activation of RAF by Ras. Moreover, we will show how this structural information can be integrated with microscopy data that provide nanoscale resolution in cell biological experiments. Synthesizing the available data, we propose to distinguish between two types of Ras nanoclusters, an active, immobile RAF-dependent type and an inactive/ neutral membrane anchor-dependent. We conclude that it is possible that Ras reorientation enables dynamic Ras dimerization, while the whole Ras/ RAF complex transits into an active state. These transient di/oligomer interfaces of Ras may be amenable to pharmacological intervention. We close by highlighting a number of open questions including, whether all effectors form active nanoclusters and whether there is an isoform specific composition of Ras nanocluster.

Ubiquitin binding domains (UBDs) are modular elements that bind non-covalently to ubiquitin and act as downstream effectors and amplifiers of the ubiquitination signal. With few exceptions, UBDs recognize the hydrophobic path centered on Ile44 (Leu-8, Ile-44, Val-70). Nevertheless, a variety of different orientations, which can be attributed to specific contacts between each UBD and surface residues surrounding the hydrophobic patch, specify how each class of UBD recognizes ubiquitin. Here, we describe the structure of a novel ubiquitin-binding domain that we identified in NEDD4 binding protein 1 (N4BP1). By performing protein sequence analysis, mutagenesis and NMR spectroscopy of the ¹⁵N isotopically labelled protein, we demonstrate that a Phe-Pro motif in N4BP1 recognizes the canonical hydrophobic patch of ubiquitin. This recognition mode resembles the molecular mechanism evolved in the CUE (Coupling of ubiquitin conjugation to ER degradation) domain family, where an invariant proline, usually following a phenylalanine, is required for binding to ubiquitin. Interestingly, the UBD of N4BP1 is evolutionary related to CUBAN (Cullin binding domain associating with NEDD8) (40% identity and 47% similarity), a protein module that also recognizes the ubiquitin-like NEDD8, which is the closest relative of ubiquitin (58% identity and 80% similarity). By performing circular dichroism and ¹⁵N NMR chemical shift perturbation of N4BP1 in complex with ubiquitin, we demonstrate that the UBD of N4BP1 lacks the NEDD8 binding properties observed in CUBAN and it recognizes the Ile44-centered patch of ubiquitin through a dedicated binding site, which share some of the features observed in the CUE domain family. Moreover, we show that, in addition to mediating the interaction with ubiquitin and ubiquitinated substrates, both the CUBAN and the UBD of N4BP1 are poly-ubiquitinated in cells. This modification is dependent on the presence of a functional domain. We believe that the structural and functional characterization of this novel UBD will allow a deeper understanding of the molecular mechanisms governing N4BP1 function, while at the same time providing a valuable tool for clarifying how the discrimination between ubiquitin and the highly related NEDD8 is achieved.

Purification of biologically-derived therapeutics is a major cost contributor to the production of this rapidly growing class of pharmaceuticals. Monoclonal antibodies comprise a large percentage of these products therefore new antibody purification tools are needed. Small peptides, as opposed to traditional antibody affinity ligands such as Protein A, may have advantages in stability and production costs. Multiple heptapeptides that demonstrate Fc binding behavior that have been identified from a combinatorial peptide library using M13 Phage Display are presented herein. Seven unique peptide sequences of diverse hydrophobicity and charge were identified. All seven peptides showed strong binding to the four major human IgG isotypes, human IgM, as well as binding to canine, rat, and mouse IgG. These seven peptides were also shown to bind human IgG4 from DMEM cell culture media with 5% FCS and 5 g/L ovalbumin present. These peptides may be useful as surface ligands for antibody detection and purification purposes. Molecular docking and classical molecular dynamics (MD) simulations were conducted to elucidate the mechanisms and energetics for the binding of these peptides to the Fc region. The binding site was found to be located between the two glycan chains inside the Fc fragment. Both hydrogen bonding and hydrophobic interactions were found to be crucial for the binding interactions. Excellent agreement for the binding strength was obtained between experimental results and simulations.

Initially, retinol-binding protein (RBP), was thought to be a biomarker for proximal convoluted tubule dysfunction could be important in chronic kidney diseases (CKD). Membranous glomerulonephritis (MGN) is an important cause of CKD and end-stage renal disease (ESRD). Therefore, monitoring MGN patients using urinary RBP is important in effective treatment decision making and prognostication of MGN patients. Enzyme-linked immunosorbent assay (ELISA) technique was used to detect the RBP in the urine samples of 69 MGN patients comprising 47 primary and 22 secondary MGN, at the end of the follow-up period. The test for the urinary biomarker gave the following results: urinary RBP was detected in 27 (39.1%) and 6 (8.7%) of the primary and secondary MGN patients, respectively. The correlation analysis demonstrated a significant relationship between urinary RBP and renal function test parameters, in addition to a logistic regression analysis that proved urinary RBP as a prognostic non-invasive biomarker for primary MGN. Therefore, urinary RBP could be employed to monitor and provide effective prognosis and early treatment decisions in primary MGN.

Physics behind collimated highly directional nature of lasers, and factors that keep the seven coloured waves that form white light together during their journey from Sun to Earth, in the face of the natural disruptive forces, is not fully understood. Energy levels were measured, in terms of alterations in induced current and voltage, in beams from a red laser, white LED light and the Sunlight before and during their disruption by diffusers (frosted glass for the lasers) and diffractors (diffraction grating for the white light) using a photovoltaic solar cell panel attached to a digital multimeter. Results show that disruption of the beams results in release of extra energy named as ‘Latent Light Binding’ Energy’. It is hypothesized that the ‘binding’ energy keeps laser waves firmly bound together both end-on and side-on enabling laser beams to travel long distances in collimated manner. Likewise, the 7 coloured waves that constitute white light are kept together, probably side-on, in their journey from the Sun to the Earth. The observation that diffraction of sunbeam is associated with increased power generation provides a new lead to improve harnessing of solar energy, where, currently, the focus is mainly on improving efficiency of photovoltaic cell.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light 22 Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to low micrometric sizes. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. More in detail, in the dimer formation achieved by molecular self-docking, two distinct poses were observed, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.

The optical properties of the Nafion polymer membrane containing colloidal CdSe/CdS/ZnS nanocrystals embedded by diffusion have been studied. The CdSe/CdS/ZnS nanocrystals have a core/shell/shell appearance. A toluene solution was used to provide mobility of the active sul-fone groups of the Nafion membrane and to embed the nanocrystals inside the membrane. The kinetics of the process of nanocrystal embedding into the membrane matrix was studied using luminescence analysis, absorption spectroscopy and laser emission spectroscopy techniques. The diffusion of colloidal CdSe/CdS/ZnS nanocrystals into the Nafion proton exchange membrane resulted in a new molecular complex «Nafion-colloidal CdSe/CdS/ZnS nanocrystals». The pres-ence of new luminescence centers based on CdSe/CdS/ZnS nanocrystals in the membrane was registered using laser emission spectroscopy. Colloidal nanocrystals located in the Nafion ma-trix represent an analogue of a luminescent transducer. The lines contained in the luminescence spectrum of the membrane, which has been in solution with colloidal nanocrystals for a long time, registered upon its drying, show the kinetics of the formation of the molecular complex «Nafion membrane - nanocrystals». The luminescence spectrum of the membrane with nano-crystals contains additional intensity maxima that do not coincide with the spectral lines of the solvent and Nafion membrane. The intensity of the luminescence spectrum of the membrane with embedded nanocrystals is higher than the intensity of the secondary emission peak of the initial nanocrystals, which is important for the practical use of the complex «Nafion-colloidal nanocrystals» in optical systems.

The air is a fundamental element for the life on Earth. Rapid urbanization and industrialization release large amounts of pollutants (harmful gases, microorganisms, and particulate matter, among others) into the atmosphere, leading to health hazards. Air filtration is still the most used and promising technique for protecting air against pollutants. The quality and efficiency of filtering process are dependent of material used for the filter and other filter’s properties. Several methods can be used for manufacturing filters, one of them uses fibrous membranes obtained through electrospinning from polymeric solutions. Electrospinning is a technique that combines the application of an electrostatic field to a moving fluid which results in the fibers formation. Electrospun membranes are constituted by fibers that the sizes spread on submicro and or nanometric scales. This review focuses on fiber membranes obtained by electrospinning for filtration of particulate matter. It is addressed the effect of solution, processing and ambient parameters on the morphology and dimensional characteristics of fiber membranes. The basic principles of air filtration and test and characterization of filter performance are presented. The research progress on electrospun nanofibers as air filters in recent years is summarized and examined. Finally, conclusion and future perspectives in electrospun fibers for air filtration are provided and discussed.

The generation and maintenance of membrane potential is a fundamental part of Membrane Pump Theory. One of the key points of this hypothesis is based on a natural or facilitated molecular diffusion through several types of ion channels and pumps like the Na/K ATPase. Following the principles of chemistry, electrostatics and geometry, it becomes clear that ion channels cannot function in this way. The ions channels cannot by their location have both a filter function and be ion concentrators, and the Na/K pump by its position in the membrane and by the proposed assumptions is not able to perform its regulatory function. The current model must absolutely be revised according to the current state of our knowledge and allow an advance in the understanding of the phenomena opening new research perspectives.

A new method is proposed to increase rejection in microfiltration by applying membrane oscillation using a new type of microfiltration membranes with slotted pores. The oscillations applied to the membrane surface result in reducing membrane fouling and increasing separation efficiency. An exact mathematical solution of the flow in the surrounding solution outside the oscillating membrane is developed. The oscillation results in appearance of the lift velocity, which moves oil particles away from the membrane. The latter results in both reducing membrane fouling and increasing oil droplets rejection. This developed model was supported by the experimental results for oil water separation in produced water treatment. It was proven that oil droplet concentration reduced notably in the permeate due to the membrane oscillation and that applied shear rate caused by the membrane oscillation is also reduce pore blockage. New generation of microfiltration membranes with slotted pores was used in the experiments.

Production of wastewater related to the oil and gas industries is increasing over the years. The compounds found in industrial wastewater typically show high toxicity, and in this way, they have become a primary environmental concern. Several techniques have been applied in industrial effluents remediation. In spite of the efforts, these techniques are yet ineffective to treat oily wastewater before it can be discharged safely to the environment. Membrane technology is an attractive approach to treat oily wastewater. This is dedicated to the immobilisation of TiO2 nanoparticles on poly (vinylidene fluoride–trifluoro ethylene) (PVDF-TrFE) porous matrix by solvent casting. Membranes with interconnected pores with an average diameter of 60 micrometres and the contact angle of 97°, decorated with TiO2 nanoparticles, are obtained. The degradation of oily wastewater demonstrated the remarkable photocatalytic efficiency of the nanocomposite membranes: under sunlight irradiation for 7 hours, colourless water was obtained. These results show the suitability of TiO2/P(VDF–TrFE) nanocomposite for photocatalytic applications for oily wastewater remediation.

This study proposed the combination system consisting of biogas dry reforming reactor and solid oxide fuel cell (SOFC). Since a biogas dry reforming is an endothermic reaction, this study adopted a membrane reactor operated due to the non-equilibrium state with H2 separation from the reaction space. This study aimed to clarify the characteristics of Ni/Cr/Ru catalyst using for a biogas dry reforming membrane reactor. Additionally, this study also investigated the comparison of the characteristics of Ni/Cr/Ru catalyst with that of Ni/Cr catalyst. The impact of operation temperature, the molar ratio of CH4 : CO2, the differential pressure between the reaction chamber and the sweep chamber and the introduction of sweep gas on the characteristics of the biogas dry reforming membrane reactor using Pd/Cu membrane and Ni/Cr/Ru catalyst was examined. The concentration of H2 using Ni/Cr/Ru catalyst was larger than that using Ni/Cr catalyst by 2871 ppmV for the molar ratio of CH4 : CO2 = 1.5 : 1 at the reaction temperature of 600 ℃ and the differential pressure of 0 MPa without a sweep gas, especially. Under this condition, CH4 conversion, H2 yield and thermal efficiency were 67.4 %, 1.77×10-2 % and 0.241 %, respectively.

This study focuses on a biogas dry reforming to produce H2. Biogas contains CO2 of 40 vol% approximately, indicating that the efficiency of the power generation is reduced because of the smaller heating value compared with a natural gas. The authors have proposed the combination system consisting of biogas dry reforming reactor and solid oxide fuel cell (SOFC). Since a biogas dry reforming is an endothermic reaction, this study adopts a membrane reactor which can be operated by causing the non-equilibrium state with H2 separation from the reaction space. This study aims to clarify the impact of thickness of Pd/Cu membrane on the characteristics of the biogas dry reforming membrane reactor using Pd/Cu membrane and Ni/Cr catalyst. The impact of the operation temperature, the molar ratio of CH4:CO2 and the differential pressure between the reaction chamber and the sweep chamber on the characteristics of the biogas dry reforming membrane reactor using Pd/Cu membrane and Ni/Cr catalyst is examined changing the thickness of Pd/Cu membrane. As a result, the highest concentration of H2 is 122711 ppmV which is obtained in case of CH4:CO2 =1:1 at the reaction temperature of 600 ℃ and the differential pressure of 0 MPa using the Pd/Cu membrane whose thickness of 40 m.

Nowadays there is a growing interest in membrane modification processes, to improve their characteristics, the effectiveness of their treatments and reduce the possible fouling. In this sense, in this work a modification of an ultrafiltration membrane with tree different materials has been carried out: reduced graphene oxide (rGO), chitosan and MgCl2. For both the native and the modified membranes, a study has been carried out to remove the emerging contaminant sul-fomethoxazole. SEM and SEM-EDX analyses have been performed to confirm membrane surface modifications. In the characterization of the membranes, it is noteworthy that the values of the permeability coefficient, Aw, have been lower in the modified membranes, which is unexpected. Regarding the pollutant removal tests, the influence of pressure and initial concentration on permeate flows and rejections has been studied. Native membrane shows the highest permeate flow values. Comparing the modified membranes, the highest rejection values are obtained with the rGO-modified membrane, which can be explained by its greater hydrophilic character. Finally, a fouling study has been carried out, verifying that in almost all cases such fouling occurs after the passage of the pollutant, due to the blockage of the membrane pores.

membrane separation technology shows promise, particularly gas separation membranes, including ceramic membrane. Ceramic membranes are increasingly gaining attention for their acid and alkali stability, corrosion resistance, high-temperature tolerance, and mechanical strength. This study focuses on alumina support ceramic membrane for CO2 capture. The membranes were characterized using contact angle measurements, scanning electron microscopy (SEM), and Fourier Transform Infrared spectroscopy (FTIR) analysis. The contact angle measurements confirmed the hydrophilic, while SEM analysis showed even particle distribution in the alumina ceramic membranes respectively. EDAX analysis revealed the elemental composition in the alumina support matrix. FTIR analysis demonstrated chemical interactions of the support membrane. Single gas permeation experiments were conducted. It can be observed that Nitrogen gas permeated faster with increase in feed pressure through the unmodified ceramic inorganic hydrophobic membrane more than the other two single gases, O2, and CO2). As a result, only high permeance separation membranes with realistic size and pressure conditions may be considered of as a practical alternative for CO2 capture. However, the presence of non-selective defects limited the improvement in selectivity of hydrophilic ceramic membrane. In this case, there is need to modify the ceramic membrane used to increase the flux, permeance of CO2, and selectivity of CO2.

Abstract: membrane separation technology shows promise, particularly gas separation membranes, including ceramic membrane. Ceramic membranes are increasingly gaining attention for their acid and alkali stability, corrosion resistance, high-temperature tolerance, and mechanical strength. This study focuses on alumina support ceramic membrane for CO2 capture. The membranes were characterized using contact angle measurements, scanning electron microscopy (SEM), and Fourier Transform Infrared spectroscopy (FTIR) analysis. The contact angle measurements confirmed the hydrophilic, while SEM analysis showed even particle distribution in the alumina ceramic membranes respectively. EDAX analysis revealed the elemental composition in the alumina support matrix. FTIR analysis demonstrated chemical interactions of the support membrane. Single gas permeation experiments were conducted. It can be observed that Nitrogen gas permeated faster with increase in feed pressure through the unmodified ceramic inorganic membrane more than the other two single gases, O2, and CO2). As a result, only high permeance separation membranes with realistic size and pressure conditions may be considered of as a practical alternative for CO2 capture. However, the presence of non-selective defects limited the improvement in selectivity of hydrophilic ceramic membrane. In this case, there is need to modify the ceramic membrane used to increase the flux, permeance of CO2, and selectivity of CO2.

Autophagy is a cellular mechanism that utilizes lysosomes to degrade its own components and is performed using Atg5 and other molecules originating from the endoplasmic reticulum membrane. On the other hand, we identified an alternative type of autophagy, namely, Golgi membrane-associated degradation (GOMED), which also utilizes lysosomes to degrade its own components, but does not use Atg5 originating from the Golgi membranes. The GOMED pathway involves Ulk1, Wipi3, Rab9 and other molecules, and plays crucial roles in a wide range of biological phenomena, such as the regulation of insulin secretion and neuronal maintenance. We here describe the overview of GOMED, the methods to detect autophagy and GOMED, and to distinguish GOMED from autophagy.

In a large variety of organisms, antimicrobial peptides (AMPs) are primary defences against pathogens. BP100 (KKLFKKILKYL-NH2), a short, synthetic, and cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires an α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the mechanism of action of BP100, the selectivity of its biological effects, and its applications are far from consensual. In this work, we synthesized a fluorescent BP100 analog containing naphthalimide linked to its N-terminal end, Napht-BP100 (Napht-AAKKLFKKILKYL-NH2). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against different types of cells are known. A wide variety of techniques were used to demonstrate that a-helical Napht-BP100 was bound and permeabilized POPC and POPG LUV. Napht-BP100, different from that observed for BP100, was bound to, and permeabilized POPC LUV. With zwitterionic (POPC) and negatively charged (POPG) containing LUVs, membrane surface high peptide/lipid ratios triggered complete disruption of the liposomes in a detergent-like manner. This disruption was driven by charge neutralization, lipid aggregation, and membrane destabilization. Napht-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes in addition to membrane destabilization. Napht-BP100 showed superior antibacterial activity, increased hemolytic activity compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide antimicrobial properties, Napht-BP100 was bound more efficiently to the bacterial membrane and could destabilize the membrane and enter the cell by interacting with its cytoplasm- exposed DNA.

Polyvinyl guanidineacetic (PVG) was prepared by the chemical grafting between poly(vinyl alcohol) (PVA) and guanidineacetic acid. The results showed that the guanidineacetic groups were successfully introduced into the polyvinyl alcohol by fourier transform infrared (FTIR) and thermogravimetry (TG). The effects of the amount of catalyst and reaction time on the PVG grafting rate were investigated. The PVG/NWF composite membrane as a heterogeneous catalyst for biodiesel production was successfully prepared by the solvent phase inversion. The effects of mass ratio of methanol/soybean oil and reaction temperature on the conversions using the composite membrane for transesterification were studied. And the reusability of the composite membrane and the kinetics of the reaction catalyzed by the composite membrane were also investigated. The conversions obtained from the model are in good agreement with the experimental data.

African trypanosomes are an early branch in eukaryotic evolution and developed a unique endomembrane system as an adaptation to their parasitic life style. The key virulence mechanism of many pathogens is successful immune evasion to enable survival within the host, which is a feature requiring both genetic events and membrane transport in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unravelled some of the connections between these processes and highlighted how immune evasion mechanisms associated with adaptations in membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purpose.

The global polyvinyldene flouride market is estimated to reach $937,278.5 thousand by 2019, therefore to develop new membranes and gain pioneering ideas, which could create innovative business opportunities, a fundamental knowledge about membrane properties fabricated from recent commercially available PVDF polymers is highly mandatory. In this study, we successfully prepared nine non-woven supported PVDF membranes using a phase inversion precipitation method starting from a 15 wt% PVDF solution in N-methyl-2-pyrrolidone. Various membrane morphologies were obtained by using (1) PVDF polymers with diverse molecular weight in a range from 300.000 Da to 700.000 Da and (2) different temperatures of the coagulation bath (20, 40, and 60 ±2°C) used for the films precipitation. Environmental Scanning Electron Microscope (ESEM) was used for surface and cross-section morphologies characterization. Atomic Force Microscope (AFM) was employed to investigate surface roughness, while Contact Angle (CA) instrument was used for membranes wettability studies. Fourier Transform Infrared Spectroscopy (FTIR) results show that the fabricated membranes are formed by a mixture of TGTG’ chains in α phase crystalline domains and all-TTTT trans planar zigzag chains characteristic to β phase. Moreover, generated results indicate that the phases content and membrane morphologies depend on the polymer molecular weight and conditions used for the membranes preparation. The diversity of fabricated membranes could be applied by the End User Industries for different applications.

We are presenting a new method for the treatment of large macular holes (MH) with the use of an inverted flap consisting of both internal limiting membrane (ILM) and epiretinal proliferation (EP). A prospective interventional case series was conducted from September 2021 to January 2023. MH patients with coexistent EP visualized preoperatively in macula optical coherence tomography and MH minimum linear diameter larger than 400 microns underwent standard pars plana vitrectomy with the creation of an inverted petaloid flap (consisting of both ILM and EP) and gas tamponade. 16 eyes were included in our study. MH closure was successful in all the eyes with a single procedure. Preoperative minimum linear diameter was 707.63(±164.02μm) and preoperative best corrected visual acuity was 1.11±0.52. Postoperative BCVA was 0.51±0.20 (p=0.01) at 6weeks postoperatively and final BCVA was 0.45±0.20 (p=0.008). EP can be safely combined with ILM for the creation of an inverted, petaloid flap to cover and facilitate the closure of large MH.

The catalytic parameters describing enzyme catalysis are discussed in the context of the design of de novo enzymes. It is shown that high values of the catalytic efficiency may in some cases reflect tight substrate binding and lead to an immediate levelling-off of rates to reach a low plateau, an undesirable scenario for many industrial applications. It is argued that increasing the catalytic rate constant should be a main target in de novo enzyme engineering.

Zinc plays a crucial role in the process of virion maturation inside the host cell. The accessory Cys-rich proteins expressed in SARS-CoV-2 by genes ORF7a and ORF8 are likely involved in zinc binding and in interactions with cellular antigens activated by extensive disulfide bonds. In this report we provide a proof of concept for the feasibility of a structural study of orf7a and orf8 proteins. A conceivable hypothesis is that lack of cellular zinc, or substitution thereof, might lead to a significant slowing down of viral maturation.

Affordances are an important concept in cognition, which can be applied to robots in order to perform a successful human-robot interaction (HRI). In this paper we explore and discuss the idea of emotional affordances and propose a viable model for implementation into HRI. We consider “2-ways” affordances: perceived object triggering an emotion, and perceived human emotion expression triggering an action. In order to make the implementation generic, the proposed model includes a library that can be customised depending on the specific robot and application’s scenario. We present the AAA (Affordance-Appraisal-Arousal) model, which incorporates Plutchik’s Wheel of Emotions, and show some examples of simulation and possible scenarios.

Ice-binding proteins (IBPs) have several functions that permit their hosts to thrive in the presence of ice. The ability of IBPs to control ice growth makes them potential additives in various industries ranging from food storage and cryopreservation to anti-icing systems. For IBPs to be used in commercial applications, however, methods are needed to produce sufficient quantities of high-quality proteins. Here, we describe a new method for IBP purification, termed falling water ice purification (FWIP). The method is based on the affinity of IBPs for ice. A crude IBP solution is allowed to flow continuously over the large chilled vertical surface of a commercial ice machine. The temperature of the surface is lowered gradually until ice crystals are produced, to which the IBPs bind but other solutes do not. As in other ice affinity methods, FWIP does not require molecular tags and is suitable for purifying recombinant IBPs as well as IBPs from natural sources. The advantage of FWIP over other ice affinity methods is that it exploits an ice machine designed to produce large volumes of clear ice daily. This system can be easily scaled up and suits the purification of industrial quantities of IBPs. The FWIP method significantly advances the use of IBPs in research and industry.

Ferric uptake regulation protein is a repressor protein which binds an AT rich region of DNA (the iron box). Fur binds as a dimer in a helix turn helix mode and it is activated by iron(II) and other divalent transition metal ions at elevated concentrations in a process to regulate the ion uptake. Each transition metal ion induces certain conformational changes to aid the Fur binding, both the N-terminal and C-terminal domains take part in binding to DNA in addition to His 88 and His 86 residues. The process is discussed in view of experimental reports. Fe(II), Mn(II) and Co(II) activate Fur to bind DNA experimentally but Zinc plays a structural role and does not activate Fur to bind DNA.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

The combined efect of shape and electrostatic complementarities (Sc, EC) at the interface of the interacting protein partners (PPI) serves as the physical basis for such associations and is a strong detterminant of their binding energetics. EnCPdock (https://www.scinetmol.in/EnCPdock/) presents a comprehensive web-platform for the direct conjoint comparative analyses of complementarity and binding energetics in PPIs. It elegantly interlinks the dual nature of local (Sc) and non-local complementarity (EC) in PPIs using the Complementarity Plot. It further derives an AI-based ∆G_binding with a prediction accuracy comparable to the state-of-the-art. This book-chapter presents a practical manual to conceptualize and implement EnCPdock with its various features and functionalities, collectively having the potential to serve as a valuable protein engineering tool in the design of novel protein interfaces.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in-silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physiological conditions. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in-silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared to the pertuzumab-HER2 complex.

Galectins are β-galactosyl-binding proteins that fulfill essential physiological functions. Recently, we introduced galectin-1 (Gal-1) and galectin-3 (Gal-3) as fusion proteins of a His6-tag, a SNAP-tag, and a fluorescent protein. We characterized their binding in ELISA-type assays and their application in cell-surface binding. In the present study, we have constructed further fusion proteins of galectins with fluorescent protein color code. The fusion proteins of Gal-1, Gal-3, and Gal-8 were purified by affinity chromatography. For this, we have prepared glycoprotein affinity resins based on asialofetuin (ASF) and fetuin and combined this in a two-step purification with Immobilized Metal Affinity chromatography (IMAC) to get pure and active galectins. Purified galectin fractions were analyzed by size-exclusion chromatography. The binding characteristics to ASF of solely His6-tagged galectins and galectin fusion proteins were compared. As an example, we demonstrate a 1.6-3-fold increase in binding efficiency for HSYGal-3 (His6-SNAP-yellow fluorescent protein-Gal-3) compared to the HGal-3 (His6-Gal-3). Our results reveal an apparent higher binding efficiency for galectin SNAP-tag fusion proteins compared to His6-tagged galectins which are independent of the purification mode. This is also demonstrated by the binding of galectin fusion proteins to extracellular glycoconjugates laminin, fibronectin, and collagen IV. Our results indicate the probable involvement of the SNAP-tag in apparently higher binding signals, which we discuss in this study.

Precise binding affinity predictions are essential for structure-based drug discovery (SBDD). Focal adhesion kinase (FAK) is a member of the tyrosine kinase protein family and is overexpressed in a variety of human malignancies. Inhibition of FAK using small molecules is a promising therapeutic option for several types of cancer. Here, we conducted computational modeling of FAK targeting inhibitors using 3-dimensional structure-activity relationship (3D-QSAR), molecular dynamics (MD), and hybrid topology-based free energy perturbation (FEP) methods. The structure-activity relationship (SAR) studies between the physicochemical descriptors and inhibitory activities of the chemical compounds were performed with reasonable statistical accuracy using CoMFA and CoMSIA. These are two well-known 3D-QSAR methods based on the principle of supervised machine learning (ML). Essential information regarding residue-specific binding interactions was determined using the MD and MM-PB/GBSA methods. Finally, physics-based relative binding free energy (〖∆∆G〗_RBFE^(A→B)) values of analogous ligands were estimated using the alchemical FEP simulation. An acceptable agreement was observed between the experimental and computed relative binding free energies. The overall results using ML and physics-based hybrid approaches could be useful for the rational optimization of accessible lead compounds with similar scaffolds targeting the FAK receptor.

Abstract: The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the presence of poly-PR/GR dipeptide repeats which are encoded by the C9orf72 gene. Recently, it was shown that poly-PR/GR alters chromatin accessibility which results in stabilization and enhancement of transcriptional activity of the tumor suppressor p53 in several neurodegenerative disease models. Reduction of p53 protein levels in cell and model organisms protects against neurotoxicity of poly-PR, and partially protects against neurotoxicity of poly-GR. Here, we aimed to study the detailed molecular mechanisms how p53 contributes to poly-PR/GR mediated neurodegeneration. Using a combination of biophysical techniques such as nuclear magnetic resonance (NMR) spectroscopy, fluorescence polarization, turbidity assays and differential interference contrast (DIC) microscopy, we found that p53 physically interacts with poly-PR/GR and triggers liquid-liquid phase separation of p53. We identified p53 transactivation domain 2 (TAD2) as the main binding site for PR25/GR25 and show that binding of poly-PR/GR to p53 is mediated by a network of electrostatic and/or hydrophobic interactions. Our findings might help to understand the mechanistic role of p53 in poly-PR/GR - associated neurodegeneration.

Bacterial resistance to antibiotics due to an increased efficiency of the efflux is a serious problem in clinics of infectious diseases. Knowledge of the factors affecting the activity of efflux pumps would help to find the solution. For this, fast and trustful methods for the efflux analysis are needed. Here we analyzed how the assay conditions affect the accumulation of efflux indicators ethidium (Et+) and tetraphenylphosphonium in Salmonella enterica ser. Typhimurium cells. An inhibitor phenyl-alanyl-arginyl-β-naphtylamide was applied to evaluate the input of RND family pumps into the total efflux. In parallel to spectrofluorimetric analysis, we used an electrochemical assessment of Et+ concentration. Results of our experiments indicated that Et+ fluorescence increases immediately after the penetration of this indicator into the cells. However, when cells bind a high amount of Et+, intensity of the fluorescence reaches the saturation level and stops reacting to the accumulated amount of this indicator. For this reason, electrochemical measurements provide more trustful information about the efficiency of efflux when cells accumulate high amounts of Et+. Measure-ments of Et+ interaction with the purified DNA demonstrated that affinity of this lipophilic cation to DNA depends on the medium composition. The capacity of DNA to bind Et+ considerably de-creases in presence of Mg2+, Polymyxin B or when DNA is incubated in high ionic strength media.

Proton exchange membrane (PEM) fuel cells have emerged as a viable alternative energy production source for stationary and transportation applications. Reliable and sustainable fuel cell operation requires effective water management. Membrane water content can vary along the stack during transients which can lead to losses in fuel cell performance. To control these variations a model that predicts the internal humidity dynamics of the stack is needed. In this study, a control-oriented model for predicting membrane water content variation was developed and implemented in MATLAB/Simulink. A lumped parameter model was initially developed and then further discretized into smaller control volumes to track humidity distribution along the stack. To validate the model’s predictions, the predicted results were compared to computer simulation results from GT-Suite. The root mean square error (RMSE) between the model’s prediction and GT-Suite’s simulation results was found to be within 1.5 membrane water content for all cases, demonstrating the model’s capability to capture the variation of membrane water content along the stack. The developed model will be useful for real-time control of membrane water content variation in PEM fuel cells.

We have successfully measured amyloid beta (Aβ) (1-40) protein added in human serum by a NiCr strain gauge cantilever biosensor immobilized with liposomes incorporating cholesterol. Importantly, we investigated the effect of incorporation of cholesterol in the liposome in order to suppress the interaction between the liposome and many different proteins included in human serum. It was revealed that incorporating cholesterol suppresses the interaction between the proteins other than Aβ in human serum and the liposome. Finally, we detected Aβ(1-40) in human serum with typical chronological behaviors due to Aβ aggregation and fibrillization. Furthermore, as a digital low-pass filtering procedure could reduce external noises, the cantilever sensor immobilized with liposome incorporating cholesterol can detect low-concentrated Aβ in human serum.

Sperm cells must undergo a complex maturation process after ejaculation to be able to fertilize an egg. One component of this maturation is hyperpolarization of the membrane potential to a more negative value. The ion channel responsible for this hyperpolarization, SLO3, was first cloned in 1998, and since then much progress has been made to determine how the channel is regulated and how its function intertwines with various signaling pathways involved in sperm maturation. Although SLO3 was originally thought to be present only in the sperm of mammals, recent evidence suggests that a primordial form of the gene is more widely expressed in some fish species. As with many reproductive genes, SLO3 is rapidly evolving with low conservation between closely related species and different regulatory and pharmacological profiles. Despite these differences, SLO3 appears to have a conserved role in regulating sperm membrane potential and driving large changes in response to stimuli. As with the differences in regulation of the channel, the effect of this hyperpolarization of the membrane potential may vary among mammalian species. Recent discoveries have elucidated the role of SLO3 in these processes in human sperm and provided tools to target the channel to affect human fertility.

Although there is a common physiological notion that the origin of the membrane potential is attributed to transmembrane ion transport, it is theoretically possible to explain its generation by the mechanism of ion adsorption. It was previously suggested that the ion adsorption mechanism led even to the potential formulas which are even identical to either the famous Nernst equation or Goldman-Hodgkin-Katz equation. Our further analysis shown in this paper indicates that the potential formula based on the ion adsorption mechanism leads to one equation which is the function of material surface charge density and the material surface potential. Furthermore, we confirmed that the equation holds in all the different experimental systems we studied. Although we have not succeeded in elucidating why such an equation is established, the equation appears to be the key equation governing the characteristics of the membrane potential regardless of the systems in question.

Accurate prediction of the membrane potential by membrane theory is possible on the basis that the plasma membrane is selectively permeable to ions and that permeability determines the characteristics of the membrane potential. However, an experimental and artificial cell system with an impermeable membrane serving as a model plasma membrane has a non-zero membrane potential, and this potential generated across the membrane is somehow consistent with the potential characteristics predicted by the membrane theory, despite the impermeability of the membrane to ions. A long-forgotten theory, called the association-induction hypothesis (AIH), has emerged as a more plausible mechanism for generating the membrane potential than the membrane theory to explain this unexpected behavior. The AIH asserts that ion-selective membrane permeability is not necessary for the generation of the membrane potential, which is contrary to the membrane theory. Although such an idea is not easy to accept, the experimental results clearly suggest the correctness of the AIH.

An embryonic version of membrane theory can be date back to the Bernstein's work reported more than a hundred years ago. Such an originally old work has evolved conceptually and mathematically up until today, and it plays a central role in current membrane theory. Goldman-Hodgkin-Katz equation (GHK eq.) is one of the math-based monumental works, which constitutes the present membrane theory. Goldman theoretically derived GHK eq., but its physiological meaning was provided by the two renowned scientists, Hodgkin and Katz. These two employed an assumption that the electric field (EF) across the plasma membrane is constant to validate the GHK eq. physiologically. Proposal of Hodgkin-Huxley model (HH model) is another math-based monumental works developed from the membrane theory and now forms a fundamental part of the current membrane theory. GHK eq. and HH model are quite fundamental central concepts in the current physiology. Despite the broad acceptance of GHK eq. at present time, its prerequisite that the EF within the plasma membrane is constant is hardly believable. Especially when the action potential is generated, it sounds totally nonsense. Furthermore, the existence of constant EF within the plasma membrane is conceptually almost in conflict with the HH model. The authors will discuss those problematic issues the membrane theory inherits.