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Bhattacharjee, A.

Publications and source records attributed to Bhattacharjee, A..

At least 37 records · Page 2Linked to original sources

ALIGNING BRAINS INTO A SHARED SPACE IMPROVES THEIR ALIGNMENT TO LARGE LANGUAGE MODELS

AO_SCPLOWBSTRACTC_SCPLOWRecent studies have shown that large language models (LLMs) can accurately predict neural activity measured using electrocorticography (ECoG) during natural language processing. To predict word-by-word neural activity, most prior work has estimated and evaluated encoding models within each electrode and subject--without evaluating how these models generalize across individual brains. In this paper, we analyze neural responses in 8 subjects while they listened to the same 30-minute podcast episode. We use a shared response model (SRM) to estimate a shared information space across subjects. We show that SRM significantly improves LLM-based encoding model performance. We also show that we can use this shared space to denoise the individual brain responses by projecting back into the individualized electrode space, and this process achieves a mean 38% improvement in encoding performance. The strongest improvement was observed for brain areas specialized for language comprehension, specifically in the superior temporal gyrus (STG) and inferior frontal gyrus (IFG). Critically, estimating a shared space allows us to construct encoding models that better generalize across individuals.

neuroscience↗

Co-existence of plasmid-mediated blaNDM-1 and blaNDM-5 in Escherichia coli sequence type 167 and ST101 and their discrimination through restriction digestion

The concurrent presence of multiple New Delhi metallo-{beta}-lactamase (blaNDM) variants within an isolate often goes undetected without the use of next-generation sequencing. This study detects and characterizes dual blaNDM-variants in Escherichia coli through Sanger and whole-genome sequencing. Additionally, a rapid identification method utilizing restriction digestion was designed for detecting variants carrying M154L mutation. Antibiotic susceptibility, minimal inhibitory concentration for meropenem and ertapenem, PCR and Sanger sequencing of blaNDM along with genome sequencing using Ilumina and Nanopore technology were conducted. Transmissibility and replicon types of blaNDM-harbouring plasmids were evaluated. Restriction digestion using restriction enzyme, BtsCI was developed to distinguish between blaNDM-1 and variants possessing M154L mutations. Two isolates belonging to phylogroups A; ST167 and B1; ST101 and resistant to meropenem and ertapenem ([≥]16mg/L) were recovered from the blood of a neonate and the rectal swab of a pregnant woman respectively. blaNDM was detected by PCR, and Sanger sequences of blaNDM showed two peaks at 262 (G & T) and 460 (A & C) nucleotide positions indicative of more than one blaNDM variant. Hybrid assembly confirmed co-existence of blaNDM-1 and blaNDM-5 in each isolate. blaNDM-1 was located on IncY (ST167) and IncHI1A/HI1B (ST101), while blaNDM-5 was on a IncFIA/FII (ST167) and IncC (ST101) plasmids. Digestion with BtsC1 could discriminate blaNDM-1 and blaNDM-5. Co-existence of multiple blaNDMS, blaNDM-1 and blaNDM-5 in epidemic clones of E. coli is concerning. Restriction digestion method and Sanger sequencing can facilitate quick identification of dual blaNDM variants in single isolate. ImportanceThe global dissemination of antimicrobial resistance genes is a serious concern. One such gene, blaNDM, has spread all across the globe via plasmids. blaNDM confers resistance against all {beta}-lactam antibiotics except monobactams. Most of the earlier literature reported presence of single blaNDM variants. However, this study reports the prevalence of dual blaNDM variants (blaNDM-1 and blaNDM-5) located on two separate plasmids identified in two distinct E. coli epidemic clones ST167 and ST101; isolated from a septicaemic neonate and a pregnant mother respectively. blaNDM-5 differs from blaNDM-1 due to presence of two point mutations i.e., V88L and M154L. This study detected dual blaNDM-variants through Sanger sequences and further validated through hybrid-genome assembly. Detection of multiple blaNDM-variants in a single isolate remains difficult until genome sequencing or southern blotting are carried out. Hence, a simple restriction digestion method was devised for rapid screening of dual blaNDM-variants containing M154L mutation.

microbiology↗

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms

Most human Transcription factors (TFs) genes encode multiple protein isoforms differing in DNA binding domains, effector domains, or other protein regions. The global extent to which this results in functional differences between isoforms remains unknown. Here, we systematically compared 693 isoforms of 246 TF genes, assessing DNA binding, protein binding, transcriptional activation, subcellular localization, and condensate formation. Relative to reference isoforms, two-thirds of alternative TF isoforms exhibit differences in one or more molecular activities, which often could not be predicted from sequence. We observed two primary categories of alternative TF isoforms: "rewirers" and "negative regulators", both of which were associated with differentiation and cancer. Our results support a model wherein the relative expression levels of, and interactions involving, TF isoforms add an understudied layer of complexity to gene regulatory networks, demonstrating the importance of isoform-aware characterization of TF functions and providing a rich resource for further studies.

systems biology↗

Repurposing approved protein kinase inhibitors as potent anti-leishmanials targeting Leishmania MAP kinases

Leishmaniasis is a vast array of chronic diseases caused by the protozoan parasite of the genus Leishmania transmitted by the sandfly belonging to the genus Phlebotomus (Old World) and Lutzomyia (New World). Among the various factors that contribute to the virulence and pathogenesis of the disease, protein kinases play crucial role in modulating the parasites biology in the host system. There are no specific drugs identified to treat the disease specifically. Moreover, resistance against approved anti-leishmanials has made it important to look for a few pre-clinical candidates against visceral leishmaniasis. MAP kinase is one such candidate of protein kinase family that regulates cell proliferation in eukaryotes. In this study, we have identified 23 MAPKs from Leishmania genome and have screened 12 FDA approved protein kinase inhibitors against those MAPKs in search of a potential lead for new drug exploration. Among the inhibitors, sorafenib and imatinib have been identified as potential drug candidates based on multiple criteria including binding affinity, ADME scores, absorption and their ability to cross blood-brain barrier. Furthermore, these drugs showed excellent anti-proliferative effects in Leishmania promastigotes, resulted in change of cell morphology, flagellar length, promoted cell cycle arrest through ROS generation and reduced intra-macrophage parasitic burden. Collectively, these results imply involvement of MAP kinases in infectivity and survival of the parasite and can pave the avenue for repurposing sorafenib and imatinib as anti-leishmanial agents.

bioinformatics↗

Identifying the function of the NMDA NR1C2 subunit through its interaction with Magi-2 during inflammatory pain

Much is understood about the structure and gating properties of NMDA receptors (NMDAR), but the function of the carboxy-terminal splice variant of the NR1 subunit, NR1C2 has never been identified. By studying the scaffolding protein Magi-2 in animal models of inflammatory pain, we discovered how NR1C2 protein is specifically regulated. We found that Magi-2 deficiency resulted in decreased pain behavior and a concomitant reduction in NR1C2 protein. Magi-2 contains WW domains, domains typically found in ubiquitin ligases. We identified an atypical WW-binding domain within NR1C2 which conferred susceptibility to Nedd4-1 ubiquitin-ligase dependent degradation. We used lipidated peptidomimetics derived from the NR1C2 sequence and found that NR1C2 protein levels and pain behavior can be pharmacologically targeted. The function of NR1C2 is to give lability to a pool of NMDAR, important for pain signaling.

neuroscience↗

Unraveling Coinfection Dynamics into 100 Whole Genome of Diarrheal Pathogens: A Genome-to-Systems Biology Approach with Plesiomonas shigelloides

Diarrhea is the second leading cause of mortality among infants under the age of five. One of the main causes of this disease is multipathogenic infections, which can make the conditions of patients even worse. Plesiomonas shigelloides (P. shigelloides) is one of the pathogenic bacteria that contributes to the pathophysiology of diarrhea and may be implicated in coinfection with other diarrheal pathogens. Therefore, the purpose of this study is to investigate the hypothetical proteins to explore the genetic insights of P. shigelloides and its relationships with common diarrheal diseases. For this reason, we used 16S rRNA sequencing together with several biochemical tests to identify the bacteria that we isolated from diarrheal patients (8 years). Afterwards, the whole genome of P. shigelloides was sequenced, assembled and annotated in order to obtain the genomic insights of P. shigelloides. In addition, the common virulence genes of ten (10) common diarrhea-causing bacteria were identified from 100 whole genome sequences. Finally, the system biology approach was applied to predict the coinfection pattern between P. shigelloides and the virulence genes of 10 bacteria. The complete genome sequencing analysis of this bacterium revealed 899 hypothetical proteins from which 33 hypothetical proteins shared the clusters with the 109 virulence genes of 10 distinct diarrheal pathogens, forming a strong interaction based on biological processes, molecular functions, subcellular localization, or pathways. All diarrhea causing bacteria were found to have P. shigelloides microbial interactions; however, V. cholerae exhibited the strongest relationships, while C. difficile showed the weakest. The results of this investigation clearly imply that P. shigelloides shares a coinfection pattern with other bacteria that cause diarrhea. Finally, the findings from the complete genome provide new avenues for researchers to pursue their investigation of the pathophysiology of diarrhea.

systems biology↗

Genome-Wide Exploration of the Opportunistic Providencia stuartii Unveils the Novel Genetic Interactions with the Virulence Gene of Diarrheal Pathogens

Diarrhea typically indicates an intestinal disorder, which can occur from viruses, parasites or bacterial infection. Along with the common diarrhea-causing pathogens, opportunistic bacteria may also play a role in the etiology of diarrheal disease. One of the opportunists bacteria that can cause diarrhea in both children and adults is Providencia stuartii. Therefore, the goal of this study is to explore the genetic mechanism of the opportunistic P. stuartii in microbial interactions with common diarrheal pathogens. Hence, P. stuartii was identified by utilizing the morphological observation and molecular techniques. Afterwards, the entire genome of P. stuartii was sequenced, assembled and annotated to explore the genomic insights. In addition, the virulence genes of 100 whole genome sequences from ten prevalent diarrhea-causing bacteria were identified and prioritized. Finally, the system biology approach was used to predict the protein-protein interaction network between P. stuartii and the virulence genes. The results of the present study suggests that complete genome sequencing of this bacteria contains 4011 proteins, which are crucial for this bacterium to survive. Additionally, 16 gene clusters provide 207 interacting genes that could interact with biological and molecular function, subcellular localization and pathway. The microbial interaction accompanying the virulence gene was found in all 10 diarrhea-causing bacteria except Clostridium difficile. These findings of this study could aid in the exploration of Providencia stuartii as the major causative agent of diarrhea. Additionally, the pathophysiology of diarrhea can be investigated using the microbial interactions between P. stuartii and the typical diarrheal bacteria. The results of this study may therefore be used to determine the most effective therapeutic targets for the development of medications to treat diarrhea.

genomics↗

Mice Models to Bioinformatics Methods Led to the Discovery of Antidiabetic Compounds in the F. racemosa Plant Extracts

One of the primary health issues caused by inadequate blood sugar regulation is Diabetes Mellitus (DM). Diabetes and its consequences remain clinically significant even with the development of oral hypoglycemic medications. Therefore, Ficus racemosa (F. racemosa) plant has been studied for assessing of its antidiabetic potential coupling with animal model and in silico experiments. Drug Alloxan (150 mg/kg) was injected to induce the experimental diabetes in Swiss Albino mice, and two doses methanol extract of the F. racemosa fruit (300 and 500 mg/kg) along with glibenclamide (5 mg/kg) were given orally. Oral Glucose Tolerance Test (OGTT) and acute toxicity were performed as well in both diabetic and non-diabetic mice. Later, in silico experiments including ADMET profiling, molecular docking and simulations were performed. The administration of a dosage less than 3000 mg/kg has been observed to be well-tolerated by mice, with no reported instances of mortality or adverse effects. Following oral administration for 7 days, the blood glucose level (BGL) was significantly decreased in mice model in both doses of extracts, indicating the effect of F. racemosa. Subsequent to this, molecular docking and simulations have indicated that the SIRT1 receptor exhibits a higher binding affinity towards four specific compounds, namely Friedelin, Lupeol Acetate, Gluanol, and Ferulic Acid, as indicated by the dynamics parameters and interacting residues. The current investigation provided evidence that the fruit extract of F. racemosa significantly mitigated the hyperglycemic impact. Moreover, a total of four substances have been found that play a crucial role in the mechanisms behind the reduction of diabetic effects. Hence, the current investigation could potentially serve as a viable therapeutic approach in the treatment of diabetes.

microbiology↗

From Sequence to Significance: A Thorough Investigation of the Distinctive Genome Traits Uncovered in C. werkmanii strain NIB003

Citrobacter werkmanii (C. werkmanii) is an opportunistic bacterium that has received very little investigation in Bangladesh, even though it is thought to be capable of causing diseases including diarrhea and urinary tract infections. Therefore, the present study focuses on the exploration of genomic features, including antibiotic resistance genes, virulent genes, and their distinctive nature in the pathogenesis of diseases. A complete genome was sequenced for the first time in Bangladesh after the morphological, biochemical and molecular identification of this bacteria. A total of 47,65,861 nucleotide base pairs makes up the genome, which contains 4669 genes, and many of the protein-coding genes can be classified into various ontological frameworks, including COG and KEGG pathways. Notably, C. werkmanii has the capability to have interactions with Escherichia coli, Salmonella, and Klebsiella while they possess the same domains and motifs, indicating a causal role in the development of diarrhea. Furthermore, the Bangladeshi isolate of C. werkmaii has observed genetic heterogeneity when compared to other strains of C. werkmanii: C. werkmanii FDAARGOS_616, C. werkmanii LCU-V21, and C. werkmanii BF-6. This identified genetic variation of sequenced C. werkmanii could drive the functional aberration in body homeostasis of bacteria. Later, molecular dynamics studies have proven the impact of their genetic variation on the protein structure, as indicated by the SASA, RMSD, Rg, and RMSF values. Finally, the findings of C. werkmanii from the sequenced genome might provide us with a better understanding of C. werkmanii and their possible role as opportunistic bacteria in diseases including diarrhea and urinary tract infections.

genomics↗

In vivo and in silico experiment on Mitragyna speciosa offers new insight of antidiabetic potentials

Diabetes Mellitus (DM) is a serious metabolic disease with several treatments available for managing it, however, they can be expensive and have side effects. Medicinal plants have been used for many years to treat numerous diseases. Mitragyna speciosa (M. speciosa) plant has been shown to have anti-diabetic properties in preclinical studies. Hence, this study aimed to investigate the phytochemical compositions and anti-diabetic effects of M. speciose, using both in vivo and in silico approaches. In the in vivo study, experimental diabetes was induced in Swiss albino mice using the drug alloxan (150 mg/kg). Four groups of diabetic mice were taken. Two of the groups were given extracts at doses of 200 mg/kg and 400 mg/kg respectively. Diabetic mice treated with the reference drug, glibenclamide (5mg/kg) were chosen as a positive control, and mice with only vehicles were considered as a negative control. The Oral Glucose Tolerance Test (OGTT) and the acute toxicity test were performed. In the in silico study, molecular docking and dynamics were performed for the identification of the plant compounds that could effectively bind with the DPP4 receptor. Analysis of the study suggested that the lethal dose (LD50) values were greater than 2000 mg/kg, indicating that a dose below this level can be selected. The OGTT results showed that both doses of M. speciose extracts significantly reduced blood glucose levels (P<0.0001). However, neither dose exhibited a significantly higher blood glucose reduction compared to glibenclamide (5 mg/kg) (P > 0.05). Phytochemical screening and the ADMET profile analysis suggested four key compounds: Mitragynine, Corynantheidine, Corynoxine, and Speciociliatine in M. speciosa. The molecular docking analysis revealed these four compounds as potential antidiabetic agents considering their high binding affinity to the DPP4 receptor. These compounds were also found to be stable in the DPP4 binding pocket, as evidenced by the molecular dynamics simulation. Lastly, it can be demonstrated that the in silico experiments confirmed M. speciosa extracts to be capable of reducing blood glucose levels because of the presence of compounds.

pharmacology and toxicology↗

A Non-invasive Detection of Parkinson's Disease using PitArray: An Integrative Meta-Analysis and Machine Learning Approach

Parkinsons disease (PD) is a progressive neurodegenerative disorder affecting the central nervous system, often diagnosed in its advanced stages due to the absence of sensitive biomarkers. With this objective in mind, our study conducted a comprehensive analysis of differentially expressed genes (DEGs) sourced from blood-based microarray datasets to uncover potential biomarkers and developed a machine learning based classifier to conduct two step validations. By analyzing gene expression of three projects, we identified 678 DEGs, consisting of 337 genes showing upregulation and 341 genes presenting downregulation. Additionally, insights from functional enrichment and the protein-protein network analysis indicate that HLA-F, IRF-1, and RPS28 have the potential to serve as biomarkers for diagnosing PD. Simultaneously, we employed feature selection techniques such as Least Absolute Shrinkage and Selection Operator with Cross Validation (LassoCV) followed by Recursive Feature Elimination with Cross Validation (REFCV) to filter our initial dataset of 13,249 genes down to 43 genes, which were subsequently used to train the machine learning-based classifier models. These 43 genes formed the basis for training and testing various machine learning models, including logistic regression, random forest, naive Bayes, k-nearest neighbors, support vector machine, and deep learning based artificial neural networks. Our models demonstrated robust performance, with Support Vector Machine outperforming others by 0.65 accuracy (95%CI: 0.58-0.66), 0.70 AUC-ROC (95%CI: 0.70-0.71) and 0.35 MCC (95%CI: 0.34-0.39). The model was implemented to develop the PitArray tool for non-invasive detection of PD from blood. PitArray is available at: https://github.com/Arittra95/PitArray. Key PointsO_LIHLA-F, IRF-1, and RPS28 were identified as potential biomarkers for Parkinsons disease diagnosis. C_LIO_LISeveral sophisticated feature selection methods recognized 43 genes which were then used to build a machine learning model. C_LIO_LIA Support Vector Machine based tool named PitArray was developed which could distinguish Parkinsons disease patients from healthy people based on blood transcriptome data. C_LI

bioinformatics↗

An Integrated Comparative Genomics, Subtractive Proteomics and Immunoinformatics Framework for the Rational Design of a Pan-Salmonella Multi-Epitope Vaccine

Salmonella infections are a global public health issue due to the high cost of illness surveillance, prevention, and treatment. In this study, we explored the core proteome in Salmonella to design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins presents in 30 different strains of Salmonella (reference strain-NZ CP014051) were curated. Utilizing the subtractive proteomics approach on the Salmonella core proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate. csgA is a conserved gene that is related with biofilm formation. Immunodominant B and T cell epitopes from CsgA were predicted using numerous immunoinformatics tools. T lymphocyte epitopes had adequate population coverage and their corresponding MHC alleles showed significant binding scores after peptide-protein based molecular docking. Afterward, a multiepitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine was found to be highly antigenic, non-toxic, non-allergic, and had physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit robust immune response. Using in vitro, in vivo, and clinical trials, our results would yield a Pan-Salmonella vaccine that will provide protection against various Salmonella species.

bioinformatics↗

A meta-analysis of bulk RNA-seq datasets identifies potential biomarkers and repurposable therapeutics against Alzheimers disease

Alzheimers disease (AD) poses a major challenge due to its impact on the elderly population and the lack of effective early diagnosis and treatment options. In an effort to address this issue, a study focused on identifying potential biomarkers and therapeutic agents for AD was carried out. Using RNA-Seq data from AD patients and healthy individuals, 12 differentially expressed genes (DEGs) were identified, with 9 expressing upregulation (ISG15, HRNR, MTATP8P1, MTCO3P12, DTHD1, DCX, ST8SIA2, NNAT, and PCDH11Y) and 3 expressing downregulation (LTF, XIST, and TTR). Among them, TTR exhibited the lowest gene expression profile. Interestingly, functional analysis tied TTR to amyloid fiber formation and neutrophil degranulation through enrichment analysis. These findings suggested the potential of TTR as a diagnostic biomarker for AD. Additionally, druggability analysis revealed that the FDA-approved drug Levothyroxine might be effective against the Transthyretin protein encoded by the TTR gene. Molecular docking and dynamics simulation studies of Levothyroxine and Transthyretin suggested that this drug could be repurposed to treat AD. However, additional studies using in vitro and in vivo models are necessary before these findings can be applied in clinical applications.

bioinformatics↗

AITeQ: A machine learning framework for Alzheimer's prediction using a distinctive 5-gene signature

Neurodegenerative diseases, such as Alzheimers disease, pose a significant global health challenge with their complex etiology and elusive biomarkers. In this study, we developed the Alzheimers Identification Tool using RNA-Seq (AITeQ), a machine learning model based on an optimized random forest algorithm for identification of Alzheimers from RNA-Seq data. Analysis of RNA-Seq data from 433 individuals, including 293 Alzheimers patients and 140 controls led to the discovery of 47,929 differentially expressed genes. This was followed by a machine learning protocol involving feature selection, model training, performance evaluation, and hyperparameter tuning. The feature selection process undertaken in this study, employing a combination of 4 different methodologies, culminated in the identification of a compact yet impactful set of 5 genes. Ten diverse machine learning models were trained and tested using these 5 genes (ITGA10, CXCR4, ADCYAP1, SLC6A12, VGF). Performance metrics, including precision, recall, F1-score, accuracy, receiver operating characteristic area under the curve, and confusion matrices, were assessed before and after hyperparameter tuning. Overall, the random forest model with optimized hyperparameters was identified as the best and was used to develop AITeQ. AITeQ is available at: https://github.com/ishtiaque-ahammad/AITeQ Key PointsO_LIA set of 5 genes (ITGA10, CXCR4, ADCYAP1, SLC6A12, VGF) were identified following differential gene expression and feature importance analysis. C_LIO_LITen diverse machine learning algorithms were trained and tested using the gene expression patterns of the identified 5 genes. The random forest algorithm with customized hyperparameters was found to be the best-performing model for differentiating Alzheimers disease samples from control. C_LIO_LIAITeQ, a user-friendly, reliable, and accurate machine learning framework for Alzheimers disease prediction was developed based on the 5 gene signature. C_LI

bioinformatics↗

Microglial cGAS deletion protects against amyloid-β induced Alzheimer's disease pathogenesis

Innate immune activation plays a vital role in the development of Alzheimers disease (AD) and related dementias (ADRD). Among which, the DNA sensing cyclic GMP-AMP synthase (cGAS)- STING pathway has been implicated in diverse aspects of AD progression. In the current study, we showed that the cGAS-STING signaling was up-regulated in AD and this elevation was mainly contributed by the microglial population other than non-microglial cell types in the brain. By establishing an inducible, microglia-specific cGAS knockout mouse model in 5xFAD background, we found that deleting microglial cGAS at the onset of amyloid-{beta} (A{beta}) pathology significantly limited plaque formation, and protected mice from A{beta}-induced cognitive impairment. Mechanistically, we found cGAS was necessary for plaque-associated microglial enrichment potentially driven by IRF8, and was indispensable for the development of disease-associated microglia (DAM) phenotype. Meanwhile, the loss of microglial cGAS reduced the levels of dystrophic neurites which led to preserved synaptic integrity and neuronal function. Our study provides new insights in understanding the effects of innate immune in AD via a cell-type specific manner, and lays the foundation for potential targeted intervention of the microglial cGAS-STING pathway toward the improvement of AD.

neuroscience↗

Homologous mutations in β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation

Mutations at a highly conserved homologous residue in three closely related muscle myosins cause three distinct diseases involving muscle defects: R671C in {beta}-cardiac myosin causes hypertrophic cardiomyopathy, R672C and R672H in embryonic skeletal myosin cause Freeman Sheldon syndrome, and R674Q in perinatal skeletal myosin causes trismus- pseudocamptodactyly syndrome. It is not known if their effects at the molecular level are similar to one another or correlate with disease phenotype and severity. To this end, we investigated the effects of the homologous mutations on key factors of molecular power production using recombinantly expressed human {beta}, embryonic, and perinatal myosin subfragment-1. We found large effects in the developmental myosins, with the most dramatic in perinatal, but minimal effects in {beta} myosin, and magnitude of changes correlated partially with clinical severity. The mutations in the developmental myosins dramatically decreased the step size and load-sensitive actin-detachment rate of single molecules measured by optical tweezers, in addition to decreasing ATPase cycle rate. In contrast, the only measured effect of R671C in {beta} myosin was a larger step size. Our measurements of step size and bound times predicted velocities consistent with those measured in an in vitro motility assay. Finally, molecular dynamics simulations predicted that the arginine to cysteine mutation in embryonic, but not {beta}, myosin may reduce pre-powerstroke lever arm priming and ADP pocket opening, providing a possible structural mechanism consistent with the experimental observations. This paper presents the first direct comparisons of homologous mutations in several different myosin isoforms, whose divergent functional effects are yet another testament to myosins highly allosteric nature.

biophysics↗

Adult-onset CNS sulfatide deficiency causes sex-dependent metabolic disruption in aging

The interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated. We previously reported that myelin-enriched sulfatide loss leads to CNS neuroinflammation and cognitive decline. In this study, we further investigated the impact of CNS sulfatide deficiency on peripheral metabolism while considering sex- and age-specific effects. We found that female sulfatide-deficient mice gained significantly more body weight, exhibited higher basal glucose levels, and were glucose intolerant during glucose-tolerance test (GTT) compared to age-matched controls under a normal diet, whereas male sulfatide-deficient mice only displayed glucose intolerance at a much older age compared to female sulfatide-deficient mice. Mechanistically, we found the increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypo-thalamus, in a sex-specific manner. Our results suggest that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food-intake.

neuroscience↗

A Study on multiple isotherms of Cr6+ ions using Brevibacillus brevis US575 isolated from tannery effluents

Various leather factories in West Bengal have resulted in an enormous amount of leather that is processed annually. Regular discharges of tannery effluents into land and open water have led to significant soil and water pollution, with one of the most dangerous inorganic pollutants being chromium (Cr). This study aims to recover the most harmful components from industrial water using efficient biosorbents. Brevibacillus brevis US575 has been initially found in tannery effluents, where it has a high tolerance level to Cr6+ ions. The Cr(VI) adsorbed from the solution in aqueous phase during the course of the 60-minute contact period in this experiment was nearly 74%. Studies on the concentration of biomass, pH of the medium, and the starting concentration of metal ions have also been seen to affect the rate of biosorption. According to the desorption investigation, 1 M HCl outperformed all other concentrations of HCl, NaOH and pure water. Highest capacity of adsorption of the bio-adsorbent was calculated using the Langmuir model. The monolayer adsorption process was determined, and since the Freundlich models 1/n value fell inside 1, favourable adsorption has been postulated. According to the results of this study, the bacterium isolated from tannery wastewater was found to be the best alternative and could be used to create plans for using biosorption to combat current environmental pollution.

microbiology↗