Miracle-dz/UniFAR-FTUs huggingface dataset:
TRPM7 is critical for short-term synaptic depression by regulating synaptic vesicle endocytosis

TRPM7 contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in CNS neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+ influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmission from TRPM7 KO mice. Taking together, our data suggests that Ca2+ influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.
Cortical representation variability aligns with in-class variances and can help one-shot learning

Learning invariance across a set of transformations is an important step in mapping high-dimensional inputs to a limited number of classes. After understanding the set of\ invariances, can a new class be learned from one element? We propose a representation which can facilitate such learning: if the variability in representing individual elements across trials aligns with the variability among different elements in a class, then class boundaries learned from the variable representations of one element should be representative of the entire class. In this study, we test whether such a representation occurs in mouse visual systems. We use Neuropixels probes recording single unit activity in mice observing 200 repeats of natural movies taken from a set of 9 continuous clips. We observe that the trial-by-trial variability in the representation of individual frames is well aligned to the variability in representation of multiple frames from the same clip, but not well aligned to the variability among frames from different clips. Thus, the variable representations of images in the mouse cortex can be efficiently used to classify images into their clips. We compare these representations to those in artificial neural networks. We find that, when introducing noise in networks trained for classification (both feed-forward and recurrent networks), the variability in the representation of elements aligns with the in-class variance. The networks which best reproduce the in-vivo observed directions of variability were those trained on a hierarchical classification task. Taken together, these results point to a solution which the cortex can use for one-shot learning of a class: by using noise as a mechanism for generalization. This is a potential computational explanation for the high level of noise observed in the cortex.
Gating the channel pore of ionotropic glutamate receptors with bacterial substrate binding proteins

Tetrameric ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission in the mammalian central nervous system and are involved in learning, memory formation, and pathological processes. Based on structural and sequence similarities of the ligand-binding and channel domains of iGluR subunits to bacterial binding proteins and potassium channels, iGluRs are thought to have originally arisen from their fusion. Here we report the functional coupling of the bacterial ectoine binding protein EhuB to the channel pore-forming transmembrane domains of the bacterial GluR0 receptor by stabilization of dimeric binding domains. Insertion of a disulfide bridge in the dimer interface abolished desensitization of the channel current analogous to mammalian iGluRs. These results demonstrate the functional compatibility of bacterial binding proteins to the gate of the channel pore of an iGluR. Moreover, our results highlight the modular structure and crucial role of binding domain dimerization in the functional evolution of iGluRs.
Computational Investigation of Increased Virulence and Pathogenesis of SARS-CoV-2 Lineage B.1.1.7

New variants of SARS-CoV-2 are being reported worldwide. More specifically, the variants reported in South Africa (501Y.V2) and United Kingdom (B.1.1.7) were found to be more contagious than the wild type. There are also speculations that the variants might evade the host immune responses induced by currently available vaccines and develop resistance to drugs under consideration. The first step of viral infection in COVID-19, occurs through the interaction of receptor binding domain (RBD) of the spike protein with peptidase domain of the human ACE-2 (hACE-2) receptor. So, possibly the mutations in the RBD domain of spike protein in the new variants could modulate the protein-protein interaction with hACE-2 receptor leading to the increased virulence. In this study, we aim to get molecular level understanding into the mechanism behind the increased infection rate due to such mutations in these variants. We have computationally studied the interaction of the spike protein in both wild-type and B.1. 1.7 variant with hACE-2 receptor using combined molecular dynamics and binding free energy calculations using molecular mechanics-Generalized Born surface area (MM-GBSA) approach. The binding free energies computed using configurations from minimization run and low temperature simulation show that mutant variant of spike protein has increased binding affinity for hACE-2 receptor (i.e. ΔΔG(N501Y,A570D) is in the range −20.4 to −21.4 kcal/mol)The residue-wise decomposition analysis and intermolecular hydrogen bond analysis evidenced that the N501Y mutation has increased interaction between RBD of spike protein with ACE-2 receptor. We have also carried out calculations using density functional theory and the results evidenced the increased interaction between three pairs of residues (TYR449 (spike)-ASP38 (ACE-2), TYR453-HIE34 and TYR501-LYS353) in the variant that could be attributed to its increased virulence. The free energies of wild-type and mutant variants of the spike protein computed from MM-GBSA approach suggests that latter variant is stable by about −10.4 kcal/mol when compared to wild type suggesting that it will be retained in the evolution due to increased stability. We demonstrate that with the use of the state-of-the art of computational approaches, we can in advance predict the more virulent nature of variants of SARS-CoV-2 and alert the world health-care system.
Fog Seal Treatment Effectiveness Analysis of Pavement Binders Using the t-Test Statistical Approach

Abstract In this study, sealed pavements were tested to assess the treatment impact on retarding binder aging or rejuvenating in situ binder. Asphalt rheology of extracted binders was used to compare between untreated and treated sections using a paired t-test analysis. A paired t-test statistical analysis of recovered binder stiffnesses showed that polymer-modified asphalt surface sealer (PASS) and COS-50™ treatments did not have a significant impact on binder stiffness. The only significant effect on the rheology of the in situ binder was by EB44 coal tar, which stiffened the binder, and this effect was primarily restricted to the top quarter inch or so of the pavement.
Direct and indirect effects of high temperatures on fledging success in a cooperatively breeding bird

High temperatures and low rainfall consistently constrain reproduction in arid-zone bird species. Understanding the mechanisms underlying this pattern is critical for predicting how climate change will influence population persistence and to inform conservation and management. In this study, we analysed Southern Pied Babbler Turdoides nestling survival, daily growth rate and adult investment behaviour during the nestling period over three austral summer breeding seasons. High temperatures were associated with lower body mass, shorter tarsi, and reduced daily growth rates of nestlings. Piecewise structural equation modelling suggests that direct impacts of temperature had the strongest influence, followed by changes in provisioning rates by adults to older nestlings. Adjustments to adult provisioning strategies did not compensate for direct negative effects of high air temperatures on nestling body mass, tarsus and wing length, or daily growth rates. Declining reproductive success during hot weather poses a potentially serious threat to population replacement and persistence as climate change progresses, even for currently common and widespread species. Significantly lower offspring survival as a result of climate warming will likely contribute to the collapse of animal communities well before temperatures regularly approach or exceed lethal tolerance limits. Detailed mechanistic data like these allow us to model the pathways by which high temperature causes nest failure. In turn, this could allow us to design targeted conservation action to effectively mitigate climate effects.
The Genetic Diversity of Two Subpopulations of Shenxian Pigs as Revealed by Genome Resequencing

Shenxian pigs can be divided into two main strains from their shape and appearance: Huangguazui and Wuhuatou. There are significant differences in the phenotypic characters between the two subpopulations. The Shenxian pig, as the only local pig breed listed in China Pig Breeds in Hebei Province, has the excellent traits of Chinese local pigs. In order to explore the genetic diversity and genetic distance of the different subpopulations of Shenxian pig, as well as understand their evolutionary process, whole genome resequencing and genetic structure analyses were performed for the two sub-population types of Shenxian pigs.The results showed that a total of 14,509,223 SNP sites were detected in the Huangguazui type and 13,660,201 SNP sites were detected in the Wuhuatou type. This study’s principal component analysis results showed that the genetic differentiation of the Shenxian pig population was serious, and there was obvious stratification in the population. The phylogenetic tree analysis results indicated that there was a certain genetic distance between the Huangguazui and Wuhuatou types.
Dendritic cell CX3CR1 and macrophages F4/80 play a central role in between gut micro biome and inflammation in Arsenic induced mice

Microbiota plays a crucial role to protect the intestine contrary to the harmful foreign microorganisms and organize the immune system via numerous mechanisms, which include either direct or indirect environmental factors. The underlying mechanism arsenic (As) influenced immune system and regulates inflammation by altering gut microbiome in ileum remains unclear. However, chronic exposure to arsenic (at doses of 0.15 mg or 1.5 mg or 15 mg As2O3/ L in drinking water) significantly increased mRNA and protein levels of F4/80 and CX3CR1, concurrently, the increased levels of mRNA and protein IFNγ, TNFα, IL-18 and decreased levels of IL-10 were found in both 3 and 6 months exposure periods. High-throughput sequencing analysis revealed that gut microbiota at phylum; family and taxonomical levels were showed the abundance of gut microbiota. Evidentially, the ultra-structure of intestinal villi, microbes engulfed and immune cell migration were showed by the transmission electron microscopy. Chronic exposure to As influenced the inflammation by changing immune system and altered gut microbiota. In this study we conclude that chronic exposure to As breakdown the normal gut microbial community and increase the pathogenicity, the resultant risk pathogen direct contact with intestinal immune system and regulate the inflammation.
ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the acquisition of BCR-ABL1 fusion in a hematopoietic stem cell. We identified the ENOX2 gene as up-regulated in BCR-ABL1-expressing UT-7 cell lines through a transcriptome assay. The oncofoetal ENOX2 protein (Ecto-Nicotinamide Adenine Dinucleotide Oxidase Disulfide Thiol Exchanger 2) is expressed on the external plasma membrane surface of cancer cells and can be released in cancer patients’ serum. Considering these data, we studied ENOX2 expression in CML cell lines and patients using quantitative RT-PCR, western-blots, the ELISA method, and transcriptomic dataset reanalysis. We confirmed increased ENOX2 mRNA expression in the BCR-ABL1-expressing UT-7 cell line. Comparable results were obtained in CML patients at diagnosis. Western-blot analyses on UT-7 and TET-inducible Ba/F3 cell lines established the up-regulation of ENOX2 protein. BCR-ABL1 has been found to induce ENOX2 overexpression in a kinase-dependent manner. In a series of 41 patients with CML, ELISA assays showed a highly significant increase of ENOX2 protein levels in the plasma of patients with CML (p < 0.0001) as compared to controls (n=28). Transcriptomic dataset (GSE4170) reanalyzes have shown specific ENOX2 mRNA overexpression in the chronic phase of the disease. Bioinformatic analyses identified several genes whose mRNA expression was positively correlated to ENOX2. Some of them encode proteins involved in cellular functions compatible with the growth deregulation observed in CML. All in all, our results demonstrate for the first time the upregulation of a secreted Redox protein in a BCR-ABL1-dependent manner in CML. Our data suggest that ENOX2 (through its transcriptional program) plays a significant role in the BCR-ABL1 leukemogenesis. Further studies are required to clarify the relationship between BCR-ABL1 and ENOX2.
Disrupting D2-NMDA receptor heteromerization blocks the rewarding effects of cocaine but preserves natural reward processing

Addictive drugs increase dopamine in the nucleus accumbens (NAc), where it persistently shapes excitatory glutamate transmission and hijacks natural reward processing. Herein, we provide evidence, from mice to human, that an underlying mechanism relies on drug-evoked heteromerization of glutamate NMDA receptors (NMDAR) with dopamine receptor 1 (D1R) or 2 (D2R). Using temporally-controlled inhibition of D1R-NMDAR heteromerization, we unraveled their selective implication in early developmental phases of cocaine-mediated synaptic, morphological and behavioral responses. In contrast, preventing D2R-NMDAR heteromerization blocked the persistence of these adaptations. Importantly, interfering with these heteromers spared natural reward processing. Strikingly, we established that D2R-NMDAR complexes exist in human samples and showed that, despite a decreased D2R protein expression in the NAc, psychostimulant-addicts display a higher proportion of D2R forming heteromers with NMDAR. These findings contribute to a better understanding of molecular mechanisms underlying addiction and uncover D2R-NMDAR heteromers as targets with potential therapeutic value.
Coronavirus associated molecular mimicry common to SARS-CoV-2 peptide

Relationship of COVID-19 and immunity is complex and can involve autoimmune reactions through molecular mimicry. We investigated autoimmunity related pathological mechanisms involving molecular mimicry that are common to certain coronaviruses, including SARS-CoV-2, by means of a selected peptide sequence (CFLGYFCTCYFGLFC). Accordingly, coronavirus-associated sequences that are homologous to that 15mer sequence in the SARS-CoV-2 proteome are attained first. Then, homologous human and coronavirus sequences are obtained, wherein the coronavirus sequences are homologous to the 15mer SARS-CoV-2 peptide. All the identified query-subject sequences contained at least 7 residue matches in the aligned regions. Finally, parts of those coronavirus and host sequences, which are predicted to have high affinity to the same human leukocyte antigen (HLA) alleles as that of the SARS-CoV-2 sequence, are selected among the query and subject epitope-pairs that were both (predicted to be) strongly binding to the same HLA alleles. The proteins or the protein regions with those predicted epitopes include, but not limited to, immunoglobulin heavy chain junction regions, phospholipid phosphatase-related protein type 2, slit homolog 2 protein, and CRB1 isoform I precursor. These proteins are potentially associated with certain pathologies, but especially the possible CRB1 related coronavirus pathogenicity could be furthered by autoimmunity risk in HLA*A24:02 serotypes. Overall, results imply autoimmunity risk in COVID-19 patients with HLA*A02:01 and HLA*A24:02 serotypes in general, through molecular mimicry. This is also common to other coronaviruses than SARS-CoV-2. These results are indicative at the current stage, they need to be validated. Yet, they can pave the way to autoimmunity treatment options to be used in COVID-19 and its associated diseases.
High current production of Shewanella oneidensis with electrospun carbon nanofiber anodes is directly linked to biofilm formation

We study the current production of Shewanella oneidensis MR-1 with electrospun carbon fiber anode materials and analyze the effect of the anode morphology on the micro-, meso- and macroscale. The materials feature fiber diameters in the range between 108 nm and 623 nm, resulting in distinct macropore sizes and surface roughness factors. A maximum current density of (255 ± 71) μA cm-2 was obtained with 286 nm fiber diameter material. Additionally, micro- and mesoporosity were introduced by CO2 and steam activation which did not improve the current production significantly. The current production is directly linked to the biofilm dry mass under anaerobic and micro-aerobic conditions. Our findings suggest that either the surface area or the pore size related to the fiber diameter determines the attractiveness of the anodes as habitat and therefore biofilm formation and current production. Reanalysis of previous works supports these findings.
Nodal Modulator is required to sustain endoplasmic reticulum morphology

Nodal Modulator (NOMO) is a widely conserved type I transmembrane protein of unknown function, with three nearly identical orthologs specified in the human genome. We identified NOMO1 in a proteomics approach aimed at the identification of proteins that support the structural integrity of the endoplasmic reticulum (ER). Overexpression of NOMO1 imposes a sheet morphology on the ER, while depletion of NOMO1 and its orthologs causes a collapse of ER morphology concomitant with the formation of membrane-delineated holes in the ER network. These structures are positive for the autophagy marker LAMP1, and LC3 is profoundly upregulated upon NOMO depletion. In vitro reconstitution of NOMO1 revealed a dimeric state that is mediated by the cytosolic tail domain, with each monomer featuring a “beads on a string” structure likely representing bacterial Ig-like folds. Based on these observations and a genetic epistasis analysis including the known ER-shaping proteins Atlastin2 and Climp63, we propose a role for NOMO1 in the functional network of ER-shaping proteins.
Can we put Humpty Dumpty back together again? What does protein quantification mean in bottom-up proteomics?

Bottom-up proteomics provides peptide measurements and has been invaluable for moving proteomics into large-scale analyses. In bottom-up proteomics, protein parsimony and protein inference derived from these measured peptides are important for determining which protein coding genes are present. However, given the complexity of RNA splicing processes, and how proteins can be modified post-translationally, it is overly simplistic to assume that all peptides that map to a singular protein coding gene will demonstrate the same quantitative response. Accordingly, by assuming all peptides from a protein coding sequence are representative of the same protein we may be missing out on detecting important biological differences. To better account for the complexity of the proteome we need to think of new or better ways of handling peptide data.
Unsupervised discovery of dynamic cell phenotypic states from transmitted light movies

Identification of cell phenotypic states within heterogeneous populations, along with elucidation of their switching dynamics, is a central challenge in modern biology. Conventional single-cell analysis methods typically provide only indirect, static phenotypic readouts. Transmitted light images, on the other hand, provide direct morphological readouts and can be acquired over time to provide a rich data source for dynamic cell phenotypic state identification. Here, we describe an end-to-end deep learning platform, UPSIDE (for Unsupervised Phenotypic State IDEntification), for discovering cell states and their dynamics from transmitted light movies. UPSIDE uses the variational auto-encoder architecture to learn latent cell representations, that are then clustered for state identification, decoded for feature interpretation, and linked across movie frames for transition rate inference. Using UPSIDE, we identified distinct blood cell types in a heterogeneous dataset. From acute myeloid leukemia cell movies, we then identified stem-cell associated morphological states and their inter-conversion rates. UPSIDE opens up use of transmitted light movies for systematic exploration of cell state heterogeneity and dynamics in biology and medicine.
Variant and mutation analysis of SARS-CoV-2 genomes isolated from the Kingdom of Bahrain

The challenges imposed by the ongoing outbreak of severe acute respiratory syndrome coronavirus-2 affects every aspect of our modern world, ranging from our health to our socio-economic needs. Our existence highly depends on the vaccines availability, which demands in-depth research of the available strains and their mutations. In this work, we have analyzed all the available SERS-CoV2 genomes isolated from the Kingdom of Bahrain in terms of their variance and origin analysis. We have predicted various known and unique mutations in the SERS-CoV2 isolated from Bahrain. The complexity of the phylogenetic tree and dot plot representation of the strains mentioned above with other isolates of Asia indicates the versatility and multiple origins of Bahrains SERS-CoV2 isolates. We have also identified two high impact spike mutations from these strains which increase the virulence of SARS-CoV2. Our research could have a high impact on vaccine development and distinguishes the source of SERS-CoV2 in the Kingdom of Bahrain.
Analysis and Prediction of Air Quality

– In the modern world, air pollution is one of the growing environmental issue. It poses major threat to health and climate. Air quality in cities is deteriorating day by day. Pollutants in air also impacts both water and land. This paper presents a literature review of predicting air quality using Internet of Things and Machine learning techniques and forecast the air pollution levels so that preventive measures can be taken by the people in order to minimize the air pollution.