Biology subjects

Hossain, A.

Publications and source records attributed to Hossain, A..

15 recordsLinked to original sources

bioRxiv2026

Prolactin Receptor Long Isoform ΔS1 Expression is Reduced in the Dorsal Root Ganglia of Humans with Chronic Pain

Prolactin receptor (PRLR) isoforms, specifically the short (PRLR-S) and long (PRLR-L), are differentially expressed in pathological conditions and may be involved in the induction and maintenance of pain in females. PRLR sex-dependent actions are well studied in rodent models of chronic pain, but the translatability of these findings have only been assessed in electrophysiology studies that found consistent results with previous sex differences described in mice. To increase our understanding of the sexual dimorphic nature of prolactin actions on sensory neurons and our knowledge of how this body of work applies to the human nervous system, we characterized the expression of the short and long isoforms of PRLR with RNAscope in situ hybridization in human dorsal root ganglion (DRG) neurons. Based on data in mice, we hypothesized PRLR-S and PRLR-L would be equally expressed in human DRG neurons, with higher expression in females. To test this, we used DRG tissues recovered from male and female organ donors and cervix as a positive control. Our results demonstrated human DRG neurons express more PRLR-L, specifically transcript variant 6 ({Delta}S1), than PRLR-S in both sexes and that female donors had a higher expression of PRLR overall. In DRGs from female organ donors with a history of chronic pain we observed less PRLR-L expression, a finding consistent with previous studies in pain models in female mice. Expression for both PRLR isoforms in cervix was consistent with previous reports. An analysis of previously published RNA sequencing studies on human DRGs revealed that PRLR expression is confined mostly to TRPV1-positive nociceptors in humans, consistent with our RNAscope-based findings. We conclude that the PRLR-L ({Delta}S1) form is the major isoform expressed in human DRG neurons, that this expression is higher in females than in males, and that PRLR-L ({Delta}S1) expression is suppressed in chronic pain conditions in females.

neuroscience↗

bioRxiv2026

Native oligomerisation of a small type I antifreeze protein from winter flounder

Antifreeze proteins and peptides adhere to ice crystals and inhibit their growth, resulting in freezing point depression. AFP6 is an abundant antifreeze peptide in the blood serum of winter flounder (Pseudopleuronectes americanus). This 37-residue peptide forms an amphiphilic -helix with a hydrophobic ice-binding surface. In this study, prediction of the peptide structure suggested the formation of an antiparallel dimer burying the hydrophobic surfaces of both subunits. The oligomerisation of AFP6 was therefore examined in aqueous solutions using size-exclusion chromatography and chemical crosslinking along with ice-binding evaluation. Crosslinking of non-amidated AFP6, followed by denaturing electrophoresis, revealed bands consistent with monomers and dimers, whereas results for the amidated form and a recombinant mutant suggested additional larger forms. Bands consistent with the presence of monomers and dimers were also predominant following non-amidated AFP6 crosslinking under a variety of solution conditions, with smaller proportions of peptide assembled up to tetrameric sizes; however, the larger oligomers appeared to be absent from AFP6 treated with sodium bicarbonate. Isolated oligomers of non-amidated AFP6 produced ice crystal morphologies and thermal hysteresis comparable to those for the unfractionated peptide suggesting similar interaction with ice. Oligomerisation of AFP6 may allow greater solubility of this amphiphilic -helical peptide in aqueous solutions.

biochemistry↗

bioRxiv2026

A 5-hydroxymethylcytosine DNA glycosylase provides defense against T-even bacteriophages

The most abundant prokaryotic mechanisms of defense against phage predation involve the recognition and destruction of the infecting DNA. One method of counter-defense is the incorporation of modified nucleobases into the phage genome to avoid interaction with enzymes that target the viral DNA. T-even coliphages replace cytosine with 5-hydroxymethylcytosine (5hmC) that in some cases are further decorated with glucosyl groups. To explore the diversity of immunity genes that recognize 5hmC, we infected a library of metagenomic DNA inserts from uncultured, non-sequenced soil bacteria with a mutant T4 phage that harbored only non-glucosylated 5hmC on its genome. Bacteria that resisted infection carried a DNA glycosylase, Brig3, that specifically excises 5hmC nucleobases to generate abasic sites in the phage genome and prevent viral proliferation. The crystal structure of Brig3 bound to its substrate revealed a catalytic mechanism in which the 5hmC nucleobase is flipped out of the DNA into the active site and replaced by an asparagine residue that inserts into the double helix to contact the complementary guanosine. Brig3 is encoded within an operon that also encodes BapA, a hydrolase that removes glucosyl groups from glucosyl-5hmC present in the genome of otherwise Brig3-resistant T-even phages carrying this hypermodified base. Our results uncover a defense strategy in which the combined action of BapA and Brig3 widens the immune response to restrict the infection of T-even phages with genomes that are either partially or completely glucosylated.

microbiology↗

bioRxiv2025

Quantifying the impact of genetic mutations on enhancer dynamics

Transcriptional regulation is mediated by enhancers, yet how genetic perturbations alter enhancer activity and gene expression remains poorly understood. We developed UDI-UMI-STARR-seq, which integrates dual indexes and unique molecular identifiers, and combined it with RNA-seq to profile the effects of perturbations on enhancer activity and target gene expression. We applied this approach to a library of 253,632 fragments representing 46,142 cell type-specific candidate enhancers and assessed the impact of CRISPR/Cas9-mediated deletion of six transcription factors (or TFs; ATF2, CTCF, FOXA1, LEF1, TCF7L2, and SCRT1) with diverse regulatory roles. Across knockout lines, we identified responsive enhancers that were either repressed or induced, often through motifs such as the p53 family of TFs. Enhancer-gene mapping revealed TF-specific programs, including repression of Wnt/p53 targets with ATF2 or LEF1 loss, downregulation of the FIRRE locus with CTCF loss, and compensatory upregulation of RNA polymerase II regulators following FOXA1 depletion. A deep learning model trained on enhancer sequences recapitulated core principles of enhancer grammar, including cooperative motif syntax and the influence of flanking sequence context. Applying this framework to the neurodevelopmental disorder-associated 16p12.1 deletion identified responsive enhancers linked to genes involved in axon guidance, synaptic plasticity, and translational control, providing a scalable readout of enhancer dynamics generalizable to genetic mutations.

genomics↗

bioRxiv2025

Hylocereus polyrhizus peel extract restricts DMBA- Croton oil induced skin carcinogenesis: An integrated in vivo and in silico approach

Hylocereus polyrhizus, locally known as red dragon fruit, is valued for its nutritional benefits including high levels of antioxidants and is gaining popularity as both a food and a medicinal plant. The present study addressed the in vivo and in silico chemopreventive potential of Hylocereus polyrhizus peel extract (HPPE) in DMBA-croton oil induced skin carcinogenic model mice. The mRNA expression level of pro-inflammatory cytokines and inflammatory mediators in tumor mass were estimated by real time-RT-qPCR. In addition, molecular docking and molecular dynamic simulation analyses were conducted on the reported compounds. In the in vivo chemopreventive activity assessment, the peel extract at 500 mg/kg was found effective in reducing total tumor number, yield, burden, incidence, and weight. Total proteins and endogenous antioxidants (GSH, SOD, CAT) levels in liver and skin tissues from mice were significantly (P<0.05) elevated. In addition, the HPPE at 500 mg/kg dose significantly reduced (P<0.05) the gene expression of pro-inflammatory cytokines such as TNF-, IL-1{beta}, IL-6, IL-18, and inflammatory mediators like TGF-{beta}1, COX-2, and NF{kappa}B. In the molecular docking studies, reported compounds including Quercimeritrin, Rutin, and Kaempferol 3-O-{beta}-D-glucopyranoside were identified as the top-performing compounds, with a docking score of - 7.4, -7.1 and -7.0 kcal/mol against TGF-{beta}1 protein. This indicates stronger binding interactions compared to vincristine (-5.3 kcal/mol). In drug-likeness assessment, all compounds demonstrated the most favourable ADMET and pharmacokinetic profile. Furthermore, MDS data showed greater dynamic stability for Kaempferol 3-O-{beta}-D-glucopyranoside and Rutin, while vincristine exhibited higher fluctuations. The results suggest that HPPE may serve as a potential inhibitor of skin carcinogenesis through upregulating endogenous antioxidants as well as suppressing different proinflammatory and inflammatory cytokines. Quercimeritrin, Rutin, and Kaempferol 3-O-{beta}-D-glucopyranoside might be the probable leads responsible for this chemopreventive activity. Highlights{checkmark} Hylocereus polyrhizus peel extract (HPPE) demonstrated notable chemopreventive potential against skin cancer. {checkmark}HPPE significantly increased endogenous antioxidants (GSH, SOD, CAT) in liver and skin tissues, suggesting enhanced cellular defense mechanisms. {checkmark}Gene expression of pro-inflammatory cytokines (TNF-, IL-1{beta}, IL-6, IL-18) and inflammatory mediators (TGF-{beta}1, COX-2, NF{kappa}B) were notably suppressed by HPPE. {checkmark}Quercimeritrin (CID: 5282160) demonstrated strong binding to TGF-{beta}1 with a docking score of -7.4 kcal/mol, outperforming vincristine (-5.3 kcal/mol). {checkmark}Kaempferol 3-O-beta-D-glucopyranoside (CID: 5282102) and rutin (CID: 5280805) showed the best ADMET, pharmacokinetic profiles, and molecular stability, supporting their potential as lead compounds.

cancer biology↗

bioRxiv2024

Anti-HIV-1 B cell antigen receptor signaling and structure

The B cell antigen receptor (BCR) complex, comprised of antigen recognition and signaling components, functions in initiating B cell activation. While structural studies have described BCR domain organization, gaps remain in our understanding of its antigen binding domain (Fab, fragment antigen-binding) disposition, and how antigen binding is sensed to initiate signaling. Here, we report antigen affinity and signaling of the immunoglobulin (Ig) class IgM and IgG BCRs and define conformational states of full-length BCRs of two human broadly neutralizing antibodies, the glycan-specific, heavy chain domain-swapped, I-shaped 2G12, and a canonical Y-shaped antibody, CH31, that recognizes the CD4-binding site on the HIV-1 Envelope protein (Env). The BCRs adopted the shapes (I or Y) of their respective soluble antibodies, and both Ig class of BCRs of the same specificity bound Env trimers with similar affinities. We observed antigen-valenc y dependent differential signaling by the 2G12 IgM and IgG BCRs with trimeric Envs. Cryo-electron microscopy of the 2G12 IgG and CH31 IgM BCRs revealed varied Fab orientations. Structural comparisons revealed hinge points and regions of flexibility in the BCRs suggesting a highly dynamic structure of the BCR complex. Taken together, our results provide an integrated understanding of BCR structure, conformation, antigen recognition and signaling, and provide the basis for understanding antigen induced BCR signal transmission. One Sentence SummaryCryo-electron microscopy structures of full-length B cell antigen receptor complex provide a novel dynamic BCR model and a basis for understanding antigen binding induced signal transmission.

immunology↗

bioRxiv2022

Challenges and considerations for reproducibility of STARR-seq assays

High-throughput methods such as RNA-seq, ChIP-seq and ATAC-seq have well-established guidelines, commercial kits, and analysis pipelines that enable consistency and wider adoption for understanding genome function and regulation. STARR-seq, a popular assay for directly quantifying activity of thousands of enhancer sequences simultaneously, has seen limited standardization across studies. The assay is long with >250 steps, and frequent customization of the protocol and variations in bioinformatics methods raise concerns for reproducibility of STARR-seq studies. Here, we assess each step of the protocol and analysis pipelines from published sources and in-house assays, and identify critical steps and QC checkpoints necessary for reproducibility of the assay. We also provide guidelines for experimental design, protocol scaling, customization, and analysis pipelines for better adoption of the assay. These resources will allow better optimization of STARR-seq for specific research needs, enable comparisons and integration across studies, and improve reproducibility of results.

genomics↗

bioRxiv2022

Evaluating the Phytotoxicity of Methanolic Extracts of Parthenium hysterophorus L. on Selected Crops and Weeds

Herbicides made from natural molecules may be a good environmentally friendly alternative to synthetic chemical herbicides for weed control. As a result, this investigation was carried out to ascertain the phytotoxicity of Parthenium hysterophorus L. as well as to identify its phenolic components. Germination of seeds and development of seedlings of Vigna subterranea (L.) Verdc, Raphanus sativus (L.) Domin, Cucurbita maxima Duchesne., Cucumis sativus L., Solanum lycopersicum L., Capsicum frutescens L., Zea mays L., Abelmoschus esculentus (L.) Moench, Daucus carota L., Digitaria sanguinalis (L.) Scop and Eleusine indica (L.) Gaertn were investigated using P. hysterophorus leaf, stem, and flower methanol extracts. Six concentrations (25, 50, 75, 100, and 150 g L-1) were comparison to the control (distilled water). The concentration of extracts increased, the rate of the seed sprouting and seedling growth decreased. EC50 values showed that the extraction of leaf of P. hysterophorus (811) was phytotoxic in comparison to the stem (1554) and flower (1109) extract. According to PCA analysis, Raphanus sativus, Solanum lycopersicum, Capsicum frutescens, Abelmoschus esculentus, Daucus carota, Digitaria sanguinalis, and Eleusine indica were all very susceptible to allelochemicals. A LC-MS analysis revealed that the P. hysterophorus leaf extract contained 7 phenolic compounds that were responsible for inhibition. These studies also revealed that the leaf of P. hysterophorus is a major source of phytotoxicity, which could be valuable in the future for developing a natural herbicide.

plant biology↗

bioRxiv2021

Automated Model-Predictive Design of Synthetic Promoters to Control Transcriptional Profiles in Bacteria

Transcription rates are regulated by the interactions between RNA polymerase, sigma factor, and promoter DNA sequences in bacteria. However, it remains unclear how non-canonical sequence motifs collectively control transcription rates. Here, we combined massively parallel assays, biophysics, and machine learning to develop a 346-parameter model that predicts site-specific transcription initiation rates for any {sigma}70 promoter sequence, validated across 17396 bacterial promoters with diverse sequences. We applied the model to predict genetic context effects, design {sigma}70 promoters with desired transcription rates, and identify undesired promoters inside engineered genetic systems. The model provides a biophysical basis for understanding gene regulation in natural genetic systems and precise transcriptional control for engineering synthetic genetic systems. One-Sentence SummaryA 346-parameter model predicted DNAs interactions with RNA polymerase initiation complex, enabling accurate transcription rate predictions and automated promoter design in bacterial genetic systems.

synthetic biology↗

bioRxiv2021

Mitochondrial dysfunction triggers secretion of the immunosuppressive factor α-fetoprotein

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identify a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that results in atrophy of the spleen and thymus and causes a peripheral white blood cell deficiency. We demonstrate that the leukopenia is caused by -fetoprotein, which requires copper and the cell surface receptor CCR5 to promote white blood cell death. We further show that -fetoprotein expression is upregulated in several cell types upon inhibition of oxidative phosphorylation, including a muscle cell model of Barth syndrome. Collectively, our data argue that -fetoprotein secreted by bioenergetically stressed tissue suppresses the immune system, an effect which may explain the recurrent infections that are observed in a subset of mitochondrial diseases or in other disorders with mitochondrial involvement.

cell biology↗

bioRxiv2021

Selenium-dependent metabolic reprogramming during inflammation and resolution

Trace element selenium (Se) is incorporated as the 21st amino acid, selenocysteine (Sec), into selenoproteins through tRNA[Ser]Sec. Selenoproteins act as gatekeepers of redox homeostasis and modulate immune function to effect anti-inflammation and resolution. However, mechanistic underpinnings involving metabolic reprogramming during inflammation and resolution remain poorly understood. Bacterial endotoxin lipopolysaccharide (LPS) activation of murine bone marrow-derived macrophages (BMDMs) cultured in the presence or absence of Se (as selenite) was used to examine temporal changes in the proteome and metabolome by multiplexed tandem mass tag-quantitative proteomics, metabolomics, and machine-learning approaches. Kinetic deltagram and clustering analysis indicated addition of Se led to extensive reprogramming of cellular metabolism upon stimulation with LPS enhancing PPP, TCA cycle, and OXPHOS, to aid in the phenotypic transition towards alternatively activated macrophages, synonymous with resolution of inflammation. Remodeling of metabolic pathways and consequent metabolic adaptation towards pro-resolving phenotypes began with Se treatment at 0 h and became most prominent around 8 h post LPS stimulation that included succinate dehydrogenase complex (Sdh), pyruvate kinase (Pkm), and sedoheptulosekinase (Shpk). Se-dependent modulation of these pathways predisposed BMDMs to preferentially increase OXPHOS to efficiently regulate inflammation and its timely resolution. Use of macrophages lacking selenoproteins, indicated that all three metabolic nodes were sensitive to selenoproteome expression. Furthermore, inhibition of Sdh with dimethylmalonate affected the pro-resolving effects of Se by increasing the resolution interval in a murine peritonitis model. In summary, our studies provide novel insights into the role of cellular Se via metabolic reprograming to facilitate anti-inflammation and proresolution.

immunology↗

bioRxiv2020

Transcription factor-based gene therapy to treat glioblastoma through direct neuronal conversion

Glioblastoma (GBM) is the most prevalent and aggressive adult primary cancer in the central nervous system (CNS). Therapeutic approaches for glioblastoma are under intense investigation, such as the emerging immunotherapy, but so far only marginal progress has been made due to the heterogeneity and highly invasive nature of glioblastoma. Here, we propose an alternative approach to tackle GBM through reprogramming proliferative GBM cells into non-proliferative neurons. We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1 (NeuroD1), Neurogenin-2 (Neurog2) or Achaete-scute homolog 1 (Ascl1). Subtype characterization reveals that the majority of Neurog2- and NeuroD1-converted neurons are glutamatergic, while Ascl1 favors GABAergic neuron generation. The GBM cell-converted neurons not only express pan-neuronal markers, such as NeuN and MAP2, but also exhibit neuron-specific electrophysiological activities. We further conducted transcriptome analyses to investigate the underlying cell conversion mechanism. Our RNA-seq analyses discover that neuronal genes are activated among glioma cells after overexpression of neural transcription factors, and different signaling pathways are activated by different neural transcription factors. Importantly, the neuronal conversion of GBM cells is accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models. Therefore, these results suggest that GBM cells can be reprogrammed into different subtypes of neurons, leading to a potential alternative approach to treat brain tumor. SignificanceConverting dividing glioblastoma cells into non-dividing neurons may provide an innovative therapeutic approach to treat glioblastoma. HighlightsO_LIEfficient neuronal conversion of human glioblastoma cells achieved by overexpression of neural transcription factors C_LIO_LINeurog2- and NeuroD1-converted neurons are mostly glutamatergic, while Ascl1-converted neurons are mainly GABAergic C_LIO_LITranscriptome analyses reveal the activation of neuronal genes after overexpression of neural transcription factors in glioblastoma cells C_LIO_LIInhibition of cell proliferation during glioblastoma cell conversion both in vitro and in vivo C_LI

neuroscience↗

bioRxiv2020

The Synthesis Success Calculator: Predicting the Rapid Synthesis of DNA Fragments with Machine Learning

The synthesis and assembly of long DNA fragments has greatly accelerated synthetic biology and biotechnology research. However, long turnaround times or synthesis failures create unpredictable bottlenecks in the design-build-test-learn cycle. We developed a machine learning model, called the Synthesis Success Calculator, to predict whether a long DNA fragment can be readily synthesized with a short turnaround time. The model also identifies the sequence determinants associated with the synthesis outcome. We trained a random forest classifier using biophysical features and a compiled dataset of 1076 DNA fragment sequences to achieve high predictive performance (F1 score of 0.928 on 251 unseen sequences). Feature importance analysis revealed that repetitive DNA sequences were the most important contributor to synthesis failures. We then applied the Synthesis Success Calculator across large sequence datasets and found that 84.9% of the Escherichia coli MG1655 genome, but only 34.4% of sampled plasmids in NCBI, could be readily synthesized. Overall, the Synthesis Success Calculator can be applied on its own to prevent synthesis failures or embedded within optimization algorithms to design large genetic systems that can be rapidly synthesized and assembled.Competing Interest StatementThe authors have declared no competing interest.View Full Text

synthetic biology↗

bioRxiv2020

Establishing Preclinical Withdrawal Syndrome Symptomatology Following Heroin Self-Administration in Male and Female Rats

Opioid use disorder (OUD) is a significant health problem, and understanding mechanisms of various aspects of OUD including drug use and withdrawal is important. Preclinical models provide an ideal opportunity to evaluate mechanisms underlying opioid withdrawal. Current models are limited by their reliance upon forced opioid administration, focus on the acute (and not protracted) syndrome, and exclusion of females. In this study, male and female rats self-administered heroin (maintenance dose of 12.5 g/kg/infusion) opioid withdrawal following abrupt discontinuation was measured. In Phase 1, acute withdrawal symptoms were rated in male and female rats at 0, 16, 48, and 72 hrs following the last self-administration session. Total somatic signs increased until 48 hrs (predominantly in females), and heroin intake positively correlated with total somatic signs at the 48 and 72 hr timepoints. Measures of hyperactivity and anxiety-like behavior increased by 16 and 48 hrs, respectively. In Phase 2, symptoms were assessed at baseline, acute, and protracted (168 and 312 hrs after self-administration) timepoints in a subset of male and female rats from Phase 1. The total number of somatic signs did not differ across timepoints, though females displayed significantly higher body temperature at all timepoints compared to males, indicating sex-specific protracted withdrawal symptomatology. These data provide a thorough characterization of rodent opioid withdrawal symptomatology following self-administration and abrupt discontinuation that serve as a foundation for future studies designed to mimic the human experience, and demonstrate the importance of characterizing acute and protracted withdrawal with sex-specificity in preclinical models of opioid self-administration.

animal behavior and cognition↗

bioRxiv2019

Road traffic delays and musculoskeletal health complaints among full-time bank employees: A cross-sectional study in Dhaka city

BackgroundThe factors of road traffic delays (RTDs) have significant consequences for both commuters health and the countrys economy as a whole. Addressing the musculoskeletal health complaints (MHCs) among full-time employees has not been fully explored. The current study investigates the association between RTDs-related factors and MHCs among bank employees.\n\nMethodsWe conducted a cross-sectional study among full-time employees from 32 banks in Dhaka city. Descriptive statistics summarized the gaps in the socio-demographic and RTDs-related factors on the one-month prevalence of MHCs. Random intercept logistic regression models were used to identify the associate factors of the MHCs.\n\nResultsOut of 628 full-time bank employees, the one-month prevalence of MHCs was 57.7%. The MHCs are more prevalent among adults of age group 40-60 years (68%) than the age group 20-40 years (54%). The one-month prevalence of lower back pain (LBP) was highest (36.6%), followed by neck pain (22.9%) and upper back pain (21.2%). Multilevel logistic regression analysis of employees showed that the odds of MHCs were lower among male employees (AOR=0.42, 95% CI= 0.27, 0.64), car commuters (AOR = 0.38, 95% CI=0.19-0.76, reference: bus commuters) and rickshaw commuters (AOR=. = 0.39, 95% CI=0.22-0.69, reference: bus commuters). The MHCs were significantly higher among employees with following factors: obesity (AOR= 1.50, 95% CI= 1.02-2.21), prolonged commute time to the office (AOR = 7.48, 95% CI =3.64-15.38) and working extended-time in a day (AOR= 1.50, 95% CI= 1.02-2.21).\n\nConclusionsThe study indicates a high burden of musculoskeletal health complaints among the employees in Dhaka city, and the most prevalent complaint was low back pain. Our study suggests that factors related to road traffic delays might act synergistically on developing musculoskeletal problems in full-time employees.

scientific communication and education↗