Biology subjects

Hossain, M. M.

Publications and source records attributed to Hossain, M. M..

18 recordsLinked to original sources

bioRxiv2026

VESTA: Machine Learning-Enabled Estimation of ViscoElastic Ratios from On-Axis Spatio-Temporal ARFI Features

Viscoelastic characterization of tissue has significant diagnostic value in oncology, as tumor progression alters both elasticity and viscosity in ways that neither property alone can fully capture. Existing acoustic radiation force (ARF)-based methods such as Viscoelastic Response (VisR) ultrasound estimate relative elasticity and viscosity through per-A-line nonlinear model fitting, which is computationally intensive and requires auxiliary simulations to correct elasticity-dependent bias. This work presents VESTA (Machine Learning-Enabled Estimation of ViscoElastic Ratios from On-Axis Spatio-Temporal ARFI Features), a two-stage data-driven pipeline that predicts elasticity ratio (ER) and viscosity ratio (VR) directly from seven normalized ARFI displacement features at the A-line level, without model fitting or compensation. Stage 1 is an MLP classifier that detects inclusion boundaries from normalized peak displacement and negative peak velocity ratios; Stage 2 is a dilated Conv1D regression model that estimates ER and VR along the full axial sequence using the predicted mask alongside displacement features. The pipeline was trained on 500 simulated inclusion scenarios spanning three geometries, five focal depths, two F-numbers, and a broad range of material contrasts. In silico, mean predicted ER and VR were within 12% of ground truth across all geometries, with performance best when ER and VR were moderate or decoupled. Experimental validation on a chicken breast phantom demonstrated plausible generalization to real tissue heterogeneity. Applied to an in vivo murine 4T1 breast cancer model, the pipeline tracked treatment-related attenuation of mechanical contrast in paclitaxel-treated tumors relative to controls over a 36-day imaging period, supporting its relevance for tumor monitoring.

bioengineering↗

bioRxiv2026

APRIL: Adaptive Regression-Based Two-Dimensional Quantitative Anisotropy Imaging Using Acoustic Radiation Force Impulse

ObjectiveThis study aims to develop and validate a quantitative, depth-resolved anisotropy imaging framework that extends ARFI-based focal degree-of-anisotropy (DoA) estimation into two-dimensional mapping by modeling the depth-dependent relationship between shear modulus ratio (SMR) and peak displacement ratio (PDR). MethodsWe propose APRIL (Adaptive Polynomial Regression for anisotropy Imaging via ARFI-induced DispLacements), a framework for quantitative, depth-resolved DoA imaging that adaptively selects polynomial regression or shape-preserving spline interpolation based on excitation PSF asymmetry. Training data were generated using an LS-DYNA3D + Field II simulation pipeline in homogeneous transversely isotropic media (SMR 0.9-4.9). Testing included shifted SMRs under varied acoustic conditions and three heterogeneous inclusion configurations (anisotropic inclusion in isotropic background and vice versa). Experimental validation was performed in an in-vivo murine tumor model over the time, ex-vivo chicken breast, and tissue-mimicking gelatin phantoms, using a Verasonics system with an L11-5v transducer. ResultsAPRIL achieved depth-resolved SMR prediction errors below 9% over 10-30 mm, with highest accuracy in the focal region (MAE 2.3%, RMSE < 0.1) and stable performance across PSF transition zones. In heterogeneous phantoms, it reconstructed anisotropy maps with SSIM up to 86% and MPE below 7%, accurately delineating inclusion boundaries. Under acoustic parameter variations, mean absolute errors remained below 10%, demonstrating robustness to system and tissue heterogeneity. ConclusionAPRIL enables robust, two-dimensional anisotropy imaging beyond focal estimates. SignificanceThe method provides a physically grounded and generalizable framework for clinically viable anisotropy biomarkers in muscle, tendon, kidney, tumor and breast tissues. HighlightsO_LINovelty: APRIL introduces LoA-conditioned adaptive polynomial-spline regression to extend ARFI-based anisotropy estimation from focal point estimates into full 2D depth-resolved SMR imaging. C_LIO_LIResults: APRIL achieved SMR prediction errors below 9% over 10-30 mm, SSIM up to 86% in heterogeneous phantoms, MAE below 10% under acoustic variations, tracked tumor anisotropy progression in vivo, and differentiated anisotropic inclusion versus isotropic background in tissue-mimicking gelatin phantom. C_LIO_LISignificance: APRIL enables clinically viable, spatially resolved anisotropy biomarker imaging in muscle, tendon, kidney, and tumor tissues without requiring heterogeneous training data. C_LI

bioengineering↗

bioRxiv2026

Comparative single-cell atlases reveal injury-driven tubal epithelial regeneration as a window for ovarian carcinoma initiation

High-grade serous carcinoma (HGSC), the most lethal form of ovarian cancer, preferentially originates in the tubal epithelium (TE) of the distal uterine tube (also known as Fallopian tube or oviduct). Mouse models are widely used to study how HGSC initiates in humans; however, the extent to which mouse and human uterine tubes are comparable remains unclear. Here, we conduct cross-species single-cell transcriptomic comparative analyses and organoid assay validations to reveal conserved differentiation trajectories from bipotent progenitors to secretory or ciliated cell fates. Regional analyses of both datasets reveal enriched injury repair features in the distal human TE, where mice lack such a trend. Experimentally inducing mechanical injury to the mouse TE yields significant expansion of pre-ciliated cells compared to uninjured counterparts. Furthermore, inactivation of Trp53 and Rb1, whose pathways are commonly altered in HGSC, in regenerating pre-ciliated cells leads to rapid neoplastic transformation, implicating post-traumatic repair as a permissive window for malignant transformation. Together, our findings establish a comparative atlas of cell states between mice and humans, show that injury-associated regeneration may contribute to the known vulnerability of the fimbrial region, and raise potential concerns regarding procedures or conditions that mechanically perturb the tubal epithelium.

cancer biology↗

bioRxiv2026

Integrated physiological performance and Nax1-mediated sodium exclusion reveal mechanisms of salinity tolerance in spring wheat (Triticum aestivum L.)

Soil salinity is a rapidly intensifying abiotic stress that significantly limits wheat productivity, particularly in coastal and irrigated agroecosystems. Although sodium (Na+) ion exclusion has been recognized as a key tolerance mechanism, the integration of physiological performance with Nax1-mediated molecular regulation among regionally adapted wheat genotypes remains insufficiently characterized. The present study aimed to dissect salinity tolerance by combining hydroponic phenotyping, multivariate trait analysis, molecular marker profiling, and quantitative expression analysis of the Na+ ion transporter gene Nax1. Seventeen spring wheat genotypes were evaluated under four salinity levels (0.0, 10, 12, and 14 dS m-{superscript 1}). Germination and survival rate, shoot and root growth, and biomass accumulation were measured. Principal component analysis (PCA) and hierarchical clustering were performed to classify genotypes, while SSR (simple sequence repeat) and Nax-linked markers assessed genetic diversity. Relative Nax1 expression was quantified using qRT-PCR (quantitative real-time polymerase chain reaction). Salinity significantly reduced germination, survival, elongation, and biomass, with strong genotype-dependent variation. Multivariate analyses clearly separated tolerant and sensitive genotypes, with biomass retention and survival contributing most to total variation. Marker analysis revealed moderate genetic polymorphism. Notably, tolerant genotypes exhibited 3-6-fold induction of Nax1 under severe salinity, positively correlating with biomass maintenance. These findings demonstrate that salinity tolerance in wheat is associated with coordinated physiological resilience and enhanced Nax1-mediated Na ion exclusion, thereby advancing mechanistic understanding and supporting molecular-assisted breeding for salt-affected environments.

plant biology↗

bioRxiv2025

TurboID-based proximity labeling enables in vivo mapping of Plasmodiophora brassicae secretome in Arabidopsis

O_LIPlasmodiophora brassicae, the causal agent of clubroot disease, is an obligate biotrophic protist belonging to the poorly characterized Rhizaria. Its intracellular lifestyle and resistance to genetic manipulation have hindered functional analysis of its effector repertoire, leaving mechanisms underlying disease development unresolved. Here, we sought to experimentally define the P. brassicae secretome within infected plant cells and identify effectors targeted to specific host subcellular compartments. C_LIO_LIA proximity labeling approach based on the TurboID biotin ligase was used to capture pathogen-derived proteins within the nucleus, cytosol, endoplasmic reticulum, and plasma membrane of infected Arabidopsis roots during primary and secondary stages of clubroot disease. C_LIO_LIThis strategy yielded the first in planta experimental view of the P. brassicae secretome, identifying both established and previously uncharacterized effectors. The resulting dataset provides a valuable resource and methodological framework for dissecting effector function in this and other intracellular plant pathogens. C_LIO_LIThis study expands our understanding of Rhizarian pathogenicity and provides a methodological template for identifying the secretomes of other obligatory intracellular plant pathogens. C_LI

plant biology↗

bioRxiv2025

Functional and genomic insights into landfill-isolated Brucella intermedia strains capable of degrading Linear Low-Density Polyethylene (LLDPE)

The global accumulation of linear low-density polyethylene (LLDPE) waste has created an urgent need for sustainable biodegradation strategies. Here, we report the identification and characterization of two landfill-derived Brucella intermedia isolates associated with LLDPE biodegradation. Soil samples collected from the Matuail landfill in Dhaka, Bangladesh, were screened on minimal salt medium supplemented with LLDPE. Both isolates demonstrated sustained growth under carbon-limited conditions in which LLDPE was the principal carbon source. LLDPE recovered from bacterial cultures showed chemical and surface morphological changes, as supported by Fourier-transform infrared (FTIR) spectroscopy, droplet-spreading analysis, and scanning electron microscopy (SEM). FTIR analysis revealed additional carbonyl, hydroxyl, and C-O bands consistent with oxidative modification of the polymer surface, while SEM showed roughening, fissures, and fragmentation-like surface features. Whole-genome sequencing identified both isolates as closely related but distinct strains of Brucella intermedia and revealed enrichment of candidate functions associated with oxidative activation, depolymerization, and downstream assimilation. Transcriptomic analysis under LLDPE growth further showed expression of multiple candidate plastic degradation- and biofilm-associated genes. Resistome, virulome, and phenotypic antimicrobial susceptibility analyses indicated that both isolates are environmentally resilient, low-pathogenic variants with a limited intrinsic resistome. Both strains also exhibited biofilm-associated growth under hydrocarbon-substituted and plastic-associated conditions. Collectively, these findings identify environmental B. intermedia as an unexpected plastic-associated lineage and expand current understanding of the ecological and genomic diversity of bacteria linked to LLDPE biodegradation. Environmental ImplicationThis study identifies landfill-derived Brucella intermedia strains that can support biodegradation of linear low-density polyethylene (LLDPE), a major persistent plastic pollutant in landfill environments. Functional, genomic, and transcriptomic evidence indicate that these isolates use coordinated oxidative, depolymerization, and biofilm-associated responses during growth under plastic-associated, carbon-limited conditions. Their low-pathogenic environmental profiles and limited intrinsic resistomes further support their relevance as candidates for future biodegradation-focused biotechnological research. Overall, these findings expand the known diversity of plastic-associated bacteria and highlight naturally adapted landfill microorganisms as promising resources for sustainable strategies to mitigate plastic accumulation in terrestrial ecosystems. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/687417v2_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@5f84f2org.highwire.dtl.DTLVardef@111626dorg.highwire.dtl.DTLVardef@54f51eorg.highwire.dtl.DTLVardef@1a8910c_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Exploring brain lobe-specific insights in an explainable framework for EEG-based schizophrenia detection

Schizophrenia (ScZ) is a growing global health concern that affects millions of people and puts severe pressure on healthcare systems. Early detection and accurate diagnosis are crucial for adequate management. Electroencephalography (EEG) has evolved into a promising non-invasive tool for detecting ScZ in contemporary research. However, specific biomarkers, especially those related to brain lobes, cannot often be identified by current EEG-based diagnostic methods. Different brain lobes are associated with distinct cognitive functions and patterns of diseases. Also, there is a gap in the incorporation of the XAI technique, as medical diagnosis needs trustworthiness and explainability. This study strives to address these gaps by developing a framework using mel-spectrogram images with Convolutional Neural Networks (CNNs). EEG signals are converted into mel-spectrogram images using Short-Time Fourier Transform (STFT). After that, these images are analyzed using a CNN model to perform classification between ScZ and healthy control (HC). To identify the most critical brain regions, the full brain regions are divided into five different regions, and the same classification process is performed. The performance of the proposed framework is evaluated using two publicly available EEG datasets: repOD and the kaggle basic sensory task dataset, which provides a remarkable accuracy of 99.82% and 98.31% respectively. Among regions, the frontal lobe has the most significant performance with an accuracy of 97.02% and 88.03%, respectively, in these datasets, followed by the temporal lobe. Conversely, the occipital lobe shows the lowest accuracy among lobes, with only 79.30 % and 68.33% accuracy on both occasions, showing its lower significance in the diagnosis. To bring result explainability, LIME, SHAP, and the Grad-CAM methods are applied, providing valuable insights for clinicians and researchers. These findings emphasize the potential of EEG-based brain lobe analysis in enhancing ScZ detection, diagnostic accuracy, explainability, and clinical guidance.

bioinformatics↗

bioRxiv2025

Perinatal Asphyxia Alters Physiological Responses and Ex Vivo Cardiovascular Function of Preterm Growth-Restricted Lambs

IntroductionFetal growth restriction (FGR) arises from chronic hypoxia and increases the risk of cardiovascular dysfunction following perinatal asphyxia, although the underlying mechanisms are unknown. We investigated whether FGR lambs have altered cardiovascular responses to perinatal asphyxia compared to control lambs, and whether impairments in 1 and {beta}1 adrenergic receptor function underlie these responses. MethodsSingle or twin-bearing ewes underwent sterile fetal surgery at 89 days gestation (dGA; term=148d) to induce FGR (single umbilical artery ligation) or sham surgery (Control). At 126dGA, lambs were delivered via caesarean section, instrumented and randomised to immediate ventilation (ControlVENT n=6; FGRVENT n=6), or asphyxia (ControlASPHYXIA n=12; FGRASPHYXIA n=11) induced by umbilical cord occlusion while withholding resuscitation until diastolic blood pressure (BP) decreased to 10mmHg. Lambs were ventilated for 8 hours before baseline ex vivo cardiac function was assessed via Langendorff perfusion to measure left ventricular developed pressure (LVDP), heart rate (HR) and coronary perfusion pressure (CPP). Ex vivo 1 and {beta}1 adrenergic responses were assessed via phenylephrine (10-5 to 10-2 mmol/L) and dobutamine (10-7 to 10-4) administration, respectively. ResultsFGRASPHYXIA lambs had lower BP during asphyxia (p<0.05 vs ControlASPHYXIA) and took longer to reach a diastolic BP of 10mmHg (14.5 {+/-} 0.8 min vs. 19.2 {+/-} 1.3 min; p=0.005). FGRASPHYXIA lambs had lower BP in the first 5 minutes after return of spontaneous circulation (p<0.05) due to impaired vascular contractility, with reduced Tau, dP/dtmax and dP/dtmin (p<0.03 vs ControlASPHYXIA). Baseline LVDP, HR and CPP were similar between groups, however FGRASPHYXIA lambs had increased LVDP responses to phenylephrine and dobutamine (p<0.05 vs ControlASPHYXIA), without significant changes to HR or CPP. ConclusionFGR lambs have altered physiological responses to perinatal asphyxia due to impaired vascular contractility and dysregulated cardiac 1 and {beta}1 adrenergic receptor function, which may increase susceptibility to cardiovascular dysfunction in the neonatal period.

physiology↗

bioRxiv2024

Functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS and fUS revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We saw a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with the brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV response with peak CBV, activated area, and correlation coefficient increasing with ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalizes and linearly correlates with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths and the evoked hemodynamic responses colocalized and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as an understanding of how FUS displaces brain tissue and affects cerebral hemodynamics.

bioengineering↗

bioRxiv2024

Development of non-sedating antischistosomal benzodiazepines

The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970s. Meclonazepam was not brought to market because of dose-limiting sedative side effects. However, the human target of meclonazepam that causes sedation (GABAARs) are not orthologous to the parasite targets that cause worm death. Therefore, we were interested in whether the structure of meclonazepam could be modified to produce antiparasitic benzodiazepines that do not cause host sedation. We synthesized 18 meclonazepam derivatives with modifications at different positions on the benzodiazepine ring system and tested them for in vitro antiparasitic activity. This identified five compounds that progressed to in vivo screening in a murine model, two of which cured parasite infections with comparable potency to meclonazepam. When these two compounds were administered to mice that were run on the rotarod test, both were less sedating than meclonazepam. These findings demonstrate the proof of concept that meclonazepam analogs can be designed with an improved therapeutic index, and point to the C3 position of the benzodiazepine ring system as a logical site for further structure-activity exploration to further optimize this chemical series.

pharmacology and toxicology↗

bioRxiv2023

Unveiling multi-drug resistant (MDR) gram negative pathogenic bacteria from poultry chickens in the Noakhali region of Bangladesh

Rapidly increasing antibiotic-resistant bacterial strains in Bangladeshs food and farm animals stem from the excessive and inappropriate use of antibiotics. To assess the prevalence of multi drug resistant (MDR) gram-negative bacteria in poultry chicks, we sought to isolate and identify strains carrying antimicrobial resistance genes. Isolation and identification involved biochemical tests, 16S rRNA sequencing, and PCR screening of species-specific genes. MDR patterns were evaluated using CLSI guidelines with seventeen antibiotics across twelve classes. Targeted gene sequences were amplified for detection of ESBL, carbapenem, tetracycline, sulfonamide, and colistin resistance genes. Common isolates, such as Escherichia coli, Klebsiella pneumoniae, Proteus penneri, and Enterobacter hormaechei, exhibited average Multiple Antimicrobial Resistance (MAR) indices of 0.66, 0.76, 0.8, 0.84, and 0.81, 0.76, 0.84, 0.41 for broiler and layer chicken, respectively. Providencia stuartii and Salmonella enterica, exclusive to broiler samples, had MAR indices of 0.82 and 0.84, respectively. Additional isolates Morganella morganii, Aeromonas spp., and Wohlfahrtiimonas chitiniclastica were found in layers (Average MAR indices: 0.73, 0.71, and 0.91). Notably, M. morganii, E. hormaechei and W. chitiniclastica were identified for the first time in Bangladeshi poultry chicken, although their evolution is yet to understand. In this study, Pan-drug resistance was observed in one P. stuartii (broiler) and one Aeromonas spp. (layer) with a MAR index 1, while all isolates exhibited MAR indices >0.2, indicating MDR. Antimicrobial resistance (AMR) gene screening identified blaTEM, blaSHV, tetA, and sul1 in a majority of the MDR strains. Interestingly, E. coli (lactose positive and negative) and E. hormaechei were exclusively found to possess the tetB gene. In addition, E. coli (lactose negative), Klebsiella pneumoniae, Enterobacter hormaechei, M. morganii, and P. stuartii were observed to carry the colistin-resistant mcr1 gene, whereas sul2 was detected in E. coli (lactose positive and negative), E. hormaechei, P. stuartii, and P. penneri. These findings emphasize the health risk of our consumers of both broiler and layer chickens as they have turned to a potent reservoir of various AMR gene carrying MDR and Pan-drug resistant bacteria.

microbiology↗

bioRxiv2020

BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response

Effective vaccine against SARS-CoV-2 is the utmost importance in the current world. More than 1 million deaths are accounted for relevant pandemic disease COVID-19. Recent data showed that D614G genotype of the virus is highly infectious and responsible for almost all infection for 2nd wave. Despite of multiple vaccine development initiatives, there are currently no report that has addressed this critical variant D614G as vaccine candidate. Here we report the development of an mRNA-LNP vaccine considering the D614G variant and characterization of the vaccine in preclinical trial. The surface plasmon resonance (SPR) data with spike protein as probe and competitive neutralization with RBD and S2 domain revealed that immunization generated specific antibody pools against the whole extracellular domain (RBD and S2) of the spike protein. The anti-sera and purified IgGs from immunized mice on day 7 and 14 neutralized SARS-CoV-2 pseudovirus in ACE2-expressing HEK293 cells in a dose dependent manner. Importantly, immunization protected mice lungs from pseudovirus entry and cytopathy. The immunologic responses have been implicated by a balanced and stable population of CD4+ cells with a Th1 bias. The IgG2a to IgG1 and (IgG2a+IgG2b) to (IgG1+IgG3) ratios were found 1{+/-}0.2 and 1.24{+/-}0.1, respectively. These values are comparatively higher than relevant values for other published SARS-CoV-2 vaccine in development,1, 2 and suggesting higher viral clearance capacity for our vaccine. The data suggested great promise for immediate translation of the technology to the clinic.

immunology↗

bioRxiv2020

Whole genome analysis of four Bangladeshi individuals

Whole-genome sequencing (WGS) is a comprehensive method for analysing entire genomes and this has been instrumental in characterizing the single nucleotide polymorphisms associated with different diseases including cancer, diabetes, cardiovascular diseases and many others. In this paper we undertake a pilot study for sequencing four Bangladeshi individuals and profiling their single nucleotide variants. Our findings shed possible light on specific biological pathways effected by such variants in this population.

genomics↗

bioRxiv2020

Genome Analysis of SARS-CoV-2 Isolate from Bangladesh

Recently the first genome sequence for a Severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 isolate from Bangladesh became available. The sequencing was carried out by the Child Health Research Foundation and provided the first insight into the genetic details of the viral strain responsible for the SARS-CoV-2 infections in Bangladesh. Here we carried out a comparative study were we explored the phylogenetic relationship between the Bangladeshi isolate with other isolates from different parts of the world. Afterwards we identified single nucleotide variants in the Bangladeshi isolate, using the Wuhan virus reference sequence. We found a total of 9 variants in the Bangladeshi isolate using 2 separate tools. Barring 2, the rest of these variants were also observed in other isolates from different countries. Most of the variants occurred in the ORF1ab gen. Another noteworthy finding was a sequence of three consecutive variants in the N protein gene that were observed in other isolates as well. Lastly the phylogenetic analysis revealed a close relationship between the Bangladeshi isolate and those from Taiwan, Kazakhstan, Greece, California, Spain, Israel, and Sri Lanka.

genomics↗

bioRxiv2020

Antimicrobial Resistance Profile and mcr-1 gene Detection in Salmonella Isolates from Poultry in Bangladesh: Molecular and Bioinformatics Characterization

Antimicrobial resistance gene mcr-1 has been disseminated globally since its first discovery in Southern China in late 2015. However, the mcr-1 gene had not been identified previously in Salmonella isolates from poultry in Bangladesh. Here, we aimed to explore antimicrobial resistance gene mcr-1 in Salmonella isolates. Eighty two Salmonella isolates were isolated and characterized from suspected poultry specimens received from different zones of the country. A phenotypic disc diffusion assay with 15 antimicrobial agents was performed following CLSI standard. The disk diffusion assay showed that, all of the isolates presented high resistance to colistin (92.68%), oxytetracycline (86.59%), co-trimoxazole (76.83%), ciprofloxacin (73.17%) and enrofloxacin (65.85%). Further, randomly selected 10 Salmonella isolates were analyzed by polymerase chain reaction (PCR) targeting genus-specific invA and antimicrobial (colistin) resistance mcr-1 genes. Five were confirmed for the presence of the mcr-1 gene belonging to Salmonella spp. Further, sequencing followed by phylogenetic analysis revealed divergent evolutionary relation between the LptA and MCR proteins rendering them resistant to colistin. Three-dimensional homology structures of MCR-1 proteins were constructed and verified using different bioinformatics tools. Moreover, molecular docking interactions suggested that, MCR-1 and LptA share a similar substrate binding cavity which could be validated for the functional analysis. The results represent here is the first molecular and in silico analysis of colistin resistance mcr-1 gene of Salmonella in poultry in Bangladesh, which may emphasize the importance of the study on antibiotic resistance genes requiring for national monitoring and strategic surveillance in the country.

microbiology↗

bioRxiv2019

Computational Approach for Screening the Whole Proteome of Hantavirus and Designing a Multi-Epitope Subunit Vaccine

Hantaviruses are a newly zoonotic emerging group of rodent-borne viruses that have a significant impact on global public health by increasing amplitude and magnitude of outbreaks. As no permanent cure yet, it is now growing and challenging interest to develop a vaccine against Hantavirus. This study endeavored to design a robust subunit vaccine using a novel immunoinformatics approach. After meticulous evaluation, top ones from predicted CTL, HTL, and B-cell epitopes were considered as potential vaccine candidates. Among generated four vaccine models with different adjuvant, the model with TLR-4 agonist adjuvant was selected for its high antigenicity, non-allergenicity, and structural quality. The conformational B-cell epitope prediction assured its humoral response inducing ability. Thereafter, the molecular docking and dynamics simulation confirmed a good binding affinity with immune receptor TLR-4 and stability of the vaccine-receptor complex. In immune simulation, significantly high levels of IgM and IgG1 immunoglobulins, TC and TH-cell populations, and various cytokines (i.e. IFN-{gamma}, IL-2 etc.) are coherence with actual immune response and also showed faster antigen clearance for repeated exposures. Finally, disulfide engineering enhanced vaccine stability and in silico cloning confirmed the better expression in E. coli K12. Nonetheless, experimental validation can proof the proposed vaccines safety and ability to control Hantavirus infection.

bioinformatics↗

bioRxiv2019

Profiling Gene Specific Changes to RNA Editome in Preeclampsia

RNA editing is a form of post-transcriptional modification that results in changes to the messenger RNA sequence. At the onset of the study we focused on detecting the changes in RNA editing patterns in cell lines exposed to hypoxic conditions followed by the detection of changes in RNA editing patterns in the fetuses of preeclamptic mothers using publicly available RNA sequence data from the NCBI SRA database. The results showed an increase in RNA editing activity in hypoxic cell lines and a decrease in RNA editing activity in the fetuses with preeclamptic mothers. A total of 85 genes common in the cell lines and 33 in the fetus disease models and not present in controls were identified as harboring editing sites in exonic, downstream, upstream or splicing regions. Subsequently we focused on unique editing sites in genes and categorized in order of relevance to Preeclampsia as A, B and C (A being most closely related to the disease and C the least). The genes implicated ones involved in respiration chains, blood cell growth, cytokine and complement activation. Among the most significant of the genes were CTSB, GSR, CASP10, and MAPK13. Total number of common editing sites were found in different conditions and these were 667 for cell lines and 23 for fetuses. Validation of these variations in a larger samples size determines refined editing sites which could be used as potential diagnostic markers for intervention.

genomics↗

bioRxiv2018

Identifying Changes in RNA Editome Unique to Major Depressive Disorder

Major Depressive Disorder (MDD) is one of the most significant psychiatric disorders in the world today. Its incidence is widespread in society and its heavy adverse impact on the quality of life is well documented. Previously genetic studies on MDD had identified a hereditary component of the disease as well as crediting RNA editing with a role in its development. The later due to an overexpression of a heavily edited isoform of the Serotonin 2c receptor. Here we used publicly available RNA sequence data from suicide patients diagnosed with MDD as well as controls for identifying RNA editing sites unique to MDD. After variant calling and several steps of filtering, we identified 142 unique RNA editing sites in the MDD patients. These included intronic, downstream, UTR3 and exonic edits. The latter comprising several amino acid changes in the encoded protein. The genes implicated to be uniquely edited in MDD included the aforementioned and previously implicated Serotonin 2c receptor, others involved in functions that play roles in depression and suicide such as Cannabinoid Receptor 1, Frizzled Class 3 Receptor, Neuroligin 3 and others.

genomics↗