Biology subjects

Chowdhury, M.

Publications and source records attributed to Chowdhury, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Differences between males and females in psychostimulant/sucrose self-administration (when observed) may not necessarily be driven by biological sex.

BackgroundSex differences in psychostimulant-related behaviors are often attributed to biological sex; however, individual variability may also strongly influence behavioral outcomes. The new MISSING (Mapping Intrinsic Sex Similarities as an Integral quality of Normalized Groups) model identifies mixed-sex behavioral groups in which differences are driven primarily by individual variability rather than sex. The goal of this study was to validate the MISSING model for psychostimulant/sucrose self-administration. MethodsLong Evans rats self-administered methamphetamine (METH, male n = 25, female n = 32, 0.1 mg/kg/infusion, FR1, 6h per day for 20 days), sucrose (male n = 20, female n = 22, one-20 mg pellet/delivery, all other conditions being equal) and saline (male n = 3, female n = 10, other things being equal). We developed a new Quantitative Structure of Curve Analytical (QSCAn) model (using exponential-plateau and linear fit) for the assessment of individual drug self-administration time curve profiles irrespective of biological sex. We analyzed our data using regression analysis and ANOVA. ResultsQSCAn identified three distinct self-administration profiles (consisting of both sexes), which we named exponential-plateau negative (EP-), exponential-plateau positive (EP+), and undefined (EP0). There were no differences in self-administration profiles when we compared males and females within the same group. Differences between sexes (when observed) were due to mismatched comparisons (males from one group versus females from a different group). ConclusionsOur study reinforces the MISSING model for psychostimulant and sucrose self-administration by indicating that differences between males and females (when observed) may not necessarily be driven by biological sex. Significance StatementCurrent approaches often interpret variability in psychostimulant self-administration between males and females primarily through the lens of biological sex. However, this framework may overlook meaningful behavioral phenotypes shared across sexes. The present quantitative model suggests that individual patterns of behavior may better account for variability than sex alone, particularly in behaviors not strongly driven by sex-hormone-dependent mechanisms such as drug self-administration. By classifying animals according to behavioral profiles rather than biological sex, this approach may foster the identification of clinically and biologically relevant phenotypes underlying psychostimulant reinforcement.

neuroscience↗

bioRxiv2026

The recreational-to-habitual shift in psychostimulant use is an economic demand parameter that is unrelated to drug consumption levels (under normal and punishment conditions).

RationaleThe progression of psychostimulant abuse is associated with a shift from recreational to habitual use (R2H-shift). Because this R2H-shift can be modeled using behavioral economics, we developed a novel Behavioral Economic model for the Analysis of Self-administration Time-curve (BEAST) to obtain R2H-shift variable(s). The relationship(s) between R2H-shift variables and drug intake (under normal and/or punishment conditions) is/are unknown. Our goal was to determine if the R2H-shift variable and intake variables obtained during the initial self-administration training phase were related to 1) drug intake at that time, and subsequent drug intake under 2) normal, 3) punishment, 4) post-punishment, and 5) price-constrained conditions. MethodLong Evans rats self-administered methamphetamine (METH, males n = 16, females n = 14), sucrose (males n = 22, females n = 22) and/or saline (males n = 3, females n = 10) under FR1 for 6 h per day for 20 days to obtain 1) followed by the assessment of subsequent drug intake under different conditions (2-5 above). We obtained all variables referenced above. We determined the relationships between all variables (multivariate analysis). ResultsThere were no sex differences detected in the METH and sucrose studies. For METH and sucrose, prior drug intake levels could predict drug intake under normal/punishment but not under price-constrained conditions. The R2H-shift variable could predict drug intake under a consumption-price curve but could not predict intake under normal/punishment conditions. ConclusionsWhile related to economic demand, the recreational-to-habitual shift rate was unrelated to drug intake levels (under normal and punishment conditions).

neuroscience↗

bioRxiv2024

GenoSiS: A Biobank-Scale Genotype Similarity Search Architecture for Creating Dynamic Patient-Match Cohorts

Many patients do not experience optimal benefits from medical advances because clinical research does not adequately represent them. While the diversity of biomedical research cohorts is improving, ensuring that individual patients are adequately represented remains challenging. We propose a new approach, GenoSiS, which leverages machine learning-based similarity search to dynamically find patient-matched cohorts across different populations quickly. These cohorts could serve as reference cohorts to improve a range of clinical analyses, including disease risk score calculations and dosage decisions. While GenoSiS focuses on finding genetic similarity within a biobank, our similarity search architecture can be extended to represent other medically relevant patient characteristics and search other biobanks.

bioinformatics↗

bioRxiv2024

STIX: Long-reads based Accurate Structural Variation Annotation at Population Scale

The prioritization of Structural Variants (SV), which is needed to rank and identify potential pathogenic alleles, is still in its infancy. This is exemplified over gnomAD only being able to annotate 33.5% of GIAB SVs. To overcome this, we present the first long-read based annotation resource for both GRCh38 and CHM13-T2T reference using STIX. In contrast to previous methods, STIX indexes SV-informative long-reads themselves, can thus be easily extended and accurately annotate all SV types including insertions. STIX successfully annotated 95.9% of GIAB Tier1 SVs. STIX further improved cancer based SV prioritization by highlighting 3,563 SV from COSMIC being common in the population. We further showcase that mosaic SV can be independently gained and may be widely spread throughout the population. This highlights the need for accurate SV population frequency annotation to further facilitate the adoption of SV via long-read sequencing in medical research and clinical applications.

bioinformatics↗

bioRxiv2024

Touch inhibits cold: non-contact cooling reveals a novel thermotactile gating mechanism

Skin stimuli reach the brain via multiple neural channels specific for different stimulus types. These channels interact in the spinal cord, typically through inhibition. Interchannel interactions can be investigated by selectively stimulating one channel and comparing the sensations that result when another sensory channel is or is not concurrently stimulated. Applying this logic to thermal-mechanical interactions proves difficult, because most existing thermal stimulators involve skin contact. We used a novel non-tactile stimulator for focal cooling (9mm2) by using thermal imaging of skin temperature as a feedback signal to regulate exposure to a dry ice source. We could then investigate how touch modulates cold sensation by delivering cooling to the human hand dorsum in either the presence or absence of light touch. Across three signal detection experiments, we found that sensitivity to cooling was significantly reduced by touch. This reduction was specific to touch, since it did not occur when presenting auditory signals instead of the tactile input, making explanations based on distraction or attention unlikely. Our findings suggest that touch inhibits cold perception, recalling interactions of touch and pain previously described by Pain Gate Theory. We show, for the first time, a thermotactile gating mechanism between mechanical and cooling signals.

neuroscience↗

bioRxiv2024

Genomic Epidemiology of Monkeypox Virus During the 2022 Outbreak in New York City

New York City (NYC) was one of the hotspots of monkeypox virus (MPXV) infections in the United States during the multi-country mpox outbreak in 2022. This study used the most comprehensive dataset to date to investigate the genomic characteristics of MPXV in NYC. We performed Nextclade lineage assignment, phylogenetic and mutational analyses on 1,138 specimens from 748 individuals at the NYC Public Health Lab in the context of 2,968 MPXV sequences sampled globally. Nextclade lineage assignment showed B.1.12 as a NYC specific lineage and phylogenetic analysis showed NYC and North America specific clades. The majority of mutations showed signatures of APOBEC3 activity. When looking at the intra-host genomic diversity for MPXV, distinct MPXV genomic profiles were observed in 6.4% of individuals with multiple sampled specimens, with at least 4.2% of NYC cases due to multiple MPXV infections from distinct viral strains. Further, 13% of the sequences in infected patients had a lack of concordance between epidemiologic and genetic linkages. This study identified NYC-specific MPXV genomic profiles and provided a conservative estimate of simultaneous infections with multiple MPXV variants, likely due to behavioral risk factors during the peak of the outbreak in July 2022. Improving concordance between genomic and epidemiological clusters for mpox investigations may require expanding partnerships with testing labs, clinics, and community groups to enhance the representativeness of MPXV samples that are available for sequencing.

genomics↗

bioRxiv2024

Implications of noncoding regulatory functions in the development of insulinomas

Insulinomas are rare neuroendocrine tumours arising from the pancreatic {beta}-cells. While retaining the ability to produce insulin, insulinomas feature aberrant proliferation and altered hormone secretion resulting in failure to maintain glucose homeostasis. With the aim of uncovering the role of noncoding regulatory regions and their aberrations to the development of these tumors, we coupled epigenetic and gene expression profiling with whole-genome sequencing. As a result, we mapped H3K27ac sites in the tumoral tissue and unraveled overlapping somatic mutations associated with changes in regulatory functions. Critically, these regions impact insulin secretion, tumor development and epigenetic modifying genes, including key components of the polycomb complex. Chromatin remodeling is apparent as insulinoma-selective regions are mostly clustered in regulatory domains, shared across patients and containing a specific set of regulatory sequences dominated by the binding motif of the transcription factor SOX17. Moreover, a large fraction of these regions are H3K27me3-repressed in unaffected {beta}-cells, suggesting that tumoral transition is coupled with derepression of {beta}-cell polycomb-targeted domains. Our work provides a compendium of aberrant cis-regulatory elements and transcription factors that alter {beta}-cell function and fate in their progression to pancreatic neuroendocrine tumors and a framework to identify coding and noncoding driver mutations.

genomics↗

bioRxiv2023

Pax Protein Depletion in Proximal Tubules Triggers Conserved Mechanisms of Resistance to Acute Ischemic Kidney Injury and Prevents Transition to Chronic Kidney Disease

Acute kidney injury (AKI) is a common condition that lacks effective treatments. In part this shortcoming is due to an incomplete understanding of the genetic mechanisms that control pathogenesis and recovery. Pax2 and Pax8 are homologous transcription factors with overlapping functions that are critical for kidney development and are re-activated in AKI. In this report, we examined the role of Pax2 and Pax8 in recovery from ischemic AKI. We found that Pax2 and Pax8 are upregulated after severe AKI and correlate with chronic injury. Surprisingly, we then discovered that proximal-tubule-selective deletion of Pax2 and Pax8 resulted in a less severe chronic injury phenotype. This effect was mediated by protection against the acute insult, similar to preconditioning. Prior to injury, Pax2 and Pax8 mutant mice develop a unique subpopulation of S3 proximal tubule cells that display features usually seen only in acute or chronic injury. The expression signature of these cells was strongly enriched with genes associated with other mechanisms of protection against ischemic AKI including caloric restriction, hypoxic preconditioning, and female sex. Taken together, our results identify a novel role for Pax2 and Pax8 in mature proximal tubules that regulates critical genes and pathways involved in both injury response and protection from ischemic AKI. TRANSLATIONAL STATEMENTIdentifying the molecular and genetic regulators unique to the nephron that dictate vulnerability to injury and regenerative potential could lead to new therapeutic targets to treat ischemic kidney injury. Pax2 and Pax8 are two homologous nephron-specific transcription factors that are critical for kidney development and physiology. Here we report that proximal-tubule-selective depletion of Pax2 and Pax8 protects against both acute and chronic injury and induces an expression profile in the S3 proximal tubule with common features shared among diverse conditions that protect against ischemia. These findings highlight a new role for Pax proteins as potential therapeutic targets to treat AKI.

pathology↗

bioRxiv2023

On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity.

To combat the global burden of malaria, development of new drugs to replace or complement current therapies are urgently required. As drug resistance to existing treatments and clinical failures continue to rise, compounds targeting multiple life cycle stages and species need to be developed as a high priority. Here we show that the compound MMV1557817 is a nanomolar inhibitor of both Plasmodium falciparum and Plasmodium vivax aminopeptidases M1 and M17, leading to inhibition of end stage haemoglobin digestion in asexual parasites. Multi-stage analysis confirmed that MMV1557817 can also kill sexual stage P. falciparum, while cross-resistance studies confirmed the compound targets a mechanism of action distinct to current drug resistance mechanisms. Analysis of cross reactivity to homologous human enzymes shows the compound exhibits a high level of selectivity, whilst safety as well as druggability was confirmed in the murine model P. berghei. MMV1557817-resistant P. falciparum parasites displayed only low-level resistance (<3-fold) and exhibited a slow growth rate that was quickly outcompeted by wild type parasites. MMV1557817-resistant parasites digest significantly more haemoglobin and possess a mutation in PfA-M17 that induces partial destabilisation of the PfA-M17 homohexamer, resulting in high-level resistance to specific PfA-M17 inhibition, but enhanced sensitivity to specific PfA-M1 inhibition, and importantly, these parasites were highly sensitive to artemisinin. Overall, these results confirm MMV1557817 as a potential lead compound for further drug development and highlight the potential of dual inhibition of M1 and M17 as an effective multi-species drug targeting strategy.

microbiology↗

bioRxiv2023

An intrinsically Disordered RNA Binding Protein Modulates mRNA Translation and Storage

Many proteins with intrinsically disordered regions interact with cytoplasmic ribosomes. However, many of the molecular functions related to these interactions are unclear. In this study, using an abundant RNA-binding protein with a structurally well-defined RNA recognition motif and an intrinsically disordered RGG domain as a model system, we investigated how this protein modulates mRNA storage and translation. Using genomic and molecular approaches, we show that the presence of Sbp1 slows ribosome movement on cellular mRNAs and promotes polysome stalling. Sbp1-associated polysomes display a ring-shaped structure in addition to a beads-on-string morphology visualized under electron microscope. Moreover, post-translational modifications at the RGG motif play important roles in directing cellular mRNAs to either translation or storage. Finally, binding of Sbp1 to the 5UTRs of mRNAs represses both cap-dependent and cap-independent translation initiation of proteins functionally important for general protein synthesis in the cell. Taken together, our study demonstrates an intrinsically disordered RNA binding protein regulates mRNA translation and storage via distinctive mechanisms under physiological conditions and establishes a framework with which functions of important RGG-proteins can be investigated and defined.

biochemistry↗

bioRxiv2023

Embracing firefly flash pattern variability with data-driven species classification

Many nocturnally active fireflies use precisely timed bioluminescent patterns to identify mates, making them especially vulnerable to light pollution. As urbanization continues to brighten the night sky, firefly populations are under constant stress, and close to half of the species are now threatened. Ensuring the survival of firefly biodiversity depends on a large-scale conservation effort to monitor and protect thousands of populations. While species can be identified by their flash patterns, current methods require expert measurement and manual classification and are infeasible given the number and geographic distribution of fireflies. Here we present the application of a recurrent neural network (RNN) for accurate automated firefly flash pattern classification. Using recordings from commodity cameras, we can extract flash trajectories of individuals within a swarm and classify their species with a precision and recall of approximately seventy percent. In addition to scaling population monitoring, automated classification provides the means to study firefly behavior at the population level. We employ the classifier to measure and characterize the variability within and between swarms, unlocking a new dimension of their behavior. Our method is open source, and deployment in community science applications could revolutionize our ability to monitor and understand firefly populations.

ecology↗

bioRxiv2022

Bacterial communities associated with the surfaces of the fresh fruits sold around Dhaka Medical College and Hospital and their anti-microbial profiles

BackgroundNow-a-days, fresh fruits are popular sources of healthy diets with low energy density. Since they are consumed raw, it may act as a source of foodborne disease and a reservoir for antibiotic resistant organisms. This study aimed to determine microbial prevalence among the fruits sold outside Dhaka Medical College Hospital (DMCH) along with their antimicrobial profiles and to detect antimicrobial resistance genes among the resistant organisms. MethodsThirty-five different types of fruits were bought from around DMCH and analyzed for the presence of bacteria. Antibiotic sensitivity was done and ESBL, AmpC {beta}-lactamase, and MBL positive strains were identified by standard methods followed by PCR to detect ESBL, AmpC {beta}-lactamase, and MBL genes. FindingsTwenty seven different organisms were isolated and identified which were-Klebsiella spp (33{middle dot}33%), Citrobacter spp (29{middle dot}64%), Enterobacter spp (22{middle dot}22%), Escherichia coli (11{middle dot}11%), and Staphylococcus aureus (3{middle dot}70%). Among them 48{middle dot}15% organisms were resistant to different antibiotics. Only one organism (Citrobacter spp) produced ESBL phenotypically (7{middle dot}69%). Two (15{middle dot}38%) were positive for AmpC {beta}-lactamase and one of these (Enterobacter spp) possessed both SHV and CTX-M15A genes by PCR. Imipenem resistance was 84{middle dot}62% of the antibiotic resistant organisms, and 10 (90{middle dot}91%) were phenotypically MBL positive by CD test, DDS test, and MHT. By PCR, one Enterobacter spp had MBL encoding gene OXA-48. InterpretationFresh fruits, contaminated with pathogens, might be a source of transmission of resistant organisms and attribute to public health issues. FundingThe office of Directorate General of Health Service, Ministry of Health and Family Welfare, Bangladesh. ImportanceFruits sold around Dhaka Medical College and Hospital (DMCH) are usually consumed by patients, patients attendant and Health care worker. This investigation emphasized not only on the extent of bacterial contamination but also attempted to measure the anti-microbial profile of these organisms isolated from the fruits commonly available and readily consumed in and around DMCH.

microbiology↗

bioRxiv2022

Cold stimulation without touch: a method for perceptual and neurophysiological studies of thermal processing and multimodal interactions

BackgroundThermal and tactile stimuli are transduced by different receptor classes. However, mechano- and thermo-sensitive afferents interact at spinal and supraspinal levels. Yet, most studies on responses to cooling stimuli are confounded by mechanical contact, making these interactions difficult to isolate. Methods for precise control of non-mechanical thermal stimulations remain challenging, particularly in the cold range. New MethodWe developed a non-tactile, focal, temperature-controlled, multi-purpose cooling stimulator. This method controls the exposure of a target skin region to a dry-ice source. Using a thermal camera to monitor skin temperature, and adjusting the source-skin distance accordingly, we could deliver non-tactile cooling stimuli with customisable profiles, for studying different aspects of cold sensation. ResultsTo validate our method, we measured absolute and relative thresholds for cold sensation without mechanical contact in 13 human volunteer participants, using the method of limits. We found that the absolute cold detection threshold was 32.71{degrees}C {+/-} 0.88 {degrees}C. This corresponded to a threshold relative to each participants baseline skin temperature of -1.08 {degrees}C {+/-} 0.37 {degrees}C. Comparisons with Existing MethodOur method allows cooling stimulation without the confound of mechanical contact, in a controllable and focal manner. ConclusionsWe report a non-contact cooling stimulator and accompanying control system. We used this to measure cold thresholds in the absence of confounding touch. Our method enables more targeted studies of both cold sensory pathways, and of cold-touch interactions. HighlightsMost studies on cold sensation fail to control for concomitant tactile input. A method to deliver non-tactile cooling stimuli was developed. The method combines dry ice, a thermal camera, and motorised stages. The method delivers rapid ramps and feedback-controlled pulses. Thresholds for contactless cold perception were estimated in humans.

neuroscience↗

bioRxiv2020

Samplot: A Platform for Structural Variant Visual Validation and Automated Filtering

Visual validation is an essential step to minimize false positive predictions resulting from structural variant (SV) detection. We present Samplot, a tool for quickly creating images that display the read depth and sequence alignments necessary to adjudicate purported SVs across multiple samples and sequencing technologies, including short, long, and phased reads. These simple images can be rapidly reviewed to curate large SV call sets. Samplot is easily applicable to many biological problems such as prioritization of potentially causal variants in disease studies, family-based analysis of inherited variation, or de novo SV review. Samplot also includes a trained machine learning package that dramatically decreases the number of false positives without human review. Samplot is available via the conda package manager or at https://github.com/ryanlayer/samplot. ContactRyan Layer, Ph.D., Assistant Professor, University of Colorado Boulder, ryan.layer@colorado.edu.

genetics↗

bioRxiv2020

In-vivo evaluation of the anti-diarrheal effect of Lactococcus lactis subspecies lactis and Lactococcus piscium isolated from yogurt.

Lactobacillus and Lactococcus species found in the yogurt of different sources are most widely assayed and used all over the world as a probiotic agent. This study aimed to isolate and identify novel probiotic agents with therapeutic value against diarrhea. Initially, the probiotic properties of the isolated lactic acid bacteria from the yogurt samples of the Chittagong division, Bangladesh, were evaluated. All probiotic candidates inhibited the growth of selected pathogens, including Escheriachia coli, Serratia sp. Salmonella paratyphi, Streptococcus Group-B, Staphylococcus aureus, Haemophillus influenzae, Bacillus subtillis, and Klebsiella pneumoniae. Lactococcus lactis subsp lactis were found most useful in inhibiting all the selected pathogens. When the probiotics were applied against castor oil-induced diarrhea in the rat model, Lactococcus lactis subspecies lactis and Lactococcus piscium were found significantly effective relative to the controls indicating their potentiality as an alternative therapeutic against diarrhea. HighlightsO_LILactococcus lactis subspecies lactis and Lactococcus piscium has shown potentiality to be a therapeutic agent against castor-oil induced diarrhea in an animal model. C_LIO_LILactococcus lactis subspecies lactis and Lactococcus piscium inhibited the growth of specified pathogens. C_LI

microbiology↗

bioRxiv2020

Learning What a Good Structural Variant Looks Like.

Structural variations (SVs) are an important class of genetic mutations, yet SV detectors still suffer from high false-positive rates. In many cases, humans can quickly determine whether a putative SV is real by merely looking at a visualization of the SVs coverage profile. To that end, we developed Samplot-ML, a convolutional neural network (CNN) trained to genotype genomic deletions using Samplot visualizations that incorporate various forms of evidence such as genome coverage, discordant pairs, and split reads. Using Samplot-ML, we were able to reduce false positives by 47% while keeping 97% of true positives on average across several test samples.

bioinformatics↗

bioRxiv2019

First report of reference guided genome assembly of Black Bengal goat (Capra hircus)

ObjectivesBlack Bengal goat (Capra hircus), a member of the Bovidae family with the unique traits of high prolificacy, skin quality and low demand for food is the most socioeconomically significant goat breed in Bangladesh. Furthermore, the aptitude of adaptation and disease resistance capacity of it is highly notable which makes its whole genome information an area of research interest.\n\nData descriptionThe genomic DNA of local (Chittagong, Bangladesh) healthy Black Bengal goat (Capra hircus) was extracted and then sequenced. The de novo assembly and structural annotations are being presented here. Sequencing was done using Illumina sequencing platform and the draft genome assembled is about 3.04 Gb. 26458 Genes were annotated using Maker gene annotations tool which predicted BUSCO Gene models. Universal Single Copy Orthologs refer 82.5% completeness of the assembled genome.

genomics↗

bioRxiv2019

ATAC-seq signal processing and recurrent neural networks can identify RNA polymerase activity

Nascent transcription assays are the current gold standard for identifying regions of active transcription, including markers for functional transcription factor (TF) binding. Here we present a signal processing-based model to determine regions of active transcription genome-wide using the simpler assay for transposase-accessible chromatin, followed by high-throughput sequencing (ATAC-seq). The focus of this study is twofold: First, we perform a frequency space analysis of the "signal" generated from ATAC-seq experiments short reads, at a single-nucleotide resolution, using a discrete wavelet transform. Second, we explore different uses of neural networks to combine this signal with its underlying genome sequence in order to classify ATAC-seq peaks on the presence or absence of bidirectional transcription. We analyze the performance of different data encoding schemes and machine learning architectures, and show how a hybrid signal/sequence representation classified using recurrent neural networks (RNNs) yields the best performance across different cell types. Contactrobin.dowell@colorado.edu

bioinformatics↗