Biology subjects

Sarker, A.

Publications and source records attributed to Sarker, A..

10 recordsLinked to original sources

bioRxiv2026

Aryl Hydrocarbon Receptor (Ahr) Pathway Drives TBBPA Induced Cartilage Development Defects.

Tetrabromobisphenol A (TBBPA), is one the most widely produced brominated flame retardant, detected in human matrices including cord plasma, raising concern over its impact on embryonic development. Our previous work demonstrated that TBBPA disrupts craniofacial cartilage development in zebrafish; however, inhibition of bone morphogenetic protein (BMP) signaling did not rescue these defects, suggesting the involvement of alternative molecular mechanisms. Transcriptomic profiling revealed significant upregulation of aryl hydrocarbon receptor (Ahr) signaling genes, including cyp1a and cyp1c, as well as reactive oxygen species (ROS) responsive genes, such as nfe and gstp. Consistent with these findings, KEGG pathway enrichment analysis identified significant enrichment of pathways involved in xenobiotic metabolism, cytochrome P450-mediated metabolism, and molecular docking predicted stronger binding of TBBPA to Ahr2 than the Ahr2 agonist TCDD. Then we investigated the role of Ahr signaling and ROS in TBBPA-induced craniofacial cartilage defects using microinjection of Ahr2 translation-blocking morpholino and the antioxidant N-acetylcysteine (NAC), respectively. Immunohistochemistry confirmed concentration-dependent induction of Cyp1a and ROS at environmentally relevant concentrations (0.05;0.005 uM). Ahr2 knockdown using a translation-blocking morpholino rescued TBBPA-induced alterations in Cyp1a expression, ROS levels, DNA damage, the expression of chondrogenesis-related markers (Sox10 and Sox2), and epithelial to mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and Snail2). Furthermore, Ahr2 knockdown rescued several TBBPA-induced alterations in craniofacial cartilage parameters. Co-exposure of TBBPA with the antioxidant NAC rescued the ROS and DNA damage and rescued only ceratohyal cartilage length, whereas other cartilage parameters remained disrupted. These findings establish a causal role for the Ahr-Cyp1a axis in TBBPA-induced craniofacial cartilage developmental toxicity and identify ROS as an important downstream contributor, indicating that both ROS-dependent and ROS-independent Ahr mechanisms underlined the observed TBBPA induced craniofacial defects.

pharmacology and toxicology↗

bioRxiv2026

Heavy Metal-Resistant, Plastic-Degrading Bacillus sp. Isolated from Landfill Leachate: Identification and Characterization

Landfill leachates in rapidly urbanizing regions like Dhaka present a complex ecological challenge owing to the concurrent buildup of heavy metals and plastic waste. Despite the severity of this pollution, the role of indigenous multi-functional bacteria in mitigating these mixed contaminants remains poorly understood. This research sought to isolate and characterize bacteria resistant to heavy metals and capable of degrading plastics from the Aminbazar and Matuail landfills and evaluate their bioremediation potential. Physicochemical analysis confirmed extreme contamination, with heavy metal levels (Pb, Cr, Cd, Cu) significantly exceeding WHO safety limits. Out of 81 isolates, nearly half exhibited multi-metal resistance and polyethylene (PE) degradation capacity. Statistical analysis showed a significant correlation between plastic degradation and multi-metal tolerance, suggesting a linked evolutionary adaptation. Enzymatic assays confirmed enzymes (e.g., urease, catalase, citrate and esterase) as drivers of both plastic degradation and heavy metal tolerance in leading isolates. Molecular screening identified the resistance genes pbrA and alkB, while the high prevalence of Class 1 integrons (80% in pbrA-positive isolates) points to a high potential for horizontal gene transfer in these environments. Furthermore, MALDI-TOF MS identified the functional isolates as Bacillus sp. with FTIR verifying the contribution of specific cell-surface functional groups to metal biosorption. These results underscore the promise of native Bacillus strains as promising agents for the development of sustainable, integrated biotechnologies for landfill restoration and complex waste management.

microbiology↗

bioRxiv2025

DNA Polymerase α has pyrimidine dimer translesion activity that is suppressed during normal replication

To ensure rapid and accurate DNA replication during S-phase, the cell uses DNA damage tolerance (DDT) pathways, leaving lesions to be repaired after completion of replication. One established DDT pathway is Translesion Synthesis (TLS), in which lesions are bypassed by specialized TLS Polymerases that work in conjunction with the replisome. Here we demonstrate that DNA Polymerase alpha (Pol ), the replicative primase/polymerase, can also unexpectedly replicate through bulky lesions in vitro. We use biochemical and single-molecule fluorescence assays to characterize cyclobutane pyrimidine dimer (CPD) TLS activity of Pol . We observe that Pol {varepsilon}, the leading strand replicative polymerase, and RPA, a single-stranded DNA binding protein complex, both strongly inhibit CPD TLS activity of Pol . In contrast, Pol , the canonical TLS Pol for pyrimidine dimers, is unaffected by Pol {varepsilon} and is conversely stimulated by RPA. Finally, we demonstrate with single-molecule Fluorescence Resonance Energy Transfer (FRET) that the DNA binding cleft of Pol must remain in the open state to accommodate a bulky CPD lesion during TLS, possibly accounting for the relatively slow kinetics of CPD bypass that we observe. The results suggest that the intrinsic bulky TLS activity of Pol is likely suppressed at the replication fork by the replisome itself during normal replication. RESEARCH HIGHLIGHTSO_LIPolymerase has translesion synthesis (TLS) activity past a CPD lesion, the first demonstration of TLS activity at a bulky lesion by a replicative polymerase at physiological nucleotide levels. C_LIO_LIIntrinsic Pol TLS activity is suppressed during normal replication by replisome components Pol {varepsilon} and RPA. C_LIO_LIPol {varepsilon} suppresses TLS incorporation by Pol by proofreading C_LIO_LIThe binding cleft of Pol stays open to accommodate a pyrimidine dimer. C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/662766v2_ufig1.gif" ALT="Figure 1"> View larger version (12K): org.highwire.dtl.DTLVardef@1750e05org.highwire.dtl.DTLVardef@1eb8cdcorg.highwire.dtl.DTLVardef@16cdd39org.highwire.dtl.DTLVardef@2fd532_HPS_FORMAT_FIGEXP M_FIG Pol harbors CPD TLS activity that is suppressed by RPA and Pol {varepsilon} at the replication fork during normal replication. C_FIG

biochemistry↗

bioRxiv2024

Heavy Metal and Antibiotic Co-resistance in Bacteria Isolated from Poultry Samples in Bangladesh: An Emerging Environmental Threat

The excessive use of heavy metals and antibiotics as additives in livestock feed may significantly contribute to bacterial resistance in poultry environments by exerting selective pressure. This study aimed to comprehensively analyze bacterial isolates from poultry farms across Bangladesh, focusing on their resistance to heavy metals and antibiotics. Through microbial phenotypic screening, 23 cadmium-resistant and 28 chromium-resistant bacterial isolates were identified. The minimum inhibitory concentrations (MICs) for cadmium and chromium in metal-resistant bacterial isolates varied significantly, ranging from 200 g/ml to 1600 g/ml. All cadmium-resistant isolates were fully resistant to cefixime and ceftazidime, while chromium-resistant isolates showed 90% resistance to tetracycline. The cadmium resistance gene, such as czc, was detected in 26% (6/23) of cadmium-resistant isolates, and the chromium reductase gene chrR was detected in 18% (5/28) of chromium-resistant isolates. Among the chromium-reductase isolates, 40% (2/5) exhibited co-resistance and harbored the chrR gene, beta-lactam resistance genes (bla-TEM, bla-NDM), and the colistin resistance gene (mcr-2). A significant association (p = 0.026) was observed between the presence of the chrR gene and these antibiotic resistance genes. However, no co-resistance was found in cadmium-resistant isolates. Mobile genetic elements, specifically Class 1 integrons, were found in 33.33% (2/6) of the isolates carrying the cadmium resistance gene (czc) and in 100% (5/5) of the isolates containing the chromium reductase gene (chrR). These findings underscore poultry environments in Bangladesh as significant reservoirs for bacteria with dual resistance to heavy metals and antibiotics, emphasizing the need for further investigation into the genetic mechanisms driving microbial resistance and its implications for public health.

microbiology↗

bioRxiv2023

Enhancing Rice Growth and Yield with Weed Endophytic Bacteria Alcaligenes faecalis and Metabacillus indicus Under Reduced Chemical Fertilization

Endophytic bacteria, recognized as eco-friendly biofertilizers, have demonstrated the potential to enhance crop growth and yield. While the plant growth-promoting effects of endophytic bacteria have been extensively studied, the impact of weed endophytes remains less explored. In this study, we aimed to isolate endophytic bacteria from native weeds and assess their plant growth-promoting abilities in rice under varying chemical fertilization. The evaluation encompassed measurements of mineral phosphate and potash solubilization, as well as indole-3-acetic acid (IAA) production activity by the selected isolates. Two promising strains, tentatively identified as Alcaligenes faecalis (BTCP01) from Eleusine indica (Goose grass) and Metabacillus indicus (BTDR03) from Cynodon dactylon (Bermuda grass) based on 16S rRNA gene phylogeny, exhibited noteworthy phosphate and potassium solubilization activity, respectively. BTCP01 demonstrated superior phosphate solubilizing activity, while BTDR03 exhibited the highest potassium (K) solubilizing activity. Both isolates synthesized IAA in the presence of L-tryptophan, with the detection of nifH and ipdC genes in their genomes. Application of isolates BTCP01 and BTDR03 through root dipping and spraying at the flowering stage significantly enhanced the agronomic performance of rice variety BRRI dhan29. Notably, combining both strains with 50% of recommended N, P, and K fertilizer doses led to a substantial increase in rice grain yields compared to control plants receiving 100% of recommended doses. Taken together, our results indicate that weed endophytic bacterial strains hold promise as biofertilizers, potentially reducing the dependency on chemical fertilizers by up to 50%, thereby fostering sustainable rice production.

microbiology↗

bioRxiv2023

Intrathecal Cu-albumin PET reveals age-related decline of cerebrospinal fluid (CSF)-lymphatic efflux

Age-related cognitive decline is associated with dysfunctional lymphatic efflux of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. Intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice for the evaluation of lymphatic efflux of CSF and its age-related variation. [64Cu]Cu-albumin PET was done at multiple time points after intrathecal injection of [64Cu]Cu-albumin with the infusion speed of 700 nl/min in the adult and aged mice of 15-25 months old age. CSF clearance and paravertebral lymph nodes were quantified after injection and at later stationary phase. Representing perturbed state by 6 l (1/7 of CSF volume with twice the production rate for 9 minutes of intrathecal injection) and at the next day of stationary return of CSF dynamics in mice, CSF clearance half-time from the subarachnoid space was 93.4 {+/-} 19.7 in adult and 123.3 {+/-} 15.6 minutes in aged mice (p = 0.01). The % injected dose at 4, 6 and 24 hours were higher in aged mice than in the adult mice (p < 0.05) and the visualized paravertebral lymph node activity tended to be lower in the aged, which was different from [64Cu]Cu-NOTA or [64Cu]Cu-ESION PET. [64Cu]Cu-albumin PET enabled quantification of CSF-lymphatic efflux over all the levels of brain spinal cords and visualization with quantifiability of lymph node activity. [64Cu]Cu-albumin PET revealed an age-related decrease in CSF-lymphatic efflux due to less efflux from the subarachnoid space, especially at stationary phase in the aged mice.

neuroscience↗

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↗

bioRxiv2020

Understanding photothermal interactions will help expand production range and increase genetic diversity of lentil (Lens culinaris Medik.)

O_LILentil (Lens culinaris Medik.) is cultivated under a wide range of environmental conditions, which led to diverse phenological adaptations and resulted in a decrease in genetic variability within breeding programs due to reluctance in using genotypes from other environments. C_LIO_LIWe phenotyped 324 genotypes across nine locations over three years to assess their phenological response to the environment of major lentil production regions and to predict days from sowing to flowering (DTF) using a photothermal model. C_LIO_LIDTF was highly influenced by the environment and is sufficient to explain adaptation. We were able to predict DTF reliably in most environments using a simple photothermal model, however, in certain site-years, results suggest there may be additional environmental factors at play. Hierarchical clustering of principal components revealed the presence of eight groups based on the responses of DTF to contrasting environments. These groups are associated with the coefficients of the photothermal model and revealed differences in temperature and photoperiod sensitivity. C_LIO_LIExpanding genetic diversity is critical to the success of a breeding program; understanding adaptation will facilitate the use of exotic germplasm. Future climate change scenarios will result in increase temperature and/or shifts in production areas, we can use the photothermal model to identify genotypes most likely to succeed in these new environments. C_LI

plant biology↗

bioRxiv2019

Effective buprenorphine use and tapering strategies: Endorsements and insights by people in recovery from opioid use disorder on a Reddit forum

Opioid use disorder (OUD) is a public health emergency in the United States. Over 47,000 overdose-related deaths in 2017 involved opioids. Medication-assisted treatment (MAT), in particular, buprenorphine and buprenorphine combination products such as Suboxone(R), is the most effective, evidence-based treatment for OUD. However, there are a limited number of conclusive scientific studies that provide guidance to medical professionals about strategies for using buprenorphine to achieve stable recovery. In this study, we used data-driven natural language processing methods to mine a total of 16,146 posts about buprenorphine from 1933 unique users on the anonymous social network Reddit. Analysis of a sample of these posts showed that 74% of the posts described users personal experiences and that the top three topics included advice on using Suboxone(R) (55.0%), Suboxone(R) dosage information (35.5%) and information about Suboxone(R) tapering (32.0%). Based on two models, one that incorporated upvoting by other members and one that did not, we found that Reddit users reported more successful recovery with longer tapering schedules, particularly from 2.0 mg to 0.0 mg (median: 93 days; mean: 95 days), as compared to shorter tapering schedules investigated in past clinical trials. Diarrhea, insomnia, restlessness, and fatigue were commonly reported adverse events. Physical exercise, clonidine, and Imodium(R) were frequently reported to help during the recovery process. Due to the difficulties of conducting longer-term clinical trials involving patients with OUD, clinicians should consider other information sources including peer discussions from the abundant, real-time information available on Reddit. Significance StatementOpioid use disorder (OUD) is a national crisis in the United States and buprenorphine is one of the most effective evidence-based treatments. However, few studies have explored successful strategies for using and tapering buprenorphine to achieve stable recovery, particularly due to the difficulties of conducting long-term studies involving patients with OUD. In this study, we show that discussions on the anonymous social network Reddit may be leveraged, via automatic text mining methods, to discover successful buprenorphine use and tapering strategies. We discovered that longer tapering schedules, compared to those investigated in past clinical trials, may lead to (self-reported) sustained recovery. Furthermore, Reddit posts also provide key information regarding buprenorphine withdrawal, cravings, adjunct medications for withdrawal symptoms and relapse prevention strategies.

pharmacology and toxicology↗

bioRxiv2019

Drosophila models of pathogenic copy-number variant genes show global and non-neuronal defects during development

While rare pathogenic copy-number variants (CNVs) are associated with both neuronal and non-neuronal phenotypes, functional studies evaluating these regions have focused on the molecular basis of neuronal defects. We report a systematic functional analysis of non-neuronal defects for homologs of 59 genes within ten pathogenic CNVs and 20 neurodevelopmental genes in Drosophila melanogaster. Using wing-specific knockdown of 136 RNA interference lines, we identified qualitative and quantitative phenotypes in 72/79 homologs, including 21 lines with severe wing defects and six lines with lethality. In fact, we found that 10/31 homologs of CNV genes also showed complete or partial lethality at larval or pupal stages with ubiquitous knockdown. Comparisons between eye and wing-specific knockdown of 37/45 homologs showed both neuronal and non-neuronal defects, but with no correlation in the severity of defects. We further observed disruptions in cell proliferation and apoptosis in larval wing discs for 23/27 homologs, and altered Wnt, Hedgehog and Notch signaling for 9/14 homologs, including AATF/Aatf, PPP4C/Pp4-19C, and KIF11/Klp61F. These findings were further supported by tissue-specific differences in expression patterns of human CNV genes, as well as connectivity of CNV genes to signaling pathway genes in brain, heart and kidney-specific networks. Our findings suggest that multiple genes within each CNV differentially affect both global and tissue-specific developmental processes within conserved pathways, and that their roles are not restricted to neuronal functions. AUTHOR SUMMARYRare copy-number variants (CNVs), or large deletions and duplications in the genome, are associated with both neuronal and non-neuronal clinical features. Previous functional studies for these disorders have primarily focused on understanding the cellular mechanisms for neurological and behavioral phenotypes. To understand how genes within these CNVs contribute to developmental defects in non-neuronal tissues, we assessed 79 homologs of CNV and known neurodevelopmental genes in Drosophila models. We found that most homologs showed developmental defects when knocked down in the adult fly wing, ranging from mild size changes to severe wrinkled wings or lethality. Although a majority of homologs tested showed defects when knocked down specifically in wings and eyes, we found no correlation in the severity of the observed defects in these two tissues. A subset of the homologs showed disruptions in cellular processes in the developing fly wing, including alterations in cell proliferation, apoptosis, and cellular signaling pathways. Furthermore, human CNV genes also showed differences in gene expression patterns and interactions with signaling pathway genes across multiple human tissues. Our findings suggest that genes within CNV disorders affect global developmental processes in both neuronal and non-neuronal tissues.

genomics↗