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Haque, M. M.

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

10 recordsLinked to original sources

Genome-resolved metagenomics reveals microbial potential for CO2 and CH4 emissions in prawn ponds

Recognizing the central role of microorganisms in greenhouse gas (GHG) cycling in aquaculture systems, we provide a genome- and gene-centric perspective on the metabolic potential for CO2 and CH cycling in prawn aquaculture ponds across seasons and contrasting culture practices. Using TaxVAMB, we recovered 78 high- and medium-quality metagenome-assembled genomes (MAGs), including previously underappreciated taxa such as Bathyarchaeia and Terriglobia. Metabolic profiling revealed that CO2 and CH cycling constitute a minor fraction of the ponds metabolic potential, dominated instead by heterotrophic processes such as fermentation, oxygen metabolism, and iron reduction. The relative metabolic weight of these carbon-cycling pathways was lower than that reported for permafrost, wetland, peatland, deep-sea, and human gut microbiomes. An integrated metabolic network suggested that genetic potential for CO2 production is primarily driven by pyruvate and acetyl-CoA oxidation, while methanogenesis and methane oxidation genes together encode the potential for internal carbon-recycling loops via canonical archaeal and bacterial pathways. Seasonal dynamics, rather than management treatment, strongly influenced functional gene abundances, with CO2 fixation and CH4 oxidation genes increasing toward the late season. Bathyarchaeia emerged as the most versatile taxon for CO2 cycling and methanogenesis, with stable relative abundance across seasons and treatments. This study underscores the role of seasonally evolving microbial networks in regulating carbon turnover and the potential for CO2 and CH4 emissions in prawn aquaculture ponds.

microbiology↗

Transcript architecture predetermines m6A remodeling and sensory neuron vulnerability in chemotherapy-induced peripheral neuropathy

Whether individual transcripts carry intrinsic features that predetermine their response to perturbations is unknown. Here we used nanopore direct RNA sequencing of male mouse dorsal root ganglia (DRG) to simultaneously profile N6-methyladenosine (m6A) modifications, poly(A) tail dynamics, and full-length isoform identity from mice treated with bortezomib, a proteasome inhibitor that causes painful peripheral neuropathy. Machine learning revealed that transcript-intrinsic features predetermine the magnitude of perturbation-induced m6A loss (R{superscript 2} = 0.983). Expression level contributed just 2.6% of predictive importance. Bortezomib removed a fixed [~]73.5% fraction of m6A marks, meaning absolute loss scaled linearly with baseline density and a transcripts epitranscriptomic fate was encoded in its architecture before drug exposure. Unsupervised clustering identified four response programs where the dominant m6A erosion cluster enriched for oxidative phosphorylation (OXPHOS, p = 1.0 x 10-{superscript 1}) and proteasome (p = 2.8 x 10-{superscript 1}) genes, recapitulating bortezomibs established mechanisms without prior biological knowledge. Isoform-resolved analysis uncovered m6A remodeling patterns suggesting post-transcriptional regulation of glycolytic and OXPHOS genes, and Western blot confirmed protein-level suppression of OXPHOS components. Integration with single-nuclei sequencing showed sensory neurons carried 2.2-fold greater m6A loss burden than non-neuronal cells, a direct consequence of architectural determinism applied to cell-type-specific transcriptomes. These findings establish that epitranscriptomic bortezomib response is predetermined by transcript architecture, with pathway specificity and cell-type vulnerability emerging as downstream consequences of intrinsic RNA structure.

neuroscience↗

Tracking vaginal microbiome transitions in bacterial vaginosis for cues of antibiotic resilience

BackgroundBacterial vaginosis (BV) is a common and difficult-to-treat vaginal disorder, with significant implications for reproductive health, particularly in low and middle-income countries. Clinical cure based on symptom resolution or Nugent scores often do not correspond to restoration of healthy vaginal microbiome. Factors underlying treatment failure remain poorly defined, warranting the need for understanding post-treatment microbiome dynamics to improve long-term outcomes. ObjectivesTo delineate longitudinal vaginal bacteriome dynamics, integrating microbial composition, transition patterns, and clinical symptoms in a closely followed cohort of women with BV based on treatment outcome. MethodsVaginal swabs from reproductive-age women (18-45 years) were collected and classified as BV-positive ([≥]7) or healthy ([≤]3) using Nugent scoring. BV cases were treated using single-dose secnidazole and followed for three months. Sociodemographic, clinical, and behavioral data were statistically analyzed across groups. Vaginal microbiome composition was assessed using 16S rRNA sequencing, evaluating taxonomic profiles, alpha and beta diversity, differential abundance, and co-occurrence networks. ResultsAntibiotic treatment reduced overall microbial diversity and shifted community composition toward healthy controls, though relapse samples retained higher diversity of BV-associated taxa such as Sneathia, Dialister, and Gardnerella, while no-relapse and control groups showed higher Lactobacillus abundance. Corynebacterium amycolatum appeared protective, while Mycoplasma and Fusobacterium played symptom-specific roles. Microbial network analysis showed denser and more persistent associations in baseline and relapse groups, with Sneathia remaining a central node. ConclusionShort-term symptom resolution in BV does not correspond to full microbial recovery; necessary for long-term remission. Functional traits of resilient taxa like Sneathia, Fannyhessea and Dialister may confer resilience and enable recolonization, undermining long term treatment efficacy.

microbiology↗

Targeted medial prefrontal cortex stimulation prevents incubation of cocaine craving and restores functional connectivity

BackgroundRelapse remains a central obstacle in the treatment of cocaine use disorder (CUD), for which no medications have received approval from the U.S. Food and Drug Administration. Transcranial magnetic stimulation (TMS) has shown promise as a potential therapeutic intervention. However, current clinical trials often rely on a "trial-and-error" approach in target selection and experimental design. We previously developed a novel TMS platform and high-density theta burst stimulation (hdTBS) technology, enabling precise, focal stimulation of the rat medial prefrontal cortex (mPFC), including the prelimbic and anterior cingulate cortices. MethodsWe applied hdTBS intervention to a well-established rat model of cocaine relapse and craving after cessation of extended access intravenous drug self-administration and assessed brain response using resting-state functional magnetic resonance imaging (fMRI). ResultsAs expected, we observed robust time-dependent increases in cocaine seeking (incubation of cocaine craving) in control rats receiving sham stimulation over 3 weeks of abstinence accompanied by a reduction in prefrontal functional connectivity. In contrast, daily sessions of hdTBS for 7 days delivered on abstinence days 14-20 prevented the emergence of the incubation effect and restored prefrontal network functional connectivity. ConclusionsThis study provides strong preclinical evidence demonstrating that precise circuit modulation of medial prefrontal subregions causally reverses both behavioral and network-level adaptations associated with relapse vulnerability. Given the clinical accessibility and established safety profile of TMS, this work provides a mechanistically grounded framework for target selection and supports the translation of focal TMS of the mPFC for relapse prevention in CUD patient. One Sentence SummaryFocal transcranial magnetic stimulation (TMS) of the mPFC using the hdTBS procedure prevents incubation of cocaine craving and restores functional connectivity.

neuroscience↗

Focal Transcranial Magnetic Stimulation of the Rat Anterior Cingulate Cortex Inhibits Incubation of Opioid Craving after Voluntary Abstinence

Relapse remains a major challenge in opioid addiction treatment, underscoring the need for innovative therapies. Progress in neuromodulation therapies has been limited by insufficient mechanistic understanding of stimulation engagement and disease-related changes in the brain. We used a novel, focal transcranial magnetic stimulation (TMS) system to deliver high-density theta burst stimulation (hdTBS) combined with resting-state fMRI to test whether anterior cingulate cortex (ACC) stimulation reduces relapse-like behavior and alters functional circuitry in a rodent model of opiate dependence. The coil focality and stimulation parameters approximate human TMS protocols, and the targeted region represents a functional homolog of the human ACC. We trained rats to self-administer oxycodone intravenously for 14 days. We then introduced an electric barrier for 13 days, which caused cessation of drug self-administration. We assessed relapse to oxycodone seeking immediately after training (early abstinence) and after electric-barrier exposure (late abstinence). We administered daily hdTBS or sham stimulation for 7 days before the late-abstinence test. Sham-treated rats showed a time-dependent increase in oxycodone seeking during abstinence (incubation of oxycodone craving) and reduced ACC functional connectivity. In contrast, hdTBS prevented the incubation of oxycodone craving and restored ACC connectivity with the dorsal and ventral striatum. Tracer-based axonal-projection data further showed that stimulation-induced effects aligned with regions receiving dense projections from the stimulation site, suggesting that the projection architecture is critical to the propagation of focal stimulation across distributed networks. These findings identify ACC-centered circuits as mechanistically informed targets for TMS-based interventions that aim to reduce opioid relapse during abstinence. One sentence SummaryPrefrontal TMS stimulation reduced relapse-like behavior and restored corticostriatal circuits, highlighting translational targets for addiction treatment.

neuroscience↗

Deep Learning-Driven Discovery of Mitochondrial Factors Modulating Influenza A Virus Infection

Influenza A virus exploits host cellular machinery across subcellular compartments, yet the organelle-level changes that distinguish infected from uninfected cells and the molecular players driving them remain poorly defined. Here, we combine organelle image-based deep learning with proximity labeling chemoproteomics to address this gap. A convolutional neural network identified mitochondrial morphology as the strongest single-cell predictor of infection status (precision = 84.9%). Proximity labeling profiling of mitochondrial matrix proteome revealed 99 proteins with significantly altered upon infection, of which five (CH60, ETHE1, LONM, MPPB, and SQOR) were validated as host restriction factors whose depletion elevated interferon-{beta} expression, enhanced viral RNA accumulation, or increased progeny virus production. Notably, two of these factors, ETHE1 and SQOR, operate within the mitochondrial hydrogen sulfide oxidation pathway, and pharmacological scavenging of H2S by hydroxocobalamin dose-dependently reversed their knockdown phenotypes, directly linking mitochondrial sulfide metabolism to antiviral defense against influenza.

microbiology↗

norCBD disruption affects the H2-type six secretion system and multiple virulence factors in Pseudomonas aeruginosa

The type six secretion system (T6SS) is a macromolecular weapon used by many Gram-negative bacteria. The T6SS functions as a needle injection system that delivers effector proteins directly into neighboring bacterial cells, thereby affecting their gene expression and physiological processes. Pseudomonas aeruginosa possesses three distinct T6SSs, designated as H1-, H2-, and H3-T6SS. Although extensive studies have been carried out on these T6SS systems in recent years, the regulatory mechanisms of T6SS remain incomplete. Here, we report the identification of norCBD as an operon that modulates the transcriptional activity of H2-T6SS. Both transposon insertion at norCBD and the deletion of the norCBD genes significantly reduced the CTX-H2-T6SS reporter activity. The norCBD operon encodes nitric oxide reductase (NorCBD), which reduces nitric oxide (NO) to nitrous oxide (N2O), a crucial step in reducing the toxic levels of intracellular NO and facilitating anaerobic respiration. As the transcriptional regulatory Dnr activates H2-type VI secretion system (H2-T6SS) in response to NO, experiments were carried out to examine whether norCBD deletion caused intracellular NO accumulation, which in turn disrupted Dnr-dependent regulation of H2-T6SS and virulence factors. The NO levels and Dnr-regulated gene expression were measured, and several virulence-related phenotypes were examined. The effects of NO donor sodium nitroprusside (SNP) and NO scavenger carboxy-phenyl-tetramethylimidazolineoxyl (CPTIO) were also tested. The data obtained indicate that deletion of norCBD led to intracellular NO accumulation, reduced H2-T6SS expression, and affected motility, pyocyanin production, and biofilm formation. Complementation of norCBD on a plasmid in the deletion mutant was able to restore H2-T6SS expression and the examined phenotypes to the wild-type levels. Treatment with CPTIO also restored H2-T6SS expression in the PAO1({Delta}norCBD). These results indicate that NorCBD plays a critical role in maintaining NO homeostasis that is necessary for effective Dnr-mediated gene regulation and multiple virulence-related traits, highlighting the importance of redox balance in coordinating respiration and pathogenesis in P. aeruginosa.

microbiology↗

High-density theta burst stimulation (hdTBS) at 100 Hz triples the aftereffects of the conventional intermittent TBS

Slice electrophysiological studies have experimentally demonstrated that theta burst stimulation, consisting of electrical pulses delivered at 10 ms (100 Hz) inter-pulse intervals, optimally induces long-term potentiation in the hippocampus. Inspired by this observation, a novel transcranial magnetic stimulation (TMS) paradigm, 100 Hz high-density theta burst stimulation (100 Hz hdTBS), is presented. This paradigm delivers 6 pulses per burst with an inter-pulse interval of 10 ms - doubling the pulse frequency and total pulse count of the conventional intermittent TBS (iTBS). The effect of this new paradigm was studied in the motor cortex of awake rats using a rat-specific focal TMS coil and a hdTBS stimulator developed in house. Results reveal that 100 Hz hdTBS triples the after-effects of conventional iTBS. In a separate group of animals that received two consecutive iTBS session back-to-back (prolonged iTBS), we observed an inhibitory effect. Since that prolonged iTBS matches the total pulse count of 100 Hz hdTBS but produced opposite after-effects, our results underscore the critical roles of the temporal structure of TMS pulses--not merely the total number of pulses--in driving neuroplasticity. This new paradigm has the potential to significantly enhance therapeutic efficacy if confirmed to be safe and effective in humans.

neuroscience↗

Composition of nasopharyngeal microbiota in individuals with SARS-COV-2 infection across three COVID-19 waves in India

Multiple variants of the SARS-CoV-2 virus have been plaguing the world through successive waves of infection over the past three years. Studies by independent research groups across geographies have shown that the microbiome composition in COVID-19 patients (CP) differ from that of healthy individuals (CN). However, such observations were based on limited-sized sample-sets collected primarily from the early days of the pandemic. Here, we study the nasopharyngeal microbiota in COVID-19 patients, wherein the samples have been collected across the three COVID-19 waves witnessed in India, which were driven by different variants of concern. We also present the variations in microbiota of symptomatic vs asymptomatic COVID-19 patients. The nasopharyngeal swabs were collected from 589 subjects providing samples for diagnostics purposes at Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India. CP showed a marked shift in the microbial diversity and composition compared to CN, in a wave-dependent manner. Rickettsiaceae was the only family that was noted to be consistently depleted in CP samples across the waves. The genera Staphylococcus, Anhydrobacter, Thermus, and Aerococcus were observed to be highly abundant in the symptomatic CP patients when compared to the asymptomatic group. In general, we observed a decrease in the burden of opportunistic pathogens in the host microbiota during the later waves of infection. To our knowledge, this is the first longitudinal study which was designed to understand the relation between the evolving nature of the virus and the changes in the human nasopharyngeal microbiota. Such studies not only pave way for better understanding of the disease pathophysiology but also help gather preliminary evidence on whether interventions to the host microbiota can help in better protection or faster recovery.

microbiology↗

The Diversity and Ubiquity of Antibiotic Resistant Genes in Finfish Culture Ponds in Bangladesh

In Bangladesh, fish provide over 60% of animal-source food with 56.2% of this coming from aquaculture produced predominantly in rural freshwater ponds. Increasing demand for fish products is driving intensification and resulting in higher disease prevalence, posing a risk to food security. Biosecurity is often absent in rural aquaculture practices in Bangladesh and antibiotics are commonly used to treat and prevent disease outbreaks. Antibiotics are often administered incorrectly - a key factor associated with the development of antimicrobial resistance (AMR). AMR can be disseminated rapidly within microbial ecosystems via mobile genetic elements, posing a risk for humans and animals infected with AMR pathogens as treatments with antibiotics become ineffective. Early AMR detection and understanding of the spread of antimicrobial resistant genes (ARGs) in rural aquaculture practices is critical for both food security and human health protection. Here, we apply a metagenomic approach to assess the ARG composition in pond water from six finfish (tilapia and pangasius) farms in the Mymensingh division of North-central Bangladesh. We found microbial communities within the ponds had similar alpha and beta diversities, with multiple ARGs predicted to confer resistance to eighteen different classes of antimicrobials. The most common ARGs conferred resistance to aminoglycosides and sulphonamides and were present in taxa associated with both fish and human pathogens. This ARG diversity potentially confers resistance to a wide variety of antibiotic classes and questions the effectiveness of current and future treatment of diseases with antibiotics in earthen aquaculture ponds. The microbial and ARG compositions between fish ponds within each farm were similar, which may relate to parallels in farming practices creating similar microbial selection pressures and thus comparable microbial populations. Without a more controlled approach towards antibiotic usage, will inevitably further exacerbate the challenges in treating and preventing disease outbreaks as aquaculture production intensifies in Bangladesh. HighlightsO_LIARGs in Bangladesh rural fishponds indicate resistance to 18 different antibiotics C_LIO_LIThe most common AMR were to aminoglycosides and sulphonamides C_LIO_LIARGs were present in plasmids and taxa-associated pathogens C_LIO_LIFarming practices strongly influence microbial and ARG compositions C_LIO_LIIdentified ARGs question antibiotic treatment of disease in rural aquaculture C_LI

microbiology↗