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Biology subjects

Hossain, M. S.

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

At least 19 recordsLinked to original sources

Sparse Autoencoders Reveal Structural and Family-level Features in BiRNA-BERT

RNA language models learn useful representations for structure and function, but the biological concepts encoded by their hidden states remain difficult to interpret. BiRNA-BERT is an RNA language model with adaptive byte-pair tokenization, making it an attractive target for mechanistic analysis. We present SPIRAL (Sparse autoencoders for Interpretable RNA Analysis), a layer-wise sparse-autoencoder (SAE) analysis of BiRNA-BERT that extracts interpretable sparse features while preserving the behaviour of the underlying language model. We train independent sparse autoencoders at layers 0, 5, and 11, each expanding the 768-dimensional hidden state into 6,144 dictionary features. Analysis of the learned features reveals biologically meaningful structure and family selectivity. Sparse features align with bpRNA nucleotide-level secondary-structure annotations and RNAcentral type labels: at layer 5, 44.3% of tested features show statistically significant structure association (mean enrichment of 1.61 x), and all 1,237 eligible features show significant RNA-type association. RNA-type-selective sparse profiles modestly improve k-nearest-neighbour balanced accuracy over dense BiRNA-BERT embeddings at layer 5. Together, these results show that sparse autoencoders can recover faithful, nucleotide-aware, and biologically interpretable feature decompositions from BiRNA-BERT.

bioinformatics↗

Knowledge, Attitudes and Practices (KAP) of Cat Owners Towards Flea Infestation and Flea-Borne Diseases (FBDs) in Selected Regions of Bangladesh

Background: Flea infestation is an important companion-animal health problem and a prime source of zoonotic exposure. However, information on cat owners awareness and preventive behavior regarding fleas and flea-borne diseases (FBDs) in Bangladesh is limited. This study assessed the knowledge, attitudes and practices (KAP) of cat owners regarding flea infestation and flea-borne diseases in selected areas of central Bangladesh. Methods: A cross-sectional survey was conducted from November 2025 to July 2026 among 238 cat owners attending veterinary clinics in Savar, Dhamrai and Manikganj Upazila. Data were collected using a pretested structured questionnaire covering respondent characteristics, flea biology and transmission, perceived risks, and flea-prevention and control practices. Descriptive statistics were used to summarize the findings, and respondents were classified according to their overall KAP scores. Results: Of the respondents, 47.1% owned cats with outdoor access and 77.7% reported that their pets had previously experienced flea infestation. Although 65.5% used flea-control treatments, awareness of zoonotic and disease-transmission risks was limited. Only 14.7% recognized that fleas can parasitize humans, while 17.6% knew that fleas can transmit infectious agents. Overall, 83.2% of respondents had poor knowledge, whereas 69.7% demonstrated moderate attitudes and 63.9% showed moderate practices. Good knowledge and good practice were uncommon, accounting for only 3.8% and 4.6% of respondents, respectively. Veterinary recommendation was the most frequently reported motivation for using flea-control products. Conclusions: Cat owners attending in the surveyed areas frequently reported flea exposure and treatment use, but substantial gaps remained in their understanding of flea biology, zoonotic potential and comprehensive control. Targeted veterinary education emphasizing routine prevention, treatment of all susceptible household animals and environmental management is needed. These findings provide regional baseline evidence and should not be interpreted as nationally representative. Keywords: Bangladesh; cat owners; ectoparasites; flea-borne diseases; flea control; knowledge, attitudes and practices; One Health.

scientific communication and education↗

Adaptive Replication Fork Acceleration by CDK1-Cyclin B1 Sustains Genome Duplication despite Impaired Origin Firing

Although MTBP is essential for replication origin firing, we show here that strong depletion of MTBP can have minor effects on DNA replication rates. This suggests an adaptive process in the DNA replication program, so we examined mechanisms underlying this plasticity. Using an auxin-inducible degron to deplete MTBP, we found that acute suppression of MTBP blocked DNA replication, but that replication rates recovered over time. The timing of this recovery paralleled S phase expression of Cyclin B1, and inhibition of CDK1-Cyclin B1 prevented the recovery. Recovery did not involve restoration of origin firing; instead, replication recovered through accelerated fork progression. Consistent with CDK1 driving this acceleration, ATR inhibition, which activates CDK1, stimulated DNA replication in MTBP-depleted cells through CDK1-dependent increased fork progression rather than increased origin firing. Knockdown of RIF1, a known CDK1 target, phenocopied this effect. Although RIF1 is best known for opposing DDK-dependent MCM phosphorylation at origins, we find that RIF1 knockdown stimulates replication even when DDK is inhibited. Furthermore, RIF1 loss increased replication by accelerating fork progression rather than increasing origin firing. Together, these findings reveal a CDK1-RIF1-dependent mechanism that promotes fork speed during S phase and defines a form of replication plasticity in which fork rate compensates for reduced origin firing. SIGNIFICANCE STATEMENTAccurate genome duplication requires thousands of replication origins to fire and replication forks to complete DNA synthesis on schedule. When origin firing is compromised, it is unclear how cells avoid replication failure. We show that cells adapt to persistent loss of the origin-firing factor MTBP by accelerating replication fork progression through a CDK1-RIF1-dependent mechanism, partially compensating for reduced initiation. This adaptive response defines a form of replication plasticity in which cells rebalance origin usage and fork speed to sustain DNA synthesis. This mechanism may be especially relevant in cancer cells or other contexts where replication initiation is chronically stressed.

molecular biology↗

ITK Deficiency Attenuates Alveolar Hemorrhage by Enhancing Regulatory T Cell-Mediated Tissue Resilience

Pulmonary hemorrhage (PH) is a life-threatening manifestation of systemic autoimmunity caused by immune-mediated disruption of the alveolar capillary barrier. Despite high mortality, the molecular checkpoints that shift destructive inflammation toward protective immune regulation remain poorly defined. Here, using the pristane-induced PH model, we identify interleukin-2-inducible T cell kinase (ITK) as a critical regulator of autoimmune lung injury. ITK deficiency (ITK-/- ) conferred near-complete protection from PH and associated multiorgan injury, accompanied by reduced proinflammatory monocytes and neutrophils and increased Foxp3 regulatory T cells (Tregs). Adoptive transfer of ITK-/-; Tregs protected wild-type recipients from PH and suppressed systemic proinflammatory cytokines, identifying Tregs as key mediators of tissue protection. Mechanistically, lung ITK-/- ; Tregs exhibited increased amphiregulin, a mediator of tissue repair. Transcriptomic profiling further showed that ITK loss reprogrammed Tregs toward a metabolically and functionally enhanced state, with enrichment of oxidative phosphorylation, mTORC1 and STAT5 signaling, and tissue-repair programs. These findings establish ITK as a regulator of the balance between pulmonary injury and reparative immunity and support targeting the ITK axis in severe inflammatory lung disease.

immunology↗

Chemical Proteomic Profiling of the Histaminylation Proteome in Cancer Cells Unveils Uncharted Epigenetic Marks on Core Histones

Histamine is a key signaling molecule in pathophysiology that can exhibit significant regulatory roles in diverse health and disease status. Besides the well-studied noncovalent interactions between histamine and its receptors, protein histaminylation is a recently discovered mechanism of action, through which histamine regulates cellular signaling pathways in a covalent modification manner. Histaminylation is an emerging protein post-translational modification, where an isopeptide bond is formed between the histamine primary amine and {gamma}-carboxyl group of glutamine through a transamidation reaction catalyzed by transglutaminase 2 (TGM2). However, due to the lack of efficient pan-specific antibodies targeting histaminylated glutamine, the histaminylation proteome in cells remains poorly explored. Here, we report the design and development of a novel N{tau}-propargylated histamine (N{tau}-PH) probe as well as its successful application in chemical proteomic profiling of the histaminylation proteome in cancer cells. Notably, new TGM2-catalyzed epigenetic marks on core histones, e.g., H2AX-Q84 and Q104 histaminylation, have been identified from cancer cells and verified. Lastly, the crosstalk between H2AX histaminylation and {gamma}H2AX formation was discovered in this study, suggesting that TGM2-mediated histaminylation plays a critical role in DNA damage responses.

biochemistry↗

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↗

Plasmalogen-Independent Neuroprotection: Synthetic alkyl ether lipids activate signaling to mitigate neuroinflammation and enhance cognitive function

Neuroinflammation is a key driver of neurodegenerative disorders, with chronic activation of the NF-{kappa}B pathway contributing to neuronal dysfunction and disease progression. In this study, we report that KIT-8, a synthetic alkyl ether lipid, exerts potent anti-inflammatory and neuroprotective effects despite its inability to be converted into plasmalogens within cells unlike its analog KIT-13, which is known to generate plasmalogens. Remarkably, KIT-8 activates key intracellular signaling pathways, including phosphorylation of ERK and AKT, and enhances brain-derived neurotrophic factor (Bdnf) expression in Neuro2A cells, thereby mimicking the actions of both KIT-13 and natural plasmalogens. Furthermore, KIT-8 significantly improves memory function in mice, underscoring its inherent therapeutic potential. Importantly, the biological activity of KIT-8 suggests that plasmalogen synthesis is not required for its functional effects, introducing a novel concept in ether lipid biology. Supporting this notion, we identified additional alkyl ether lipid analogs, KIT-19 and KIT-20, which also demonstrated anti-inflammatory properties despite lacking the ability to generate plasmalogens. These findings indicate that the ether bond structure alone may be sufficient to confer biological activity. To explore this further, we designed and synthesized a series of structurally distinct alkyl ether lipids (KIT compounds) retaining an ether bond at the sn-2 position. In an LPS-induced inflammatory model using mouse-derived microglial MG6 cells, selected compounds KIT-8, KIT-19, and KIT-20 significantly suppressed NF-{kappa}B signaling, reduced p65 nuclear translocation, and downregulated the expression of pro-inflammatory mediators IL-1{beta} and NOS2. Given the cognitive benefits associated with plasmalogens in Alzheimers disease, our findings position alkyl ether lipids as promising standalone bioactive molecules, capable of mitigating neuroinflammation and enhancing neuronal function independently of plasmalogen synthesis.

neuroscience↗

β-Catenin Stabilization Protects Against Pulmonary Hemorrhage Through Amphiregulin and BATF- Mediated Regulatory T Cells

Pulmonary hemorrhaging (PH) is a life-threatening condition with a high mortality rate, yet the role of immune cells in its pathogenesis remains poorly defined. Here, we investigated the protective function of {beta}-catenin stabilization in T cells and its impact on PH. Using a novel transgenic mouse model (CAT-Tg) with stabilized {beta}-catenin, we demonstrate that {beta}-catenin stabilization induces a distinct T-cell phenotype characterized by an expansion of central effector memory cells (CD44, CD122, Eomes, T-bet). Mechanistically, this effect was associated with suppression of key proinflammatory pathways, including reduced phosphorylation of STAT1, STAT3, and JAK1. PH was induced using pristane, and CAT-Tg mice were significantly protected from lung damage, showing reduced proteinuria and decreased pulmonary proinflammatory cytokine production compared with wild-type (WT) and T cell-specific {beta}-catenin knockout (cKO) mice. This protection correlated with a marked increase in FOXP3 regulatory T cells (Tregs) in CAT-Tg mice. We further identified a novel mechanism in which {beta}-catenin stabilization enhances lung expression of Amphiregulin and BATF, two molecules essential for Treg function and tissue repair. Adoptive transfer of CAT-Tg Tregs into WT mice with pristane-induced PH conferred superior protection, as evidenced by reduced lung inflammation and proteinuria. The systemic administration of a {beta}-catenin agonist to mice with PH significantly attenuated disease severity. Our bioinformatic analysis confirmed that {beta}-catenin stabilization upregulates pathways associated with tissue repair and immune homeostasis, including PI3K-Akt, angiogenesis, and STAT5 signaling. Collectively, these findings reveal that {beta}-catenin stabilization protects against pulmonary hemorrhage by inducing a specialized T-cell phenotype and establishing a protective Amphiregulin-BATF-Treg axis. This study identifies a novel immunomodulatory pathway with therapeutic potential for PH and other inflammatory lung diseases.

immunology↗

Metatranscriptomic Insights into Host-Microbiome Interactions Underlying Asymptomatic COVID-19 Cases

In recent years, the research on Coronavirus disease 2019 (COVID-19) has surged rapidly due to its infectious nature and epidemiological importance as a pandemic. Association of other pathogenic microbes or different human microbiomes with COVID-19 severity is well established. While much is known about COVID-19, studies exploring how host-pathogen interactions at the transcriptomic level influence disease severity are still limited. This research focuses on metatranscriptomic perspective of COVID-19 patients from different Bangladeshi cohorts. Metatranscriptomic sequencing was performed using the extracted RNA of forty different nasopharyngeal samples. After preprocessing and assembly of the genome sequence data, taxonomic identification and diversity along with antibiotic resistance pattern was analyzed using different bioinformatic pipelines. COVID-19 positive and asymptomatic positive patients had a higher abundance of pathogenic and multidrug resistant bacteria whereas the Healthy or recovered patients had higher fungal population. Differential gene expression analysis was also performed to identify the upregulated and downregulated genes responsible for different biological and immunological pathways of humans. Here, immunological response related genes were mostly upregulated in positive cases which was also evident in the proinflammatory cytokines upregulation. Moreover, asymptomatic positive cases showed low TLR-4 expression, which is key to recognizing pathogen-associated molecular patterns (PAMPs) and triggering pro-inflammatory immune responses. This study can clarify the gene expression and signaling pattern of COVID-19 patients with different severity. This may also suggest that some populations exhibit reduced basal expression of TLR-4, which may suppress innate immune activation following infection and contribute to asymptomatic clinical outcomes; however, this hypothesis requires further investigation. Future studies should aim to validate these associations using larger, ethnically diverse cohorts with comprehensive clinical and demographic data.

microbiology↗

Structure-Guided Discovery and Characterization of Novel FLT3 Inhibitors for Acute Myeloid Leukemia Treatment

FLT3 (FMS-like tyrosine kinase 3), a receptor tyrosine kinase, is frequently mutated in acute myeloid leukemia (AML), a hematologic malignancy marked by aggressive proliferation, poor prognosis, and high relapse rates. Although FDA-approved FLT3 inhibitors exist, their clinical efficacy is often undermined by resistance and off-target effects, underscoring the critical necessity for more effective and selective agents. Here, we employed a structure-based computational approach combining pharmacophore screening via Pharmit and the MolPort compound library to identify novel FLT3 inhibitors. Pharmacophore modeling, virtual screening, and docking identified two promising leads, MolPort-002-705-878 and MolPort-007-550-904, with binding affinities of -11.33 and -10.66 kcal/mol, correspondingly. These compounds were further characterized through molecular dynamics (MD) simulations, incorporating Principal Component Analysis (PCA), free energy landscape (FEL) analysis, density functional theory (DFT) calculations, and ADMET profiling. MD results supported the integrity of the FLT3-lead complexes; DFT revealed favorable reactivity, and ADMET predictions indicated drug-likeness with low toxicity, pending experimental confirmation. This integrated in silico pipeline highlights the potential of these molecules as next-generation FLT3 inhibitors and offers a scalable strategy for targeted AML therapeutics.

biochemistry↗

Alcohol consumption drives sex- and region- specific disruption of somatostatin signaling in mice

The prefrontal cortex (PFC), which is thought to be disrupted early in the cycle of substance use and addiction [1], is comprised of a complex microcircuit of long-range glutamatergic pyramidal neurons controlled by GABAergic-expressing local inhibitory neurons [2, 3]. Somatostatin (SST)-expressing neurons are a subpopulation of these local GABAergic inhibitory cells and provide both peptidergic and GABAergic control over these PFC circuits [3, 4], and are disturbed following alcohol consumption in humans [5] and in rodent models [6, 7]. However, little is known about how endogenous SST peptide signaling is affected by alcohol. Using ex vivo electrophysiology, immunohistochemistry, in situ hybridization, and behavior, we demonstrate robust down-regulation of SST control over pyramidal output activity in the prelimbic (PL), but not infralimbic (IL), PFC after alcohol exposure. We also show this is likely mediated by changes in SST receptor expression levels and not disrupted expression or capacity for release of SST peptide, suggesting postsynaptic homeostatic changes to SST signaling following binge alcohol consumption in mice that may underlie post-alcohol dysregulation in mood. This provides insight into how voluntary alcohol consumption disrupts PFC peptide signaling and suggests a potential therapeutic target for the treatment of alcohol use disorder (AUD).

neuroscience↗

Novel plasmalogen derivative KIT-13 restores neurological function in a mouse model of Rett syndrome by reducing neuroinflammation and restoring mitochondrial function

Neurodevelopmental disorders, including Rett Syndrome (RTT), have no functional cure and cause substantial levels of disability. Neuroinflammation is now strongly associated with both neurodevelopmental disorders and neurodegenerative diseases, providing a strong rationale for development of novel therapeutics targeting common neuroinflammatory mechanisms. RTT is caused by mutations in the methylated DNA binding factor MECP2. Mecp2-deficient (Mecp2-KO) mice, which have been extensively characterized as a mouse model of RTT, exhibit high levels of neuroinflammation, mitochondrial dysfunction, and severe neurological symptoms similar to RTT patients. KIT-13 is a novel plasmalogen derivative being developed for the treatment of neurodevelopmental disorders including RTT. This study evaluated KIT-13 in both cell-based and in vivo models for its potential to inhibit neuroinflammation and address underlying mitochondrial dysfunction, as well as effects on RTT-like neurological symptoms in the RTT mouse model. Oral administration of KIT-13 to Mecp2-KO mice significantly reduced neurological symptoms assessed by a composite score evaluating mobility, gait, hindlimb clasping, tremor, breathing, and general condition and improved the life span of the RTT model mice. In addition, KIT-13 suppressed mitochondrial DNA leakage associated with Mecp2 deficiency, and significantly suppressed neuroinflammation as measured by microglial cell morphology. These results suggest that KIT-13 may be a promising therapeutic agent for RTT and other neuroinflammation-related diseases.

neuroscience↗

Dynamic regulation of origin firing factors links CDK activity to dormant origin activation

Dormant replication origins help ensure complete genome duplication when replication forks stall, yet how these origins are activated remains poorly understood. Here, we identify a novel regulatory mechanism by which cyclin-dependent kinase (CDK) activity controls the abundance and chromatin recruitment of the origin firing factors TRESLIN and MTBP to promote dormant origin activation. Inhibition of WEE1 kinase during S phase increases CDK activity, which blocks the PCNA-dependent degradation of TRESLIN and enhances its chromatin association along with MTBP. This increased loading is required for elevated helicase recruitment and DNA synthesis under CDK-hyperactive conditions. These effects are reversed by CDK inhibition and depend on both TRESLIN and MTBP. We define a conserved sequence within TRESLIN required for its CDK-sensitive degradation. Significantly, the recruitment of TRESLIN-MTBP and loading of helicase exceed levels observed in unperturbed S phase, supporting a model in which dormant origin firing is actively upregulated through CDK-mediated stabilization of the initiation machinery. These findings uncover a new control point in replication origin usage with implications for genome stability and therapeutic kinase inhibition.

cell biology↗

Adolescent alcohol consumption alters sex-specific behaviors associated with prefrontal functional connectivity in mice

The prefrontal cortex (PFC) is one of the last brain regions to fully mature, making it particularly sensitive to drug use early in life. Both human and rodent studies find long-lasting behavioral changes after adolescent alcohol exposure that implicate underlying disruptions in PFC development, including structural abnormalities and altered brain functional connectivity. Few rodent studies have been conducted to understand the network-level implications of these disruptions. We assessed how adolescent binge-like alcohol consumption in a drinking in the dark (DID) model affected adult alcohol consumption, behavioral exploration, and brain-wide functional connectivity in mice. Approximately one month after the conclusion of DID, only female mice exposed to alcohol during adolescence exhibited aversion-resistant alcohol preference in adulthood. Adult females exhibited additional sex-specific changes in exploratory behavior in the elevated plus maze after adolescent alcohol consumption. Resting state neuroimaging revealed sex-specific changes in prefrontal cortical connections with sensory motor, hippocampal, striatal, and other networks, providing insights into the putative systems underlying deficits caused by adolescent alcohol exposure. Critically, our data corroborate a growing body of literature in human and rodent studies demonstrating that adolescent alcohol use may increase risk for adult alcohol use more strongly in females. Finally, we identify neural correlates of this effect that include both known and novel neural networks and tie these back to human datasets, allowing biological and mechanistic targets to be further explored for future study and interventions.

neuroscience↗

Dirt floors and domestic animals are associated with soilborne exposure to antimicrobial resistant E. coli in rural Bangladeshi households

Soil can harbor enteropathogens and antimicrobial-resistant organisms in settings with domestic animals. We enrolled 49 households with young children (28 soil floors, 21 concrete floors) in Bangladesh and recorded animal ownership/management. Staff swabbed the floor of childrens sleeping area with a sterile sponge and collected floor dust and a child hand rinse. We used IDEXX QuantiTray/2000 with and without cefotaxime supplementation to enumerate cefotaxime-resistant and generic E. coli. There was 8.0 g/m2 of dust on soil floors vs. 0.2 g/m2 on concrete floors (p-value=0.005). We detected E. coli on 100% of soil vs. 86% of concrete floors and cefotaxime-resistant E. coli on 89% of soil vs. 43% of concrete floors (p-values<0.05). Cefotaxime-resistant E. coli prevalence on floors was 36% in compounds without animals, 79% in compounds with animals and 100% if animals stayed indoors overnight or the floor had animal feces; associations were strongest for chickens. In multivariable models, generic and cefotaxime-resistant E. coli counts were 1.5-2 log higher on soil vs. concrete floors, and counts on floors and child hands were 0.17-0.24 log higher for every 10 additional chickens owned (p-values<0.05). Efforts to mitigate infections and antimicrobial resistance in low-income countries should test flooring improvements and hygienic animal management. SynopsisIn rural Bangladeshi households, generic and cefotaxime-resistant E. coli were more common on soil floors than concrete floors and among households with higher cohabitation intensity with domestic animals, especially chickens.

microbiology↗

Type-I nNOS neurons orchestrate cortical neural activity and vasomotion

It is unknown how the brain orchestrates coordination of global neural and vascular dynamics. We sought to uncover the role of a sparse but unusual population of genetically distinct interneurons known as type-I nNOS neurons, using a novel pharmacological strategic to unilaterally ablate these neurons from the somatosensory cortex of mice. Region-specific ablation produced changes in both neural activity and vascular dynamics, decreased power in the delta-band of the local field potential, reduced sustained vascular responses to prolonged sensory stimulation, and abolished the post-stimulus undershoot in cerebral blood volume. Coherence between the left and right somatosensory cortex gamma-band power envelope and blood volume at ultra-low frequencies was decreased, suggesting type-1 nNOS neurons integrate long-range coordination of brain signals. Lastly, we observed decreases in the amplitude of resting-state blood volume oscillations and decreased vasomotion following the ablation of type-I nNOS neurons. This demonstrates that a small population of nNOS-positive neurons are indispensable for regulating both neural and vascular dynamics in the whole brain, raising the possibility that loss of these neurons could contribute to the development of neurodegenerative diseases and sleep disturbances.

neuroscience↗

Biflavonoids can potentially inhibit amyloid beta internalization to mitigate its cytotoxic events

Amyloid-{beta}-42 (A{beta}) peptides are key contributors to Alzheimers disease (AD), with recent studies highlighting a strong link between A{beta} toxicity and its internalization into cells. Targeting the internalization of A{beta} using naturally occurring small molecules could represent a promising strategy for developing therapeutic interventions. In this study, we investigated the effects of biflavonoids on inhibiting the internalization of A{beta} and its impact on cellular processes that lead to cell death. Various biochemical techniques were employed to assess the ability of biflavonoids to prevent A{beta}42 uptake and to elucidate the underlying mechanisms of their inhibitory action. Our findings revealed that biflavonoids exert a dose-dependent inhibitory effect on A{beta} toxicity. The cytoprotective effects of biflavonoids were primarily attributed to their ability to block A{beta} internalization, as confirmed through confocal microscopy and validated by western blot analysis. By preventing A{beta} entry into cells, biflavonoids also inhibited A{beta}-induced lamin fragmentation and caspase activation, both of which are critical steps in A{beta}-mediated cytotoxicity. Furthermore, we explored the influence of biflavonoids on the aggregation process of A{beta}, including fibril, oligomer, and {beta}-sheet formation, and found that biflavonoids effectively inhibited these conformational changes. Based on these results, we propose that biflavonoids suppress A{beta} cytotoxicity by blocking its conformational changes and subsequent internalization, thereby highlighting their potential as anti-amyloidogenic therapeutic agents.

cell biology↗

Pathogens and Antimicrobial Resistance Genes in Household Environments: A Study of Soil Floors and Cow Dung in Rural Bangladesh

In low- and middle-income countries, living in homes with soil floors and animal cohabitation may expose children to fecal organisms, increasing risk of enteric and antimicrobial-resistant infections. Our objective was to understand whether cow cohabitation in homes with soil floors in rural Bangladesh contributed to the presence and diversity of potential pathogens and antimicrobial resistance genes (ARGs) in the home. In 10 randomly selected households in rural Sirajganj District, we sampled floor soil and cow dung, which is commonly used as sealant in soil floors. We extracted DNA and performed shotgun metagenomic sequencing to explore potential pathogens and ARGs in each sample type. We detected 6 potential pathogens in soil only, 49 pathogens in cow dung only, and 167 pathogens in both soil and cow dung. Pathogen species with relative abundances >5% in both soil floors and cow dung from the same households included E. coli (N=8 households), Salmonella enterica (N=6), Klebsiella pneumoniae (N=2), and Pseudomonas aeruginosa (N=1). Cow dung exhibited modestly higher pathogen genus richness compared to soil floors (Wilcoxon signed-rank test p=0.002). Using Bray-Curtis dissimilarity, pathogen species community composition differed between floors and cow dung (PERMANOVA p<0.001). All soil floors and cow dung samples contained ARGs against antibiotic classes including sulfonamides, rifamycin, aminoglycosides, lincosamides, and tetracycline. Paired floor and cow dung samples shared ARGs against rifamycin. Our findings support the development of interventions to reduce soil and animal feces exposure in rural, low-income settings. ImportanceIn low-income countries, inadequate housing materials and animal cohabitation can lead to fecal contamination of rural homes. Contaminated soil floors are difficult to clean and may harbor organisms causing illness and antibiotic resistance, especially in young children, who frequently ingest soil. We sequenced soil floor and cow dung samples from households in Sirajganj district, Bangladesh and identified pathogens and antibiotic resistance genes. We detected 167 pathogens in both soil and cow dung; pathogens present in both sample types at the highest relative abundances were E. coli, Salmonella enterica, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Antibiotic resistance genes were found in all samples. In cow dung, the most common genes conferred resistance to the antibiotics lincosamide, rifamycin, cephamycin, and tetracycline. In soil floors, the most common genes conferred resistance to rifamycin, sulfonamides, and aminoglycosides. Household soil and cow dung may be important reservoirs of pathogens and antimicrobial resistance in low-income countries.

microbiology↗