Biology subjects

Rahman, M. T.

Publications and source records attributed to Rahman, M. T..

At least 19 recordsLinked to original sources

bioRxiv2026

Establishment of a cochlear lymphatic vascular network and immune surveillance system following cochlear implantation

Hearing loss is a highly prevalent sensory abnormality often addressed with cochlear implants (CI) that provide auditory rehabilitation for deaf patients. However, a universal inflammatory foreign body response (FBR) to the implanted materials negatively impacts CI outcomes. The mechanistic basis for immune cell infiltration and propagation of the FBR directed against CIs is not defined. Using mouse CI models and quantitative, highly tractable reporters for lymphatics, blood vessels, and immune cells, we identify inner ear lymphatic vessels and changes to the immune surveillance system following cochlear implantation. Histopathological analysis of implanted temporal bones from human subjects shows that both blood vessels and lymphatics are evident within the scala tympani of the implanted cochlea. Our data reveal a rich lymphatic vascular network in the inner ear, closely associated with the perilymphatic and endolymphatic spaces. Lymphatics proliferate within the perilymphatic space of the implanted cochleae and appear to traffic immune cells. Together, our data provide direct evidence that concurrent proliferation of blood vessels and recruitment of blood-borne immune cells comprise an 'immune surveillance system' in the implanted cochleae that promotes the FBR. Our findings also highlight potential opportunities to limit adverse FBR outcomes following cochlear implantation.

systems biology↗

bioRxiv2026

Long-term mitigation of the foreign-body response with dexamethasone-eluting cochlear implants in mice

The inflammatory foreign body response that follows cochlear implantation produces intracochlear fibrosis, neo-ossification, and elevated electrode impedances that can compromise implant performance. Dexamethasone-eluting cochlear implants reduce this response, but the durability of their anti-inflammatory effect over long implantation intervals has not been established. Using a murine model of chronic cochlear implantation in CX3CR1+/eGFP Thy1+/eYFP dual-reporter mice, we compared dexamethasone-eluting and standard mouse cochlear implants at 224 and 336 days post-implantation. Density of CX3CR1+ macrophages, MHCII+CX3CR1+ antigen-presenting macrophages, -SMA+ fibrosis, and neo-ossification were quantified in the scala tympani, Rosenthal canal, and lateral wall of the basal turn. Standard implants produced persistent macrophage and antigen-presenting macrophage infiltration, accompanied by an -SMA+ fibrotic response and neo-ossification. Dexamethasone-eluting implants suppressed macrophage infiltration in all three regions out to 336 days and reduced fibrosis at 224 days. In the subset of cochleae with electrode array translocation, dexamethasone-eluting implants attenuated macrophage infiltration and confined the fibrotic and osseous response to the site of translocation, whereas standard implants produced a widespread response. A reduction in immune cell density was also observed in the contralateral, unimplanted cochleae of animals implanted with dexamethasone-eluting implants, suggesting a wider component to the drug's effect. Dexamethasone-eluting cochlear implants therefore provide sustained, long-term suppression of the cochlear foreign body response in mice, supporting their continued translation toward clinical application. This effect was associated with continued low-level dexamethasone elution out to 336 days post-implantation; further work is needed to assess the durability of this effect at the conclusion of drug elution.

neuroscience↗

bioRxiv2026

CBR4 is essential for mice but not for skeletal muscle function

The mitochondrial fatty acid synthesis (mtFAS) pathway is a highly conserved process in mitochondria implicated in metabolic state sensing. Aberrant functioning of this pathway leads to neurodegenerative diseases in humans. Animal experiments indicates that the mtFAS pathway is essential in mammals, and mtFAS inactivation leads to neuronal cell death. Nuclear encoded mitochondrial 3-ketoacyl-acyl carrier protein reductase (KAR) is a heterotetrameric enzyme in this process, consisting of two CBR4 and two HSD17B8 polypeptides. CBR4 works as the catalytic subunit of the enzyme. Here, we provide evidence that CBR4 function is essential in mammals. In contrast, a skeletal muscle-specific Cbr4 KO in mice did not result in any measurable defects in muscle strength and endurance, and the overall structure of the muscle remained unchanged. The Cbr4 KO did not affect the lipoylation process in quadriceps muscle samples, and high-resolution respirometry analysis of soleus muscle samples showed no defects in mitochondrial respiration capacity. The lack of a phenotype of a muscle-specific Cbr4 KO is consistent with previous reports on a lack of effects of mtFAS inactivation in muscle and re-iterates the question about the existence of bypass mechanisms that can alleviate mtFAS deficiencies in non-neuronal cell types.

physiology↗

bioRxiv2026

DyGraphTrans: A temporal graph representation learning framework for modeling disease progression from Electronic Health Records

MotivationElectronic Health Records (EHRs) contain vast amounts of longitudinal patient medical history data, making them highly informative for early disease prediction. Numerous computational methods have been developed to leverage EHR data; however, many process multiple patient records simultaneously, resulting in high memory consumption and computational cost. Moreover, these models also often lack interpretability, limiting insight into the factors driving their predictions. Efficiently handling large-scale EHR data while maintaining predictive accuracy and interpretability therefore remains a critical challenge. To address this gap, we propose DyGraphTrans, a dynamic graph representation learning framework that represents patient EHR data as a sequence of temporal graphs. In this representation, nodes correspond to patients, node features encode temporal clinical attributes, and edges capture patient similarity. DyGraphTrans models both local temporal dependencies and long-range global trends, while a sliding-window mechanism reduces memory consumption without sacrificing essential temporal context. Unlike existing dynamic graph models, DyGraphTrans jointly captures patient similarity and temporal evolution in a memory-efficient and interpretable manner. ResultsWe evaluated DyGraphTrans on Alzheimers Disease Neuroimaging Initiative (ADNI) and National Alzheimers Coordinating Center (NACC) for disease progression prediction, as well as on the Medical Information Mart for Intensive Care (MIMIC-IV) dataset for early mortality prediction. We further assessed the model on multiple benchmark dynamic graph datasets to evaluate its generalizability. DyGraphTrans achieved strong predictive performance across diverse datasets. We also demonstrated interpretability of DyGraphTrans aligned with known clinical risk factors. The source code and datasets are available at https://github.com/bozdaglab/DyGraphTrans. ContactSerdar.Bozdag@unt.edu SupplementaryUploaded as an attachment.

bioinformatics↗

bioRxiv2025

In vitro model of human subcutaneous adipocyte spheroids for studying mitochondrial dysfunction and mitochondria activating compounds

Mitochondrial abnormalities drive subcutaneous white adipose tissue dysfunction in obesity, leading to metabolic complications. A key challenge in obesity research is the lack of in vitro models to study human adipocyte mitochondria. Here, we establish a human subcutaneous adipocyte spheroid model to characterize mitochondrial metabolism under obesity-relevant conditions and drug exposure. Human preadipocyte spheroids were differentiated in ultra-low attachment plates for 3 weeks in media free of thiazolidinediones. The differentiated adipocyte spheroids showed increased lipid accumulation, adipogenic gene expression, mitochondrial respiration and adiponectin secretion, and a proper response to hormonal stimulation. Lipid mixture administration during differentiation induced metabolic disturbances including mitochondrial respiration failure associated with increased mitochondrial biogenesis. Post-differentiation treatment with rosiglitazone, a peroxisome proliferator-activated receptor {gamma} agonist, improved mitochondrial bioenergetics and adiponectin secretion in lipid mixture-administered adipocyte spheroids. Our model enables precise measurement of adipocyte mitochondria under various conditions, providing a platform for mitochondria-related research and drug discovery in obesity.

molecular biology↗

bioRxiv2024

Antimicrobial resistance, pathogenicity and virulence patterns of Escherichia coli isolated from cockroaches (Blattella germanica) across diverse environments: a public health concern

This investigation explores the prevalence and antimicrobial resistance (AMR) of Escherichia coli isolated from Blattella germanica (cockroaches) from diverse locations, including homes, kitchens, and laboratories, over the course of six months, from August 2022 to January 2023. A total of 125 cockroaches were analyzed, yielding 67 (53%) of positive E. coli isolates, with kitchen environments having the highest incidence (57.77%). The existence of virulence genes (stx1, stx2, and rfbO157) was confirmed by pathogenicity assessments carried out on mouse model, which led to a considerable increase in morbidity and mortality. 82.08% of isolates showed evidence of resistance to at least one antibiotic, according to the antimicrobial susceptibility test with {beta}-lactams displaying the highest rates of resistance. Remarkably, complex resistance patterns were observed in 77.61% of the isolates, which were categorized as multidrug-resistant. Multiple antibiotic resistance genes (ARGs) were found by molecular analysis, particularly blaTEM and tetA as well as virulence-associated genes (VAGs) linked to extraintestinal pathogenic E. coli. Phylogenetic grouping indicated that 90.38% of the MDR isolates belonged to virulent groups B2 and D. These findings highlight the role of cockroaches as potential reservoirs for pathogenic E. coli, raising significant public health concerns regarding AMR. The study underscores the imperative need for thorough investigation and feasible control strategies to ease the dissemination of AMR in diverse contexts.

microbiology↗

bioRxiv2024

Identifying Alzheimer's disease-associated genes using PhenoGeneRanker

Alzheimers disease (AD) is a neurogenerative disease that affects millions worldwide with no effective treatment. Several studies have been conducted to decipher to genomic underpinnings of AD. Due to its complex nature, many genes have been found to be associated with AD. Despite these findings, the pathophysiology of the disease is still elusive. To discover new putative AD-associated genes, in this study, we integrated multimodal gene and phenotype datasets of AD using network biology methods to prioritize potential AD-related genes. We constructed a multiplex heterogeneous network composed of patient and gene similarity networks utilizing phenotypic and omics datasets of AD patients from the Alzheimers Disease Neuroimaging Initiative (ADNI) database. We applied PhenoGeneRanker to traverse this network to discover potential AD-associated genes. To assess the impact of each network layer and seed gene, we also run PhenoGeneRanker on different variants of the network and seed genes. Our results showed that top-ranked genes captured several known AD-related genes and were enriched in Gene Ontology (GO) terms related to AD. We also observed that several top-ranked genes that are not in AD-associated gene list had literature supporting their potential relevance to AD.

bioinformatics↗

bioRxiv2024

Phytochemical screening, analgesic, anti-pyretic and antibacterial potentials of Litsea glutinosa (L) leaves extracts in vivo and in vitro technique

BackgroundLitsea glutinosa leaves (LG) have been used as traditional medicine to treat diseases since ancient times. This study aimed to investigate the cold methanol extract of LG for its analgesic, antipyretic and antibacterial activities, along with preliminary phytochemical screening and acute toxicity test. MethodsIn this study, we first investigated the major phytochemicals group present applying modern chromatographic technique HPLC in addition to conventional methods for Phyto screening in cold methanol extracts LG leaves. Both methods simultaneously demonstrated major bioactive compounds found in the extract were phenol, flavonoid. The purposive efficacy and toxicity were then assessed through preclinical testing ResultsIn hot plate method, the highest pain inhibitory activity was found at a dose of 500 mg/kg of crude extract (3.37{+/-} 0.31sec) which differed significantly (P <0.01 and P <0.001) with that of the standard drug morphine (6.47{+/-} 0.23 sec). The extract significantly prolonged reaction latency to thermal-induced pain in hotplate model. Analgesic activity at 500 mg/kg, LG extract produced a 70% suppression of writhing in mice, which was statistically significant (p<0.001) compared to standard morphines (77.5%) inhibition. In antipyretic activity assay, the crude extract showed notable reduction in body temperature (36.17 {+/-} 0.32{degrees}C) at dose of 300 mg/kg-body weight, when the standard (at dose 100 mg/kg-body weight) exerted (36.32 {+/-} 0.67{degrees}C) after 3 h of administration. In antibacterial studies, results showed that inhibition of bacterial growth at 400 g dose of each extract clearly inhibited growth of bacteria from 11 to 22 mm. The extractives carbon tetrachloride fraction, chloroform soluble fraction, ethyl acetate fraction demonstrated notably greater inhibitory zone widths (p < 0.05) against tested strains. ConclusionOverall, the cold methanol extract of LG leaves demonstrates the therapeutic potential in preclinical settings.

pharmacology and toxicology↗

bioRxiv2024

Supervised Automation of Cell Counting in Confocal Microscopic Cochlear Imaging Datasets Using Macro in Imaris

Analyzing confocal microscopic data of biological samples using the Imaris software poses challenges due to its time-consuming nature involving tedious multiple steps and possibility of human errors. Here, we developed a supervised automation protocol to minimize manual input in cell and spot counting on confocal images obtained from mouse cochlear sections. The protocol increases efficiency by incorporating image recognition and object-oriented macros. Moreover, the protocol being adaptable allows scientists in diverse other fields to customize it for their specific needs. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/604970v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@11b4aa0org.highwire.dtl.DTLVardef@c08c7dorg.highwire.dtl.DTLVardef@1479b59org.highwire.dtl.DTLVardef@280227_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Spiral ganglion neuron degeneration in deafened rats involves innate and adaptive immune responses not requiring complement

Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for effective functioning of cochlear implants, which stimulate SGNs when hair cells are missing. SGNs slowly degenerate following aminoglycoside-induced hair cell loss, a process thought to involve an immune response. However, the specific immune response pathways involved remain unknown. We used RNAseq to gain a deeper understanding immune-related and other transcriptomic changes that occur in the rat spiral ganglion after kanamycin-induced deafening. Among the immune and inflammatory genes that were selectively upregulated in deafened spiral ganglia, the complement cascade genes were prominent. We then assessed SGN survival, as well as immune cell infiltration and activation, in the spiral ganglia of rats with a CRISPR-Cas9-mediated knockout of complement component 3 (C3). Similar to previous findings in our lab and other deafened rodent models, we observed infiltration of macrophages and increased expression of CD68, a marker of phagocytic activity and cell activation, in the deafened ganglia. Moreover, we found that the immune response also includes MHCII+ macrophages and CD45+ and lymphocytes, indicative of an adaptive response. However, C3 knockout did affect SGN survival or macrophage infiltration/activation, indicating that complement activation does not play a role in SGN death after deafening. Together, these data suggest that both innate and adaptive immune responses are activated in the deafened spiral ganglion, with the adaptive response directly contributing to cochlear neurodegeneration.

neuroscience↗

bioRxiv2023

Characterization of β-lactamase and virulence genes in Pseudomonas aeruginosa isolated from clinical, environmental and poultry sources in Bangladesh

The emergence and spread of multidrug-resistant pathogens like Pseudomonas aeruginosa are major concerns for public health worldwide. This study aimed to investigate the prevalence of circulating P. aeruginosa isolated from clinical, environmental and poultry sources in Bangladesh, their antibiotic susceptibility, {beta}-lactamase and virulence gene profiling using standard molecular and microbiology techniques. We collected 110 samples from five different locations, viz., BAU residential area (BAURA; n=15), BAU Healthcare Center (BAUHCC; n = 20), BAU Veterinary Teaching Hospital (BAUVTH; n=22), Poultry Market (PM; n=30) and Mymensingh Medical College Hospital (MCCH; n=23). After overnight enrichment in nutrient broth, 89 probable Pseudomonas isolates (80.90%) were screened through selective culture, gram-staining and biochemical tests. Using genus- and species-specific PCR, we confirmed 22 isolates (20.0%) as P. aeruginosa from these samples. Antibiogram profiling revealed that 100.0% P. aeruginosa isolates (n = 22) were multidrug-resistant isolates, showing resistance against Doripenem, Penicillin, Ceftazidime, Cefepime, and Imipenem. Furthermore, resistance to aztreonam was observed in 95.45% isolates. However, P. aeruginosa isolates showed a varying degree of sensitivity against Amikacin, Gentamicin, and Ciprofloxacin. The blaTEM gene was detected in 86.0% isolates, while blaCMY, blaSHV and blaOXA, were detected in 27.0%, 18.0% and 5.0% of the P. aeruginosa isolates, respectively. The algD gene was detected in 32.0% isolates, whereas lasB and exoA genes were identified in 9.0% and 5.0% P. aeruginosa isolates. However, none of the P. aeruginosa isolates harbored exoS gene. Thus, this study provides novel and important data on the resistance and virulence of P. aeruginosa currently circulating in clinical, environmental and poultry environment of Bangladesh. These data provide important insights into the emergence of {beta}-lactamase resistance in P. aeruginosa, highlighting its usefulness in the treatment and control of P. aeruginosa infections in both humans and animals.

microbiology↗

bioRxiv2022

Genomic diversity of Streptococcus uberis isolated from clinical mastitis of cattle in selected areas of Bangladesh

Streptococci are the major etiology in mastitis, a cause of huge economic losses in the dairy industries. Streptococcus (S.) agalactiae, S. dysagalactiae and S. uberis are mostly encountered in bovine mastitis; however, data on the diversity and characteristics of Streptococcus in clinical mastitis of cattle in Bangladesh is lacking. Thus, the present study was aimed to determine the diversity and antimicrobial resistance pattern of Streptococcus spp. isolated from clinical mastitis of cattle reared in Bangladesh. A total of 105 milk samples comprising eighty (80) from cattle with clinical mastitis (CCM) and twenty-five (25) from apparently healthy cattle (AHC) in four prominent dairy farms and one dairy community were purposively collected and examined in this study. Milk samples were enriched in Luria Bertani broth (LB) and Streptococcus spp. was isolated on Modified Edwards Medium and identified by 16S rRNA gene sequencing. Among eighty (80) clinical samples, eighteen (18) were positive for Streptococcus spp. while none of the milk from AHC revealed Streptococcus by cultural and molecular examination. Sequencing and phylogenetic analysis identified 55.6%, 33.3%, 5.6% and 5.6% of the Streptococcus isolates as S. uberis, S. agalactiae, S. hyovaginalis and S. urinalis, respectively. Antibiotic sensitivity testing with antimicrobials commonly used to treat clinical mastitis revealed 100%, 100%, and 30% of the S. agalactiae, S. hyovaginalis, and S. uberis as multidrug-resistant, respectively. Molecular characterization through whole genome sequencing of five (5) S. uberis isolates identified at least two novel ST types of S. uberis circulating in the study areas with one ST (4/5 isolates) clustered with the isolates from China, India and Thailand, and the other (1/5) with UK, Ireland and Australia. Pan-genome analysis and phylogeny of the core genome sequences also clustered the isolates into two sub-clusters, indicating the presence of at least two different subtypes of S. uberis in the study area. On virulence profiling, all the isolates of this study were found to harbor at least 35 virulence and putative virulence genes probably associated with intramammary infection (IMI) indicating all the S. uberis isolated in this study as potential pathogen. From the overall findings it was evident that Strepococcus occurring in bovine mastitis are diverse and S. uberis genome carries an array of putative virulence factors which need to be investigated genotypically and phenotypically to identify a specific trait or determinant governing the virulence and fitness of this bacterium. Moreover, Streptococcus isolated in this study carried multidrug resistance which needs careful consideration during the selection of a treatment regimen for mastitis.

microbiology↗

bioRxiv2022

Genomic characteristics, virulence and antimicrobial resistance in avian pathogenic Escherichia coli MTR_BAU02 strain isolated from layer farms in Bangladesh

BackgroundColibacillosis, caused by avian pathogenic Escherichia coli (APEC), is one of the most significant infectious diseases affecting poultry worldwide. APEC is one of the leading causes of mortality and morbidity associated with significant economic losses in the poultry industry. ObjectiveThis study was aimed to determine the genomic diversity, virulence factor genes (VFGs) and antimicrobial resistance (AMR) genes in the APEC isolated from layer chickens using whole-genome sequencing (WGS). MethodAPEC MTR_BAU02 strain was isolated from the sick and dead birds. Genomic DNA from APEC MTR_BAU02 strain was extracted using commercial DNA extraction kit, WGS libraries were prepared using the Nextera DNA Flex Library Prep Kit, and finally, paired-end (2 x 250) WGS performed using Illumina MiSeq sequencer. ResultsThe genome size of strain APEC MTR_BAU02 is 4,924,680 bp with a GC content of 51.1% and 4,681 protein-coding sequences. Among the annotated WGS reads, 99.71% reads mapped to Enterobacteriaceae genomes. Based on the phylogenetic analysis of the APEC MTR_BAU02 genome and 99 reference genomes of E. coli, the APEC MTR_BAU02 genome showed sequence similarities with enterotoxigenic E. coli strains isolated from infections of different clinical severity. Metabolic functional annotations detected 380 SEED subsystems including genes coding for carbohydrate metabolism (17.34%), amino acid and derivatives (14.20%), protein metabolism (10.64%), cofactors, vitamins, prosthetic groups and pigments (7.49%), respiration (4.72%), membrane transport (4.49%), stress response (4.47%), motility and chemotaxis (4.46%), and virulence, disease and defense (2.22%). We also detected 92 VFGs and 122 AMR genes in the APEC MTR_BAU02 strain. ConclusionAssessment of these genomic features with functional genomic validation in commonly occurring serogroups of APEC will increase our understanding of the molecular pathogenesis, pave the way to early diagnosis and more effective control of colibacillosis, and improved animal welfare.

genomics↗

bioRxiv2021

Anti-inflammatory therapy protects spiral ganglion neurons after aminoglycoside antibiotic-induced hair cell loss

AO_SCPLOWBSTRACTC_SCPLOWSpiral ganglion neurons (SGNs) relay auditory information from cochlear hair cells to the central nervous system. After hair cells are destroyed by aminoglycoside antibiotics, SGNs gradually die. However, the reasons for this cochlear neurodegeneration are unclear. We used microarray gene expression profiling to assess transcriptomic changes in the spiral ganglia of kanamycin-deafened and age-matched control rats and found that many of the genes upregulated after deafening are associated with immune/inflammatory responses. In support of this, we observed increased numbers of macrophages in the spiral ganglion of deafened rats. We also found, via CD68 immunoreactivity, an increase in activated macrophages after deafening. An increase in CD68-associated nuclei was observed by postnatal day 23, a time before significant SGN degeneration is observed. Finally, we show that the immunosuppressive drugs dexamethasone and ibuprofen, as well as the NAD salvage pathway activator P7C3, provide at least some neuroprotection post-deafening. Ibuprofen and dexamethasone also decreased the degree of macrophage activation. These results suggest that activated macrophages specifically, and perhaps a more general neuroinflammatory response, are actively contributing to SGN degeneration after hair cell loss.

neuroscience↗

bioRxiv2021

CAMO: A molecular congruence analysis framework for evaluating model organisms

CAMO provides a rigorous and user-friendly solution for quantification and mechanistic exploration of omics congruence in model organisms and humans. It performs threshold-free differential analysis, quantitative concordance/discordance scoring, pathway-centric investigation, and topological subnetwork detection. Instead of dichotomous claims of "poorly" or "greatly" mimicking humans, CAMO facilitates discovery and visualization of specific molecular mechanisms that are best or least mimicked, providing foundations for hypothesis generation and subsequent translational investigations.

genomics↗

bioRxiv2021

Virulence and antimicrobial resistance profile of non-typhoidal Salmonella enterica serovars recovered from poultry processing environments at wet markets in Dhaka, Bangladesh

The rapid emergence of virulent and multidrug-resistant (MDR) non-typhoidal Salmonella (NTS) enterica serovars are a growing public health concern globally. The present study focused on the assessment of the pathogenicity and antimicrobial resistance (AMR) profiling of NTS enterica serovars isolated from chicken processing environments at wet markets in Dhaka, Bangladesh. A total number of 870 samples consisting of carcass dressing water (CDW), chopping board swabs (CBS), and knife swabs (KS) were collected from 29 wet markets. The prevalence of Salmonella was found to be 20% in CDW, 19.31% in CBS and 17.58% in KS, respectively. Meanwhile, the MDR Salmonella was found to be 72.41%, 73.21% and 68.62% in CDW, CBS, and KS, respectively. All isolates were screened by polymerase chain reaction (PCR) for eight virulence genes, namely invA, agfA, IpfA, hilA, sivH, sefA, sopE, and spvC. The S. Enteritidis and untyped Salmonella isolate harbored all virulence genes while S. Typhimurium isolates carried six virulence genes except sefA and spvC. Phenotypic resistance revealed decreased susceptibility to ciprofloxacin, streptomycin, ampicillin, tetracycline, gentamycin, sulfamethoxazole-trimethoprim, amoxicillin-clavulanic acid and azithromycin. Genotypic resistance showed higher prevalence of plasmid mediated blaTEM followed by tetA, sul1, sul2, sul3, and strA/B genes. Harmonic and symmetrical trend was observed among the phenotypic and genotypic resistance patterns of the isolates. The research findings anticipate that MDR and virulent NTS enterica serovars are prevailing in the wet market environments which can easily enter into the human food chain. There was a resilient and significant correlation existent among the phenotypic and genotypic resistance patterns and virulence genes of Salmonella isolate recovered from carcass dressing water, chopping board swabs, and knife swabs (p < 0.05), respectively.

microbiology↗

bioRxiv2020

Genetic dissection of the mitochondrial lipoylation pathway in yeast

BackgroundLipoylation of 2-ketoacid dehydrogenases is essential for mitochondrial function in eukaryotes. While the basic principles of the lipoylation processes have been worked out, we still lack a thorough understanding of the details of this important post-translational modification pathway. Here we used yeast as a model organism to characterize substrate usage by the highly conserved eukaryotic octanoyl/lipoyl transferases in vivo and queried how amenable the lipoylation system is to supplementation with exogenous substrate. ResultsWe show that the requirement for mitochondrial fatty acid synthesis to provide substrates for lipoylation of the 2-ketoacid dehydrogenases can be bypassed by supplying the cells with free lipoic acid (LA) or octanoic acid (C8) and a mitochondrially targeted fatty acyl/lipoyl activating enzyme. We also provide evidence that the S. cerevisiae lipoyl transferase Lip3, in addition to transferring LA from the glycine cleavage system H protein to the pyruvate dehydrogenase (PDH) and -ketoglutarate dehydrogenase (KGD) E2 subunits, can transfer this cofactor from the PDH complex to the KGD complex. In support of yeast as a model system for human metabolism, we demonstrate that the human octanoyl/lipoyl transferases can substitute for their counterparts in yeast to support respiratory growth and protein lipoylation. Like the wild-type yeast enzyme, the human lipoyl transferase LIPT1 responds to LA supplementation in the presence of the activating enzyme LplA. ConclusionsIn the yeast model system, the eukaryotic lipoylation pathway can use free LA and C8 as substrates when fatty/lipoic acid activating enzymes are targeted to mitochondria. Lip3 LA transferase has a wider substrate specificity than previously recognized. We show that these features of the lipoylation mechanism in yeast are conserved in mammalian mitochondria. Our findings have important implications for the development of effective therapies for the treatment of LA or mtFAS deficiency-related disorders.

molecular biology↗

bioRxiv2019

The P387 Thrombospondin-4 Variant Promotes Accumulation of Macrophages in Atherosclerotic Lesions

AimsThrombopspondin-4 (TSP4) is a pro-angiogenic protein that has been implicated in tissue remodeling and local vascular inflammation. TSP4 and, in particular, its SNP variant, P387 TSP4, have been associated with cardiovascular disease.\n\nMacrophages are central to initiation and resolution of inflammation and development of atherosclerotic lesions, but the effects of the P387 TSP4 on macrophages remain essentially unknown. We examined the effects of the P387 TSP4 variant on macrophages in cell culture and in vivo in a murine model of atherosclerosis. Further, the levels and distributions of the twoTSP4 variants were assessed in human atherosclerotic arteries.\n\nMethods and ResultsIn ApoE-/-/P387-TSP4 knock-in mice, atherosclerotic lesions accumulated more macrophages than lesions bearing A387 TSP4. The levels of inflammatory markers were increased in lesions of ApoE-/-/P387-TSP4 knock-in mice compared to ApoE-/- mice. Lesions in human arteries from individuals carrying the P387 variant had higher levels of TSP4 and higher macrophage accumulation. P387 TSP4 was more active in supporting adhesion of cultured human and mouse macrophages in experiments using recombinant TSP4 variants and in cells derived from P387-TSP4 knock-in mice.\n\nConclusionsTSP4 supports the adhesion of macrophages and their accumulation in atherosclerotic lesions. P387 TSP4 is more active in supporting these pro-inflammatory events in the vascular wall, which may contribute to the increased association of P387 TSP4 with cardiovascular disease.\n\nAbbreviationsBSA, bovine serum albumin; DMSO, dimethyl sulfoxide; ECM, extracellular matrix; Thbs4-/-, thrombospondin-4 gene knock-out; WT, wild type; P387-TSP4 KI, P387 TSP4 knock-in mice; OCT, Optimum Cutting Temperature; vWF, von Willebrand factor; -SMA, alpha-smooth muscle actin; Egr2, Early Growth Response 2; PBS, Phosphate Buffer saline; DMEM, Dulbeccos Modified Eagle Medium.

pathology↗