Biology subjects

Hasan, M. S.

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

9 recordsLinked to original sources

bioRxiv2026

Bispecific VSV-G Engagers: A Platform for Cell-Type-Specific Delivery of Viral Vectors

VSV-G-pseudotyped lentiviral vectors (LVVs) enable highly efficient ex vivo gene delivery through the broadly expressed LDL receptor (LDLR) but lack the cell-type specificity required for in vivo applications. To provide cell-type specificity, we developed reversible engagers consisting of a cell-specific ligand or antibody fused to the ~40-amino-acid VSV-G-binding domains of LDLR. Following endocytosis, the engager dissociates, releasing unmodified VSV-G for efficient delivery of the vector cargo. An engager comprising the CEACAM8 N-terminal domain enables selective transduction of CEACAM6-positive epithelial cells. A trimeric CEACAM8-based engager matching the VSV-G homotrimeric spike blocked non-specific VSV infection through LDLR with an IC50 of 16.7 pM, while enabling effective VSV-mediated lysis of CEACAM6-positive tumor cells. An anti-CD3-based trimeric engager selectively transduced non-preactivated T cells in human PBMCs with high transduction efficiency. Engager-mediated in vivo CAR T cell generation resulted in sustained control of human OPM2 multiple myeloma tumors in NSG mice. This platform may further advance in vivo gene therapy, including in vivo CAR T-cell therapy and tumor-directed oncolytic virotherapy.

cell biology↗

bioRxiv2024

Study of Plasma Adiponectin Levels in Patients with Metabolic Syndrome and Therapeutic Indication in Bangladesh

BackgroundThe metabolic syndrome (Met-S) is a cluster of some interrelated common clinical disorders, including central obesity, dyslipidemia, hypertension, and glucose intolerance. Central obesity, accompanied by insulin resistance, is a key factor for the development of metabolic syndrome. Adiponectin is an adipose-specific plasma protein, secreted from adipocyte with anti-atherogenic and insulin-sensitizing activities. PurposeThis study aimed to investigate the relationship of plasma adiponectin levels with metabolic syndrome, related disorders and its drug repurposing through in silico approach. Materials and MethodsFor this study, 269 individuals were recruited with written consent. The participants were selected based on their full medical history, clinical examination, and laboratory reports. Anthropometric measurements as well as blood pressure was measured before sample collection. Fasting blood samples were collected for the estimation of lipid profile, blood glucose, and serum adiponectin levels. ResultsOur results show that the adiponectin levels in the subjects with Met-S were significantly lower than those of without Met-S (p <0.0001). Among the metabolic syndrome risk factors, adiponectin levels were associated with hypertriglyceridemia and reduced HDL-cholesterol (p<0.0001). Three drugs (Saquinavir, Candesartan and Glimepiride) were suggested to control the plasma adiponectin level in the subjects with Met-S. ConclusionsSince the plasma adiponectin levels are significantly lower in patients with Met-S, it might be used as diagnostic & prognostic marker for Met-S disorder and adiponectin targeted drugs might be minimize the Met-S of the subjects.

biochemistry↗

bioRxiv2022

Root architecture plasticity in response to endoparasitic cyst nematodes is mediated by damage signaling

O_LIPlant root architecture plasticity in response to biotic stresses has not been thoroughly investigated. Infection by the endoparasitic cyst nematodes induces root architectural changes that involve the formation of secondary roots at infection sites. However, the molecular mechanisms regulating secondary root formation in response to cyst nematode infection remain largely unknown. C_LIO_LIWe first assessed whether secondary roots form in a nematode-density dependent manner by challenging wild type Arabidopsis plants with increasing numbers of cyst nematodes (Heterodera schachtii). Next, by using jasmonate-related reporter lines and knock-out mutants, we tested if tissue damage by nematodes triggers secondary root formation. Finally, we verified whether damage-induced secondary root formation depends on local auxin biosynthesis at nematode infection sites. C_LIO_LIIntracellular host invasion by H. schachtii triggers a transient local increase in jasmonates, which activates the expression of ERF109 in a COI1-dependent manner. Knock-out mutations in COI1 and ERF109 disrupt the nematode-density dependent increase of secondary roots observed in wildtype plants. Furthermore, ERF109 regulates secondary root formation upon H. schachtii infection via local auxin biosynthesis. C_LIO_LIHost invasion by H. schachtii triggers secondary root formation via the damage-induced jasmonate-dependent ERF109 pathway. This points at a novel mechanism underlying plant root plasticity in response to biotic stress. C_LI

plant biology↗

bioRxiv2021

The genome and lifestage-specific transcriptomes of a plant-parasitic nematode and its host reveal susceptibility genes involved in trans-kingdom synthesis of vitamin B.

Plant-parasitic nematodes are a major, and in some cases a dominant, threat to crop production in all agricultural systems. The relative scarcity of classical resistance genes highlights a pressing need to identify new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major stages of the interaction. This novel approach enabled the analysis of the hologenome of the infection site, to identify metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that the highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is critically important for parasitism. Knockout of either the plant-encoded or the now nematode-encoded steps in the pathway blocks parasitism. Our experiments establish a reference for cyst nematodes, use this platform to further our fundamental understanding of the evolution of plant-parasitism by nematodes, and show that understanding congruent differential expression of metabolic pathways represents a new way to find nematode susceptibility genes, and thereby, targets for future genome editing-mediated generation of nematode-resistant crops.

genetics↗

bioRxiv2021

Glutathione contributes to plant defense against parasitic cyst nematodes

Cyst nematodes (CNs) are an important group of root-infecting sedentary endoparasites that severely damage many crop plants worldwide. An infective CN juvenile enters the hosts roots and migrates towards the vascular cylinder, where it induces the formation of syncytial feeding cells, which nourish the CN throughout its parasitic stages. Here, we examined the role of glutathione (L-{gamma}-glutamyl-L-cysteinylglycine, GSH) in Arabidopsis thaliana upon infection with the CN Heterodera schachtii. Arabidopsis lines with mutations pad2, cad2, or zir1 in the glutamate-cysteine ligase (GSH1) gene, which encodes the first enzyme in the glutathione biosynthetic pathway, displayed enhanced CN susceptibility, but susceptibility was reduced for rax1, another GSH1 allele. Biochemical analysis revealed differentially altered thiol levels in these mutants that was independent of nematode infection. All GSH-deficient mutants exhibited impaired activation of defense marker genes as well as genes for biosynthesis of the antimicrobial compound camalexin early in infection. Further analysis revealed a link between glutathione-mediated plant susceptibility to CN infection and the production of camalexin upon nematode infection. These results suggest that GSH levels affects plant susceptibility to CN by fine-tuning the balance between the cellular redox environment and the production of compounds related to defense against infection.

plant biology↗

bioRxiv2021

Metagenomic diagnosis and pathogenic network profile of SARS-CoV-2 in patients co-morbidly affected by type 2 diabetes

BackgroundThe mortality of COVID-19 disease is very high among males or elderly or individuals having comorbidities with obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes SARS-CoV-2 infected patients metagenomic features with or without type 2 diabetes to identify the microbial interactions associated with its fatal consequences. MethodThis study compared the baseline nasopharyngeal microbiome of SARS-CoV-2 infected diabetic and non-diabetic patients with controls adjusted with age and gender. The mNGS were performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R. ResultsAll three groups possessed significant bacterial diversity and dissimilarity indexes (p<0.05). Spearmans correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r=0.6-1.0, p<0.05), and 109 positive correlations among normal-flora and probiotic bacteria (r>0.6, p<0.05). The SARS-CoV-2 diabetic group exhibited a significant increase of pathogens (p<0.05) and opportunistic pathogens (p<0.05) with a simultaneous decrease of normal-flora (p<0.05). The molecular docking analysis of Salivaricin, KLD4 (alpha), and enterocin produced by several enriched probiotic strains presented strong binding affinity with Shiga toxin, outer membrane proteins (ompA, omp33) or hemolysin. ConclusionThe dysbiosis of the bacterial community might be linked with severe consequences of COVID-19 infected diabetic patients, although few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal-flora and probiotics through dietary changes and reduction of excessive pro-inflammatory states by preventing pathogenic environment might lead to a better outcome for those co-morbid patients.

genomics↗

bioRxiv2019

Mechanism of Interaction of BMP and Insulin Signaling in C. elegans Development and Homeostasis

A small number of peptide growth factor ligands are used repeatedly in development and homeostasis to drive programs of cell differentiation and function. Cells and tissues must integrate inputs from these diverse signals correctly, while failure to do so leads to pathology, reduced fitness, or death. Previous work using the nematode C. elegans identified an interaction between the bone morphogenetic protein (BMP) and insulin/IGF-1-like signaling (IIS) pathways in the regulation of lipid homeostasis. The molecular components required for this interaction, however, were not known. Here we report that INS-4, one of 40 insulin-like peptides (ILPs), is regulated by BMP signaling to modulate fat accumulation. Furthermore, we find that the IIS transcription factor DAF-16/FoxO, but not SKN-1/Nrf, acts downstream of BMP signaling in lipid homeostasis. Interestingly, BMP activity alters sensitivity of these two transcription factors to IIS-promoted cytoplasmic retention in opposite ways. Finally, we probe the extent of BMP and IIS interactions by testing two additional IIS functions, dauer formation and autophagy induction. Coupled with our previous work and that of other groups, we conclude that BMP and IIS pathways have at least three modes of interaction: independent, epistatic, and antagonistic. The molecular interactions we identify provide new insight into mechanisms of signaling crosstalk and potential therapeutic targets for IIS-related pathologies such as diabetes and metabolic syndrome.

cell biology↗

bioRxiv2018

Uncovering missed indels by leveraging unmapped reads

In current practice, Next Generation Sequencing (NGS) applications start with mapping/aligning short reads to the reference genome, with the aim of identifying genetic mutations. While most short reads can be mapped to the reference genome accurately by existing alignment tools, a significant number remain unmapped and excluded from downstream analyses thus potentially discarding important biological information hidden in the unmapped reads. This paper describes Genesis-indel, a computational pipeline that explores the unmapped reads to identify novel indels that are initially missed in the alignment procedure. Genesis-indel is applied to the unmapped reads of 30 Breast Cancer patients from TCGA. Results show that the unmapped reads are conserved between the two subtypes of breast cancer investigated in this study and might contribute to the divergence between the subtypes. Genesis-indel is able to leverage the unmapped reads to identify 72,997 small to large novel high-quality indels previously not found in the original alignments and among them, 16,141 have not been annotated in the widely used mutation database. Statistical analysis shows that these new indels mostly altered the oncogenes and tumor suppressor genes. Functional annotation further reveals that these indels are strongly correlated to pathways of cancer and can have high to moderate impact on protein functions. Additionally, these indels overlap with the genes that are missed in the indels from the originally mapped reads and contribute to the tumorigenesis in multiple carcinomas.

bioinformatics↗

bioRxiv2017

UPS-indel: A Universal Positioning System For Indels

BackgroundIndels, though differing in allele sequence and position, are biologically equivalent when they lead to the same altered sequences. Storing biologically equivalent indels as distinct entries in databases causes data redundancy, and may mislead downstream analysis and interpretations. About 10% of the human indels stored in dbSNP are redundant. It is thus desirable to have a unified system for identifying and representing equivalent indels in publically available databases. Moreover, a unified system is also desirable to compare the indel calling results produced by different tools. This paper describes UPS-indel, a utility tool that creates a universal positioning system for indels so that equivalent indels can be uniquely determined by their coordinates in the new system, which also can be used to compare indel calling results produced by different tools.\n\nResultsUPS-indel identifies nearly 15% indels in dbSNP (version 142) as redundant across all human chromosomes, higher than previously reported. When applied to COSMIC coding and noncoding indel datasets, UPS-indel identifies nearly 29% and 13% indels as redundant, respectively. Comparing the performance of UPS-indel with existing variant normalization tools vt normalize, BCFtools, and GATK LeftAlignAndTrimVariants shows that UPS-indel is able to identify 456,352 more redundant indels in dbSNP; 2,118 more in COSMIC coding, and 553 more in COSMIC noncoding indel dataset in addition to the ones reported jointly by these tools. Moreover, comparing UPS-indel to other state-of-the-art approaches for indel call set comparison demonstrates that UPS-indel is clearly superior to other approaches in finding indels in common among call sets.\n\nConclusionsUPS-indel is theoretically proven to find all equivalent indels, and is thus exhaustive. UPS-indel is written in C++ and the command line version is freely available to download at http://ups-indel.sourceforge.net. The online version of UPS-indel is available at http://bench.cs.vt.edu/ups-indel/.

bioinformatics↗