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Fatima, T.

Publications and source records attributed to Fatima, T..

6 recordsLinked to original sources

Metabolite profiles distinguish exposure to Dengue and Zika flaviviruses in human induced pluripotent stem cells (hiPSCs)

Flaviviruses such as Dengue virus (DENV), Zika virus (ZIKV) and West Nile Virus (WNV) pose growing public health threats, exacerbated by asymptomatic infections and non-vector transmission. Current diagnostics, including nucleic acid tests and serology, are limited by transient viremia and antibody cross-reactivity, underscoring the need for improved detection methods. We utilized untargeted metabolomics to differentiate DENV and ZIKV infections in human induced pluripotent stem cells (hiPSCs), a model relevant to study virus-host interactions, drug screening, and therapeutic safety. LC-MSbased profiling revealed virus-specific metabolic reprogramming during both acute and long-term infections. DENV3 induced early and sustained activation of metabolic features, while ZIKV-MR766 triggered transient suppression. Long term infection with DENV2, DENV3, or ZIKV-PRV resulted in distinct metabolic signatures in hiPSCs, with ZIKV-PRV showing the greatest divergence. Shared metabolite changes across conditions included amino acids (e.g., tryptophan, glutamate), lipids, and nucleosides. Functional studies demonstrated that tryptophan metabolism regulates infection dynamics: inhibiting serotonin biosynthesis reduced viral load, whereas blocking kynurenine synthesis enhanced viral replication. These findings position metabolomics as a viable approach for flavivirus detection and highlight metabolic pathways as potential therapeutic targets. ImportanceAccurate diagnosis of flavivirus infections remains challenging due to short periods of viremia, high rates of asymptomatic infection, and extensive serologic cross-reactivity among related viruses such as DENV and ZIKV. These limitations complicate clinical diagnosis, surveillance, and screening of human donor tissues. In this study, we demonstrate that untargeted metabolomics can distinguish ZIKV and DENV infections by identifying virus-specific host metabolic signatures during both acute and long-term infection. Using human induced pluripotent stem cells as a clinically relevant model, we show that metabolic reprogramming persists even in the absence of overt cytopathic effects and can reveal functional pathways that regulate viral replication. Our findings highlight host metabolite profiling as a complementary diagnostic strategy that may improve detection of flavivirus exposure, particularly in asymptomatic individuals or settings where conventional molecular and serologic tests are insufficient.

microbiology↗

Zika and Dengue Viruses Differentially Modulate Host mRNA Processing Factors Defining Its Virulence

Rising global temperatures coupled with increasing international travel, and trade are contributing to spread of vectors such as ticks and mosquitoes, resulting in a surge of vector-borne flavivirus infection in human population. Furthermore, this increase in flavivirus infection pose threat to the safety of biologics such as cell and gene therapy products as human-derived materials are commonly used during manufacturing of these drug products. In this study, we conducted time-course transcriptomic and protein analyses to uncover the host molecular factors driving the virulence of Zika virus (ZIKV) and Dengue virus (DENV) in the context of host defense mechanisms, as these two viruses have caused the most recent and significant flavivirus outbreaks. Compared to DENV, ZIKV exhibited stronger virulence and cytopathic effects. RNA sequencing analysis revealed differential expression of various cellular factors, including RNA processing factors. Further investigation identified cell-type and time-dependent upregulation nonsense-mediated RNA decay (NMD), RNA degradation factors and nuclear pore complex (NPC) transcripts. Protein analysis showed that ZIKV, unlike DENV, degrades NMD factors in host cells, which along with mis-regulation of RNA degradation factors resulted in accumulation in host intronic transcripts as revealed by RNA-seq data. We also found that active nuclear transport is required for ZIKV replication, suggesting that therapeutic targeting of the NPC could potentially be effective in controlling ZIKV infection. Furthermore, from our findings we hypothesize that, ZIKV, but not DENV, drives early host cell cytopathy through targeted protein degradation. Current studies are underway to develop novel strategies to detect ZIKV, DENV and other flaviviruses in biologics based on transcriptomics and proteomics. TeaserExploring the molecular basis of flavivirus virulence in host cells.

genomics↗

DNA barcode developement based on chloroplast and ITS genes for species identification of endangered and threated species of Western Ghats, India

Accurate identification is crucial for conserving species, especially in regions such as the Western Ghats, where trade poses a significant threat to endangered and threatened forest species. Traditional morphology-based identification can be challenging and time-consuming, leading to inaccuracies, especially with similar-looking species or dried specimens. Therefore, DNA barcoding offers a potent solution for precise species identification to address illicit trade and address impactful conservation measures. DNA barcoding is a taxonomic technique that uses standardized short DNA sequences to differentiate and classify species. This approach is especially valuable when morphological characteristics alone are insufficient for accurate species identification. In this study, we focused on the development of a DNA barcoding system for the efficient and accurate identification of threatened and endangered important forest species of Western Ghats Karnataka. To develop the DNA barcoding system, a multilocus approach utilizing sixteen standard DNA barcoding markers was used. A total of 47 threatened and endangered forest species from the Western Ghats were selected for this study. Using a larger number of markers to develop DNA barcodes led to the most precise species identification rates. Moreover, the wide availability of DNA barcode databases allows for quick and accurate species identification. In our study, we observed the highest amplification rates for rbcL1 (40 species), psbtrnH2 (36 species), and PsbA-trnH1 (33 species). DNA amplification varied from 11.76% to 94.11%. Notably, the highest DNA amplification rates were detected for A. wightii (94.11%) and A. hondala (92.34%), both of which belong to the Arecaceae and Passifloraceae families, respectively. Sequencing success rates ranged from 37.5% to 100%. This study will aid in the development of a database of available threatened forest species in western Ghats Karnataka and other regions.

plant biology↗

Assessment of Genetic Diversity and Population Genetic Structure of Santalum album L. in India by Genic and Genomic SSR markers

Sandalwood (Santalum album L.) is highly valued aromatic tropical tree. It is known for its high quality heartwood and oil. In this study, 39 genic and genomic SSR markers were used to analyze the genetic diversity and population structure of 177 S. album accessions from 14 populations of three states in India. High genetic diversity was observed in terms of number of alleles 127, expected heterozygosity (He) ranged from 0.63-0.87 and the average PIC was 0.85. The selected population had relatively high genetic diversity with Shannons information index (I) >1.0. 0.02 mean coefficient of genetic differentiation (FST) and 10.55 gene flow were observed. AMOVA revealed that 92% of the variation observed within individuals. Based on cluster and Structure result, individuals were not clustered as per their geographical origin. Furthermore the clusters were clearly distinguished by principal component analysis analysis and the result revealed that PC1 reflected the moderate contribution in genetic variation (6%) followed by PC2 (5.5%). From this study, high genetic diversity and genetic differentiation was found in S. album populations. The genetic diversity information of S. album populations can be used for selection of superior genotypes and germplasm conservation to promote the tree improvement of S. album populations.

molecular biology↗

Comparative Transcriptome Profiling of High and Low oil yielding Santalum album L.

East Indian Sandalwood (Santalum album L.) is highly valued for its heartwood and its oil. There have been no efforts to comparative study of high and low oil yielding genetically identical sandalwood trees grown in similar climatic condition. Thus we intend to study a genome wide transcriptome analysis to identify the corresponding genes involved in high oil biosynthesis in S. album. In this study, 15 years old S. album (SaSHc and SaSLc) genotypes were targeted for analysis to understand the contribution of genetic background on high oil biosynthesis in S. album. A total of 28,959187 and 25,598869 raw PE reads were generated by the Illumina sequencing. 2.12 million and 1.811 million coding sequences were obtained in respective accessions. Based on the GO terms, functional classification of the CDS 21262, & 18113 were assigned into 26 functional groups of three GO categories; (4,168; 3,641) for biological process (5,758;4,971) cellular component and (5,108;4,441) for molecular functions. Total 41,900 and 36,571 genes were functionally annotated and KEGG pathways of the DEGs resulted 213 metabolic pathways. In this, 14 pathways were involved in secondary metabolites biosynthesis pathway in S. album. Among 237 cytochrome families, nine groups of cytochromes were participated in high oil biosynthesis. 16,665 differentially expressed genes were commonly detected in both the accessions (SaHc and SaSLc). The results showed that 784 genes were upregulated and 339 genes were downregulated in SaHc whilst 635 upregulated 299 downregulated in SaSLc S. album. RNA-Seq results were further validated by quantitative RT-PCR. Maximum Blast hits were found to be against Vitis vinifera. From this study we have identified additional number of cytochrome family in SaHc. The accessibility of a RNA-Seq for high oil yielding sandalwood accessions will have broader associations for the conservation and selection of superior elite samples/populations for further genetic improvement program.

plant biology↗

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying several physiological functions such as touch and pain sensing, hearing and proprioception. This process is carried out by specialized mechanosensitive ion channels whose identities have been discovered for most functions except pain sensing. Here we report the identification of TACAN (Tmem120A), an essential subunit of the mechanosensitive ion channel responsible for sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically-evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, knocking down TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to mechanical but not to thermal pain stimuli, without affecting the sensitivity to touch stimuli. We propose that TACAN is a pore-forming subunit of the mechanosensitive ion channel responsible for sensing mechanical pain.

neuroscience↗