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Panchal, S.

Publications and source records attributed to Panchal, S..

5 recordsLinked to original sources

Serum Bile Acid Dysregulation in Polycystic Ovary Syndrome: Quantitative Insights from Mass Spectrometry-Based Profiling

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with substantial metabolic comorbidities, including obesity, insulin resistance, and dyslipidaemia. Beyond their classical digestive role, bile acids (BAs) function as metabolic signalling molecules that regulate glucose and lipid homeostasis and inflammation through receptors such as the farnesoid X receptor (FXR) and Takeda G-protein receptor 5 (TGR5). However, bile acid dysregulation in PCOS remains inadequately characterised. MethodsTargeted serum bile acid profiling was performed in PCOS (n = 86) and healthy controls (n = 60) using a validated LC-MS/MS method. Individual bile acids were quantified and classified into primary, secondary, and conjugated forms. Multivariate analyses were applied to identify group-level metabolic patterns. Functional bile acid indices reflecting hepatic conjugation and microbial transformation were calculated. Correlation analyses assessed between bile acids and clinical variables. ResultsPCOS women exhibited significantly higher serum levels of cholic acid and conjugated bile acids. Multivariate analyses revealed distinct bile acid signatures differentiating PCOS from controls, with deoxycholic acid, taurocholic acid, and cholic acid contributing most strongly to group separation. Pathway-based indices demonstrated an expanded conjugated bile acid pool, an increased conjugated-to-unconjugated bile acid ratio, and altered secondary-to-primary bile acid balance in PCOS. Several bile acids showed significant associations with androgen levels and gonadotropin ratios. ConclusionPCOS is characterised by coordinated alterations in bile acid metabolism, including hepatic synthesis, conjugation, and gut microbial transformation, highlighting bile acids as integrative metabolic signals linking endocrine and metabolic dysfunction in PCOS.

biochemistry↗

Metabolomic Profiling of Serum Biomarkers in Women with Polycystic Ovary Syndrome: Insights from an Untargeted Approach

BackgroundPolycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by metabolic dysregulation. Identifying serum biomarkers can enhance our understanding of its pathophysiology. This study employs an untargeted metabolomic approach to investigate metabolic alterations in PCOS. MethodsSerum samples were collected from 71 women with PCOS and 54 healthy controls. Untargeted Metabolomic profiling was performed using liquid chromatography-mass spectrometry (LC-MS) to identify differentially abundant metabolites. Pathway analysis was conducted to identify key metabolic disruptions, and correlations between identified metabolites and clinical parameters were assessed. ResultsThe metabolomics analysis identified 24 upregulated and 17 downregulated metabolites in PCOS compared with controls. These metabolites mainly include glycerophospholipids, fatty acids, sphingolipids, peptides, ceramides, and steroids. Pathway analysis indicated that these metabolites were enriched in pathways including bile acid biosynthesis, glycerolipid metabolism, tryptophan metabolism, the citric acid cycle, and fatty acid metabolism. Increased levels of branched-chain and aromatic amino acids suggested potential links to insulin resistance. Disruptions in bile acid metabolism pointed to altered gut microbiome interactions. Additionally, metabolites related to oxidative stress and mitochondrial function indicated metabolic dysfunction. Correlation analyses revealed associations between altered metabolites and clinical markers such as insulin resistance and androgen levels. ConclusionThis study reveals distinct serum metabolic alterations in PCOS, emphasizing their association with insulin resistance and inflammation. These findings highlight the potential of metabolomics to identify novel biomarkers for early diagnosis and to develop targeted therapeutic strategies.

biochemistry↗

Cortex-Wide Cellular Imaging in Freely Locomoting Mice Using Cortex Camera Array Microscope (CortexCAM)

Understanding single-cell neuronal activity across multiple brain regions in the context of ethologically relevant behaviors is a major goal in systems neuroscience. We have engineered the Cortex Camera Array Microscope (CortexCAM), integrating four miniaturized fluorescence imaging microscopes to simultaneously capture cellular activity from contiguous fields of view spanning over 48 mm2 of the dorsal cortex. The CortexCAM is capable of imaging > 9000 individual neurons across much of the primary and secondary motor, somatosensory, visual, retrosplenial, and association cortices across both hemispheres of the dorsal cortex. The compact nature of the CortexCAM allows integration into a passive mechanical gantry system to form the mobile CortexCAM. The mobile CortexCAM allows volitional control of the animals translational motion (x, y) and rotational motion (yaw) in physical behavior arenas. We then use the mobile CortexCAM to perform cortex-wide cellular resolution imaging in freely locomoting mice performing alternating choice tasks, as well as during social interactions. Thus the CortexCAM allows studying cortex-wide cellular dynamics in behaviors that cannot be achieved in headfixed settings.

neuroscience↗

Multi omics aided small RNA profiling of wheat rhizosphere and their potential targets in contrasting soils for Rhizoctonia solani-AG8 suppression

Next-generation sequencing helps describe microbial communities in rhizosphere environments, but understanding rhizosphere-plant interactions synergistic effects on plant traits and health outcomes remains challenging. This study analyses rhizosphere sRNAs ability to manipulate host gene targets in plants grown in suppressive (SP) and non-suppressive (NSP) soils with an integrated multi omics dataset. The results showed that rhizosphere sRNAs exhibited specific compositional features that may be important for rhizosphere-plant interaction. Small RNAs, less than 30 nt in size, were predominant in both samples, with a 5-prime bias towards cytosine enrichment, suggesting potential association with wheat specific argonauts. Mapping of sRNA reads to microbial metagenomes assembled draft genomes from SP and NSP soils showed sRNA loci were differentially expressed (DE) between the soils with contrasting disease suppressive capacities. In total, 96 and 132 non redundant rhizosphere sRNAs were abundant in SP and NSP rhizosphere communities, respectively. While 55 known bacterial sRNA loci were predicted from both SP and NSP metagenomes, 127 sRNAs originated from these loci were differentially expressed. Global wheat target prediction and functional analysis from DE rhizosphere sRNAs showed both soil type specific and common pathways. Upregulated NSP sRNAs target metabolic pathways, secondary metabolite biosynthesis, MAPK signalling, while SP sRNAs target glycerophospholipid metabolism, pathways such as polycomb repressive complex, starch/sucrose metabolism, and plant-pathogen interactions were targeted by both sets of sRNAs. This is the first study showing evidence for rhizosphere sRNAs and their corresponding plant transcripts in the context of biological disease suppression in agricultural soils. ImportanceSmall RNAs (sRNAs) have gained attention in host-microbe interactions due to their diverse roles in controlling biological processes. Studies have identified numerous sRNAs with novel functions across various organisms. Echoing growing evidence of sRNAs in different plant-microbe interaction, we show an evidence of rhizosphere sRNAs regulating wheat genes in soil disease suppression context. This understanding could significantly enhance our comprehension of gene regulation in biological functions, potentially paving the way for the development of microbiome-based methods to influence host traits. Understanding the microbiome communitys mechanisms in different environments offers opportunities to modify them for agriculture, including modifying farming practices, host genetics/immunity, and synthetic communities for disease suppression.

molecular biology↗

Early diverging fungus Mucor circinelloides lacks centromeric histone CENP-A and displays a mosaic of point and regional centromeres

Centromeres are rapidly evolving across eukaryotes, despite performing a conserved function to ensure high fidelity chromosome segregation. CENP-A chromatin is a hallmark of a functional centromere in most organisms. Due to its critical role in kinetochore architecture, the loss of CENP-A is tolerated in only a few organisms, many of which possess holocentric chromosomes. Here, we characterize the consequence of the loss of CENP-A in the fungal kingdom. Mucor circinelloides, an opportunistic human pathogen, lacks CENP-A along with the evolutionarily conserved CENP-C, but assembles a monocentric chromosome with a localized kinetochore complex throughout the cell cycle. Mis12 and Dsn1, two conserved kinetochore proteins were found to bind nine short overlapping regions, each comprising an [~]200-bp AT-rich sequence followed by a centromere-specific conserved motif that echoes the structure of budding yeast point centromeres. Resembling fungal regional centromeres, these core centromere regions are embedded in large genomic expanses devoid of genes yet marked by Grem-LINE1s, a novel retrotransposable element silenced by the Dicer-dependent RNAi pathway. Our results suggest that these hybrid features of point and regional centromeres arose from the absence of CENP-A, thus defining novel mosaic centromeres in this early-diverging fungus.

genetics↗