Biology subjects

Shaheen, N.

Publications and source records attributed to Shaheen, N..

7 recordsLinked to original sources

bioRxiv2026

Critical roles of MCM8 in meiotic recombination during mouse spermatogenesis

Meiotic DNA double-strand break (DSB) formation and repair by homologous recombination is crucial for ensuring proper chromosome segregation. In mice, the mini-chromosome maintenance family protein, MCM8, has been proposed to function in meiotic recombination and its loss leads to infertility, but the underlying mechanisms are poorly understood. Here we used cytological and genomic assays to infer the role of MCM8 during meiotic recombination in mouse spermatocytes. We show that MCM8-deficient spermatocytes exhibit increased levels of SPO11-dependent DSBs at recombination hotspots during early prophase. DSBs are resected normally and accumulate strand-exchange proteins. However, downstream recombination intermediates are barely detected and recombination intermediate-associated MutSgamma foci do not form efficiently. Consistent with a role in early recombination intermediate processing, MCM8 binds to displacement loop (D-loop) structures in vitro. We propose that MCM8 controls meiotic recombination in at least two ways. MCM8 participates in regulating meiotic DSB number. Further, MCM8 plays a role in the formation and/or stability of post-resection recombination intermediates, steps that are critical for DSB repair via recombination and for efficient synapsis of homologous chromosomes during mouse meiosis.

molecular biology↗

bioRxiv2025

High-Frequency Spinal Cord Stimulation Reorganizes Cortical Cross-Frequency Coupling in a Region- and Time-Dependent Manner

Pain management strategies have progressed beyond traditional pharmacologic and physical interventions, integrating advanced neuromodulation techniques such as deep brain stimulation, peripheral nerve stimulation, and high-frequency spinal cord stimulation (hSCS). Despite its clinical efficacy, the supraspinal mechanisms underlying hSCS remain poorly understood. Prior work in sheep demonstrated that hSCS modulates gamma ({gamma}) band (70-150 Hz) activity in the primary somatosensory and association cortices, implicating cortical involvement in pain modulation. Given, the interaction between low and high oscillations, we hypothesized that hSCS modulates {gamma} activity in a region- and time-dependent manner through specific coupling with theta ({square}) rhythms (4-8 Hz). Using 96-channel subdural electrocorticography (ECoG), we computed {square}-{gamma} phase-amplitude coupling (PAC) and the corresponding modulation index (MI) to quantify the effects of hSCS. While the preferred {square}phase of {gamma} activity remained consistent across conditions and regions, MI increased significantly post-stimulation--most prominently in the association cortex, where robust -{gamma} phase locking was observed. In contrast, the somatosensory cortex exhibited weaker and more variable locking. Temporally, both cortices demonstrated an early, rapid increase in MI post-hSCS, accompanied by a shift (association) and attenuation (somatosensory) of the secondary peak. These findings reveal distinct regional and temporal dynamics in PAC following hSCS and suggest complementary roles of somatosensory and association cortices in processing neuromodulatory input. hSCS appears to reorganize cortical cross-frequency interactions, supporting its role in reorganizing functional network dynamics relevant to sensory processing and the subjective pain experience.

neuroscience↗

bioRxiv2025

Proteomic characterization of major fish allergy responsive protein parvalbumins in Hilsa (Tenualosa ilisha): A commercially important fish in Southeast Asia

The protein parvalbumin (PRV)-beta (PRVB) is the primary cause of food allergies to bony fish. Although PRVB is a well-characterized protein in many bony fishes, little is known about the Hilsa, an anadromous fish with great economic importance and predominantly found in Southeast Asia. In this study, we characterized the Hilsa PRV utilizing various proteomic approaches in response to two major riverine habitats and developmental stages. Unique peptide sets corresponding to three PRV isoforms were identified in Hilsa muscle tissues. Label-free quantitative proteomic analysis coupled with ELISA revealed higher levels of PRVB in young fish compared to adults, irrespective of their riverine habitats. A comparative quantitative analysis of PRVB further demonstrated that Hilsa had less PRVB than other commonly consumed freshwater fish species. Multiple reaction monitoring (MRM)-based targeted proteomic approach showed the potential of PRV as a marker protein for allergen quantitation and authenticating the presence of Hilsa in a complex freshwater fish mixture. Our findings collectively offer fundamental knowledge on Hilsa PRVs for further investigation on the food safety and quality evaluation of Hilsa fish.

biochemistry↗

bioRxiv2021

Anti-allergic and anti-inflammatory activities of black cumin extracts in in vitro and in vivo model systems

Black cumin (Nigella sativa) is a widely used ingredient of traditional medicine for its broad-spectrum pharmacological actions, including anti-allergic, bronchial asthma, and anti-inflammatory properties. We sought to evaluate BC extracts efficacy for their anti-allergic and anti-inflammatory properties using a comprehensive in vitro, in vivo, and silico experimental setup. To investigate whether BC extract has anti-inflammatory, anti-allergic, and analgesic therapeutic potentials in vitro and in vivo. The activity of BC was assessed through anti-allergic activity on rat basophilic leukemia-2H3 cell line, anti-inflammatory activity on J774.1A cell line, anti-inflammatory activity by carrageenan-induced rat paw edema, analgesic activity by acetic acid-induced writhing test, and ingenuity analysis of the BC extracts in inflammation control. BC exerted potent anti-allergic activity by inhibiting antigen-induced degranulation. An anti-inflammatory effect is shown by inhibiting TNF- production. The acetic acid-induced writhing test shown a dose-dependent reduction of writhing number following BC administration. Rat paw edema test shown the dose-dependent reduction of paw edema volume following BC administration. Ingenuity Pathway Analysis (IPA) suggested BC extracts containing ferulic acid, p-coumaric acid, kaempferol, and quercetin can inhibit inflammation. This study suggests that bioactive compounds in BC extract act as an anti-allergic and anti-inflammatory agent by regulating several downstream and upstream inflammation pathways.

plant biology↗

bioRxiv2021

Polycomb requires Tcp-1η chaperonin for maintaining gene silencing in Drosophila

In metazoans, heritable states of cell type specific gene expression patterns linked with specialization of various cell types constitute transcriptional cellular memory. Evolutionarily conserved Polycomb group (PcG) and trithorax group (trxG) proteins contribute to the transcriptional cellular memory by maintaining heritable patterns of repressed and active expression states, respectively. Although chromatin structure and modifications appear to play a fundamental role in maintenance of repression by PcG, the precise targeting mechanism and the specificity factors that bind PcG complexes to a defined region in chromosomes remain elusive. Here we report a serendipitous discovery that uncovers a direct molecular interaction between Polycomb (PC) and TCP-1 Ring Complex (TRiC) chaperonin subunit, Tcp-1{eta} in Drosophila. Tcp-1{eta} interacts with PC at chromatin to maintain repressed states of homeotic and non-homeotic targets of PcG, which supports a strong genetic interaction observed between Pc and Tcp-1{eta} mutants. Depletion of Tcp-1{eta} results in dissociation of PC from chromatin and redistribution of an abundant amount of PC in cytoplasm. We propose that Tcp-1{eta} is an important modulator of PC, which helps PC recruitment at chromatin and compromising Tcp-1{eta} can directly influence an evolutionary highly conserved epigenetic network that supervises the appropriate cellular identities during development and homoeostasis of an organism. Significance StatementSilencing of key developmental genes, e.g, Hox genes, by PcG is a hallmark of differential gene expression patterns associated with cell fate determination. Here we describe a previously unknown molecular and genetic interaction of Polycomb (PC) with Tcp-1{eta} subunit of TRiC chaperonin complex in Drosophila. Compromising Tcp-1{eta} function results in de-repression of PcG targets and a concomitant loss of PC from chromatin. Moreover, depletion of Tcp-1{eta} leads to redistribution of PC in cytoplasm. Molecular interaction of PC with Tcp-1{eta} highlights a novel factor which helps PC recruitment at chromatin. We propose that Tcp-1{eta} chaperonin is one of the specificity factors and part of the targeting mechanism that binds PC to specific regions on chromosomes.

genetics↗

bioRxiv2020

Kinome-wide RNAi screen uncovers role of Ballchen in maintenance of gene activation by trithorax group in Drosophila

Polycomb group (PcG) and trithorax group (trxG) proteins are evolutionary conserved factors that contribute to cell fate determination and maintenance of cellular identities during development of multicellular organisms. The PcG behaves as repressors to maintain heritable patterns of gene silencing and trxG act as anti-silencing factors by maintaining activation of cell type specific genes. Genetic and molecular analysis has revealed extensive details about how different PcG and trxG complexes antagonize each other to maintain cell fates, however the cellular signaling components that contribute to maintenance of gene expression by PcG/trxG remain elusive. Here, we report an ex vivo kinome-wide RNAi screen in Drosophila aimed to identify cell signaling genes that facilitate trxG to counteract PcG mediated repression. From the list of trxG candidates, Ballchen (BALL), a histone kinase, known to phosphorylate histone H2A at threonine 119 (H2AT119p), was characterized as a trxG regulator. The ball mutant exhibit strong genetic interaction with Polycomb (Pc) and trithorax (trx) mutants and loss of BALL also affects expressions of trxG target genes in ball mutant embryos. BALL co-localizes with Trithorax on chromatin and depletion of BALL results in increased H2AK118 ubiquitination, a histone mark central to PcG mediated gene silencing. Moreover, analysis of genome-wide binding profile of BALL shows an overlap with 85% known binding sites of TRX across the genome. Both BALL and TRX are highly enriched at actively transcribed genes, which also correlate with presence of H3K4me3 and H3K27ac. We propose that BALL mediated signal positively contributes to the maintenance of gene activation by trxG by counteracting the repressive effect of PcG.

molecular biology↗

bioRxiv2020

Comprehensive studies of Head Maralla, Punjab, Pakistan vegetation for ethnopharmacological and ethnobotanical uses and their elaboration through quantitative indices

Head Maralla is a non-recognized wetland with diversified flora that becomes focus of current studies. Whole plant or their parts are being used for treating various maladies and they are the integral part of livelihood in the area. Unique species including Osmunda regalis is used for blood and renal diseases purifier. Wild plant resources are key to traditional ethnobotanical knowledge based practices and industrial applications. Current study reports Head Marala inhabitants interaction with these resources and identify priorities at species and habitat level for conservation. Four sites viz., River Tavi, Upstream Chenab, River Manawarwala Tavi and Bhalolpur were designated to record traditional knowledge through questionnaire and interviews during field trips. One hundred nineteen (119) plant species were identified belonging to 54 families, of which 87 species were of dicot, 12monocots, 05ferns, and 4 species of bryophytes. Fifty percent of the plant species were utilized as a whole for therapeutic purposes, followed by leaves which had more than 20% usage of total consumption. Ailments viz., urination (14%) followed by cough (8%), cold (7%), stomach (6%), asthma (6%), constipation (5%), laxative (5%), diarrhea (4%) etc., were associated with vegetation. Bronchial disorders, pneumonia, dyspepsia, anthelmintic and kidney stones, etc., were also among other diseases commonly cured by traditional knowledge. Fifteen percent of vegetation contributes as fodder species consumed by local community for livestock while almost 17% of local plants were utilized for industrial purposes like timber, fuel, furniture, wooden pots and sports goods. In conclusion the ecosystem of Head Maralla is a complex of aquatic, terrestrial and agricultural land that is located on climatic and geographical divides, which further add to botanical interest as included many wetland habitats with unique diversity of plants. It is suggested to devise comprehensive conservation strategies to safe indigenous knowledge in systematic way for comprehending ecological services.

plant biology↗