Biology subjects

Shahid, M.

Publications and source records attributed to Shahid, M..

11 recordsLinked to original sources

bioRxiv2026

Heritable morphology-environment correlations among lake populations of threespine stickleback

Phenotypic differences among populations can arise through heritable genetic divergence, phenotypic plasticity, or both, making it difficult to determine whether trait-environment correlations observed in nature reflect adaptive evolution. Within threespine stickleback (Gasterosteus aculeatus) studies, numerous document morphological differences among allopatric-, parapatric-, and even sympatric populations. These phenotypic differences among populations are often correlated with diet and lake habitat (e.g., lake size), suggesting an adaptive value to the population differences. However, many studies of ecomorphological divergence in stickleback use wild-caught stickleback, which may differ due to evolution or plasticity. Although common garden experiments have confirmed that population differences can be heritable, such experiments typically entail small numbers of populations. Consequently, we still do not know to what extent well-known trait-environment correlations in stickleback are a result of evolution. To address this gap, we reared stickleback embryos from 27 lake populations on Vancouver Island, in a laboratory environment. Morphological differences among populations persist in common-garden fish, confirming a large role for divergent evolution. These heritable differences were associated with environmental variation among lakes, implying an adaptive value. However, some well-known trait-environment relationships in stickleback did not persist in common-garden fish and may be primarily plastic.

evolutionary biology↗

bioRxiv2026

Toward Large-Scale Preclinical Neuroimaging: Quantifying Inter-Scanner Variability in Mouse Brain MRI

Multi-site MRI studies in preclinical neuroimaging are emerging, but unlike in human studies, characterization of inter-scanner variability remains limited. In this study, we assessed intra- and inter-scanner variability between two similarly equipped 7 Tesla MRI scanners using a phantom and ex vivo mouse brain specimens. Diffusion-weighted imaging revealed slight differences in gradient amplitudes between the scanners, while estimated apparent diffusion coefficient (ADC) values showed a coefficient of variation below 1.5% and inter-scanner differences below 2% near the magnet center. Volumetric analysis based on proton density-weighted images showed negligible intra-scanner differences across sessions, while inter-scanner volumetric differences were mostly less than 2% and spatially non-uniform across the brain. Quantitative maps of R1, R2*, and MTsat showed inter-scanner relative differences of less than 5%, 10%, and 20%, respectively, with white matter exhibiting greater variability than gray matter. These findings provide a foundation for future large-scale, multi-scanner preclinical neuroimaging studies.

bioengineering↗

bioRxiv2026

Constitutive and inducible fibrosis explain immune variation among threespine stickleback populations

Understanding how immune variation arises in natural populations requires disentangling the relative contributions of host genetic differences, environmental variation, and parasite effects, which is rarely possible in wild systems. Threespine stickleback populations vary in their use of intraperitoneal fibrosis as a defense against the helminth parasite Schistocephalus solidus, providing a natural system to study the genetic and ecological drivers of immune variation. We combined a 46-lake field survey with common garden experiments on 20 representative populations exposed to multiple parasite genotypes to test whether population differences in fibrosis persist under controlled conditions and whether they depend on parasite genotype or lake ecology. Fibrosis variation was strongly heritable, with both constitutive and inducible components persisting under common garden conditions. In contrast, parasite genotype had only a weak effect on fibrosis responses. Moreover, inducible fibrosis covaried with lake environmental conditions, with populations from more eutrophic-like lakes exhibiting stronger responses than those from more oligotrophic-like lakes. Together, these results reveal ecologically structured divergence in heritable immune responses among natural populations.

evolutionary biology↗

bioRxiv2025

Uncovering the Genetic Blueprint of the UAE's National Tree: Genomic Evidence to Guide Prosopis cineraria (L.) Druce Conservation

Prosopis cineraria (L.) Druce is a keystone tree species of the arid and semi-arid regions of the West and South Asia, with critical ecological, cultural, and consevation significance. In the United Arab Emirates (UAE) and other regions of the Arabian Peninsula this beneficial tree is called Ghaf. Despite its importance, genomic resources and population-level diversity data for the tree remain limited. Here, we present the first comprehensive population genomics study of Ghaf, based on whole-genome re-sequencing of 204 individual trees collected across the UAE. Following Single Nucleotide Polymorphism (SNP) discovery and stringent filtering, we analyzed 57, 183 high-quality LD-pruned SNPs to assess population structure, diversity, and gene flow. Principal component analysis (PCA), sparse non-negative matrix factorization (sNMF), and discriminant analysis of principal components (DAPC) revealed four well-defined genetic clusters, broadly corresponding to geographic origins. Genetic diversity varied significantly among groups, with observed heterozygosity (Ho), inbreeding coefficients (F), and nucleotide diversity ({pi}) showing strong population-specific trends. Genome-wide Fixation index F ST scans identified multiple highly differentiated genomic regions, enriched for genes involved in stress response, transport, and signaling. Functional enrichment using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Pfam annotations indicated overrepresentation of protein kinase activity, ATP binding, and hormone signaling pathways. TreeMix analysis revealed gene flow into one of the genetic clusters from both others, suggesting historical admixture and geographic connectivity. To support data interpretation and stakeholder engagement, we developed two web-based tools for interactive visualization of sample geolocation and genetic structure. This work provides foundational insights into the genetic landscape of P. cineraria (L.) Druce, supporting conservation planning and long-term monitoring in the region.

genomics↗

bioRxiv2021

The diversity of quinoa morphological traits and seed metabolic composition

Quinoa (Chenopodium quinoa Willd.) is an herbaceous annual crop of the amaranth family (Amaranthaceae). It is increasingly cultivated for its nutritious grains, which are rich in protein and essential amino acids, lipids, and minerals. Quinoa exhibits a high tolerance towards various abiotic stresses including drought and salinity, which supports its agricultural cultivation under climate change conditions. The use of quinoa grains is compromised by anti-nutritional saponins, a terpenoid class of secondary metabolites deposited in the seed coat; their removal before consumption requires extensive washing, an economically and environmentally unfavorable process; or their accumulation can be reduced through breeding. In this study, we analyzed the seed metabolomes, including amino acids, fatty acids, and saponins, from 471 quinoa cultivars, including two related species, by liquid chromatography - mass spectrometry. Additionally, we determined a large number of agronomic traits including biomass, flowering time, and seed yield. The results revealed considerable diversity between genotypes and provide a knowledge base for future breeding or genome editing of quinoa. O_TBL View this table: org.highwire.dtl.DTLVardef@160e784org.highwire.dtl.DTLVardef@ff8bd1org.highwire.dtl.DTLVardef@13446daorg.highwire.dtl.DTLVardef@11796eeorg.highwire.dtl.DTLVardef@1b607b8_HPS_FORMAT_FIGEXP M_TBL C_TBL

plant biology↗

bioRxiv2021

A chemical strategy toward novel brain-penetrant EZH2 inhibitors

Aberrant gene-silencing through dysregulation of polycomb protein activity has emerged as an important oncogenic mechanism in cancer, implicating polycomb proteins as important therapeutic targets. Recently, an inhibitor targeting EZH2, the methyltransferase component of PRC2, received FDA approval following promising clinical responses in cancer patients. However, the current array of EZH2 inhibitors have poor brain-penetrance limiting their use in patients with CNS malignancies, a number of which have been shown to be sensitive to EZH2 inhibition. To address this need, we have identified a chemical strategy, based on computational modeling of pyridone-containing EZH2 inhibitor scaffolds, to minimize P-glycoprotein activity and here we report the first brain-penetrant EZH2 inhibitor, TDI-6118 (compound 5). Additionally, in the course of our attempts to optimize this compound we discovered TDI-11904 (compound 21); a novel, highly-potent, and peripherally active EZH2 inhibitor based on a 7 member ring structure.

cancer biology↗

bioRxiv2019

CSF sTREM2 correlates with CSF tau in advancing Parkinson’s disease

Parkinsons disease (PD) is the second most common neurodegenerative disease after Alzheimers disease (AD) and affects 1% of the population above 60 years old. Although PD commonly manifests with motor symptoms, a majority of patients with PD subsequently develop cognitive impairment which often progresses to dementia, a major cause of morbidity and disability. PD is characterized by -synuclein accumulation that frequently associates with amyloid beta (A{beta}) and tau fibrils, the hallmarks of AD neuropathologic changes; this co-occurrence suggests that onset of cognitive decline in PD may be associated with appearance of pathologic A{beta} and/or tau. Recent studies have highlighted the appearance of the soluble form of the Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) receptor in CSF during development of AD. Given the known association of microglial activation with advancing PD, we investigated whether CSF and/or plasma sTREM2 increased with progression to PD dementia. We examined 165 participants consisting of 17 cognitively normal elderly, 45 PD patients with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF A{beta} and tau levels revealed that CSF sTREM2 concentrations were elevated in PD subgroups with abnormal tau, but not A{beta}, CSF concentration. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in PD that is associated with cognitive decline.\n\nOne sentence summaryCSF sTREM2 correlates with CSF tau in PD

neuroscience↗

bioRxiv2019

Prototheca zopfii Genotype II induces mitochondrial apoptosis in models of bovine mastitis

Prototheca zopfii is an alga increasingly isolated from bovine mastitis. Of the two genotypes of P. zopfii (genotype I and II (GT-I and II)), P. zopfii GT-II is the genotype associated with acute mastitis and decreased milk production by unknown mechanisms. The objective was to determine inflammatory and apoptotic roles of P. zopfii GT-II in cultured mammary epithelial cells (from cattle and mice) and murine macrophages and using a murine model of mastitis. Prototheca zopfii GT-II (but not GT-I) invaded bovine and murine mammary epithelial cells (MECs) and induced apoptosis, as determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling assay. This P. zopfii GT-II driven apoptosis corresponded to mitochondrial pathways; mitochondrial transmembrane resistance ({Delta}{Psi}m) was altered and modulation of mitochondrion-mediated apoptosis regulating genes changed (increased transcriptional Bax, cytochrome-c and Apaf-1 and downregulated Bcl-2), whereas caspase-9 and -3 expression increased. Apoptotic effects by P. zopfii GT-II were more pronounced in macrophages compared to MECs. In a murine mammary infection model, P. zopfii GT-II replicated in the mammary gland and caused severe inflammation with infiltration of macrophages and neutrophils and upregulation of pro-inflammatory genes (TNF-, IL-1{beta} and Cxcl-1) and also apoptosis of epithelial cells. Thus, we concluded P. zopfii GT-II is a mastitis-causing pathogen that triggers severe inflammation and also mitochondrial apoptosis. Author summaryBovine mastitis (inflammation of the udder) reduces milk production and quality, causing huge economic losses in the dairy industry worldwide. Although the alga Prototheca zopfii is a major cause of mastitis in dairy cows, mechanisms by which it damages mammary tissues are not well known. Here, we used cell cultures and a mouse model of mastitis to determine how Prototheca caused inflammation and cell death in mammary tissues. Prototheca invaded mammary gland cells, from cattle and mice, as well as macrophages (white cells that take up and kill pathogens) and caused cell death by interfering with mitochondria. Furthermore, Prototheca causes severe inflammation and tissue damage when injected into the mammary glands of mice. Although there are two genotypes of P. zopfii, only genotype II causes tissue damage, whereas gentotype I, common in farm environments, does not damage mammary tissues. Since P. zopfii is an alga and not a bacterium, antibiotic treatments, frequently used to treat mastitis in cattle, are not effective against this organism. Understanding how P. zopfii damages mammary tissue and causes mastitis is important new knowledge to promote future development of evidence-based approaches to prevent and treat mammary gland infections with this organism.

microbiology↗

bioRxiv2018

Barley yield formation under abiotic stress depends on the interplay between flowering time genes and environmental cues

Since the dawn of agriculture, crop yield has always been impaired through abiotic stresses. In a field trial across five locations worldwide, we tested three abiotic stresses, nitrogen deficiency, drought and salinity, using HEB-YIELD, a selected subset of the wild barley nested association mapping population HEB-25. We show that barley flowering time genes Ppd-H1, Sdw1, Vrn-H1 and Vrn-H3 exert pleiotropic effects on plant development and grain yield. Under field conditions, these effects are strongly influenced by environmental cues like day length and temperature. For example, in Al-Karak, Jordan, the day length-sensitive wild barley allele of Ppd-H1 was associated with an increase of grain yield by up to 30% compared to the insensitive elite barley allele. The observed yield increase is accompanied by pleiotropic effects of Ppd-H1 resulting in shorter life cycle, extended grain filling period and increased grain size. Our study indicates that the adequate timing of plant development is crucial to maximize yield formation under harsh environmental conditions. We provide evidence that wild barley germplasm, introgressed into elite barley cultivars, can be utilized to improve grain yield. The presented knowledge may be transferred to related crop species like wheat and rice securing the rising global food demand for cereals.

genetics↗

bioRxiv2018

Proteome and microbiota analysis reveals alterations of liver-gut axis under different stocking density of Peking ducks

The aim of this study was to determine the impact of stocking density on the liver proteome and cecal microbiota of Peking ducks. A total of 1,200 ducks with 21-day old were randomly allotted into 5 stocking density groups of 5, 6, 7, 8 and 9 ducks/m2, with 6 replicates for each group. At 40 days of age, duck serum and pectorals were collected for biochemical tests; liver and cecal contents of ducks were gathered for proteome and microbiota analysis, respectively. Serum MDA increased while pectorals T-AOC reduced linearly with enhancing stocking density. Duck lipid metabolism was altered under different stocking density as well. Serum LDL-C increased linearly with increasing stocking density. Proteome analysis revealed fatty acid biosynthesis proteins such as acyl-CoA synthetase family member 2 and fatty acid oxidation related proteins including acyl-CoA dehydrogenase long chain and acyl-coenzyme A oxidase were enriched in high stocking density group. Additionally, high stocking density increased oxidative response related proteins such as DDRGK domain containing 1 while diminished anti-oxidant capacity related proteins including regucalcin and catalase. 16S rDNA analysis revealed that higher stocking density was accompanied with decreased microbial diversity, as well as depletion of anti-inflammatory bacterial taxa, including Bacteroidales, Butyricimonas and Alistipe. In addition, decreased bile acid metabolism-associated bacteria such as Ruminococcaceae, Clostridiales and Desulfovibrionaceae were found in the high-density group. Both proteome and 16S rDNA results showed inflammation and chronic liver disease trend in the high-density group, which suggests the involvement of the liver-gut axis in oxidative stress.

microbiology↗

bioRxiv2017

The genome sequence of the wild tomato Solanum pimpinellifolium provides insights into salinity tolerance

Solanum pimpinellifolium, a wild relative of cultivated tomato, offers a wealth of breeding potential for several desirable traits such as tolerance to abiotic and biotic stresses. Here, we report the genome and annotation of S. pimpinellifolium LA0480. The LA0480 genome size (811 Mb) and the number of annotated genes (25,970) are within the range observed for other sequenced tomato species. We developed and utilized the Dragon Eukaryotic Analyses Platform (DEAP) to functionally annotate the LA0480 protein-coding genes. Additionally, we used DEAP to compare protein function between S. pimpinellifolium and cultivated tomato. Our data suggest enrichment in genes involved in biotic and abiotic stress responses. Moreover, we present phenotypic data from one field experiment that demonstrate a greater salinity tolerance for fruit-and yield-related traits in S. pimpinellifolium compared with cultivated tomato. To understand the genomic basis for these differences in S. pimpinellifolium and S. lycopersicum, we analyzed 15 genes that have previously been shown to mediate salinity tolerance in plants. We show that S. pimpinellifolium has a higher copy number of the inositol-3-phosphate synthase and phosphatase genes, which are both key enzymes in the production of inositol and its derivatives. Moreover, our analysis indicates that changes occurring in the inositol phosphate pathway may contribute to the observed higher salinity tolerance in LA0480. Altogether, our work provides essential resources to understand and unlock the genetic and breeding potential of S. pimpinellifolium, and to discover the genomic basis underlying its environmental robustness.

plant biology↗