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Rasheed, A.

Publications and source records attributed to Rasheed, A..

11 recordsLinked to original sources

Whole-genome resequencing identified loci underwent divergent selection and improved local adaptability in groundnut (Arachis hypogaea)

There is an urgent need to expand groundnut genomics knowledge base to improve yield and adaptability in the target environments. Whole-genome sequencing can discover selective sweeps in the genomic regions distinguishing adaptive from non-adaptive germplasm within target environments. When combined with genome-wide association studies (GWAS), this approach can reveal genes underpinning local adaptability and yield advantage. The objective of this study was to establish a genome-wide quantitative framework form identifying genomic regions under selection, with a particular focus on narrowing down regions associated with important yield and adaptive traits. Moreover, validation of elite haplotype distributions in an independent fully sequenced groundnut panel. A panel of 197 groundnut accessions was subjected to whole-genome sequencing and phenotypic evaluation to dissect the collection into adaptive and non-adaptive subsets to uncover the genomic regions under selection. This was then combined with GWAS to uncover genetic variants governing agronomic traits associated with yield and adaptability. The stringent single and multi-trait analysis identified 60 loci for 12 agronomic traits, of which seven loci controlled multiple yield related traits and were pleiotropic. Within our diversity panel, 48 genomic regions showed signs of selection. Among these selective sweeps, six positively selected loci were co-localized with trait associated loci. A large genomic region on chr2 spanning [~]78 Mb was under divergent selection and harbored genes underpinning yield and 20-pod length. A F-box transcription factor, Arahy.37HYKA, on chr9, and an alanine transferase protein gene, Arahy.E9MTVL, on chr12 carried peak SNPs associated with yield and related traits. We further cross-validated our results in another groundnut355 panel, where the corresponding genes within LD blocks showed significant effects on HKW, pod length and pod weight. The genomic resources developed here provide a high-resolution variation map to delineate the genes underpinning yield and developmental traits in groundnut, improved our understanding of the genetic basis of important agronomic traits, and provide a valuable resource for further functional genomics studies and groundnut improvement programs.

genomics↗

Haplotypes variations of yellow stripe like (TaYSL) genes are associated with grain iron and zinc contents in wheat (Triticum aestivum L.)

The availability of pangenome and resequencing of wheat collections have facilitated the discovery of gene-trait associations in wheat. Yellow stripe-like (YSL) proteins play a key role in the uptake and translocation of metals and yet have not been fully identified and analyzed at the genome-wide level in wheat. In this study, 26 TaYSL genes were identified and divided into four distinct clades, each clade sharing similar domains and motif compositions. Most genes were upregulated under iron deficiency, whereas homoeologs of TaYSL1 were downregulated. Both SNP-based and haplotype-based association studies were used to dissect the role of TaYSLs underpinning grain iron contents (GFeC) and zinc contents (GZnC) in wheat. TaYSL6-2B and TaYSL16-1A haplotypes showed strong association with GFeC, and TaYSL14-6A showed strong association with GZnC in multiple field trials. The distribution of favorable haplotypes in global wheat collection of [~]3000 accessions showed that majority of haplotypes were more prevalent in landraces and winter wheat compared to modern cultivars and spring types, indicating their potential for use in breeding. The combination of favorable haplotypes of three YSL genes associated with GFeC and GZnC were very rare, and most of the wheat accessions has single or double favorable haplotypes. These findings provide the first comprehensive characterization of the TaYSL gene family in wheat and identify significant SNPs and elite haplotypes that can be utilized for genetic improvement and biofortification.

plant biology↗

Discovering genetic loci associated with rate of vegetative index gain using UAV-based phenomics in spring wheat

In wheat, the pre-heading stage determines spikelet formation, floret fertility, and canopy development, making it a critical window for early stress detection and yield potential. The genetic basis of pre-heading canopy development in wheat has remained constrained by the conventional phenotyping due to the low temporal resolution. Here, we quantified the rate of vegetation index gain (RVIs) during tillering to heading stages using UAV-mounted multispectral sensor in 196 spring wheat cultivars representing 112 years of breeding history. RVIs were calculated using six vegetation indices for consecutive two growing seasons, and genome wide association study (GWAS) was performed on RVIs, grain yield (GY) and thousand grain weight (TGW) using a wheat 37K SNP array. RVIs showed significant positive correlations with grain yield (r=0.28-0.43; p<0.001) and consistently increased in the modern cultivars compared to old cultivars. This indicated that resource remobilization during pre-heading canopy development significantly contributed to GY during modern wheat breeding. GWAS identified 67 loci, including 12 Group-I loci associated only with RVIs, and 18 Group-II loci associated with both RVIs and yield traits. Two stable loci on chr1B and chr5D consistently increased GY and RVIs across environments, and the tag SNPs were converted to selectable KASP markers. The allelic distribution on global wheat collection of [~]3000 accessions showcased that favorable alleles on both loci were dominant in cultivars compared to landraces. Similarly, favorable alleles showed more frequency in winter type than spring type. Across breeding eras both alleles showed increasing trend with chr5D reaching near fixation and chr1B remaining partially enriched in modern cultivars. Our work on capturing pre-heading canopy development, discovery of two stable loci underpinning yield and RVIs, and development of KASP markers provided a strong foundation to HTP assisted genetic dissection of GY and facilitated the understanding of canopy dynamics and yield formation.

plant biology↗

Unravelling the Dynamics of Bacterial-Laden Respiratory Droplets: Epidemiological Transfer from Fomites to Susceptible Host

This study provides the first comprehensive investigation into how pathogen-laden respiratory droplets transfer diseases via inanimate surfaces. Respiratory fluid ejections containing pathogens pose a significant health threat, especially in high-traffic areas like hospitals, public transport, restaurants, and schools. When these droplets dry on surfaces, they form deposits that can transfer pathogens to healthy individuals through contact and can be ingested via the oral or nasal route. The study examined the effects of varying salt and mucin concentrations in respiratory fluid droplets containing Pseudomonas aeruginosa (PA). Results showed that PA viability increased tenfold at elevated mucin concentrations, while changes in salt concentration had minimal impact. Adhesive properties of the deposits were analysed using atomic force spectroscopy and scotch tape test. Pathogen transfer from the deposit to a fingerprint patterned model thumb at different relative humidity (RH) levels was assessed using confocal microscopy, showing significant pathogen transfer at elevated RH. Out of 106 CFU/ml pathogens in deposits, 17% to 38% are potentially transferable, with most of the transfer occurring from the droplets edge deposits. The study also explored evaporation, internal flow, and precipitation dynamics, with deposit and pathogen distribution characterized by optical profilometry, scanning electron microscopy, and confocal microscopy.

microbiology↗

Weather-related changes in the dehydration of respiratory droplets on surfaces bolster bacterial endurance

HypothesisThe study shows for the first time a fivefold difference in the survivability of the bacterium Pseudomonas Aeruginosa (PA) in a realistic respiratory fluid droplet on fomites undergoing drying at different environmental conditions. For instance, in 2023, the annual average relative humidity (RH) in London (UK) is 71%, whereas in Delhi (India), it is 45%, showing that disease spread from fomites could have a demographic dependence. Respiratory fluid droplet ejections containing pathogens on inanimate surfaces are crucial in disease spread, especially in nosocomial settings. However, the interplay between evaporation dynamics, internal fluid flow and precipitation and their collective influence on the distribution and survivability of pathogens at different environmental conditions are less known. ExperimentsShadowgraphy imaging is employed to study evaporation, and optical microscopy imaging is used for precipitation dynamics. Micro-particle image velocimetry (MicroPIV) measurements reveal the internal flow dynamics. Confocal imaging of fluorescently labelled PA elucidates the bacterial distribution within the deposits. FindingsThe study finds that the evaporation rate is drastically impeded during drying at elevated solutal concentrations, particularly at high RH conditions. MicroPIV shows reduced internal flow under high RH conditions. Evaporation rate influences crystal growth, with delayed efflorescence and extending crystallisation times. PA forms denser peripheral arrangements under high evaporation rates and shows a fivefold increase in survivability under low evaporation rates. These findings highlight the critical impact of environmental conditions on pathogen persistence and disease spread from inanimate surfaces. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/579296v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@6b9876org.highwire.dtl.DTLVardef@1e6a18forg.highwire.dtl.DTLVardef@78d308org.highwire.dtl.DTLVardef@66ebe8_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Origin and evolution of the bread wheat D genome

Bread wheat (Triticum aestivum) is a globally dominant crop and major source of calories and proteins for the human diet. Compared to its wild ancestors, modern bread wheat shows lower genetic diversity caused by polyploidisation, domestication, and breeding bottlenecks1,2. Wild wheat relatives represent genetic reservoirs, harbouring diversity and beneficial alleles that have not been incorporated into bread wheat. Here, we establish and analyse pangenome resources for Tauschs goatgrass, Aegilops tauschii, the donor of the bread wheat D genome. This new pangenome facilitated the cloning of a disease resistance gene and haplotype analysis across a complex disease resistance locus, allowing us to discern alleles from paralogous gene copies. We also reveal the complex genetic composition and history of the bread wheat D genome, involving previously unreported contributions from genetically and geographically discrete Ae. tauschii subpopulations. Together, our results reveal the complex history of the bread wheat D genome and demonstrate the potential of wild relatives in crop improvement.

genomics↗

Physics of Self-Assembly and Morpho-Topological Changes of Klebsiella Pneumoniae in Desiccating Sessile Droplets

We have investigated the flow and desiccation-driven self-assembly of Klebsiella Pneumoniae in the naturally evaporating sessile droplets. Klebsiella Pneumoniae exhibits extensive changes in its morphology and forms unique patterns as the droplet dries, revealing hitherto unexplored rich physics governing its survival and infection strategies. Self-assembly of bacteria at the droplet contact line is characterized by order-to-disorder packing transitions with high packing densities and excessive deformations (bacteria deforms nearly twice its original length scales). In contrast, thin-film instability-led hole formation at the center of the droplet engenders spatial packing of bacteria analogous to honeycomb weathering. The varying physical forces acting on bacteria based on their respective spatial location inside the droplet cause an assorted magnitude of physical stress. Self-assembly favors the bacteria at the rim of the droplet, leading to enhanced viability and pathogenesis on the famously known "coffee ring" of the droplet compared to the bacteria present at the center of the droplet residue. Mechanistic insights gained via our study can have far-reaching implications for bacterial infection through droplets, e.g., through open wounds.

microbiology↗

Vapor mediation as a tool to control micro-nano scale dendritic crystallization and preferential bacterial distribution in drying respiratory droplets

Deposits of biofluid droplets on surfaces (such as respiratory droplets formed during an expiratory event fallen on surfaces) are composed of the water-based salt-protein solution that may also contain an infection (bacterial/viral).The final patterns of the deposit formed are dictated by the composition of the fluid and flow dynamics within the droplet. This work reports the spatio-temporal, topological regulation of deposits of respiratory fluid droplets and control of motility of bacteria by tweaking flow inside droplets using non-contact vapor-mediated interactions. When evaporated on a glass surface, respiratory droplets form haphazard multiscale dendritic, cruciform-shaped precipitates--using vapor mediation as a tool to control these deposits at the level of nano-micro-millimeter scales. Wemorphologically control dendrite orientation, size and subsequently suppress cruciform-shaped crystals. The nucleation sites are controlled via preferential transfer of solutes in the droplets; thus, achieving control over crystal occurrence and growth dynamics. The active living matter like bacteria is also preferentially segregated with controlled motility without attenuation of its viability and pathogenesis. For the first time, we have experimentally presented a proof-of-concept to control the motion of live active matter like bacteria in a near non-intrusive manner. The methodology can have ramifications in biomedical applications like disease detection, controlling bacterial motility, and bacterial segregation.

bioengineering↗

South Asian patient population genetics reveal strong founder effects and high rates of homozygosity - new resources for precision medicine

Population-scale genetic studies can identify drug targets and allow disease risk to be predicted with resulting benefit for management of individual health risks and system-wide allocation of health care delivery resources. Although population-scale projects are underway in many parts of the world, genetic variation between population groups means that additional projects are warranted. South Asia has a population whose genetics is the least characterized of any of the worlds major populations. Here we describe GenomeAsia studies that characterize population structure in South Asia and that create tools for economical and accurate genotyping at population-scale. Prior work on population structure characterized isolated population groups, the relevance of which to large-scale studies of disease genetics is unclear. For our studies we used whole genome sequence information from 4,807 individuals recruited in the health care delivery systems of Pakistan, India and Bangladesh to ensure relevance to population-scale studies of disease genetics. We combined this with WGS data from 927 individuals from isolated South Asian population groups, and developed a custom SNP array (called SARGAM) that is optimized for future human genetic studies in South Asia. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that approach 100 times that seen in outbred populations. We describe founder effects that increase the power to associate functional variants with disease processes and that make South Asia a uniquely powerful place for population-scale genetic studies.

genomics↗

The Secretome of Liver X Receptor Agonist Treated Early Outgrowth Cells Decreases Atherosclerosis in Ldlr-/- Mice

ObjectiveEndothelial progenitor cells (EPCs) promote the maintenance of the endothelium by the secretion of vasoreparative factors. A population of EPCs known as early outgrowth cells (EOCs) are currently being investigated as novel cell-based therapies for the treatment of cardiovascular disease. We previously demonstrated that the absence of liver x receptors (LXRs) is detrimental to the formation and function of EOCs under hypercholesterolemic conditions. Here, we investigate whether LXR gain-of-function in EOCs is beneficial for the treatment of atherosclerosis.\n\nApproach and ResultsEOCs were differentiated from the bone marrow of wildtype (WT) and LXR-knockout (Lxr{beta}-/-) mice in the presence of vehicle or LXR agonist (GW3965). WT EOCs treated with GW3965 throughout differentiation showed reduced expression of endothelial lineage markers (Cd144, Vegfr2) compared to WT vehicle and Lxr{beta}-/- cells. GW3965-treated EOCs produced secreted factors that reduced monocyte adhesion to activated endothelial cells in culture. When injected into atherosclerosis-prone Ldlr-/- mice, GW3965-treated EOCs and concentrated conditioned media (CM) from GW3965-treated EOCs, reduced plaque burden within the aortic sinus. Furthermore, when CM from human EOCs (obtained from patients with established CAD) were treated with GW3965, monocyte to endothelial adhesion was decreased suggesting the translatability of the results.\n\nConclusionsEx vivo LXR agonist treatment of EOCs produces a secretome that decreases early atherosclerosis in Ldlr-/- mice. CM from human EOCs significantly inhibits monocyte to endothelial adhesion. Thus, active factor(s) within the GW3965-treated EOC secretome have the potential to be useful for the treatment of atherosclerosis.

cell biology↗

Loss of MLKL Decreases Necrotic Core but Increases Macrophage Lipid Accumulation In Atherosclerosis

ObjectivesDuring the advancement of atherosclerosis, the cellularity of the plaque is governed by the influx of monocyte-derived macrophages and their turnover via apoptotic and non-apoptotic forms of cell death. Previous reports have demonstrated that programmed necrosis, or necroptosis, of macrophages within the plaque contribute to necrotic core formation. Knockdown or inhibition of the necrosome components RIPK1 and RIPK3 slow the progression of atherosclerosis, and activation of the terminal step of necroptosis, MLKL, has been demonstrated in advanced human atherosclerotic plaques. However, whether MLKL directly contributes to lesion development and necrotic core formation has not been investigated.\n\nApproaches and ResultsMLKL expression was knocked down in atherogenic Apoe- knockout mice via subcutaneous administration of antisense oligonucleotides (ASO). During advanced atherogenesis, Mlkl knockdown potently reduced cell death in the plaque, with a significant reduction in the necrotic core. However, total lesion area in the aortic sinus remained unchanged. Furthermore, treatment with the MLKL ASO unexpectedly reduced circulating cholesterol levels compared to control ASO, while staining for lipids within the plaque was significantly increased. Peritoneal macrophages transfected with the MLKL ASO showed increased lipid loading upon incubation with modified cholesterol-rich lipoproteins. In lipid-loaded macrophages, MLKL co-localized with Rab7, a marker of the late endosome.\n\nConclusionsThese studies confirm the requirement for MLKL as the executioner of necroptosis, and as such a significant contributor to the necrotic core during atherogenesis. We also identified a previously unknown role for MLKL in interacting with endosomal trafficking components to regulate lipid uptake in macrophages during atherogenesis.

pathology↗