Biology subjects

Iqbal, S.

Publications and source records attributed to Iqbal, S..

32 records · Page 2Linked to original sources

bioRxiv2022

Anatomical and Palynological Investigation within flora of Family Asteraceae

A comprehensive microscopic investigation of the leaf epidermis, as well as anatomical and palynological research of selected Asteraceae species from the flora of Havali (Kahutta) Azad Jammu and Kashmir (AJK) Pakistan, was carried out. This study includes 11 plant species comprising of Senecio jacobea, Leucanthemum vulgare, Halianthus annuus, Erigeron bonariensis, Achillea millifolium, Halianthus Linnaeus, Taraxacum officinale, Anaphalius nepalensis, Erigeron Canadensis, and Tagetes erecta. All the species studied were amphistomatic, with four different forms of stomata i.e tetracytic, anomocytic, anisocytic, and tricytic. The main stomatal type was tetracytic, followed by anomocytic. The abaxial epidermis has a higher stomatal density than the adaxial epidermis. Highest stomatal density was present Tagetes erecta while lowest is present in Conyza canadensis. In lower epidermis stomatal index was higher in Taraxacum officinale followed by Halianthus annuus and Tagetes erecta while in upper epidermis highest index was shown by Halianthus annuus. For this study species of family Acteraceae were properly collected. Furthermore, variation in pollen can be seen. List of palynomorph which includes family name, botanical name, local name, English name, flower colour, season and pollen description for the logical arrangement of these species. The logical ordering of these species was guided by dust characteristics such as form and pollen morphology. Palynological data has been found to be too big for taxonomists to calculate and make appropriate observations on their findings.

plant biology↗

bioRxiv2021

Necroptosis inhibition counteracts axonal degeneration, cognitive decline and key hallmarks of aging, promoting brain rejuvenation.

Age is the main risk factor for the development of neurodegenerative diseases. In the aged brain, axonal degeneration is an early pathological event, preceding neuronal dysfunction, and cognitive disabilities in humans, primates, rodents, and invertebrates. Necroptosis mediates degeneration of injured axons, but whether necroptosis triggers neurodegeneration and cognitive impairment along aging is unknown. Here we show that the loss of the necroptotic effector Mlkl was sufficient to delay age-associated axonal degeneration and neuroinflammation, protecting against decreased synaptic transmission and memory decline in aged mice. Moreover, short-term pharmacologic inhibition of necroptosis in aged mice reverted structural and functional hippocampal impairment, both at the electrophysiological and behavioral level. Finally, a quantitative proteomic analysis revealed that necroptosis inhibition leads to an overall improvement of the aged hippocampal proteome, including a subclass of molecular biofunctions associated with brain rejuvenation, such as long-term potentiation and synaptic plasticity. Our results demonstrate that necroptosis contributes to the age-dependent brain degeneration, disturbing hippocampal neuronal connectivity, and cognitive function. Therefore, necroptosis inhibition constitutes a potential geroprotective strategy to treat age-related disabilities associated with memory impairment and cognitive decline.

neuroscience↗

bioRxiv2021

Fetal-like reversion in the regenerating intestine is regulated by mesenchymal Asporin

Epithelial tissues undergo fetal-like cellular reprogramming to regenerate after damage1,2. Although the mesenchyme and the extracellular matrix (ECM) play critical roles in tissue homeostasis and regeneration2-5, their role in repurposing developmental programs in epithelium is unknown. To model epithelial regeneration, we culture intestinal epithelium on decellularized small intestinal scaffold (iECM), and identify Asporin (Aspn), an ECM bound proteoglycan, as a critical mediator of cellular reprogramming. Aspn is produced by the mesenchyme, and we show that its effect on epithelial Tgf{beta}-signalling via CD44 is critical for fetal-like conversion. Furthermore, we demonstrate that Aspn is transiently increased upon chemotherapy-induced damage and pivotal for a timely induction of the fetal-like state and tissue regeneration. In summary, we establish a platform for modelling epithelial injury responses ex vivo, and show that the mesenchymal Aspn-producing niche controls tissue repair by regulating epithelial fetal-like reprogramming.

developmental biology↗

bioRxiv2020

Polycomb Repressive Complex 2-controlled Essrg regulates intestinal Microfold cell differentiation.

Microfold cells (M cells) are immunosurveillance epithelial cells located in the Peyers patches in the intestine responsible for monitoring and transcytosis of antigens, microorganisms and pathogens. Many transcription factors, e.g., Spi-B and Sox8, necessary to M cell differentiation have been described but the exhaustive set of factors sufficient for differentiation and development of a mature M cell remains elusive. Moreover, the role of polycomb repressive complex 2 (PRC2) as an epigenetic regulator of M cell development has not yet been interrogated. Here, we show that PRC2 regulates a significant set of genes during the M cell differentiation including many transcription factors. Estrogen related receptor gamma (Esrrg) is a novel M cell specific transcription factor acting on a RankL-Rank induced NF-kB pathway, upstream of Sox8 and necessary but not sufficient for a mature M cell marker Gp2 expression. To conclude, with the aid of PRC2 target survey we identified the list of developmental genes specifically implicated in M cell development and Essrg as a necessary factor for Sox8-mediated M cell differentiation.

molecular biology↗

bioRxiv2020

KDM5 inhibition offers a novel therapeutic strategy for the treatment of KMT2D mutant lymphomas

Loss-of-function mutations in KMT2D are a striking feature of the germinal centre (GC) lymphomas, resulting in decreased H3K4 methylation and altered gene expression. We hypothesised that inhibition of the KDM5 family, which demethylates H3K4me3/me2, would re-establish H3K4 methylation and restore the expression of genes repressed upon loss of KMT2D. KDM5-inhibition increased H3K4me3 levels and caused an anti-proliferative response in vitro, which was markedly greater in both endogenous and CRISPR-edited KMT2D mutant DLBCL cell lines, whilst tumour growth was inhibited in KMT2D mutant xenografts in vivo. KDM5-inhibition reactivated both KMT2D-dependent and -independent genes, resulting in diminished B-cell receptor signalling and altered expression of BCL2 family members, including BCL2 itself, allowing it to synergise with agents targeting these pathways. KDM5-inhibition may offer an effective therapeutic strategy for ameliorating KMT2D loss-of-function mutations in GC-lymphomas.Statement of significance We detail a novel way of reverting the effects of loss-of-function mutations in the histone methyltransferase KMT2D by inhibiting the KDM5 demethylase family, increasing levels of H3K4me3 and restoring expression of KMT2D regulated genes.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

bioRxiv2020

Biodegradation of polyester polyurethane by Aspergillus flavus G10

Polyurethanes (PU) are integral to many aspects of our daily lives. Due to the extensive use of and difficulties in recycling or reusing PU, it mostly accumulates as waste. Various bacteria and fungi have been reported to degrade PU. We examined the fungus Aspergillus flavus G10 in that regard, after isolating it from the guts of Gryllus bimaculatus, a common cricket species. We observed surficial and chemical changes of PU with atomic force microscopy, scanning electron microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy. We measured physical changes as loss in tensile stress, stretching force, and weight of PU after incubations. Fungal hydrolysis of urethane bonds in the polymer backbone was demonstrated by detecting the formation of methylene di-aniline during incubations. Trapped CO2 during incubations equaled 52.6% of PU carbon. Biodegradation of PU was maximal by fungi cultured on a malt extract medium at 25 °C, pH 12, and 14:10 hrs light to dark ratio. Pretreating PU films with UV light or 1% FeSO4 or NaCl solutions further enhanced the rate of biodegradation. A range of techniques are needed to fully characterize the degradation of PU or other plastic polymers and to optimize conditions for their microbial degradation.View Full Text

bioengineering↗

bioRxiv2020

Smooth muscle-specific MMP17 (MT4-MMP) defines the intestinal ECM niche

Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.

cell biology↗

bioRxiv2020

EnhancerP-2L: A Gene regulatory site identification tool for DNA enhancer region using CREs motifs

Enhancers are DNA fragments that do not encode RNA molecules and proteins, but they act critically in the production of RNAs and proteins by controlling gene expression. Prediction of enhancers and their strength plays significant role in regulating gene expression. Prediction of enhancer regions, in sequences of DNA, is considered a difficult task due to the fact that they are not close to the target gene, have less common motifs and are mostly tissue/cell specific. In recent past, several bioinformatics tools were developed to discriminate enhancers from other regulatory elements and to identify their strengths as well. However the need for improvement in the quality of its prediction method requires enhancements in its application value practically. In this study, we proposed a new method that builds on nucleotide composition and statistical moment based features to distinguish between enhancers and non-enhancers and additionally determine their strength. Our proposed method achieved accuracy better than current state-of-the-art methods using 5-fold and 10-fold cross-validation. The outcomes from our proposed method suggest that the use of statistical moments based features could bear more efficient and effective results. For the accessibility of the scientific community, we have developed a user-friendly web server for EnhancerP-2L which will increase the impact of bioinformatics on medicinal chemistry and drive medical science into an unprecedented resolution. Web server is freely accessible at http://www.biopred.org/enpred.

bioinformatics↗

bioRxiv2019

Persistent Prolate Polymersomes for Enhanced Co-Delivery of Hydrophilic and Hydrophobic Drugs

Self-assembled polymersomes encapsulate, protect, and deliver hydrophobic and hydrophilic drugs. Though spherical polymersomes are effective, early studies suggest that non-spherical structures may enhance specificity of delivery and uptake due to similarity to endogenous uptake targets. Here we describe a method to obtain persistent non-spherical shapes, prolates, via osmotic pressure and the effect of prolates on uptake behavior. Polyethylene glycol-b-poly(lactic acid) polymersomes change in diameter from 175 {+/-} 5nm to 200 {+/-} 5nm and increase in polydispersity from 0.06 {+/-} 0.02 to 0.122 {+/-} 0.01 nm after addition of 50 mM salt. Transmission and scanning electron microscopy confirm changes from spheres to prolates. Prolate-like polymersomes maintain their shape in 50 mM NaCl for seven days. Nile Red and bovine serum albumin(BSA)-Fluorescein dyes are taken up in greater amounts by SH-SY5Y neural cells when encapsulated in polymersomes. Prolate polymersomes may be taken up more efficiently in neural cells than spherical polymersomes.

bioengineering↗

bioRxiv2019

Insights into protein structural, physicochemical, and functional consequences of missense variants in 1,330 disease-associated human genes

Interpretation of the colossal number of genetic variants identified from sequencing applications is one of the major bottlenecks in clinical genetics, with the inference of the effect of amino acid-substituting missense variants on protein structure and function being especially challenging. Here we evaluated the burden of amino acids affected in pathogenic variants (n=32,923) compared to the variants (n=164,915) from the general population in 1,330 disease-associated genes on forty protein features using over 14,000 experimentally-solved 3D structures. By analyzing the whole gene/variant set jointly, we identified 18 features associated with 3D mutational hotspots that are generally important for protein fitness and stability. Individual analyses performed for twenty-four protein functional classes further revealed 240 characteristics of mutational hotspots in total, including new associations recapitulating the sheer diversity across proteins essential structural regions. We demonstrated that the function-specific features of variants correspond to the readouts of mutagenesis experiments and positively correlate with clinically-interpreted pathogenic and benign missense variants. Finally, we made our results available through a web server to foster accessibility and downstream research. Our findings represent a crucial step towards translational genetics, from highlighting the impact of mutations on protein structure to rationalizing the pathogenicity of variants in terms of the perturbed molecular mechanisms.

genetics↗

bioRxiv2019

Predicting Functional Effects of Missense Variants in Voltage-Gated Sodium and Calcium Channels

Malfunctions of voltage-gated sodium and calcium channels (SCN and CACNA1 genes) have been associated with severe neurologic, psychiatric, cardiac and other diseases. Altered channel activity is frequently grouped into gain or loss of ion channel function (GOF or LOF, respectively) which is not only corresponding to clinical disease manifestations, but also to differences in drug response. Experimental studies of channel function are therefore important, but laborious and usually focus only on a few variants at a time. Based on known gene-disease-mechanisms, we here infer LOF (518 variants) and GOF (309 variants) of likely pathogenic variants from disease phenotypes of variant carriers. We show regional clustering of inferred GOF and LOF variants, respectively, across the alignment of the entire gene family, suggesting shared pathomechanisms in the SCN/CACNA1 genes. By training a machine learning model on sequence- and structure-based features we predict LOF- or GOF- associated disease phenotypes (ROC = 0.85) of likely pathogenic missense variants. We then successfully validate the GOF versus LOF prediction on 87 functionally tested variants in SCN1/2/8A and CACNA1I (ROC = 0.73) and in exome-wide data from > 100.000 cases and controls. Ultimately, functional prediction of missense variants in clinically relevant genes will facilitate precision medicine in clinical practice.

genetics↗

bioRxiv2019

Identification of pathogenic variant enriched regions across genes and gene families

Missense variant interpretation is challenging. Essential regions for protein function are conserved among gene family members, and genetic variants within these regions are potentially more likely to confer risk to disease. Here, we generated 2,871 gene family protein sequence alignments involving 9,990 genes and performed missense variant burden analyses to identify novel essential protein regions. We mapped 2,219,811 variants from the general population into these alignments and compared their distribution with 65,034 missense variants from patients. With this gene family approach, we identified 398 regions enriched for patient variants spanning 33,887 amino acids in 1,058 genes. As a comparison, testing the same genes individually we identified less patient variant enriched regions involving only 2,167 amino acids and 180 genes. Next, we selected de novo variants from 6,753 patients with neurodevelopmental disorders and 1,911 unaffected siblings, and observed a 5.56-fold enrichment of patient variants in our identified regions (95% C.I. =2.76-Inf, p-value = 6.66x10-8). Using an independent ClinVar variant set, we found missense variants inside the identified regions are 111-fold more likely to be classified as pathogenic in comparison to benign classification (OR = 111.48, 95% C.I = 68.09-195.58, p-value < 2.2e-16). All patient variant enriched regions identified (PERs) are available online through a user-friendly platform for interactive data mining, visualization and download at http://per.broadinstitute.org. In summary, our gene family burden analysis approach identified novel patient variant enriched regions in protein sequences. This annotation can empower variant interpretation.

genetics↗

bioRxiv2018

Wearable Eye-tracking for Research: Automated dynamic gaze mapping and accuracy/precision comparisons across devices

Wearable eye-trackers offer exciting advantages over screen-based systems, but their use in research settings has been hindered by significant analytic challenges as well as a lack of published performance measures among competing devices on the market. In this article, we address both of these limitations. We describe (and make freely available) an automated analysis pipeline for mapping gaze data from an egocentric coordinate system (i.e. the wearable eye-tracker) to a fixed reference coordinate system (i.e. a target stimulus in the environment). This pipeline allows researchers to study aggregate viewing behavior on a 2D planar target stimulus without restricting the mobility of participants. We also designed a task to directly compare calibration accuracy and precision across 3 popular models of wearable eye-trackers: Pupil Labs 120Hz Binocular glasses, SMI ETG 2 glasses, and the Tobii Pro Glasses 2. Our task encompassed multiple viewing conditions selected to approximate distances and gaze angles typical for short- to mid-range viewing experiments. This work will promote and facilitate the use of wearable eye-trackers for research in naturalistic viewing experiments.

neuroscience↗

bioRxiv2018

Screening, Characterization and Optimization of antibacterial peptides, produced by Bacillus safensis strain MK-12 isolated from waste dump soil KP, Pakistan

AimsThe current study was designed to isolate, screen and identify the indigenous soil antibacterial exhibiting bacteria (AEB) and effect of various parameters on growth of AEB and antibacterial peptides production.\n\nMethods and resultsThe soil isolates were screened for antagonistic activity against a set of ATCC and local MDR human pathogenic bacterial strains. The antibacterial compound was protein in nature, exhibited no haemolysis and molecular weight was less than 20 KDa. The potential AEB isolate was identified by morphology, biochemical testing and by 16S rRNA gene sequencing as B. safensis MK-12. Growth and antibacterial activity was optimized for B. safensis strain MK-12, exhibited maximum growth as well as antibacterial activity after 48 hours of incubation at pH 8, 30 {degrees}C in shaking incubator when fermented in optimized medium.\n\nConclusionThe current study results indicate that indigenous soil is rich source of AEB and could be a promising source of antimicrobial compounds to fight against MDR bacteria in future.\n\nSignificance and impactThis is the first scientific report on soil bacteria from northern region of Pakistan as per our knowledge. Therefore, screening of soil bacteria for antibacterial activity from unexplored area may contribute towards new antibiotic. Selected soil strain in the current study exhibited promising antibacterial activity against human pathogenic MDR bacterial strains.

microbiology↗