Biology subjects

Ismail, A. M.

Publications and source records attributed to Ismail, A. M..

6 recordsLinked to original sources

bioRxiv2025

OCT4 Negatively Regulates the Transcriptional Programming of the Early Region 3 Immune Evasion Genes of Human Adenovirus

Genomes of viruses are constrained by the virions nanoscale, and viral nucleotide sequences without function are a luxury. Yet the double-stranded DNA genome of human adenovirus (HAdV) contains large regions without known purpose. Using TRANSFAC and ChIP-Seq analysis, we identified binding of OCT4 (octomer-binding transcription factor 4) to a noncoding region of HAdV-D37 DNA. Manipulation of OCT4 expression impacted viral E3 gene transcription and gp19k protein expression, altering subsequent MHC Class I expression. These effects were specific to OCT4 binding to the adenovirus 5' inverted terminal repeat (ITR) within nucleotides 101-159. Using targeted mutations to OCT4, we found one of two OCT4 binding motifs in the ITR to be crucial for repression of E3 gene expression. In OCT4-siRNA treated cells, E3 RID- gene expression was also upregulated to inhibit pro-apoptotic signals, suggesting that OCT4 binding also indirectly represses viral replication. Consistent with a role for transcription factors in epigenetic modification during infections, OCT4 knockdown also reduced histone H3 acetylation and DNA methylation. In stem cells, OCT4 sustains pluripotency, whereas in somatic cells, OCT4 plays a dispensable role in self-renewal and maintenance. Herein, we show that OCT4 binding also confers a previously unidentified function to non-coding adenovirus DNA. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/650321v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1a94a11org.highwire.dtl.DTLVardef@13dc8e5org.highwire.dtl.DTLVardef@1505f22org.highwire.dtl.DTLVardef@195be29_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2025

Virus and Cell Specific HMGB1 Secretion and Subepithelial Infiltrate Formation in Adenovirus Keratitis

A highly contagious infection caused by human adenovirus species D (HAdV-D), epidemic keratoconjunctivitis (EKC) results in corneal subepithelial infiltration (SEI) by leukocytes, the hallmark of the infection. To date, the pathogenesis of corneal SEI formation in EKC is unresolved. HMGB1 (high-mobility group box 1 protein) is an alarmin expressed in response to infection and a marker of sepsis. Earlier studies using a different adenovirus species, HAdV-C, showed retention of HMGB1 in the infected cell nucleus by adenovirus protein VII, enabling immune evasion. Here, using HAdV-D we show cell-specific HMGB1 secretion by infected cells, and provide an HAdV-D specific mechanism for SEI formation in EKC. HMGB1 was secreted only upon infection of human corneal epithelial cells, not from other cell types, and only upon infection by HAdV-D types associated with EKC. Acetylated HMGB1 translocation from the nucleus to the cytoplasm, then to the extracellular milieu, was tightly controlled by CRM1 and LAMP1, respectively. Primary stromal cells when stimulated by rHMGB1 expressed proinflammatory chemokines. In a novel 3D culture system in tune with the architecture of the cornea, HMGB1 released by infected corneal epithelial cells induced leukocytic infiltrates either directly and/or indirectly via stimulated stromal cells, which together explains SEI formation in EKC.

microbiology↗

bioRxiv2024

Assessing Stress Tolerance of SUBI and DRO1 Introgression lines Under Flooding and Drought Conditions at Different Growth Stages

Rice varieties tolerant to submergence and drought regulate shoot elongation during short-term submergence by expressing the SUB1A gene, while the deep-rooted DRO1 is effectively expressed under drought conditions to enhance water and nutrient uptake. This study investigates the growth and yield of rice with both SUB1A and DRO1 in the background of IR64, under early season flooding and mid-season drought. The study used randomized complete design with two factors: soil moisture treatments (submergence, drought, and their combination) and genotypes. The genotypes included IR64, and three near-isogenic lines (NILs): NIL-SUB1DRO1, NIL-SUB1, and NIL-DRO1. Complete submergence was imposed for 7 days on 14-days old seedlings, while drought was imposed on control and submerged plants following a 21-day recovery period from submergence, using 42-day old plants. Variables were measured before and after treatments, and at harvest. The stresses negatively affected the genotypes. At harvest, IR64 and NIL-SUB1DRO1 under both stresses showed significant reduction in tiller numbers, shoot dry weights, and yields than their control plants. IR64 exhibited a significant delay in reaching flowering under all stresses. The rice introgression lines showed significant improvements of tolerance to the stress. The study showed no negative consequences of combining drought and submergence tolerance in rice.

physiology↗

bioRxiv2024

Evaluation of stress tolerance in IR64 rice near-isogenic lines carrying SUB1 and DRO1 genes

Flooding and drought significantly reduce rice yield in rainfed environments. Rice varieties that tolerate complete inundation for up to two weeks carry the SUB1A gene, while those enduring deeper water conditions for weeks or months have the SK1 and SK2 genes. Conversely, the DRO1 gene, responsible for deep-rooting, helps in water acquisition under drought. In this study, we compared the growth of NIL-SUB1DRO1 a novel rice genotype with an IR64 background regarding its dual tolerance to submergence and drought. Additionally, we assessed its recovery capacity after exposure to stress. Sixteen and thirteen-days old seedlings of three genotypes (Experiment 1-1 and 2-1) and fourteen-days old seedlings of the two genotypes (Experiment 1-2 and 2-2) were tested under submergence and drought stress in a greenhouse experimental condition respectively. Seedlings were submerged for 10 and 7 days and then allowed to recover for 10 and 7 days respectively. In the drought experiment, seedlings underwent 29 days of drought (Experiment 2-1) and 18 days of drought, followed by 10 days of rewatering (Experiment 2-2). Growth parameters were measured before and after treatment, 4 days after submergence in experiment 1-1 and after the recovery periods. Submergence and drought adversely affected growth and performance. Shoot elongation in submerged plants was reduced by 29.2% for NIL-SUB1DRO1 compared to IR64. Accelerated shoot elongation of IR64 negatively affected its recovery. Chlorophyll content and maximum fluorescence of IR64 were significantly lower than other genotypes after 10 and 7 days of complete submergence. Ten days after recovery in experiment 1-1 the Chlorophyll content and maximum fluorescence of IR64 were not significantly different compared to other genotypes. Seven days after of recovery in experiment 1-2, NIL-SUB1DRO1 had significantly higher chlorophyll content and maximum fluorescence than IR64. After 29 days of drought the tiller number and leaf area of IR64 was lower than other genotypes (Experiment 2-1), while in Experiment 2-2 during drought treatment and recovery, NIL-SUB1DRO1 had greater relative water content, leaf water potential, leaf area, SPAD value, dry weights of shoots and roots, root length, surface area and volume compared to IR64. stomatal conductance of IR64 was higher than NIL-SUB1DRO1 during drought, leading to greater water loss and reduced growth during recovery. NIL-SUB1DRO1 absorbed and retained water more effectively under dry conditions. NIL-SUB1DRO1 and NIL-SUB1 is tolerant to submergence and NIL-SUB1DRO1 and NIL-DRO1 to drought, with no negative effects from combining these genes in modern rice varieties for rainfed lowlands.

physiology↗

bioRxiv2021

Genome-wide association mapping and systems-level analysis reveal genetic architecture and physiological mechanisms linked with tolerance to flooding during germination in rice

Rice is the staple food of more than half of the worlds population; yet, it faces numerous challenges to meet the rising food demands and worsening climates. An urgent global imperative is to address imminent food shortages through intensive and sustainable agri-food systems and steady genetic gains. Intensification of rice production through direct-seeded rice (DSR) has been progressively practiced but is hindered by poor germination of existing high-yielding varieties in flooded soils. Identifying donors of anaerobic germination (AG) tolerance in rice will expedite the development of varieties suitable for DSR and will lead to enhanced and sustained agricultural productivity. This study aims to dissect the genetic architecture and physiological mechanisms of AG tolerance using systems biology and omics approaches. A Rice Diversity Panel (343 accessions) consisting of 5 subpopulations was screened for AG tolerance under greenhouse conditions, mapped through genome-wide association study (GWAS), and profiled for metabolites. Analyses revealed that most of the AG-tolerant varieties are japonicas with few indicas) and aus. Tolerant japonicas employed better root growth or rapid shoot extension, while tolerant indicas exhibited only the latter. A total of 51 significant GWAS peaks were detected across the genome, some of which were co-localized with known quantitative trait loci while others were novel, more so tolerance was found to involve different genetic controls across subpopulations. AG stress causes distinct biochemical signatures for tolerant genotypes and the profiles contrast among subpopulations implicating divergent metabolic adjustments, including shifts in sugars, intermediates, amino acids, antioxidants, and hormones. This study provides a systems-level approach for underpinning physiological mechanisms of AG tolerance; elucidating phenotypic heterogeneity, genetic architecture, transcriptomic networks, and metabolic landscapes from a genome-wide perspective. ONE SENTENCE SUMMARYThe integration of GWA mapping, gene network analysis and, non-targeted metabolite profiling elucidates genetic architecture and physiological mechanisms of tolerance to germination and early seedling growth under anaerobic conditions in rice.

plant biology↗

bioRxiv2020

Magnaporthe oryzae populations in Sub-Saharan Africa are diverse and show signs of local adaptation

Rice blast caused by Magnaporthe oryzae is one of the most economically damaging diseases of rice worldwide. The disease originated in Asia but was detected for the first time in Sub-Saharan Africa (SSA) around 100 years ago. Despite its importance, the evolutionary processes involved in shaping the population structure of M. oryzae in SSA remain unclear. In this study, we investigate the population history of M. oryzae using a combined dataset of 180 genomes. Our results show that SSA populations are more diverse than earlier perceived, and harbor all genetic groups previously reported in Asia. While M. oryzae populations in SSA and Asia draw from the same genetic pools, both are experiencing different evolutionary trajectories resulting from unknown selection pressures or demographic processes. The distribution of rare alleles, measured as Tajimas D values, show significant differences at the substructure level. Genome-wide analysis indicates potential events of population contraction strongly affecting M. oryzae in SSA. In addition, the distribution and haplotype diversity of effectors might suggest a process of local adaptation to SSA conditions. These findings provide additional clues about the evolutionary history of M. oryzae outside the center of origin and help to build customized disease management strategies.

genomics↗