Biology subjects

Ashraf, A.

Publications and source records attributed to Ashraf, A..

3 recordsLinked to original sources

bioRxiv2024

Monocytes Mobilized by Gut Neurons Remodel the Enteric Nervous System

The proper organization of the enteric nervous system (ENS) is critical for normal gastrointestinal (GI) physiology. Inflammatory bowel disease (IBD) dysregulates GI physiology, including bowel movements (motility), but in many IBD patients, GI motility disorders persist in remission through a poorly understood pathological process. Here we uncover that post-inflammatory GI dysmotility (PI-GID) stems from structural ENS remodeling driven by a combination of neuronal loss and neurogenesis. Enteric neurons respond to mucosal inflammation by upregulating CCL2 expression and facilitating the recruitment of CCR2+ monocytes into the neural myenteric plexus within the intestinal muscle. This is followed by the expansion of monocyte-derived macrophages and their migration into the myenteric ganglia and phagocytosis of neurons. However, excessive recruitment of monocytes results in disproportionate ENS remodeling and PI-GID. The expansion of inflammatory cells is known to promote tissue hypoxia. We find that enteric neurons become hypoxic upon colitis, but hypoxia-induced signaling via HIF1 initiates an adaptation program in enteric neurons to attenuate CCL2 expression and limit monocyte recruitment. We demonstrate that reinforcing HIF1 signaling in enteric neurons prevents PI-GID by reducing colitis-associated monocyte recruitment in the myenteric plexus and protecting against ENS remodeling. In summary, our findings unveil PI-GID pathogenesis and identify a regulatory axis for its prevention. One Sentence SummaryIntestinal mucosal inflammation engages enteric neurons in the inflammatory response leading to neurogenic recruitment of monocytes into the extra-mucosal myenteric plexus followed by pathological structural remodeling of the enteric nervous system by monocyte-derived macrophages.

immunology↗

bioRxiv2023

Stomatal closure in maize is mediated by subsidiary cells and the PAN2 receptor

Stomata are epidermal pores that facilitate plant gas exchange. Grasses have fast stomatal movements, likely due to their dumbbell-shaped guard cells and lateral subsidiary cells. Subsidiary cells reciprocally exchange water and ions with guard cells. However, the relative contribution of subsidiary cells during stomatal closure is unresolved. We compared stomatal gas exchange and stomatal aperture dynamics in wild type and pan1, pan2, and pan1;pan2 Zea mays (L.) (maize) mutants, which have varying percentages of aberrantly formed subsidiary cells. Stomata with 1 or 2 defective subsidiary cells cannot close properly, indicating that subsidiary cells are essential for stomatal function. Even though the percentage of aberrant stomata is similar in pan1 and pan2, pan2 showed a more severe defect in stomatal closure. In pan1, only stomata with abnormal subsidiary cells fail to close normally. In pan2, all stomata have stomatal closure defects, indicating that PAN2 has an additional role in stomatal closure. Maize Pan2 is orthologous to Arabidopsis GHR1, which is also required for stomatal closure. PAN2 acts downstream of Ca2+ in maize to promote stomatal closure. This is in contrast to GHR1, which acts upstream of Ca2+, and suggests the pathways could be differently wired.

plant biology↗

bioRxiv2023

In-silico Screening of Origanum vulgare Phytocompounds as Potential Drug Agents Against Vp35 Protein of the Ebola Virus

The leading cause of the Ebola virus outbreak during 2013-16 in Western Africa was a lack of targeted anti- viral drug choices, a fast rate of mutations and the unavailability of many of the structural proteins and annotations within its genome. The surroundings of the Ebola River in DR-Congo fail to get rid of this endemic, the reason behind this was believed to be its origin from non-human primates, which made its risk assessment and tracing difficult. The Vp35 is a multifunctional protein with innate immune antagonistic properties and is considered one of the most suitable drug targets within this virus. The main motive of this study is to discover a potential anti-viral drug against the Ebola virus by targeting the aforementioned protein with different phytocompounds of oregano that have the lowest binding energies and qualifies over different simulation parameters, so firstly, molecular docking was performed on its 28 compounds using PyRx to get the best complexes with minimum binding energies e.g., -8.9Kcal/mol. Ligands with the best docking scores were gone through Lipinskis rule of five for drug likeliness potential. For the drug affirmation, molecular dynamic simulation was also performed with the best two docked complexes using NAMD/VMD to find out their conformational stability through RMSD, RMSF, Rg, SASA and H-bond analyses. Current computer-generated prediction suggested that Ursolic acid and Oleanolic acid possess potential inhibitory effects against virus replication. Furthermore, paradigm shifts of usage of natural and herbal products for treating infectious diseases are being encouraged here, However, further wet-lab experiments and clinical trials are still needed to determine the robustness of these virtually tested phytocompounds against the Vp35 protein of the Ebola virus.

bioinformatics↗