Biology subjects

Ahmed, M. M.

Publications and source records attributed to Ahmed, M. M..

8 recordsLinked to original sources

bioRxiv2025

LOXL2 Deletion Triggers TMJ Osteoarthritis While Overexpression Protects Against NF-κB-Induced Chondrocyte Apoptosis

Temporomandibular joint osteoarthritis (TMJ-OA) affects a significant proportion of the population worldwide. However, there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms. Lysyl Oxidase Like-2 (LOXL2) promotes knee joint cartilage protection, and it is downregulated in TMJ-OA animal model. We evaluated the role of LOXL2 in TMJ cartilage, its molecular mechanism and gene networks using in vivo Loxl2 knockout mice (Acan-Cre; Loxl2flox/flox) and ex vivo goat TMJ cartilage. Our results show that Loxl2 knockout in mice cartilage upregulates Il1b, Mmp9, Mmp13, Adamts4, and Adamts5, whereas it reduces the levels of aggrecan and proteoglycan. Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response, TNFA signaling via NF-kB, extracellular matrix (ECM), and collagen degradation pathway network. Conversely, LOXL2 treatment reduces interleukin-1 beta (IL-1{beta})-induced expression of Mmp13, protects mitochondrial function and ECM from degeneration. Importantly, LOXL2 attenuates IL-1{beta}-induced chondrocyte apoptosis via phosphorylation of NF-{kappa}B and expression of pain-related gene PTGS2 (encodes COX2). Taken together, Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation, mitochondrial dysfunction, chondrocyte apoptosis, and inflammatory gene expression, whereas LOXL2 treatment mitigates these effects. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/653519v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@cb7540org.highwire.dtl.DTLVardef@17ebe2eorg.highwire.dtl.DTLVardef@1f7fd59org.highwire.dtl.DTLVardef@19fdd7_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2021

Traumatic Brain Injury Exacerbates Alzheimer's Disease Pathology in the Retinas of TgF344-AD Rats

Alzheimers disease (AD) is a neurodegenerative condition that affects 6.2 million people age 65 and older in the U.S. alone, and is the leading cause of dementia. Moreover, AD can lead to visual impairment, and AD histopathology also manifests in the retina. However, the factors that modulate AD pathophysiology and lead to varied susceptibility and presentation in the population are not well understood. In this context, traumatic brain injury (TBI), which can arise from sport concussions, military combat, and other causes, is associated with a 2.3-fold higher risk of developing AD and AD-related dementias (ADRD). Thus, we set out to evaluate the effects of TBI, AD, and their combination, on retinal histopathology. Several animal models have been developed to investigate the mechanisms underlying AD, but many have been limited by imperfect recapitulation of human pathology, and no model of TBI-associated AD (AD-TBI) has been characterized. To address this gap, we generated an innovative model of AD-TBI by taking advantage of a transgenic rat model (Tg-F344-AD) shown to recapitulate the main features of human AD pathology, and combining it with a twotime unilateral controlled cortical impact paradigm to mimic repetitive mild TBI (rmTBI). Histopathological analyses at four months post-impact confirm the presence of AD markers in transgenic retinas, and an increased severity of AD pathology due to TBI. Together, these results contribute to our understanding of the effects of TBI on AD retinopathy, with implications for patient care and therapeutic development.

neuroscience↗

bioRxiv2021

Kif11 overexpression rescues cognition, long-term potentiation, and spine defects in mouse and cell models of Alzheimer's disease

Competitive inhibition of kinesin motor proteins by amyloid-beta (A{beta}) may contribute to alterations in the neuronal microtubule cytoskeleton that can disrupt plasticity mechanisms required for learning and memory, such as long-term potentiation (LTP), thus contributing to synaptic dysfunction and cognitive impairments associated with Alzheimers disease (AD). Here, we tested the hypothesis that overexpression of the microtubule motor protein KIF11 (Kinesin-5/Eg5) will rescue A{beta}-mediated synaptic dysfunction and cognitive impairments. We found that overexpression of Kif11 prevented spatial learning and LTP deficits in the 5xFAD mouse model of AD and rescued A{beta}-mediated decreases in postsynaptic dendritic spine density in neuronal cultures. Together, these data suggest that KIF11 function is important for preserving synaptic structures and functions that are critical for learning and memory and for protection against A{beta}-mediated loss of cognition in AD. HighlightsO_LIDeficits in cognition and long-term potentiation in the 5xFAD mouse model of Alzheimers disease are prevented by Kif11 overexpression. C_LIO_LIA{beta}-mediated dendritic spine loss is blocked by Kif11 overexpression. C_LI

neuroscience↗

bioRxiv2021

Pro-inflammatory Cytokine GM-CSF Improves Learning/Memory and Brain Pathology in Dp16 Down Syndrome Mice and Improves Learning/Memory in Wild-Type Mice

Down syndrome (DS) is characterized by chronic neuroinflammation, peripheral inflammation, astrogliosis, imbalanced excitatory/inhibitory neuronal function, and cognitive deficits in both humans and mouse models. Suppression of inflammation has been proposed as a therapeutic approach to treating DS co-morbidities, including intellectual disability (DS/ID). Conversely, we discovered previously that treatment with the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) improved cognition and reduced biomarkers of brain pathology in humans with Alzheimers disease (AD), another inflammatory disorder, and in a mouse model of AD. To investigate the effects of GM-CSF treatment on DS/ID, we assessed behavior and brain pathology in 12-14 month-old DS mice (Dp[16]1Yey) and their wild-type (WT) littermates, neither of which develop amyloid, and found that GM-CSF treatment improved performance in the radial arm water maze in both Dp16 and WT mice compared to placebo. Dp16 mice also showed abnormal astrocyte morphology and aggregation and fewer calretinin-positive interneurons, both of which were improved by GM-CSF treatment. These findings suggest that stimulating and/or modulating inflammation and the innate immune system with GM-CSF treatment may enhance cognition in both people with DS/ID and in the typical aging population.

neuroscience↗

bioRxiv2019

Transgenic mouse facial nerve model of synkinesis

HypothesisOur central hypothesis is that inhibition of Schwann cell de-differentiation, in the post-injury setting, will reduce synkinesis and improve facial muscle function BackgroundNo therapies exist to improve the accuracy of facial nerve regeneration. Following peripheral nerve injury, adult reactive Schwann cells de-differentiate and express glial fibrillary acidic protein (GFAP); suggesting that reactive Schwann cells impact axonal regeneration precision. MethodsTransgenic GFAP-thymidine kinase (TK) mouse model was employed, allowing selective downregulation of reactive GFAP expressing Schwann cells on exposure of 7 day osmotic pump delivery of ganciclovir. Adult female transgenic GFAP-TK mice had right facial nerve transected and then immediately repaired with tissue glue, they then either were treated with saline or ganciclovir (GCV). At 6 weeks post-injury, mice were exposed to random air puffs events while high speed videography recorded whisker and eye movement. MatLab code video processing with publicly available BIOTACT algorithm automatically tracked whiskers. ResultsWhisker velocity was calculated using binning statistical analysis. Saline treated animals confirmed our models ability to detect aberrant movement such that intact (left) facial nerves caused whisker protraction, while repaired (right) facial nerves had retraction. Administration of GCV increased whisker retraction compared to saline. GCV did not impact intact animal whisker movement compared to repaired whiskers. ConclusionsInhibition of reactive Schwann cell proliferation appears to worse the degree of synkinesis, providing important insight into a potential therapeutic target for facial nerve injury.

neuroscience↗

bioRxiv2019

Isolation of the Astacin-like metalloprotease coding gene (astl) and assessment of its insecticidal activity against Spodoptera littoralis and Sitophilus oryzae

Astacin- like metalloprotease (astl) is a multi-domain metallopeptidase that has protease activity against a number of organisms; including fish, frogs, birds and insects. In this present investigation, the full length of astl cDNA was cloned from spider species, Hasarius adansoni. Sequencing of the cloned astl cDNA proved that its full length including 802 bp with 714bp open reading frame encoding for 238 amino acids. The catalytic domain comprised of 489 nts was cloned and expressed by the yeast expression system Pichia pastoris and its insecticidal activity was determined against two species of agricultural insects Spodoptera littoralis (Lepidoptera:Noctuidae) and Sitophilus oryzae (Coleoptera:Curculionidae). Bioassay was performed using three concentrations (100,500 and 1000 ppm) for four days for S. littoralis and 14 days for S. oryzae. In addition, the astl was fused to the GNA snowdrop lectin in the same frame and expressed in P. pastoris. The synergistic effect of astl and GNA was examined on the S. littoralis larvae and S. oryzae adults. The mortality percentages of the fused protein (Ha-astl/GNA) \"1000 ppm\" after 4 days, were 78.6%{+/-} 4.16 and 71.66% {+/-}3.51 for first and second spodpotera larval instars, respectively. While, lower mortality of the fused protein of the same concentration was observed on S. oryzae adults, 49.3{+/-}2.08 %.

molecular biology↗

bioRxiv2019

Megacities as drivers of national outbreaks: the role of holiday travel in the spread of infectious diseases

Human mobility connects populations and can lead to large fluctuations in population density, both of which are important drivers of epidemics. Measuring population mobility during infectious disease outbreaks is challenging, but is a particularly important goal in the context of rapidly growing and highly connected urban centers in low and middle income countries, which can act to amplify and spread local epidemics nationally and internationally. Here, we combine estimates of population movement from mobile phone data for over 4 million subscribers in the megacity of Dhaka, Bangladesh, one of the most densely populated cities globally. We combine mobility data with epidemiological data from a household survey, to understand the role of population mobility on the spatial spread of the mosquito-borne virus chikungunya within and outside Dhaka city during a large outbreak in 2017. The peak of the 2017 chikungunya outbreak in Dhaka coincided with the annual Eid holidays, during which large numbers of people traveled from Dhaka to their native region in other parts of the country. We show that regular population fluxes around Dhaka city played a significant role in determining disease risk, and that travel during Eid was crucial to the spread of the infection to the rest of the country. Our results highlight the impact of large-scale population movements, for example during holidays, on the spread of infectious diseases. These dynamics are difficult to capture using traditional approaches, and we compare our results to a standard diffusion model, to highlight the value of real-time data from mobile phones for outbreak analysis, forecasting, and surveillance.

ecology↗

bioRxiv2018

Stage specific classification of DEGs via statistical profiling and network analysis reveals potential biomarker associated with various stages of TB

BackgroundTuberculosis (TB) is a deadly transmissible disease that can infect almost any body-part of the host but is mostly infect the lungs. It is one of the top 10 causes of death worldwide. In the 30 high TB burden countries, 87% of new TB cases occurred in 2016. Seven countries: India, Indonesia, China, Philippines, Pakistan, Nigeria, and South Africa accounted for 64% of the new TB cases. To stop the infection and progression of the disease, early detection of TB is important. In our study, we used microarray data set and compared the gene expression profiles obtained from blood samples of patients with different datasets of Healthy control, Latent infection, Active TB and performed network-based analysis of DEGs to identify potential biomarker.\n\nObjectivesWe want to observe the transition of genes from normal condition to different stages of the TB and identify, annotate those genes/pathways/processes that play key role in the progression of TB disease during its cyclic interventions in human body.\n\nResultsWe identified 319 genes that are differentially expressed in various stages of TB (Normal to LTTB, Normal to Active TB and LTTB to active TB) and allocated to pathways from multiple databases which comprised of curated class of associated genes. These pathways importance was then evaluated according to the no. of DEGs present in the pathway and these genes show the broad spectrum of processes that take part in every state. In addition, we studied the regulatory networks of these classified genes, network analysis does consider the interactions between genes (specific for TB) or proteins provide us new facts about TB disease, which in turn can be used for potential biomarkers identification. We identified total 29 biomarkers from various comparison groups of TB stages in which 14 genes are over expressed as host responses against pathogen, but 15 genes are down regulated that means these genes has allowed the process of host defense to cease and give time to pathogen for its progression.\n\nConclusionsThis study revealed that gene-expression profiles can be used to identify and classified the genes on stage specific pattern among normal, LTTB and active TB and network modules associated with various stages of TB were elucidated, which in turn provided a basis for the identification of potential pathways and key regulatory genes that may be involved in progression of TB disease.

systems biology↗