Biology subjects

Amara, A.

Publications and source records attributed to Amara, A..

5 recordsLinked to original sources

bioRxiv2026

Selective vulnerability of intracortical projection neurons drives long-term cortical circuit rewiring after perinatal hypoxia

Cortical circuits are built at perinatal times and gradually refined in an activity-dependent manner during a so-called postnatal period of critical plasticity. Although lesions of the central nervous system (CNS) happening during this period typically recover better than those occurring later in life, they are often associated with long-term behavioral deficits. This suggests that neuronal circuits rewiring, in particular within the cortex, may either be incomplete or inappropriate. To address this possibility, we used chronic perinatal hypoxia, a mouse model of very premature birth. We confirmed that chronic hypoxia induced a decrease in cortical thickness frequently observed in very preterm babies, which rapidly recovered 8 days later. To explore the transcriptional correlates of this recovery we next performed single-nuclei transcriptomic analysis of the cortex at short (P11) and long (P45) timepoints following hypoxia. This revealed persistent transcriptional changes within neurons, including of genes involved in mitochondrial metabolism, axonogenesis and synaptogenesis. Further, histological analysis using anterograde and retrograde tracing as well as mitochondrial labelling support persistent alterations in upper cortical neurons resulting in increased cortico-cortical connectivity within the cortex of adult hypoxic mice. Finally, behavioral testing revealed altered social behavior in mice exposed to chronic hypoxia, which amplified with age. Altogether, our results unravel how brain lesions happening early in life, alter normal cortical development and have long term consequences on cortical wiring, contributing to the observed behaviors defects appearing later in life.

neuroscience↗

bioRxiv2025

First identification of camel prion disease in Tataouine, Tunisia: an emerging animal prion disease in North Africa

Prion diseases are fatal neurodegenerative disorders affecting humans and animals. Among these, camel prion disease (CPrD) was recently identified in Algeria as a novel disease. In this study, we report six CPrD cases in dromedary camels (Camelus dromedarius) from Tunisia, providing further evidence of its occurrence in North Africa. Affected animals exhibited neurological signs and showed PrPSc accumulation in both brain and lymphoid tissues. Molecular and pathological analyses revealed features consistent with Algerian CPrD cases and distinct from classical scrapie and bovine spongiform encephalopathy. The detection of PrPSc in lymphoid organs, together with the relatively young age of some affected individuals, suggests the possibility of a contagious etiology, including potential vertical or early-life transmission mechanisms, as observed in scrapie and chronic wasting disease affecting small ruminants and cervids, respectively. These findings underscore the need for continued surveillance and further investigation into the epidemiology, transmission mechanisms and potential public health implications of CPrD.

microbiology↗

bioRxiv2021

RACK1 associates with RNA-binding proteins Vigilin and SERBP1 to control dengue virus replication

Dengue virus (DENV), a re-emerging virus transmitted by Aedes mosquitoes, causes severe pathogenesis in humans. No effective treatment is available against this virus. We recently identified the scaffold protein RACK1 as a component of the DENV replication complex, a macromolecular complex essential for viral genome amplification. Here, we show that RACK1 is important for DENV infection. RACK1 mediates DENV replication through binding to the 40S ribosomal subunit. Mass spectrometry analysis of RACK1 partners coupled to a loss-of-function screen identified the RNA binding proteins Vigilin and SERBP1 as DENV host dependency factors. Vigilin and SERBP1 interact with DENV viral RNA (vRNA), forming a ternary complex with RACK1 to mediate viral replication. Overall, our results indicate that RACK1 recruits Vigilin and SERBP1, linking the DENV vRNA to the translation machinery for optimal translation and replication.

microbiology↗

bioRxiv2021

Characterization and functional interrogation of SARS-CoV-2 RNA interactome

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has caused a devastating global health crisis. The emergence of highly transmissible novel viral strains that escape neutralizing responses emphasizes the urgent need to deepen our understanding of SARS-CoV-2 biology and to develop additional therapeutic strategies. Using a comprehensive identification of RNA binding proteins (RBP) by mass spectrometry (ChIRP-M/S) approach, we identified 142 high-confidence cellular factors that bind the SARS-CoV-2 viral genome during infection. By systematically knocking down their expression in a human lung epithelial cell line, we found that the majority of the RBPs identified in our study are proviral factors that regulate SARS-CoV-2 genome replication. We showed that some of these proteins represented drug targets of interest for inhibiting SARS-CoV-2 infection. In conclusion, this study provides a comprehensive view of the SARS-CoV-2 RNA interactome during infection and highlights candidates for host-centered antiviral therapies.

microbiology↗

bioRxiv2018

Drug Interactions Between Dolutegravir and Artemether-Lumefantrine or Artesunate-Amodiaquine

Across sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artmether-lumefantrine (AL) or artesunate-amodiaquine (AS-AQ) given with 50mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artmether-lumefantrine or artesunate-amodiaquine and DTG. The DTG/artmether-lumefantrine interaction was evaluated in a two-way cross-over study and measured artemether (ARM), dihydroartemisinin (DHA), lumefantrine (LF), desbutyl-lumefantrine (DBL) over 264h. The DTG/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine (DEAQ) and measured artesunate (ARS), amodiaquine (AQ), DEAQ over 624h. Non-compartmental analysis was performed, and geometric mean ratios and 90% confidence intervals generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, time to maximum concentration and area under the concentration-time curve (AUC) for ARM, DHA, LF and DBL nor significantly alter AUC for ARS, DHA, AQ and DEAQ. Co-administration of dolutegravir with AL resulted in a 37% decrease in DTG trough concentrations. Co-administration of dolutegravir with AS-AQ resulted in a decrease of approximately 42% and 24% in DTG trough concentrations and AUC respectively. Study drugs were well-tolerated with no serious adverse events. Standard doses of artmether-lumefantrine and artesunate-amodiaquine should be used in patients receiving DTG. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and DTG exposure with artesunate-amodiaquine are unlikely to be of clinical significance as DTG trough concentrations were above DTG target concentrations of 64ng/mL.

pharmacology and toxicology↗