Pathogenesis of Junonia coenia densovirus in Spodoptera frugiperda: A route of infection that leads to hypoxia

AbstractTo evaluate densovirus potential against lepidopteran pests and their capacity to invade new hosts, we have characterised in vivo the infection and pathogenesis of the Junonia coenia densovirus (JcDNV) in the noctuid pest Spodoptera frugiperda. Here we show that infection starts with the ingestion of viral particles that cross the midgut epithelium without replicating. By quantitative PCR we established the kinetic and the route of infection, from virus ingestion to replication in visceral tracheae and hemocytes. JcDNV has a high particle-to-infection ratio mostly due to the barrier function of the midgut. Pathology and cytopathology suggested that infection of tracheal cells impairs oxygen delivery to demanding tissues leading to cytopathic effects in all the tissues. Finally, larval death results from several physiological shocks, including molting arrest and anoxia

Appropriateness of clinical severity classification of new WHO childhood pneumonia guidance : a multi-hospital, retrospective, cohort study

Background: Management of pneumonia in many low-income and middle-income countries is based on WHO guidelines that classify children according to clinical signs that define thresholds of risk. We aimed to establish whether some children categorised as eligible for outpatient treatment might have a risk of death warranting their treatment in hospital. Methods: We did a retrospective cohort study of children aged 2–59 months admitted to one of 14 hospitals in Kenya with pneumonia between March 1, 2014, and Feb 29, 2016, before revised WHO pneumonia guidelines were adopted in the country. We modelled associations with inpatient mortality using logistic regression and calculated absolute risks of mortality for presenting clinical features among children who would, as part of revised WHO pneumonia guidelines, be eligible for outpatient treatment (non-severe pneumonia). Findings: We assessed 16 162 children who were admitted to hospital in this period. 832 (5%) of 16 031 children died. Among groups defined according to new WHO guidelines, 321 (3%) of 11 788 patients with non-severe pneumonia died compared with 488 (14%) of 3434 patients with severe pneumonia. Three characteristics were strongly associated with death of children retrospectively classified as having non-severe pneumonia: severe pallor (adjusted risk ratio 5·9, 95% CI 5·1–6·8), mild to moderate pallor (3·4, 3·0–3·8), and weight-for-age Z score (WAZ) less than −3 SD (3·8, 3·4–4·3). Additional factors that were independently associated with death were: WAZ less than −2 to −3 SD, age younger than 12 months, lower chest wall indrawing, respiratory rate of 70 breaths per min or more, female sex, admission to hospital in a malaria endemic region, moderate dehydration, and an axillary temperature of 39°C or more. Interpretation: In settings of high mortality, WAZ less than −3 SD or any degree of pallor among children with non-severe pneumonia was associated with a clinically important risk of death. Our data suggest that admission to hospital should not be denied to children with these signs and we urge clinicians to consider these risk factors in addition to WHO criteria in their decision making

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Les isoformes M1 et M3 de Sirt3 régulent le métabolisme basal et le maintien de la masse musculaire

Au sein de la famille des déacetylases NAD dépendantes ou sirtuines, Sirt3 est une déacétylase principalement localisée dans la mitochondrie. En fonction de l’état énergétique cellulaire, elle régule l’activité de l’organite en déacétylant des enzymes impliquées dans l’oxydation des lipides, la cétogenèse, le métabolisme des acides aminés, le fonctionnement de la chaîne respiratoire, et le niveau des défenses antioxydantes. Sirt3 participe ainsi à la régulation du métabolisme des nutriments, de la synthèse d’ATP et de la production d’espèces réactives de l’oxygène. Chez la souris, Sirt3 est exprimée dans tous les tissus, et il existe deux isoformes de Sirt3, une isoforme longue (SIRT3-M1) de localisation mitochondriale et une isoforme courte (SIRT3-M3) de localisation cytoplasmique (1, 2). A ce jour, le rôle respectif de ces deux isoformes n’est pas établi. Les souris dépourvues de Sirt3 (KO SIRT3) présentent une hyperacétylation des protéines mitochondriales qui entraîne un certain nombre de défauts métaboliques importants (baisse de la sensibilité à l’insuline et augmentation du stress oxydant). De plus, les animaux KO SIRT3 sont plus susceptibles aux pathologies telles que le diabète ou l’obésité, et sont incapables de réguler leur métabolisme en conditions de jeûne, restriction calorique ou d’hypothermie (3, 4). Dans le muscle squelettique, le rôle de Sirt3 reste à définir (5). Dans les cellules musculaires C2C12, nous avons montré que Sirt3 participait à la régulation de la différenciation des myoblastes (6). Afin de déterminer quelles sont les conséquences de cette régulation sur le développement et le métabolisme du tissu musculaire, et le rôle spécifique de chacune des isoformes, nous avons mis en place une approche in vivo à l’aide de souris transgéniques. Dans le cadre d’une collaboration avec Qiang Tong (Houston, USA), nous avons obtenu des souris transgéniques surexprimant les isoformes SIRT3-M1 et SIRT3-M3 spécifiquement dans le muscle. Les premières données de phénotypage de ces souris mettent en évidence un rôle distinct des deux isoformes : le métabolisme de base est diminué chez les souris surexprimant l’isoforme mitochondriale (M1) alors qu’il est augmenté chez les souris surexprimant l’isoforme cytoplasmique (M3). Ces variations du métabolisme global ne s’accompagnent cependant pas de modification de l’activité mitochondriale au niveau du tissu musculaire. Par ailleurs, la surexpression de l’isoforme M3 induit une atrophie musculaire précoce qui s’accentue avec l’âge. Ces résultats montrent que Sirt3 joue un rôle dans le maintien de la masse musculaire, et le contrôle du métabolisme basal, paramètre important de la capacité d’adaptation des animaux. Il reste à déterminer comment s’effectue la régulation de l’expression de ces deux isoformes, et à identifier par quels mécanismes elles sont capables de réguler le métabolisme basal via leur expression musculaire

Les sirtuines mitochondriales

Les sirtuines mitochondriales. 7. Colloque Meetochondri

Les sirtuines mitochondriales

Les sirtuines mitochondriales . 7. Colloque du réseau MeetOchondri

Chronic AMPK activation improved mitochondrial function and endurance capacity of aged myostatin deficient mice

Chronic AMPK activation improved mitochondrial function and endurance capacity of aged myostatin deficient mice. 8. Congrès de Physiologie, de Pharmacologie et de Thérapeutiqu

Impact de génotypes musculaires sur les caractéristiques fonctionnelles et métaboliques du muscle in vivo

Impact de génotypes musculaires sur les caractéristiques fonctionnelles et métaboliques du muscle in vivo. Journées d’Animation des Crédits Incitatifs du Département de Physiologie Animale et Systèmes d’Elevage (JACI Phase 2016