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Dans un contexte où la pandémie de COVID-19 se propage rapidement à travers le monde depuis fin 2019, il nous paraît important de décrire l’impact sociodémographique, cliniques et évolutifs de COVID-19 sur les patients tuberculeux hospitalisés à la clinique de pneumologie de l’hôpital FANN du 1erjanvier 2018 au 31 décembre 2021 dans le but de contribuer à l’atteinte des objectifs du PNT dans le cadre du programme mondial d’éradication de la TB d’ici l’an 2050.

Eukaryotic RNA pol II transcripts are capped at the 5′ end by the methylated guanosine (m7G) moiety. In higher eukaryotes, CMTR1 and CMTR2 catalyze cap-proximal ribose methylations on the first (cap1) and second (cap2) nucleotides, respectively. These modifications mark RNAs as “self,” blocking the activation of the innate immune response pathway. Here, we show that loss of mouse Cmtr1or Cmtr2leads to embryonic lethality, with non-overlapping sets of transcripts being misregulated, without activation of the interferon pathway. In contrast, Cmtr1mutant adult mouse livers exhibit chronic activation of the interferon pathway, with multiple interferon-stimulated genes being expressed. Conditional deletion of Cmtr1in the germline leads to infertility, while global translation is unaffected in the Cmtr1mutant mouse liver and human cells. Thus, mammalian cap1 and cap2 modifications have essential roles in gene regulation beyond their role in helping cellular transcripts to evade the innate immune system.

In mammals, circadian oscillators exist not only in the suprachiasmatic nucleus, which harbors the central pacemaker, but also in most peripheral tissues. It is believed that the SCN clock entrains the phase of peripheral clocks via chemical cues, such as rhythmically secreted hormones. Here we show that temporal feeding restriction under light-dark or dark-dark conditions can change the phase of circadian gene expression in peripheral cell types by up to 12 h while leaving the phase of cyclic gene expression in the SCN unaffected. Hence, changes in metabolism can lead to an uncoupling of peripheral oscillators from the central pacemaker. Sudden large changes in feeding time, similar to abrupt changes in the photoperiod, reset the phase of rhythmic gene expression gradually and are thus likely to act through a clock-dependent mechanism. Food-induced phase resetting proceeds faster in liver than in kidney, heart, or pancreas, but after 1 wk of daytime feeding, the phases of circadian gene expression are similar in all examined peripheral tissues.

ABSTRACTTo study the molecular mechanisms of circadian gene expression, we have sought to identify genes whose expression in mouse liver is regulated by the transcription factor DBP (albumin D-site-binding protein). This PAR basic leucine zipper protein accumulates according to a robust circadian rhythm in nuclei of hepatocytes and other cell types. Here, we report that the Cyp2a4gene, encoding the cytochrome P450 steroid 15a-hydroxylase, is a novel circadian expression gene. This enzyme catalyzes one of the hydroxylation reactions leading to further metabolism of the sex hormones testosterone and estradiol in the liver. Accumulation of CYP2A4 mRNA in mouse liver displays circadian kinetics indistinguishable from those of the highly related CYP2A5 gene. Proteins encoded by both theCyp2a4and Cyp2a5genes also display daily variation in accumulation, though this is more dramatic for CYP2A4 than for CYP2A5. Biochemical evidence, including in vitro DNase I footprinting on the Cyp2a4and Cyp2a5promoters and cotransfection experiments with the human hepatoma cell line HepG2, suggests that the Cyp2a4and Cyp2a5genes are indeed regulated by DBP. These conclusions are corroborated by genetic studies, in which the circadian amplitude of CYP2A4 and CYP2A5 mRNAs and protein expression in the liver was significantly impaired in a mutant mouse strain homozygous for a dbpnull allele. These experiments strongly suggest that DBP is a major factor controlling circadian expression of the Cyp2a4and Cyp2a5genes in the mouse liver.

To study the molecular mechanisms of circadian gene expression, we have sought to identify genes whose expression in mouse liver is regulated by the transcription factor DBP (albumin D-site-binding protein). This PAR basic leucine zipper protein accumulates according to a robust circadian rhythm in nuclei of hepatocytes and other cell types. Here, we report that the Cyp2a4gene, encoding the cytochrome P450 steroid 15α-hydroxylase, is a novel circadian expression gene. This enzyme catalyzes one of the hydroxylation reactions leading to further metabolism of the sex hormones testosterone and estradiol in the liver. Accumulation of CYP2A4 mRNA in mouse liver displays circadian kinetics indistinguishable from those of the highly related CYP2A5 gene. Proteins encoded by both the Cyp2a4and Cyp2a5genes also display daily variation in accumulation, though this is more dramatic for CYP2A4 than for CYP2A5. Biochemical evidence, including in vitro DNase I footprinting on the Cyp2a4and Cyp2a5promoters and cotransfection experiments with the human hepatoma cell line HepG2, suggests that the Cyp2a4and Cyp2a5genes are indeed regulated by DBP. These conclusions are corroborated by genetic studies, in which the circadian amplitude of CYP2A4 and CYP2A5 mRNAs and protein expression in the liver was significantly impaired in a mutant mouse strain homozygous for a dbpnull allele. These experiments strongly suggest that DBP is a major factor controlling circadian expression of the Cyp2a4and Cyp2a5genes in the mouse liver.

Hepatic leukemia factor (HLF) is a member of the PAR family of transcription regulatory proteins. We have characterized the rat HLF gene and studied its expression and activity. The rat HLF gene is transcribed from two alternative promoters, alpha and beta, with different circadian amplitudes and tissue specificities. The alpha RNA isoforms produce a 43 kDa protein, HLF43, abundant in brain, liver and kidney, like the previously described human HLF RNA. The beta RNA HLF isoforms use a CUG codon to initiate translation of a novel 36 kDa protein, HLF36, which is shorter at its N‐terminus relative to the 43 kDa form. HLF36 is expressed uniquely in the liver, where it is the most abundant HLF protein. Surprisingly, the two proteins accumulate in the liver with different circadian amplitudes and have distinct liver‐specific promoter preferences in transfection experiments. Thus, HLF43 stimulates transcription from the cholesterol 7 alpha‐hydroxylase promoter much more efficiently than from the albumin promoter, while the converse is true for HLF36.

Genetic analysis of sorghum resistance to stem-borers was performed in a 6 × 6 diallel cross. The results indicated that resistance to stem-borers is polygenically inherited. F1hybrids did not differ significantly from mid-parental values suggesting intermediate inheritance. However, resistance was partially dominant to susceptibility. Combining ability analysis showed that resistance to primary damage, i.e. % ‘dead heart’ was governed by both additive and non-additive type of gene actions while secondary damage, i.e. % stem tunnelling was governed predominantly by additive gene action. It was noted that the inheritance patterns of primary and secondary damage were different. Tunnel length showed positive correlation with the number of larvae per plant and negative association with plant height, but had no correlation with grain yield per plant. On the basis of larvae recovered from the tunnelled plants, Chilo partelluswas found to be the predominant stem-borer species followed by Sesamia calamistis, Eldana saccharinaand Busseola fusca. Significance of genetic studies of host plant resistance in deciding breeding strategies for insect resistance has been discussed.

SummaryA clear understanding of protein‐energy malnutrition (PEM), parasite infection and their interactions is essential in formulating health and development policies. We studied the prevalence of PEM indicators and the prevalence and/or intensity of infection in 558 Zairian children aged 4 months to 10 years. Multivariate analyses were used to estimate relationships between PEM indicators and parasitic infection. Stunting was found in 40.3% of children, wasting in 4.9% and kwashiorkor in 5.1%. The risk of stunting was significantly higher in children with Ascaris lumbricoides.The risk of wasting was higher in children with A. lumbricoidesor Trichuris trichiura, whereas the risk of kwashiorkor was high with T. trichiurabut very reduced in those with A. lumbricoides. Plasmodium infection was not related to nutritional indicators. These relationships highlight important interactions, both synergistic and antagonistic, between nutrition and parasites in central Africa.

ABSTRACTPoor performance among health service providers is a key barrier to high quality, adolescent-responsive health services. Collaborative learning has been shown to strengthen health service provider performance, but few studies have examined its implementation in adolescent health services. In this paper, we describe a collaborative learning approach for adolescent health service providers implemented as part of a project aiming to prevent HIV in adolescent girls and young women in the Democratic Republic of the Congo (DRC) and explore its feasibility, acceptability, benefits and challenges. To do so, we reviewed plans, budgets and progress reports, as well as nested implementation research related to the project. We also carried out a quantitative analysis of the number, location, participants and topics of collaborative learning sessions conducted as part of this initiative, and thematic analysis to synthesise findings on perceived benefits and challenges. Under the project, 32 collaborative learning sessions of approximately two-hour duration were held with up to 15 participants, most of whom were nurses, between June 2018 and May 2019. The project cost was approximately USD 135,000 over three years. Reported benefits included improving health service provider attitudes, knowledge and skills; ensuring delivery of non-judgemental, empathic and confidential health services; and improving communication and collaboration between health services and adolescents together with their parents. While the novelty of the approach in this context presented challenges, our results suggest that collaborative learning in adolescent health services is feasible, acceptable, and inexpensive. It may help strengthen the knowledge and skills of health service providers, build positive attitudes and motivation, and improve their performance and thereby the adolescent-responsiveness of health services. Further research is needed to confirm these results in other settings and to examine the impact of collaborative learning on the acceptability and uptake of health services.

RNA polymerase II transcripts receive a protective 5ʹ,5ʹ-triphosphate-linked 7-methylguanosine (m7G) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (NAD), generating NAD-RNAs. Here, we identify human NUDT12 as a cytosolic NAD-RNA decapping enzyme. NUDT12 is active only as homodimers, with each monomer contributing to creation of the two functional catalytic pockets. We identify an ∼600-kDa dodecamer complex between bleomycin hydrolase (BLMH) and NUDT12, with BLMH being required for localization of NUDT12 to a few discrete cytoplasmic granules that are distinct from P-bodies. Both proteins downregulate gene expression when artificially tethered to a reporter RNA in vivo. Furthermore, loss of Nudt12results in a significant upregulation of circadian clock transcripts in mouse liver. Overall, our study points to a physiological role for NUDT12 in the cytosolic surveillance of NAD-RNAs.

In a previous work, we started investigating the concept of hyperconvexity in quasipseudometric spaces which we called ??-hyperconvexity or Isbell-convexity. In this paper, we continue our studies of this concept, generalizing further known results about hyperconvexity from the metric setting to our theory. In particular, in the present paper, we consider subspaces of q-hyperconvex spaces and also present some fixed point theorems for nonexpansive self-maps on a bounded q-hyperconvex quasipseudometric space. In analogy with a metric result, we show among other things that a set-valued mapping ??* on a q-hyperconvex ??0-quasimetric space (X, d) which takes values in the space of nonempty externally q-hyperconvex subsets of (X, d) always has a single-valued selection T which satisfies ??(??(??),??(??))=????(??*(??),??*(??)) whenever ??,?????. (Here, ???? denotes the usual (extended) Hausdorff quasipseudometric determined by ?? on the set ??0(??) of nonempty subsets of X.)