Several recent public health crises have shown that the surveillance of zoonotic agents in wildlife is important to prevent pandemic risks. High-throughput sequencing (HTS) technologies are potentially useful for this surveillance, but rigorous experimental processes are required for the use of these effective tools in such epidemiological contexts. In particular, HTS introduces biases into the raw data set that might lead to incorrect interpretations. We describe here a procedure for cleaning data before estimating reliable biological parameters, such as positivity, prevalence, and coinfection, using 16S rRNA amplicon sequencing on an Illumina MiSeq platform. This procedure, applied to 711 rodents collected in West Africa, detected several zoonotic bacterial species, including some at high prevalence, despite their never before having been reported for West Africa. In the future, this approach could be adapted for the monitoring of other microbes such as protists, fungi, and even viruses.
The Rhône-Loire metropolitan areas’ 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.
The intracellular signaling mechanisms underlying the pathogenesis of cardiac diseases are not fully understood. We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in mice, leading to heart failure and premature mortality. Development of cardiomyopathy in this mouse model is coupled with insulin resistance, glucose intolerance, and impaired glucose uptake in striated muscle cells. Shp2 deficiency leads to upregulation of leukemia inhibitory factor-stimulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes. Insulin resistance and impaired glucose uptake in Shp2-deficient mice are at least in part due to impaired protein kinase C-/ and AMP-kinase activities in striated muscle. Thus, we have generated a mouse line modeling human patients suffering from cardiomyopathy and insulin resistance. This study reinforces a concept that a compound disease with multiple cardiovascular and metabolic disturbances can be caused by a defect in a single molecule such as Shp2, which modulates multiple signaling pathways initiated by cytokines and hormones.Heart failure is a serious life-threatening health problem worldwide. Numerous studies have demonstrated a link between cardiac dysfunction and insulin resistance, as well as deficiency in glucose transport (9,35,48). In the absence of manifest diabetes, insulin resistance and minor degrees of glucose intolerance are thought to be associated with and contribute to the development of nonischemic cardiomyopathy or idiopathic dilated cardiomyopathy (35,45). However, the molecular basis for this link is poorly understood.Muscle-specific gene knockout mice have presented unprecedented opportunities to decipher molecular signaling mechanisms underlying cardiomyopathic changes. Deletion of PTEN in cardiomyocytes mediated by Mck-Cre results in cardiac hypertrophy in mice (8). Dilated cardiomyopathy was also observed to various degrees in mice with conditional ablation of ErbB2 (HER2),  1 integrin, and the gp130 cytokine receptor component in the heart or muscle (16,34,37). Interestingly, despite the development of cardiomyopathy, most of these mutant mice survive to adulthood with a normal life span, suggesting limitations in their modeling of human patients' pathological processes. These mutant mouse models also show no correlation between cardiomyopathy and insulin resistance. In fact, although muscle-specific PTEN knockout mice develop cardiac hypertrophy (8), they are protected against insulin resistance and diabetes induced by high-fat diet due to enhanced insulin-stimulated glucose uptake in soleus muscle (43).Shp2 is a widely expressed cytoplasmic tyrosine phosphatase with two SH2 domains that has been implicated in signaling events downstream of receptors for growth factors, cytokines, and hormones (25, 32). In particular, Shp2 has been shown to participate in leptin and insulin signaling for the regulation of energy balance and metabolism (23...
Ticks transmit the most diverse array of disease agents and harbor one of the most diverse microbial communities. Major progress has been made in the characterization of the taxonomic profiles of tick microbiota. However, the functional profiles of tick microbiome have been comparatively less studied. In this proof of concept we used state-of-the-art functional metagenomics analytical tools to explore previously reported datasets of bacteria found in male and female Ixodes ovatus, Ixodes persulcatus , and Amblyomma variegatum . Results showed that both taxonomic and functional profiles have differences between sexes of the same species. KEGG pathway analysis revealed that male and female of the same species had major differences in the abundance of genes involved in different metabolic pathways including vitamin B, amino acids, carbohydrates, nucleotides, and antibiotics among others. Partial reconstruction of metabolic pathways using KEGG enzymes suggests that tick microbiome form a complex metabolic network that may increase microbial community resilience and adaptability. Linkage analysis between taxonomic and functional profiles showed that among the KEGG enzymes with differential abundance in male and female ticks only 12% were present in single bacterial genera. The rest of these enzymes were found in more than two bacterial genera, and 27% of them were found in five up to ten bacterial genera. Comparison of bacterial genera contributing to the differences in the taxonomic and functional profiles of males and females revealed that while a small group of bacteria has a dual-role, most of the bacteria contribute only to functional or taxonomic differentiation between sexes. Results suggest that the different life styles of male and female ticks exert sex-specific evolutionary pressures that act independently on the phenomes (set of phenotypes) and genomes of bacteria in tick gut microbiota. We conclude that functional redundancy is a fundamental property of male and female tick microbiota and propose that functional metagenomics should be combined with taxonomic profiling of microbiota because both analyses are complementary.
Orientia bacterium is the agent of the scrub typhus, a seriously neglected life-threatening disease in Asia. Here, we report the detection of DNA of Orientia in rodents from Europe and Africa. These findings have important implications for public health. Surveillance outside Asia, where the disease is not expected by sanitary services, needs to be improved.
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