Human Infection with Highly Pathogenic A(H7N7) Avian Influenza Virus,Italy, 2013

During an influenza A(H7N7) virus outbreak among poultry in Italy during August–September 2013, infection with a highly pathogenic A(H7N7) avian influenza virus was diagnosed for 3 poultry workers with conjunctivitis. Genetic analyses revealed that the viruses from the humans were closely related to those from chickens on affected farms.     

Gene expression and regulatory factors of the mechanistic target of rapamycin (mTOR) complex 1 predict mammalian longevity

GeroScience - Species longevity varies significantly across animal species, but the underlying molecular mechanisms remain poorly understood. Recent studies and omics approaches suggest that...     

Chitin-induced activation of immune signaling by the rice receptor CEBiP relies on a unique sandwich-type dimerization

Perception of microbe-associated molecular patterns (MAMPs) through pattern recognition receptors (PRRs) triggers various defense responses in plants. This MAMP-triggered immunity plays a major role in the plant resistance against various pathogens. To clarify the molecular basis of the specific recognition of chitin oligosaccharides by the rice PRR, CEBiP (chitin-elicitor binding protein), as well as the formation and activation of the receptor complex, biochemical, NMR spectroscopic, and computational studies were performed. Deletion and domain-swapping experiments showed that the central lysine motif in the ectodomain of CEBiP is essential for the binding of chitin oligosaccharides. Epitope mapping by NMR spectroscopy indicated the preferential binding of longer-chain chitin oligosaccharides, such as heptamer-octamer, to CEBiP, and also the importance of N-acetyl groups for the binding. Molecular modeling/docking studies clarified the molecular interaction between CEBiP and chitin oligosaccharides and indicated the importance of Ile₁₂₂ in the central lysine motif region for ligand binding, a notion supported by site-directed mutagenesis. Based on these results, it was indicated that two CEBiP molecules simultaneously bind to one chitin oligosaccharide from the opposite side, resulting in the dimerization of CEBiP. The model was further supported by the observations that the addition of (GlcNAc)₈ induced dimerization of the ectodomain of CEBiP in vitro, and the dimerization and (GlcNAc)₈-induced reactive oxygen generation were also inhibited by a unique oligosaccharide, (GlcNβ1,4GlcNAc)₄, which is supposed to have N-acetyl groups only on one side of the molecule. Based on these observations, we proposed a hypothetical model for the ligand-induced activation of a receptor complex, involving both CEBiP and Oryza sativa chitin-elicitor receptor kinase-1.Plants have the ability to detect potential pathogens through the recognition of microbe-associated molecular patterns (MAMPs; also known as pathogen-associated molecular patterns), such as flagellin, elongation factor Tu (EF-Tu), peptidoglycan, LPS, chitin, and β-glucan, which are typical molecular signatures for whole classes of microbes (1, 2). MAMP-triggered defense is the first barrier to prevent the invasion of pathogens and plays a major role in the basal resistance of plants against various pathogens. It is also well known that this defense system is strikingly similar to the innate immunity of animals (1, 3, 4).Leucine-rich repeat receptor-like kinases, flagellin-sensetive 2 (FLS2), and EF-Tu receptor, have been shown to recognize bacterial flagellin and EF-Tu, respectively, and serve as receptors for these MAMPs (5). On the other hand, two types of lysin motif (LysM) proteins, CEBiP (chitin-elicitor binding protein) and CERK1 (chitin-elicitor receptor kinase-1), were identified as the cell-surface receptor for chitin, a representative fungal molecular pattern (6–8). Knockout/-down experiments of these genes showed that both of these LysM proteins are required for chitin perception and signaling in rice, whereas CEBiP-type molecules are not involved in chitin signaling in Arabidopsis, indicating the difference between the chitin receptor systems in these model plants (8). Additionally, another LysM receptor-like kinase, LYK4, was also indicated to contribute to chitin signaling in Arabidopsis (9). In the case of rice, it was also shown that CEBiP and Oryza sativa (Os)CERK1 form a heterooligomeric receptor complex ligand dependently (10).Both CEBiP and OsCERK1 have LysMs, which have been known to bind peptidoglycan and chitin (11), in their ectodomains. In Arabidopsis, CERK1 was shown to bind chitin and trigger immune responses as a kind of “all-in-one” receptor. On the other hand, CEBiP seems to play a major role in the perception of chitin in rice, as the knockdown of CEBiP almost abolished the binding of a radio-labeled chitin oligosaccharide to the plasma membrane, whereas OsCERK1 was shown not to bind chitin (6, 12). Liu et al. recently reported that two other CEBiP homologs, OsLYP4 and -6, also bind chitin and contribute to chitin responses and disease resistance in rice (13), although it is not clear to what extent these proteins contribute as the cell surface receptor for chitin oligosaccharides.It was also shown that the perception of peptidoglycan in Arabidopsis requires CEBiP-like molecules (14). Arabidopsis homologs of CEBiP, LYM1 and LYM3, play a major role for the binding of peptidoglycan and activation of downstream defense responses through the receptor kinase, CERK1. These results showed that the receptor kinase CERK1 is required for both chitin and peptidoglycan signaling, at least in Arabidopsis. The peptidoglycan receptor system in Arabidopsis seems similar to the rice chitin receptor for the requirement of a binding protein and a receptor kinase, although the receptor complex formation by these two proteins was not confirmed.Thus, the detailed analysis of ligand recognition by these CEBiP-like molecules and succeeding formation and activation of receptor complex is critically important to understand the molecular mechanisms leading to the activation of downstream defense responses triggered by these MAMPs. Such information would also contribute to the design of novel receptor molecules suitable for future biotechnological application. We show herein the results obtained by biochemical studies on the binding site of CEBiP, epitope mapping of chitin oligosaccharides by saturation transfer difference (STD) NMR spectroscopy, and molecular modeling/docking studies combined with site-directed mutagenesis of the ectodomain of CEBiP. These results clearly indicated that two CEBiP molecules simultaneously bind to one N-acetylchitoheptaose/octaose, (GlcNAc)_7/8, through a binding site located in the central LysM region of the ectodomain, resulting in the dimerization of CEBiP. Based on these observations, we proposed a hypothetical model for the ligand-induced activation of a receptor complex, involving both CEBiP and OsCERK1.     

Association of cardiovascular risk factors with the different presentations of acute coronary syndrome

OBJECTIVE:

to identify the relationship between different presentations of acute coronary syndrome and cardiovascular risk factors among hospitalized individuals.

METHOD:

cross-sectional study performed in a teaching hospital in São Paulo, in the State of São Paulo (SP). Socio-demographic, clinical and anthropometric data of 150 individuals hospitalized due to acute coronary syndrome were collected through interviews and review of clinical charts. Association between these data and the presentation of the syndrome were investigated.

RESULTS:

there was a predominance of ST segment elevation acute myocardial infarction. There was significant association of systemic hypertension with unstable angina and high values of low density lipoprotein with infarction, without influence from socio-demographic characteristics.

CONCLUSION:

arterial hypertension and high levels of low-density lipoprotein were associated with different presentations of coronary syndrome. The results can provide support for health professionals for secondary prevention programs aimed at behavioural changing.     

Transcriptomic immune profiles of human flavivirus-specific T-cell responses

The Flavivirus genus of viruses includes dengue (DENV), Zika (ZIKV), yellow fever (YFV), Japanese encephalitis (JEV), and West Nile (WNV) viruses. Infections with these species combined are prevalent in tropical and sub-tropical areas, affecting millions of people and ranging from asymptomatic to severe forms of the disease. They therefore pose a serious threat to global public health. Several studies imply a role for T cells in the protection but also pathogenesis against the different flavivirus species. Identifying flavivirus-specific T-cell immune profiles and determining how pre-exposure of one species might affect the immune response against subsequent infections from other species is important to further define the role of T cells in the immune response against infection. Understanding the immune profiles of the flavivirus-specific T-cell response in natural infection is important to understand the T-cell response in the context of vaccination. In this review, we summarize the current knowledge on human immune profiles of flavivirus-specific T-cell reactivity, comparing natural infection with the acute form of the disease and vaccination in different flavivirus infections.     

The moderating effect of gender as a protective factor against discrimination in migrants from Latin America and China

This study analysed the association between discrimination and satisfaction with life (SWL) in migrant groups by investigating whether different types of social support (SS; emotional, instrumental, and informational) and networks (family, immigrant and native friends, neighbours, and the community) buffer the negative effects of discrimination on SWL among migrant men and women from different backgrounds. Participants were 631 migrants from Latin America and China residing in Malaga (Spain). We identified behaviour patterns that suggest that SS has different effects on men and women from the same place of origin and similar effects on women and men from different places of origin. In conclusion, the main differences in the effects of SS as a buffer mechanism are not determined by cultural factors. It is more likely that they are determined by differential gender-role socialization, which would lead women to positively value social support.     

Age and gender,two key factors in the associations between physical activity and strength during the ageing process

Objectives

The aims of this study were to identify if the associations of physical activity (PA) and muscle strength may vary throughout the ageing process; to study the differences among genders in the relationships between PA and strength in elderly people and to test whether these differences are explained by the hormonal, nutritional and inflammatory status.

Study design

A total of 1741 people ≥65 years of age participated in this cross-sectional study.

Main outcome measures

Upper- and lower-limbs maximal voluntary isometric strength was obtained using standardized techniques and equipment. PA was recorded by a validated questionnaire. The associations of PA with strength were assessed using generalized linear regression models with a Gamma-distributed dependent variable.

Results

A significant gender by PA interaction was found for all strength-related variables (all P < 0.01). Moreover, when sexual hormones, albumin or C-Reactive protein were taken into account in the model, the results did not significantly change. In women, PA was positively associated with upper and lower-body strength; however in men, PA was only associated with grip and knee strength (both P < 0.01). Higher strength values were associated with higher levels of PA, especially in women. However, this tendency had a different pattern across the age range, showing a stronger association in the ‘young’ elderly compared with the ‘old’ elderly.

Conclusion

Higher levels of PA are related to greater muscle strength, especially in women and those who were younger.