Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats

Background

The Influenza A H1N1 virus can be transmitted via direct, indirect, and airborne route to non-infected subjects when an infected patient coughs, which expels a number of different sized droplets to the surrounding environment as an aerosol. The objective of the current study was to characterize the human cough aerosol pattern with the aim of developing a standard human cough bioaerosol model for Influenza Pandemic control.

Method

45 healthy non-smokers participated in the open bench study by giving their best effort cough. A laser diffraction system was used to obtain accurate, time-dependent, quantitative measurements of the size and number of droplets expelled by the cough aerosol.

Results

Voluntary coughs generated droplets ranging from 0.1 - 900 microns in size. Droplets of less than one-micron size represent 97% of the total number of measured droplets contained in the cough aerosol. Age, sex, weight, height and corporal mass have no statistically significant effect on the aerosol composition in terms of size and number of droplets.

Conclusions

We have developed a standard human cough aerosol model. We have quantitatively characterized the pattern, size, and number of droplets present in the most important mode of person-to-person transmission of IRD: the cough bioaerosol. Small size droplets (< 1 ??m) predominated the total number of droplets expelled when coughing. The cough aerosol is the single source of direct, indirect and/or airborne transmission of respiratory infections like the Influenza A H1N1 virus.

Study design

Open bench, Observational, Cough, Aerosol study     

Toward genotype phenotype correlations in GFM1 mutations

Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases. We report two novel GFM1 mutations in two unrelated patients with encephalopathy and liver failure respectively. The first patient had intrauterine growth retardation, seizures, encephalopathy and developmental delay. Brain MRI showed hypoplasia of the vermis and severe pontine atrophy of the brainstem that were similar to those reported in patients with mitochondrial translation deficiencies. The second patient had liver failure with hypoglycemia. Respiratory chain analysis showed a complex IV deficiency in muscle of both patients. A 10K SNP genotyping detected several regions of homozygosity in the two patients. In vitro translation deficiency prompted us to study genes involved in mitochondrial translation. Therefore, we sequenced the GFM1 gene, encoding the mitochondrial translation factor EFG1, included in a shared homozygous region and identified two different homozygous mutations (R671C and L398P). Modeling studies of EFG1 protein suggested that the R671C mutation disrupts an inter-subunit interface and could locally destabilize the mutant protein. The second mutation (L398P) disrupted the H-bond network in a rich-beta-sheet domain, and may have a dramatic effect on local structure. GFM1 mutations have been seldom reported and are associated with different clinical presentation. By modeling the structure of the protein and the position of the various mutations we suggest that the clinical phenotypes of the patients could be related to the localization of the mutations.     

Unexpected and novel putative viruses in the sediments of a deep-dark permanently anoxic freshwater habitat

Morphological diversity, abundance and community structure of viruses were examined in the deep and anoxic sediments of the volcanic Lake Pavin (France). The sediment core, encompassing 130 years of sedimentation, was subsampled every centimeter. High viral abundances were recorded and correlated to prokaryotic densities. Abundances of viruses and prokaryotes decreased with the depth, contrasting the pattern of virus-to-prokaryote ratio. According to fingerprint analyses, the community structure of viruses, bacteria and archaea gradually changed, and communities of the surface (0–10 cm) could be discriminated from those of the intermediate (11–27 cm) and deep (28–40 cm) sediment layers. Viral morphotypes similar to virions of ubiquitous dsDNA viruses of bacteria were observed. Exceptional morphotypes, previously never reported in freshwater systems, were also detected. Some of these resembled dsDNA viruses of hyperthermophilic and hyperhalophilic archaea. Moreover, unusual types of spherical and cubic virus-like particles (VLPs) were observed. Infected prokaryotic cells were detected in the whole sediment core, and their vertical distribution correlated with both viral and prokaryotic abundances. Pleomorphic ellipsoid VLPs were visible in filamentous cells tentatively identified as representatives of the archaeal genus Methanosaeta, a major group of methane producers on earth.     

Association between Dietary Patterns and Depressive Symptoms Over Time: A 10-Year Follow-Up Study of the GAZEL Cohort

Background

Data on the association between dietary patterns and depression are scarce. The objective of this study was to examine the longitudinal association between dietary patterns and depressive symptoms assessed repeatedly over 10 years in the French occupational GAZEL cohort.

Methods

A total of 9,272 men and 3,132 women, aged 45–60 years in 1998, completed a 35-item Food Frequency Questionnaire (FFQ) at baseline. Dietary patterns were derived by Principal Component Analysis. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression scale (CES-D) in 1999, 2002, 2005 and 2008. The main outcome measure was the repeated measures of CES-D. Longitudinal analyses were performed with logistic regression based on generalized estimating equations.

Principal Findings

The highest quartile of low-fat, western, high snack and high fat-sweet diets in men and low-fat and high snack diets in women were associated with higher likelihood of depressive symptoms at the start of the follow-up compared to the lowest quartile (OR between 1.16 and 1.50). Conversely, the highest quartile of traditional diet (characterized by fish and fruit consumption) was associated with a lower likelihood of depressive symptoms in women compared to the lowest quartile, with OR = 0.63 [95%CI, 0.50 to 0.80], as the healthy pattern (characterized by vegetables consumption) with OR = 0.72 [95%CI, 0.63 to 0.83] and OR = 0.75 [95%CI, 0.61 to 0.93] in men and women, respectively. However, there was probably a reverse causality effect for the healthy pattern.

Conclusion

This longitudinal study shows that several dietary patterns are associated with depressive symptoms and these associations track over time.     

Modeling the influence of local environmental factors on malaria transmission in Benin and its implications for cohort study

Malaria remains endemic in tropical areas, especially in Africa. For the evaluation of new tools and to further our understanding of host-parasite interactions, knowing the environmental risk of transmission--even at a very local scale--is essential. The aim of this study was to assess how malaria transmission is influenced and can be predicted by local climatic and environmental factors.As the entomological part of a cohort study of 650 newborn babies in nine villages in the Tori Bossito district of Southern Benin between June 2007 and February 2010, human landing catches were performed to assess the density of malaria vectors and transmission intensity. Climatic factors as well as household characteristics were recorded throughout the study. Statistical correlations between Anopheles density and environmental and climatic factors were tested using a three-level Poisson mixed regression model. The results showed both temporal variations in vector density (related to season and rainfall), and spatial variations at the level of both village and house. These spatial variations could be largely explained by factors associated with the house's immediate surroundings, namely soil type, vegetation index and the proximity of a watercourse. Based on these results, a predictive regression model was developed using a leave-one-out method, to predict the spatiotemporal variability of malaria transmission in the nine villages.This study points up the importance of local environmental factors in malaria transmission and describes a model to predict the transmission risk of individual children, based on environmental and behavioral characteristics.     

Long-lasting LTP requires neither repeated trains for its induction nor protein synthesis for its development

Current thinking about LTP triggered in the area CA1 of hippocampal slices is ruled by two "dogmas": (1) A single train of high-frequency stimulation is sufficient to trigger short-lasting LTP (1-3 h), whereas multiple trains are required to induce long-lasting LTP (L-LTP, more than 4 h). (2) The development of the late phase of L-LTP requires the synthesis of new proteins. In this study, we found that a single high-frequency train could trigger an LTP lasting more than 8 h that was not affected by either anisomycin or cycloheximide (two inhibitors of protein synthesis). We ascertained that the induction of this L-LTP made use of the same mechanisms as those usually reported to be involved in LTP induction: it was dependent on NMDA receptors and on the activation of two "core" kinases, CaMKII and PI3K. These findings call into question the two "dogmas" about LTP.     

The ERMES complex and ER-mitochondria connections

Cellular organelles need to communicate in order to co-ordinate homoeostasis of the compartmentalized eukaryotic cell. Such communication involves the formation of membrane contact sites between adjacent organelles, allowing privileged exchange of metabolites and information. Using a synthetic protein designed to artificially tether the ER (endoplasmic reticulum) to mitochondria, we have discovered a yeast protein complex naturally involved in establishing and maintaining contact sites between these two organelles. This protein complex is physiologically involved in a plethora of mitochondrial processes, suggesting that ER-mitochondria connections play a central co-ordinating role in the regulation of mitochondrial biology. Recent biochemical characterization of this protein complex led to the discovery that GTPases of the Miro family are part of ER-mitochondria connections. The yeast Miro GTPase Gem1 localizes to ER-mitochondria interface and influences the size and distribution of mitochondria. Thus Miro GTPases may serve as regulators of the ER-mitochondria connection.