Differential expression of laminin chains in hepatic lipocytes

The lipocyte is an important source of laminin in the normal liver. We have investigated the expression of the 3 chains of laminin in isolated rat lipocytes. Both B₁ and B₂ chains, but not A, were found in medium from 5-day-old lipocyte primary cultures by immunoblotting and immunoprecipitation of ³⁵S-labeled proteins after reducing SDS-polyacrylamide gel electrophoresis. An additional polypeptide of M_r=380 000 was identified by immunoprecipitation. Under non-reducing conditions only one M_r=900 000 band was revealed. High levels of B₁ and B₂ mRNAs were also demonstrated in 5-day-old cultured lipocytes while at the time of seeding, only B₂ chain mRNAs were clearly detectable. A chain mRNA was constantly absent. These results suggest that lipocytes produce a variant form of laminin in primary culture and that the M_r=380 000 polypeptide could be unrelated to the A chain of laminin.     

Ecology of pathogenic and non‐pathogenic Vibrio parahaemolyticus on the French Atlantic coast. Effects of temperature,salinity, turbidity and chlorophyll a

Vibrio parahaemolyticus is one of the principal bacterial causes for seafood‐borne gastroenteritis in the world. In the present study, three sites located on the French Atlantic coast were monitored monthly for environmental parameters over 1 year. The presence of total and pathogenic V. parahaemolyticus in sediment, water and mussel samples was detected following enrichment by culture and real‐time PCR (toxR gene, tdh, trh1 and trh2 virulence genes). Using generalized linear models, we showed that the presence of V. parahaemolyticus in water could be explained by a combination of mean temperature over the 7 days before the day of sampling (P < 0.001) and turbidity (P = 0.058). In mussels, an effect of chlorophyll a (P = 0.005) was detected when an effect of the mean salinity over the 7 days before sampling was significant for the sediment (P < 0.001). We did not detect any significant effect of phytoplanktonic blooms or of the number of culturable bacteria on V. parahaemolyticus presence. No sample was revealed positive for tdh. The presence of trh1 and trh2 was positively influenced by the mean temperature during the 2 days before the day of sampling (P < 0.001 and P = 0.032). The importance of these ecological parameters is discussed in relation to the biology of V. parahaemolyticus.     

Accurate prediction of kinase-substrate networks using knowledge graphs

Phosphorylation of specific substrates by protein kinases is a key control mechanism for vital cell-fate decisions and other cellular processes. However, discovering specific kinase-substrate relationships is time-consuming and often rather serendipitous. Computational predictions alleviate these challenges, but the current approaches suffer from limitations like restricted kinome coverage and inaccuracy. They also typically utilise only local features without reflecting broader interaction context. To address these limitations, we have developed an alternative predictive model. It uses statistical relational learning on top of phosphorylation networks interpreted as knowledge graphs, a simple yet robust model for representing networked knowledge. Compared to a representative selection of six existing systems, our model has the highest kinome coverage and produces biologically valid high-confidence predictions not possible with the other tools. Specifically, we have experimentally validated predictions of previously unknown phosphorylations by the LATS1, AKT1, PKA and MST2 kinases in human. Thus, our tool is useful for focusing phosphoproteomic experiments, and facilitates the discovery of new phosphorylation reactions. Our model can be accessed publicly via an easy-to-use web interface (LinkPhinder).     

Glucocorticoid receptor gene polymorphisms associated with progression of lung disease in young patients with cystic fibrosis

Background

The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to variations in the inflammatory response.

Methods

We evaluated the association between four GR gene polymorphisms, TthIII, ER22/23EK, N363S and BclI, and disease progression in a cohort of 255 young patients with CF. Genotypes were tested for association with changes in lung function tests, infection with Pseudomonas aeruginosa and nutritional status by multivariable analysis.

Results

A significant non-corrected for multiple tests association was found between BclI genotypes and decline in lung function measured as the forced expiratory volume in one second (FEV₁) and the forced vital capacity (FVC). Deterioration in FEV₁ and FVC was more pronounced in patients with the BclI GG genotype compared to the group of patients with BclI CG and CC genotypes (p = 0.02 and p = 0.04 respectively for the entire cohort and p = 0.01 and p = 0.02 respectively for F508del homozygous patients).

Conclusion

The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function.     

ISHAPE: new rapid and accurate software for haplotyping

Background  

We have developed a new haplotyping program based on the combination of an iterative multiallelic EM algorithm (IEM), bootstrap resampling and a pseudo Gibbs sampler. The use of the IEM-bootstrap procedure considerably reduces the space of possible haplotype configurations to be explored, greatly reducing computation time, while the adaptation of the Gibbs sampler with a recombination model on this restricted space maintains high accuracy. On large SNP datasets (>30 SNPs), we used a segmented approach based on a specific partition-ligation strategy. We compared this software, Ishape (Iterative Segmented HAPlotyping by Em), with reference programs such as Phase, Fastphase, and PL-EM. Analogously with Phase, there are 2 versions of Ishape: Ishape1 which uses a simple coalescence model for the pseudo Gibbs sampler step, and Ishape2 which uses a recombination model instead.     

Detailed Contact Data and the Dissemination of Staphylococcus aureus in Hospitals

Close proximity interactions (CPIs) measured by wireless electronic devices are increasingly used in epidemiological models. However, no evidence supports that electronically collected CPIs inform on the contacts leading to transmission. Here, we analyzed Staphylococcus aureus carriage and CPIs recorded simultaneously in a long-term care facility for 4 months in 329 patients and 261 healthcare workers to test this hypothesis. In the broad diversity of isolated S. aureus strains, 173 transmission events were observed between participants. The joint analysis of carriage and CPIs showed that CPI paths linking incident cases to other individuals carrying the same strain (i.e. possible infectors) had fewer intermediaries than predicted by chance (P < 0.001), a feature that simulations showed to be the signature of transmission along CPIs. Additional analyses revealed a higher dissemination risk between patients via healthcare workers than via other patients. In conclusion, S. aureus transmission was consistent with contacts defined by electronically collected CPIs, illustrating their potential as a tool to control hospital-acquired infections and help direct surveillance.