Immunomodulatory Roles of CTRP3 in Endotoxemia and Metabolic Stress

C1q/TNF-related protein 3 (CTRP3) is a secreted hormone that modulates hepatic glucose and lipid metabolism. Its circulating levels are reduced in human and rodent models of obesity, a metabolic state accompanied by chronic low-grade inflammation. Recent studies have demonstrated an anti-inflammatory role for recombinant CTRP3 in attenuating LPS-induced systemic inflammation, and its deficiency markedly exacerbates inflammation in a mouse model of rheumatoid arthritis. We used genetic mouse models to explore the immunomodulatory function of CTRP3 in response to acute (LPS challenge) and chronic (high-fat diet) inflammatory stimuli. In a sublethal dose of LPS challenge, neither CTRP3 deficiency nor its overexpression in transgenic mice had an impact on IL-1β, IL-6, TNF-α, or MIP-2 induction at the serum protein or mRNA levels, contrary to previous findings based on recombinant CTRP3 administration. In a metabolic context, we measured 71 serum cytokine levels in wild-type and CTRP3 transgenic mice fed a high-fat diet or a matched control low-fat diet. On a low-fat diet, CTRP3 transgenic mice had elevated circulating levels of multiple chemokines (CCL11, CXCL9, CXCL10, CCL17, CX3CL1, CCL22 and sCD30). However, when obesity was induced with a high-fat diet, CTRP3 transgenic mice had lower circulating levels of IL-5, TNF-α, sVEGF2, and sVEGFR3, and a higher level of soluble gp130. Contingent upon the metabolic state, CTRP3 overexpression altered chemokine levels in lean mice, and attenuated systemic inflammation in the setting of obesity and insulin resistance. These results highlight a context-dependent immunomodulatory role for CTRP3

Decay resistance variability of European wood species thermally modified by industrial process

Thermal modification is now considered as a new ecofriendly industrial wood modification process improving mainly the material decay resistance and its dimensional stability. Most industrial thermal treatment processes use convection heat transfer which induces sometimes heterogeneous treatment temperature propagation within the oven and lead to the heterogeneity in treatment efficiency. Thus, it is common that treatment is not completely effective on several stack boards, in a same batch. The aim of this paper was to study the decay resistance variability of various European wood species thermally modified. Thermal modifications were performed around 240°C during 4h, on about 10 m3 of 27 x 152 x 2000 mm3 wood planks placed in an industrial oven having a volume of 20 m3, on the following wood species: spruce, ash, beech and poplar. All of the tests concerning the decay resistance were carried out in the laboratory using untreated beech and pine woods as reference materials. An agar block test was used to determine the resistance of thermally modified woods, leached beforehand according to EN 84 standard or not, to brown-rot and white-rot fungi, according to XP CEN/TS 15083-1. A large selection of treated wood samples was tested in order to estimate the variability of treatment efficiency. Thermal treatment increased the biological durability of all leached and un-leached modified wood samples, compared with native wood species. The treatment temperature of 240°C used in this study is sufficient to reach durability classes ''durable'' or ''very durable'' for the four wood species. However, the dispersion of weight loss values, due to the fungal attacks was very important and showed a large variability of the durability of wood which has been treated in a single batch. These results showed that there is a substantial need to develop process control and² indicator in order to insure that the quality of treated timber is properly evaluated with a view to putting this modified timber on the market under a chain of custody. (Résumé d'auteur

EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis.

Hydrops fetalis describes fluid accumulation in at least 2 fetal compartments, including abdominal cavities, pleura, and pericardium, or in body tissue. The majority of hydrops fetalis cases are nonimmune conditions that present with generalized edema of the fetus, and approximately 15% of these nonimmune cases result from a lymphatic abnormality. Here, we have identified an autosomal dominant, inherited form of lymphatic-related (nonimmune) hydrops fetalis (LRHF). Independent exome sequencing projects on 2 families with a history of in utero and neonatal deaths associated with nonimmune hydrops fetalis uncovered 2 heterozygous missense variants in the gene encoding Eph receptor B4 (EPHB4). Biochemical analysis determined that the mutant EPHB4 proteins are devoid of tyrosine kinase activity, indicating that loss of EPHB4 signaling contributes to LRHF pathogenesis. Further, inactivation of Ephb4 in lymphatic endothelial cells of developing mouse embryos led to defective lymphovenous valve formation and consequent subcutaneous edema. Together, these findings identify EPHB4 as a critical regulator of early lymphatic vascular development and demonstrate that mutations in the gene can cause an autosomal dominant form of LRHF that is associated with a high mortality rate

The effect of five years versus two years of specialised assertive intervention for first episode psychosis - OPUS II: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The Danish OPUS I trial randomized 547 patients with first-episode psychosis to a two-year early-specialised assertive treatment programme (OPUS) versus standard treatment. The two years OPUS treatment had significant positive effects on psychotic and negative symptoms, secondary substance abuse, treatment adherence, lower dosage of antipsychotic medication, and a higher treatment satisfaction. However, three years after end of the OPUS treatment, the positive clinical effects were not sustained, except that OPUS-treated patients were significantly less likely to be institutionalised compared with standard-treated patients. The major objective of the OPUS II trial is to evaluate the effects of five years of OPUS treatment versus two years of OPUS treatment.</p> <p>Methods</p> <p>The OPUS II trial is designed as a randomized, open label, parallel group trial with blinded outcome assessment. Based on our sample size estimation, 400 patients treated in OPUS for two years will be randomized to further three years of OPUS treatment versus standard treatment. The specialized assertive OPUS treatment consists of three core elements: assertive community treatment, psycho-educational family treatment, and social skills training.</p> <p>Discussion</p> <p>It has been hypothesized that there is a critical period from onset up to five years, which represents a window of opportunity where a long-term course can be influenced. Extending the specialized assertive OPUS treatment up to five years may allow the beneficial effects to continue beyond the high-risk period, through consolidation of improved social and functional outcome.</p> <p>Trial registration</p> <p>Clinical Trial.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00914238">NCT00914238</a></p

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

SARS-CoV-2-specific T cell memory with common TCRαβ motifs is established in unvaccinated children who seroconvert after infection

As establishment of SARS-CoV-2-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination. We analysed epitope-specific T cells directly ex vivo using seven HLA class-I and class-II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable spike-specific, but lower ORF1a- and N-specific memory T cell responses compared to adults. This agreed with our TCR sequencing data showing reduced clonal expansion in children. A strong stem cell memory phenotype and common T cell receptor motifs were detected within tetramer-specific T cells in seroconverted children. Conversely, children who did not seroconvert had tetramer-specific T cells of predominantly naïve phenotypes and diverse TCRαβ repertoires. Our study demonstrates generation of SARS-CoV-2-specific T cell memory with common TCRαβ motifs in unvaccinated seroconverted children after their first virus encounter