Brain effects of gestating germ-free persist in mouse neonates despite acquisition of a microbiota at birth

At birth, mammals experience a massive colonization by microorganisms. We previously reported that newborn mice gestated and born germ-free (GF) have increased microglial labeling and alterations in developmental neuronal cell death in the hippocampus and hypothalamus, as well as greater forebrain volume and body weight when compared to conventionally colonized (CC) mice. To test whether these effects are solely due to differences in postnatal microbial exposure, or instead may be programmed in utero, we cross-fostered GF newborns immediately after birth to CC dams (GF→CC) and compared them to offspring fostered within the same microbiota status (CC→CC, GF→GF). Because key developmental events (including microglial colonization and neuronal cell death) shape the brain during the first postnatal week, we collected brains on postnatal day (P) 7. To track gut bacterial colonization, colonic content was also collected and subjected to 16S rRNA qPCR and Illumina sequencing. In the brains of GF→GF mice, we replicated most of the effects seen previously in GF mice. Interestingly, the GF brain phenotype persisted in GF→CC offspring for almost all measures. In contrast, total bacterial load did not differ between the CC→CC and GF→CC groups on P7, and bacterial community composition was also very similar, with a few exceptions. Thus, GF→CC offspring had altered brain development during at least the first 7 days after birth despite a largely normal microbiota. This suggests that prenatal influences of gestating in an altered microbial environment programs neonatal brain development

Arabic validation of the Compulsive Internet Use Scale (CIUS)

<p>Abstract</p> <p>Background</p> <p>The popularity of using the Internet and related applications has grown in Arabic countries in recent years. Despite numerous advantages in terms of optimizing communications among individuals and social systems, the use of the Internet may in certain cases become problematic and engender negative consequences in daily life. As no instrument in the Arabic language is available, however, to measure excessive Internet use, the goal of the current study was to validate an Arabic version of the Compulsive Internet Use Scale (CIUS).</p> <p>Methods</p> <p>The Arabic version of the CIUS was administered to a sample of 185 Internet users and exploratory and confirmatory analyses performed.</p> <p>Results</p> <p>As found previously for the original version, a one-factor model of the CIUS had good psychometric properties and fit the data well. The total score on the CIUS was positively associated with time spent online.</p> <p>Conclusion</p> <p>The Arabic version of the CIUS seems to be a valid self-report to measure problematic Internet use.</p

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Etude comparative de carburants par analyse de leur cycle de vie

Rapport LASEN EPFL 415.105, Mandat Alcosuisse

Role of HLA-G as a predictive marker of low risk of chronic rejection in lung transplant recipients: A clinical prospective study

Human leukocyte antigen G (HLA-G) expression is thought to be associated with a tolerance state following solid organ transplantation.In a lung transplant (LTx) recipient cohort, we assessed (1) the role of HLA-G expression as a predictor of graft acceptance, and (2) the relationship between (i) graft and peripheral HLA-G expression, (ii) HLA-G expression and humoral immunity and (iii) HLA-G expression and lung microenvironment.We prospectively enrolled 63 LTx recipients (median follow-up 3.26 years [min: 0.44-max: 5.03]).At 3 and 12 months post-LTx, we analyzed graft HLA-G expression by immunohistochemistry, plasma soluble HLA-G (sHLA-G) level by enzyme-linked immunosorbent assay, bronchoalveolar lavage fluid (BALF) levels of cytokines involved in chronic lung allograft dysfunction (CLAD) and anti-HLA antibodies (Abs) in serum.In a time-dependent Cox model, lung HLA-G expression had a protective effect on CLAD occurrence (hazard ratio: 0.13 [0.03-0.58]; p = 0.008).The same results were found when computing 3-month and 1-year conditional freedom from CLAD (p = 0.03 and 0.04, respectively [log-rank test]).Presence of anti-HLA Abs was inversely associated with graft HLA-G expression (p = 0.02).Increased BALF level of transforming growth factor-β was associated with high plasma sHLA-G level (p = 0.02).In conclusion, early graft HLA-G expression in LTx recipients with a stable condition was associated with graft acceptance in the long term