Effets sur les flux d'énergie impliqués dans l'homéostasie lors d'une exposition chronique à un champ radiofréquence chez le rat juvénile

National audienceLa balance énergétique impliquant sommeil, prise alimentaire et thermorégulation, est importante pour les organismes en croissance. Nous avons étudié les effets d'une exposition chronique aux ondes radiofréquences (RF) type antenne relais sur ces 3 fonctions physiologiques chez des rats juvéniles dans 2 environnements thermiques (24°C et 31°C). 13rats mâles Wistar âgés de 3 semaines ont été exposés continuellement pendant 5 semaines aux ondes RF (900 MHz, 1V.m-1) et comparé à 11 rats non exposés. Les résultats montrent une augmentation de la fréquence des épisodes de sommeil paradoxal à 24°C et 31°C. Les autres effets sur le sommeil dépendent de l'environnement thermique. A 31°C, la température caudale des animaux exposés est moindre que celle des contrôles suggérant une vasoconstriction exacerbée ; ce qui est confirmée avec la prazosine vasodilatatrice. De plus, la prise alimentaire est plus élevée chez les animaux exposés. La plupart des effets de l'exposition chronique aux ondes RF sur le sommeil dépendent de l'environnement thermique et les animaux exposés semblent mettre en place des processus d'économie d'énergie

Acute exposure to mobile phone and assessment of internal cerebral circulation in young healthy subjects : a transcranial Doppler study

International audienceThe rapid worldwide increase in the use of mobile phones raises questions about the possible adverse effects of RF fields emitted by these devices. The temporal lobe of brain is closest to the mobile phone. This may lead to relatively high energy deposition in these parts of human head during the use of mobile phone. The cerebral circulation may be potentially affected due to the exposure to RF emitted by mobile phone. Therefore the studies on cerebral blood flow are essential in order to evaluate the possible interaction exposure to RF with the central nervous system. Data in the literature related to the brain circulation are limited and controversial due to the different methods and protocols applied in these studie

Effets spécifiques d'une exposition aux ondes radiofréquences de téléphone mobile sur le contrôle nerveux autonome du tonus vasomoteur cutané

National audienceLes résultats de l'étude effectuée sur 21 jeunes adultes volontaires ont révélé des effets athermiques de l'exposition réelle aux ondes RF de téléphone mobile sur le micro débit sanguin cutané en comparaison avec une exposition sham, par approche laser Doppler thermostatique (LD). L'analyse spectrale du signal LD en fin d'exposition a permis de montrer que ces modifications de vasomotricité cutanée étaient associées à une activité nerveuse sympathique locale plus élevée sous exposition réelle que sous exposition sham. Un test de provocation thermique spécifique induisant une hyperémie réactive maximale effectué à la 25è minute post-exposition a montré que la réserve vasodilatatrice des micro-vaisseaux cutanés exposés aux ondes RF était plus grande que celle sous exposition sham

Is the effect of mobile phone radiofrequency waves on human skin perfusion non-thermal ?

International audienceTo establish whether SkBF can be modified by exposure to the radiofrequency waves emitted by a mobile phone when the latter is held against the jaw and ear. Variations in SkBF and Tsk in adult volunteers were simultaneously recorded with a thermostatic laser Doppler system during a 20-minute radiofrequency exposure session and a 20-minute sham session. The skin microvessels' vasodilatory reserve was assessed with a heat challenge at the end of the protocol. During the radiofrequency exposure session, SkBF increased (vs. baseline) more than during the sham exposure session. The sessions did not differ significant in terms of the Tsk time-course response. The skin microvessels' vasodilatory ability was found to be greater during radiofrequency exposure than during sham exposure. Our results reveal the existence of a specific vasodilatory effect of mobile phone radiofrequency emission on skin perfusion

Human cerebellum and corticocerebellar connections involved in emotional memory enhancement

Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a whole-brain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory-related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory

Translation of mouse model to human gives insights into periodontitis etiology

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10-4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10-5) and RNASE2 (rs2771342, P = 2.84×10-5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10-14) and HLA-DPA1 (rs17214512, P = 5.14×10-5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease

Adipose Gene Expression Prior to Weight Loss Can Differentiate and Weakly Predict Dietary Responders

BACKGROUND: The ability to identify obese individuals who will successfully lose weight in response to dietary intervention will revolutionize disease management. Therefore, we asked whether it is possible to identify subjects who will lose weight during dietary intervention using only a single gene expression snapshot. METHODOLOGY/PRINCIPAL FINDINGS: The present study involved 54 female subjects from the Nutrient-Gene Interactions in Human Obesity-Implications for Dietary Guidelines (NUGENOB) trial to determine whether subcutaneous adipose tissue gene expression could be used to predict weight loss prior to the 10-week consumption of a low-fat hypocaloric diet. Using several statistical tests revealed that the gene expression profiles of responders (8-12 kgs weight loss) could always be differentiated from non-responders (<4 kgs weight loss). We also assessed whether this differentiation was sufficient for prediction. Using a bottom-up (i.e. black-box) approach, standard class prediction algorithms were able to predict dietary responders with up to 61.1%+/-8.1% accuracy. Using a top-down approach (i.e. using differentially expressed genes to build a classifier) improved prediction accuracy to 80.9%+/-2.2%. CONCLUSION: Adipose gene expression profiling prior to the consumption of a low-fat diet is able to differentiate responders from non-responders as well as serve as a weak predictor of subjects destined to lose weight. While the degree of prediction accuracy currently achieved with a gene expression snapshot is perhaps insufficient for clinical use, this work reveals that the comprehensive molecular signature of adipose tissue paves the way for the future of personalized nutrition

BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis

BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits

The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences