CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders

Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD

Relaxor behavior of K0.5La0.5Bi2Nb2O9 ceramics

K0.5La0.5Bi2Nb2O9, a relaxor, was synthesized and the structural studies confirmed it to be an n=2 member of the Aurivillius oxides. The (1/2){h00} and (1/2){hk0} types of superlattice reflections in the electron diffraction patterns reflected the presence of ordered polar regions. A broad dielectric peak with frequency dependent dielectric maximum temperature was observed. The dielectric relaxation obeyed the Vogel-Fulcher relation wherein Ea=0.04 eV, Tf=428 K,and omegao=1010 Hz. The diffuseness parameter gamma=2.003 established the relaxor nature and it was attributed to the A-site cationic disorder. The piezoelectric d31 coefficient was 0.5 pC/N at 300 K and 2 pC/N at 480 K

Optical diffraction of second-harmonic signals in the LiBO2-Nb2O5 glasses induced by self-organized LiNbO3 crystallites

The nanocrystallites (~ 3nm) of LiNbO3, evolved in the (100–x)LiBO2-xNb2O5 (5 < x < 20, in molar ratio) glass system exhibited intense second-harmonic signals in transmission mode when exposed to infrared (IR) light at g =1064 nm. The second-harmonic waves were found to undergo optical diffraction which was attributed to the presence of self-organized submicrometer-sized LiNbO3 crystallites that were grown within the glass matrix along the parallel damage fringes created by the IR laser radiation. Micro-Raman studies carried out on the laser-irradiated samples confirmed the self-organized crystallites to be LiNbO3

Interferon γ-Signature Transcript Profiling and IL-23 Upregulation in Response to Helicobacter Pylori Infection

International audienceHelicobacter pylori infection is the major cause of gastroduodenal pathologies including gastric cancer. The long persistence of bacteria and the type of immune and inflammatory response determine the clinical issue. In this study, the global gene expression profile after 6 and 12 months of H. pylori infection was investigated in the mouse stomach, using the Affymetrix GeneChip Mouse Expression Array A430. Genes related to the inflammatory and immune responses were focused. Levels of selected transcripts were confirmed by reverse transcription polymerase chain reaction. Twenty-five and nineteen percent of the differentially expressed genes observed at 6 and 12 months post-infection respectively, were related to immune response. They are characterized by an interferon (IFN)γ-dependent expression associated to a T helper 1 (Th1) polarised response. In-depth analysis revealed that an up-regulation of IL-23p19, took place in the stomach of H. pylori infected-mice. Strong IL-23p19 levels were also confirmed in gastric biopsies from H. pylori-infected patients with chronic gastritis, as compared to healthy subjects. Our microarray analysis revealed also, a high decrease of H + K + -ATPase transcripts in the presence of the H. pylori infection. Association of gastric Th1 immune response with hypochlorhydria through the down-regulation of H + K + -ATPase contributes to the genesis of lesions upon the H. pylori infection. Our data highlight that the up-regulation of IL-23 and of many IFNγ signature transcripts occur early on during the host response to H. pylori, and suggest that this type of immune response may promote the severity of the induced gastric lesions