Graph theory reveals dysconnected hubs in 22q11DS and altered nodal efficiency in patients with hallucinations.

Schizophrenia is postulated to be the prototypical dysconnection disorder, in which hallucinations are the core symptom. Due to high heterogeneity in methodology across studies and the clinical phenotype, it remains unclear whether the structural brain dysconnection is global or focal and if clinical symptoms result from this dysconnection. In the present work, we attempt to clarify this issue by studying a population considered as a homogeneous genetic sub-type of schizophrenia, namely the 22q11.

Comparative inhibition of the GH/IGF-I axis obtained with either the targeted secretion inhibitor SXN101959 or the somatostatin analog octreotide in growing male rats.

Abnormally high GH/IGF-I levels, most often caused by adenomas arising from pituitary somatotrophs, generate deleterious effects. We recently described a targeted secretion inhibitor (SXN101742) comprising a GHRH domain and the endopeptidase domain of botulinum toxin serotype D (GHRH-light chain endopeptidase type D domain [LC/D] associated to a heavy chain translocation domain [HN]) able to down-regulate the GH/IGF-I axis. In the present study, we compared the effect of a single iv bolus of a related molecule developed for clinical studies (SXN101959, 1 mg/kg) with a sc infusion of the somatostatin analog octreotide (SMS201-995, 10 μg/kg · h) to lower GH/IGF-I activity in growing male rats.

Encoding style and its relationships with schizotypal traits and impulsivity during adolescence.

This study intends to explore how individual differences in encoding style (i.e. how encoding is implicitly affected by pre-existing schemata, so called an internal style, versus by cues from the outside world, so called an external style) are associated with schizotypal traits and impulsivity expression during adolescence.

Clinical and cognitive risk factors for psychotic symptoms in 22q11.2 deletion syndrome: a transversal and longitudinal approach.

22q11.2 deletion syndrome (22q11DS) is associated with increased risk for schizophrenia. Better identifying risk factors for the emergence of psychotic symptoms in this population is needed to improve clinical assessment and early interventions.

Role of seipin in lipid droplet morphology and hepatitis C virus life cycle.

Infectious hepatitis C virus (HCV) particle assembly starts at the surface of lipid droplets, cytoplasmic organelles responsible for neutral fat storage. We analysed the relationship between HCV and seipin, a protein involved in lipid droplet maturation. Although seipin overexpression did not affect the total mean volume occupied by lipid droplets nor the total triglyceride and cholesterol ester levels per cell, it caused an increase in the mean diameter of lipid droplets by 60 %, while decreasing their total number per cell.

Action simulation in hallucination-prone adolescents.

Theoretical and empirical accounts suggest that impairments in self-other discrimination processes are likely to promote the expression of hallucinations. Studies using a variety of paradigms involving self-performed actions argue in favor of perspective taking confusion in hallucination-prone subjects. However, our understanding of such processes during adolescence is still at an early stage.

Self-reflection and positive schizotypy in the adolescent brain.

Clinical and phenomenological accounts of schizophrenia suggest that impairments in self-reflective processes significantly contribute to psychopathological expression. Recent imaging studies observe atypical cerebral activation patterns during self-reflection, especially around the cortical midline structures, both in psychosis-prone adults and individuals with schizophrenia. Given that self-reflection processes consolidate during adolescence, and that early transient expression of psychosis (positive schizotypy) also arises during this period, the present study sought to examine whether atypical cerebral activation during self-reflection task could be associated with early schizotypic expression during adolescence.

Broadly defined risk mental states during adolescence: disorganization mediates positive schizotypal expression.

While schizotypal features are common during adolescence, they can also signal increased risk for the onset of schizophreniform disorders. Most studies with adolescents find that hallucination and delusion-like symptoms (positive schizotypal features) best predict future psychopathology. Still, the developmental process of positive schizotypy remains elusive, specifically with regards to 1) its relationships to negative and disorganization schizotypal dimensions; 2) its associations to maladaptive functioning during adolescence.

Connexins and β-cell functions.

Proper functioning of pancreatic islets requires that numerous β-cells are properly coordinated. With evolution, many mechanisms have converged, which now allow individual β-cells to sense the state of activity of their neighbors as well as the changes taking place in the extracellular medium, and to regulate accordingly their own function. Here, we review one such mechanism for intercellular coordination, which depends on connexins.

A structure-based model of RIG-I activation.

A series of high-resolution crystal structures of RIG-I and RIG-I:dsRNA cocrystals has recently been reported. Comparison of these structures provides considerable insight into how this innate immune pattern recognition receptor is activated upon detecting and binding a certain class of viral RNAs.

IL-36 signaling amplifies Th1 responses by enhancing proliferation and Th1 polarization of naive CD4+ T cells.

The interleukin-1 (IL-1) superfamily of cytokines comprises a set of pivotal mediators of inflammation. Among them, the action of IL-36 cytokines in immune responses has remained elusive. In a recent study, we demonstrated a direct effect of IL-36 on immune cells.

Hippocampal volume reduction in chromosome 22q11.2 deletion syndrome (22q11.2DS): a longitudinal study of morphometry and symptomatology.

Recent studies observed an association between the structural integrity of the hippocampal structure and the manifestations of clinically significant psychotic symptoms in participants at high risk for psychosis. The present study sought to investigate the longitudinal trajectory of the hippocampal volume and its subregions among a sample of participants affected by 22q11.2 deletion syndrome (22q11.

A botulinum toxin-derived targeted secretion inhibitor downregulates the GH/IGF1 axis.

Botulinum neurotoxins (BoNTs) are zinc endopeptidases that block release of the neurotransmitter acetylcholine in neuromuscular synapses through cleavage of soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein receptor (SNARE) proteins, which promote fusion of synaptic vesicles to the plasma membrane. We designed and tested a BoNT-derived targeted secretion inhibitor (TSI) targeting pituitary somatotroph cells to suppress growth hormone (GH) secretion and treat acromegaly. This recombinant protein, called SXN101742, contains a modified GH-releasing hormone (GHRH) domain and the endopeptidase domain of botulinum toxin serotype D (GHRH-LHN/D, where HN/D indicates endopeptidase and translocation domain type D).

The intercellular synchronization of Ca2+ oscillations evaluates Cx36-dependent coupling.

Connexin36 (Cx36) plays an important role in insulin secretion by controlling the intercellular synchronization of Ca(2+) transients induced during stimulation. The lack of drugs acting on Cx36 channels is a major limitation in further unraveling the molecular mechanism underlying this effect. To screen for such drugs, we have developed an assay allowing for a semi-automatic, fluorimetric quantification of Ca(2+) transients in large populations of MIN6 cells.

Resting-state networks in adolescents with 22q11.2 deletion syndrome: associations with prodromal symptoms and executive functions.

Atypical functional connectivity in the maturing brains of 22q11.2 deletion syndrome (22q11DS) may contribute to the expression of early psychotic symptoms commonly reported by these youths. This study's objective was to examine functional connectivity in cerebral networks at rest (Resting-State Networks; RSNs) and their relationship to symptomatic and neuropsychological characteristics putting them at very high risk factor for developing psychosis.

Mice deficient in hepatocyte-specific IL-1Ra show delayed resolution of concanavalin A-induced hepatitis.

Interleukin-1 receptor antagonist (IL-1Ra) is a specific IL-1 inhibitor that possesses anti-inflammatory activities. Several studies in human and mouse suggested a protective role for IL-1Ra in liver inflammation, and we previously demonstrated that hepatocytes produce high levels of IL-1Ra in response to inflammatory challenge in vitro and in vivo. In the present study, we investigated the production and the biological function of hepatocyte-derived IL-1Ra in concanavalin A (ConA)-induced hepatitis in mice.

Depression and anxiety disorders in children and adolescents with velo-cardio-facial syndrome (VCFS).

Velo-cardio-facial syndrome (VCFS) is characterized by a high prevalence of depression and anxiety disorders in childhood and adolescence. These disorders are a source of great impairment in everyday functioning, as well as important risk factors for the emergence of later psychotic disorders. Impairment in daily and social functioning as well as loss of IQ throughout growth are also are well-established correlates of the VCFS.

Comparing the neural bases of self-referential processing in typically developing and 22q11.2 adolescents.

The investigation of self-reflective processing during adolescence is relevant, as this period is characterized by deep reorganization of the self-concept. It may be the case that an atypical development of brain regions underlying self-reflective processing increases the risk for psychological disorders and impaired social functioning. In this study, we investigated the neural bases of self- and other-related processing in typically developing adolescents and youths with 22q11.

Preliminary structure and predictive value of attenuated negative symptoms in 22q11.2 deletion syndrome.

Current research in schizophrenia suggests that negative symptoms cannot be considered a unitary construct and should be divided in two dimensions: lack of motivation and impoverishment of expression. In addition, negative symptoms are particularly related to decreased daily-life functioning. In the present study, we aimed to replicate these results in a sample of participants with 22q11.

Evaluation of cardiovascular risk in patients with rheumatoid arthritis: do cardiovascular biomarkers offer added predictive ability over established clinical risk scores?

Objective: To determine whether adding C-reactive protein, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, N-terminal pro-brain natriuretic peptide (NT-proBNP), oxidized low-density lipoprotein (ox-LDL), or anti-apolipoprotein A-I (anti-Apo A-I) IgG to the Framingham 10-year cardiovascular (CV) risk score (FRS) could improve its CV prognostic accuracy in rheumatoid arthritis (RA).

Methods: We performed an ancillary study derived from a prospective single-center cohort consisting of 118 RA patients without CV disease at baseline. The FRS and the various biomarkers were assessed at enrollment and their prognostic accuracy was determined using receiver operating characteristic (ROC) curve analysis.

How to measure cortical folding from MR images: a step-by-step tutorial to compute local gyrification index.

Cortical folding (gyrification) is determined during the first months of life, so that adverse events occurring during this period leave traces that will be identifiable at any age. As recently reviewed by Mangin and colleagues(2), several methods exist to quantify different characteristics of gyrification. For instance, sulcal morphometry can be used to measure shape descriptors such as the depth, length or indices of inter-hemispheric asymmetry(3).

The mouse interleukin (Il)33 gene is expressed in a cell type- and stimulus-dependent manner from two alternative promoters.

GenBank entries for mouse Il33 reveal the existence of two transcripts, Il33a and Il33b, with different 5'UTRs but coding for the same protein. We investigated expression of these transcripts in different mouse organs and cell types in basal and inflammatory conditions. Il33a and Il33b mRNAs start with different noncoding first exons, transcribed from different promoter regions, which both contain a consensus TATA-like sequence.

Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at a single center.

Objective: To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate (CS) therapy in patients with osteoarthritis (OA) of the hand.

Methods: This investigator-initiated, single-center, randomized, double-blind, placebo-controlled clinical trial included 162 symptomatic patients with radiographic evidence of hand OA (American College of Rheumatology criteria). Inclusion criteria included patient's assessment of global spontaneous hand pain of at least 40 mm on a 0-100-mm visual analog scale (VAS) and functional impairment of at least 6 (0-30 scale) on the Functional Index for Hand OA (FIHOA) in the most symptomatic hand.