Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome.

Importance: Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age.

Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway.

Insulin monotherapy can neither maintain normoglycemia in type 1 diabetes (T1D) nor prevent the long-term damage indicated by elevated glycation products in blood, such as glycated hemoglobin (HbA1c). Here we find that hyperglycemia, when unaccompanied by an acute increase in insulin, enhances itself by paradoxically stimulating hyperglucagonemia. Raising glucose from 5 to 25 mM without insulin enhanced glucagon secretion ∼two- to fivefold in InR1-G9 α cells and ∼18-fold in perfused pancreata from insulin-deficient rats with T1D.

Developing psychosis and its risk states through the lens of schizotypy.

Starting from the early descriptions of Kraepelin and Bleuler, the construct of schizotypy was developed from observations of aberrations in nonpsychotic family members of schizophrenia patients. In contemporary diagnostic manuals, the positive symptoms of schizotypal personality disorder were included in the ultra high-risk (UHR) criteria 20 years ago, and nowadays are broadly employed in clinical early detection of psychosis. The schizotypy construct, now dissociated from strict familial risk, also informed research on the liability to develop any psychotic disorder, and in particular schizophrenia-spectrum disorders, even outside clinical settings.

HCV 3a core protein increases lipid droplet cholesteryl ester content via a mechanism dependent on sphingolipid biosynthesis.

Hepatitis C virus (HCV) infected patients often develop steatosis and the HCV core protein alone can induce this phenomenon. To gain new insights into the pathways leading to steatosis, we performed lipidomic profiling of HCV core protein expressing-Huh-7 cells and also assessed the lipid profile of purified lipid droplets isolated from HCV 3a core expressing cells. Cholesteryl esters, ceramides and glycosylceramides, but not triglycerides, increased specifically in cells expressing the steatogenic HCV 3a core protein.

Severe neutrophil-dominated inflammation and enhanced myelopoiesis in IL-33-overexpressing CMV/IL33 mice.

IL-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Previous studies emphasized a role for IL-33 in shaping innate and adaptive immune responses. IL-33 was also reported to modulate myelopoiesis and myeloid cell activity.

Angiotensin II induces interleukin-1β-mediated islet inflammation and β-cell dysfunction independently of vasoconstrictive effects.

Pathological activation of the renin-angiotensin system (RAS) is associated with the metabolic syndrome, and the new onset of type 2 diabetes can be delayed by RAS inhibition. In animal models of type 2 diabetes, inhibition of the RAS improves insulin secretion. However, the direct effects of angiotensin II on islet function and underlying mechanisms independent of changes in blood pressure remain unclear.

Enhancement of islet engraftment and achievement of long-term islet allograft survival by Toll-like receptor 4 blockade.

Background: Toll-like receptors are key players in sterile inflammation phenomena and can link the innate and adaptive immune systems by enhancing graft immunogenicity. They are also considered mediators of types 1 and 2 diabetes development. The aim of the present study was to assess the role of Toll-like receptor-4 (TLR4) in mediating the inflammatory and immune responses to pancreatic islets, thereby promoting inflammatory destruction and immune rejection of islet grafts.

Social feedback processing from early to late adolescence: influence of sex, age, and attachment style.

Objective: The establishment of an accurate understanding of one's social context is a central developmental task during adolescence. A critical component of such development is to learn how to integrate the objective evaluation of one's behavior with the social response to the latter--here referred to as social feedback processing.

Case Report: We measured brain activity by means of fMRI in 33 healthy adolescents (12-19 years old, 14 females).

Simplified gyral pattern in severe developmental microcephalies? New insights from allometric modeling for spatial and spectral analysis of gyrification.

The strong positive-allometric relationship between brain size, cortical extension and gyrification complexity, recently highlighted in the general population, could be modified by brain developmental disorders. Indeed, in case of brain growth insufficiency, the pathophysiological relevance of the "simplified gyral pattern" phenotype is strongly disputed since almost no genotype-phenotype correlations have been found in primary microcephalies. Using surface scaling analysis and newly-developed spectral analysis of gyrification (Spangy), we tested whether the gyral simplification in groups of severe microcephalies related to ASPM, PQBP1 or fetal-alcohol-syndrome could be fully explained by brain size reduction according to the allometric scaling law established in typically-developing control groups, or whether an additional disease effect was to be suspected.

Diet and gene interactions influence the skeletal response to polyunsaturated fatty acids.

Diets rich in omega-3s have been thought to prevent both obesity and osteoporosis. However, conflicting findings are reported, probably as a result of gene by nutritional interactions. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor that improves insulin sensitivity but causes weight gain and bone loss.

Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?

Previous studies have repeatedly found altered temporal characteristics of EEG microstates in schizophrenia. The aim of the present study was to investigate whether adolescents affected by the 22q11.2 deletion syndrome (22q11DS), known to have a 30 fold increased risk to develop schizophrenia, already show deviant EEG microstates.

Effect of diet on brain metabolites and behavior in spontaneously hypertensive rats.

Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric disorder affecting 5-10% of children. One of the suggested mechanisms underlying the pathophysiology of ADHD is insufficient energy supply to neurons. Here, we investigated the role of omega 3 fatty acids in altering neural energy metabolism and behavior of spontaneously hypertensive rats (SHR), which is an animal model of ADHD.

Identifying 22q11.2 deletion syndrome and psychosis using resting-state connectivity patterns.

The clinical picture associated with 22q11.2 deletion syndrome (22q11DS) includes mild mental retardation and an increased risk of schizophrenia. While the clinical phenotype has been related to structural brain network alterations, there is only scarce information about functional connectivity in 22q11DS.

Segmented negative strand RNA virus nucleoprotein structure.

Negative strand RNA virus (NSV) genomes are never free, but always found assembled with multiple copies of their nucleoprotein, as RNPs. A flurry of papers describing the X-ray crystal structures of several segmented NSV nucleoproteins have recently appeared. The most significant feature of these various structures is that the arms that are used to oligomerize the nucleoproteins on their genome RNAs are highly flexible, permitting these RNPs to assume virtually unlimited geometries.

Covariance and specificity in adolescent schizotypal and borderline trait expression.

Aims: The first aim of the present study is to assess the overlap between borderline and schizotypal traits during adolescence. The second objective is to examine whether some psychological factors (i.e.

JAK-STAT signaling and myocardial glucose metabolism.

JAK-STAT signaling occurs in virtually every tissue of the body, and so does glucose metabolism. In this review, we summarize the regulation of glucose metabolism in the myocardium and ponder whether JAK-STAT signaling participates in this regulation. Despite a paucity of data directly pertaining to cardiac myocytes, we conclude that JAK-STAT signaling may contribute to the development of insulin resistance in the myocardium in response to various hormones and cytokines.

Testing measurement invariance of the schizotypal personality questionnaire-brief scores across Spanish and Swiss adolescents.

Background: Schizotypy is a complex construct intimately related to psychosis. Empirical evidence indicates that participants with high scores on schizotypal self-report are at a heightened risk for the later development of psychotic disorders. Schizotypal experiences represent the behavioural expression of liability for psychotic disorders.

Protein-mediated interactions of pancreatic islet cells.

The islets of Langerhans collectively form the endocrine pancreas, the organ that is soley responsible for insulin secretion in mammals, and which plays a prominent role in the control of circulating glucose and metabolism. Normal function of these islets implies the coordination of different types of endocrine cells, noticeably of the beta cells which produce insulin. Given that an appropriate secretion of this hormone is vital to the organism, a number of mechanisms have been selected during evolution, which now converge to coordinate beta cell functions.

Nicotinic cholinergic signaling in adipose tissue and pancreatic islets biology: revisited function and therapeutic perspectives.

Nicotinic acetylcholine receptors (nAChRs) are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine or other biologic compounds including nicotine. Their roles in synaptic transmission in the central and peripheral nervous system as well as in the neuromuscular junction have been extensively studied. Recent implications of nAChRs in intracellular signaling and their detection in peripheral nonneural cells (including epithelial cells and immune cells) have renewed the interest for this class of ionotropic receptors.

Decreased frontal gyrification correlates with altered connectivity in children with autism.

The structural correlates of functional dysconnectivity in autism spectrum disorders (ASD) have been seldom explored, despite the fact that altered functional connectivity is one of the most frequent neuropathological observations in the disorder. We analyzed cerebral morphometry and structural connectivity using multi-modal imaging for 11 children/adolescents with ASD and 11 matched controls. We estimated regional cortical and white matter volumes, as well as vertex-wise measures of cortical thickness and local Gyrification Index (lGI).

Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism.

Background: Intrauterine growth restriction (IUGR) is a major risk factor for both perinatal and long-term morbidity. Bovine lactoferrin (bLf) is a major milk glycoprotein considered as a pleiotropic functional nutrient. The impact of maternal supplementation with bLf on IUGR-induced sequelae, including inadequate growth and altered cerebral development, remains unknown.

Predominant negative symptoms in 22q11.2 deletion syndrome and their associations with cognitive functioning and functional outcome.

22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic condition associated with increased risk for schizophrenia.