IL-36R ligands are potent regulators of dendritic and T cells.

IL-36α (IL-1F6), IL-36β (IL-1F8), and IL-36γ (IL-1F9) are members of the IL-1 family of cytokines. These cytokines bind to IL-36R (IL-1Rrp2) and IL-1RAcP, activating similar intracellular signals as IL-1, whereas IL-36Ra (IL-1F5) acts as an IL-36R antagonist (IL-36Ra). In this study, we show that both murine bone marrow-derived dendritic cells (BMDCs) and CD4(+) T lymphocytes constitutively express IL-36R and respond to IL-36α, IL-36β, and IL-36γ.

Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease.

The Geneva brain collection.

The University of Geneva brain collection was founded at the beginning of the 20th century. Today, it consists of 10,154 formaldehyde- or buffered formaldehyde-fixed brains obtained from the autopsies of the Department of Psychiatry and, since 1971, from the Department of Geriatrics. More than 100,000 paraffin-embedded blocks and 200,000 histological slides have also been collected since 1901.

A novel method for quantitative monitoring of transplanted islets of langerhans by positive contrast magnetic resonance imaging.

The Automatic Quantitative Ultrashort Echo Time imaging (AQUTE) protocol for serial MRI allows quantitative in vivo monitoring of iron labeled pancreatic islets of Langerhans transplanted into the liver, quantifying graft implantation and persistence in a rodent model. Rats (n = 14), transplanted with iron oxide loaded cells (0-4000 islet equivalents, IEQ), were imaged using a 3D radial ultrashort echo time difference technique (dUTE) on a Siemens MAGNETOM 3T clinical scanner up to 5 months postsurgery. In vivo 3D dUTE images gave positive contrast from labeled cells, suppressing liver signal and small vessels, allowing automatic quantification.

Interleukin-33 biology with potential insights into human diseases.

Interleukin (IL)-33 is a member of the IL-1 family of cytokines. IL-33 is a nuclear protein that is also released into the extracellular space, and thus acts as a dual-function molecule, as does IL-1α. Extracellular IL-33 binds to the cell-surface receptor ST2, leading to the activation of intracellular signaling pathways similar to those used by IL-1.

Islet autotransplantation after extended pancreatectomy for focal benign disease of the pancreas.

Background: Extended pancreatectomy is associated with the risk of surgical diabetes. Islet autotransplantation is successful in the prevention of diabetes after pancreas resection for chronic pancreatitis (CP), with insulin independence rates of 50% at 1 year. The aim of the present study is to demonstrate the safety and efficiency of islet autotransplantation after extended left pancreatectomy for benign disease.

Neural correlates of reality monitoring during adolescence.

Background: Reality monitoring processes serve the critical function of discriminating between externally derived information and self-generated information. Several reality monitoring studies with healthy adult participants have identified the anterior prefrontal cortex (PFC) as consistently engaged during the recollection of self-generated contextual cues. Furthermore, reduced activity of medial PFC has been linked with schizotypal trait expression of delusion and hallucination-like symptoms in healthy adults undergoing fMRI reality-monitoring tasks.

Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys.

Arenavirus RNA genomes are initiated by a "prime and realign" mechanism, such that the initiating GTP is found as a single unpaired (overhanging) nucleotide when the complementary genome ends anneal to form double-stranded (ds) RNA panhandle structures. dsRNAs modeled on these structures do not induce interferon (IFN), as opposed to blunt-ended (5' ppp)dsRNA. This study examines whether these viral structures can also act as decoys, by trapping RIG-I in inactive dsRNA complexes.

Anosognosia for hemiplegia: a clinical-anatomical prospective study.

Anosognosia for hemiplegia is a common and striking disorder following stroke. Because it is typically transient and variable, it remains poorly understood and has rarely been investigated at different times in a systematic manner. Our study evaluated a prospective cohort of 58 patients with right-hemisphere stroke and significant motor deficit of the left hemibody, who were examined using a comprehensive neuropsychological battery at 3 days (hyperacute), 1 week (subacute) and 6 months (chronic) after stroke onset.

Small vascular and Alzheimer disease-related pathologic determinants of dementia in the oldest-old.

The relative contributions of Alzheimer disease (AD) and vascular lesion burden to the occurrence of cognitive decline are more difficult to define in the oldest-old than they are in younger cohorts. To address this issue, we examined 93 prospectively documented autopsy cases from 90 to 103 years with various degrees of AD lesions, lacunes, and microvascular pathology. Cognitive assessment was performed prospectively using the Clinical Dementia Rating scale.

BMP signaling promotes the growth of primary human colon carcinomas in vivo.

Human colon carcinomas (CCs) represent a growing worldwide problem. One of the pathways that has been negatively implicated in the genesis of CCs is triggered by bone morphogenetic protein (BMP) ligands, which activate BMP receptors leading to the function of SMAD proteins in the nucleus. BMP signaling is altered in familial human polyposis, and mice with compromised BMP signaling in the intestine develop tumors.

Eye gaze during face processing in children and adolescents with 22q11.2 deletion syndrome.

Objective: The 22q11.2 deletion syndrome (22q11DS) is a neurogenetic syndrome with high risk for the development of psychiatric disorder. There is interest in identifying reliable markers for measuring and monitoring socio-emotional impairments in 22q11DS during development.

Donor pancreata: evolving approaches to organ allocation for whole pancreas versus islet transplantation.

As islet transplantation increasingly enters the clinical arena, its coexistence with vascularized pancreas transplantation makes it necessary to reassess the questions of donor selection and allocation. In answering these questions, one must put in the balance the short-term morbidity of pancreas transplantation with the long-term attrition of islet grafts. The preferential allocation of pancreases from obese and older donors for islet isolation has been based on their association with worse pancreas transplant outcomes and better islet isolation results in islet yields.

Signaling mechanisms regulating synapse formation and function in mental retardation.

Major progress has been carried out in the last two decades in the identification of genetic alterations associated with mental retardation and autism spectrum disorders. In many instances these defects concern genes coding for synaptic proteins or proteins involved in regulation of synaptic properties. Analyses of the underlying mechanisms using gain and loss of function approaches have revealed alterations of spine morphology, density or plasticity, raising the possibility that these disorders result from synaptopathies.

Unpaired 5' ppp-nucleotides, as found in arenavirus double-stranded RNA panhandles, are not recognized by RIG-I.

Arenavirus and bunyavirus RNA genomes are unusual in that they are found in circular nucleocapsids, presumably due to the annealing of their complementary terminal sequences. Moreover, arenavirus genome synthesis initiates with GTP at position +2 of the template rather than at the precise 3' end (position +1). After formation of a dinucleotide, 5' pppGpC(OH) is then realigned on the template before this primer is extended.

Thoracoscopic and robotic tricuspid valve annuloplasty with a biodegradable ring: an initial experience.

Background And Aim Of The Study: Ring annuloplasty is a technically demanding and time-consuming thoracoscopic and/or robotic surgery. The initial experience of the authors with the intra-annular Bioring tricuspid ring using a minimally invasive access is reviewed, and some modifications are proposed to adapt to the particularities of these approaches.

Methods: Patients undergoing minimally invasive tricuspid annuloplasty were included prospectively between March and September 2008.

IL-1 pathways in inflammation and human diseases.

Interleukin (IL)-1 was first cloned in the 1980s, and rapidly emerged as a key player in the regulation of inflammatory processes. The term IL-1 refers to two cytokines, IL-1alpha and IL-1beta, which are encoded by two separate genes. The effects of IL-1 are tightly controlled by several naturally occurring inhibitors, such as IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type II (IL-1RII), and other soluble receptors.

Enhanced Th1 and Th17 responses and arthritis severity in mice with a deficiency of myeloid cell-specific interleukin-1 receptor antagonist.

Objective: The balance between interleukin-1 (IL-1) and its specific inhibitor, the IL-1 receptor antagonist (IL-1Ra), plays a major role in the development of arthritis. The purpose of this study was to investigate the role of IL-1Ra produced specifically by myeloid cells in the control of collagen-induced arthritis (CIA) by using myeloid cell-specific IL-1Ra-deficient mice (IL-1Ra(DeltaM)).

Methods: IL-1Ra(DeltaM) mice were generated by using the loxP/Cre recombinase system.

Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome.

Objective: Velocardiofacial syndrome (VCFS) is associated with cognitive deficits and high rates of schizophrenia and other neuropsychiatric disorders. We report the data from two large cohorts of individuals with VCFS from Israel and Western Europe to characterize the neuropsychiatric phenotype from childhood to adulthood in a large sample.

Method: Individuals with VCFS (n = 172) aged 5 to 54 years were evaluated with structured clinical interviews for psychiatric disorders and age-appropriate versions of the Wechsler intelligence tests.

Monitoring of self-generated speech in adolescents with 22q11.2 deletion syndrome.

Objectives: The present report examines the monitoring of self-generated speech in adolescents with 22q11.2 deletion syndrome (22q11DS), a neurogenetic disorder associated with very high risk for psychosis.

Design: Between-participant group design.

The double-stranded RNA binding domain of the vaccinia virus E3L protein inhibits both RNA- and DNA-induced activation of interferon beta.

Vaccinia virus, a large DNA virus that replicates in the cytoplasm, expresses its E3L protein to inhibit the cellular innate immune response and apoptosis. E3L is a bifunctional protein that contains an N-terminal DNA binding domain (BD) and a C-terminal double-stranded RNA (dsRNA)-BD (residues 100-190), both of which contribute to viral pathogenesis by blocking the activation of cellular genes that respond to the viral infection. We report that expression of the dsRNA-BD alone inhibits not only the dsRNA-induced activation of interferon beta (IFNbeta) but also that of 5'-triphosphate single-stranded RNA and DNA-induced IFNbeta activation even though E3L(100-190) does not bind the latter two pathogen-associated molecular patterns.

The presenilin-1 familial Alzheimer's disease mutation P117L decreases neuronal differentiation of embryonic murine neural progenitor cells.

The presenilin-1 gene is mutated in early-onset familial Alzheimer's disease. The mutation Pro117Leu is implicated in a very severe form of the disease, with an onset of less than 30 years. The consequences of this mutation on neurogenesis in the hippocampus of adult transgenic mice have already been studied in situ.

Interleukin-33 is biologically active independently of caspase-1 cleavage.

The new interleukin (IL)-1 family cytokine IL-33 is synthesized as a 30-kDa precursor. Like pro-IL-1beta, human pro-IL-33 was reported to be cleaved by caspase-1 to generate an 18-kDa fragment, which is sufficient to activate signaling by the IL-33 receptor T1/ST2. However, the proposed caspase-1 cleavage site is poorly conserved between species.

Immunomodulation by blockade of the TRANCE co-stimulatory pathway in murine allogeneic islet transplantation.

We explore herein the effect of TNF-related activation-induced cytokine (TRANCE) co-stimulatory pathway blockade on islet survival after allograft transplantation. Expression of TRANCE on murine C57Bl/6 (B6) CD4+ T cells after allogeneic activation was analyzed by fluorescence-activated cell sorter (FACS). The effect of a TRANCE receptor fusion protein (TR-Fc) and anti-CD154 antibody (MR1) on B6 spleen cell proliferation after allogeneic activation was assessed by mixed lymphocyte reaction (MLR).