The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

A diamond anvil cell with resistive heating for high pressure and high temperature x-ray diffraction and absorption studies

International audienceIn this paper we describe a prototype of a diamond anvil cel

Diagnostic utility of data from adrenal venous sampling for primary aldosteronism despite failed cannulation of the right adrenal vein.

BackgroundAdrenal venous sampling is an important lateralization study for primary aldosteronism, but inability to cannulate the right adrenal vein is not uncommon and interpreted as a failed study. We challenged this notion by examining whether data from incomplete left-sided adrenal venous sampling could accurately predict lateralization.MethodsSixty-two adrenal venous sampling studies from 2007 to 2014 at 2 tertiary-care institutions were reviewed. For this analysis, data from the right adrenal vein were excluded. The study variable was the aldosterone:cortisol ratio of the left adrenal vein compared with the inferior vena cava (LAV/IVC). Scatterplot analysis identified high and low LAV/IVC cutoffs that predicted accurately unilateral disease in 1 institutional cohort and validated in the second cohort.ResultsThirty-six studies of adrenal venous sampling were evaluated at the first institution and divided into 3 diagnostic categories: unilateral-left (n = 14), unilateral-right (n = 12), and bilateral (n = 10). Cutoff values of the ratios of LAV/IVC of ≥ 5.5 and ≤ 0.5 accurately predicted left- and right-sided disease, respectively, and were validated in 26 studies from the second institution (100% PPV). The "5.5-0.5 criteria" salvaged accuracy for predicting lateralization in 50% of cases.ConclusionEven in the setting of failed cannulation of the right adrenal vein, the actual data from the remaining adrenal venous sampling can predict lateralization accurately in many patients. A "failed" adrenal venous sampling study may be of greater predictive utility than believed traditionally

United States. Department of State Telegram

Department of State Telegram regarding President Johnson's goodbye letter to Svoboda Ludvik, President of Czechoslovakia

FcγRIIA-specific DARPins as novel tools in blood cell analysis and platelet aggregation

Fc receptors are involved in a variety of physiologically and disease-relevant responses. Among them, FcγRIIA (CD32a) is known for its activating functions in pathogen recognition and platelet biology, and, as potential marker of T lymphocytes latently infected with HIV-1. The latter has not been without controversy due to technical challenges complicated by T-B cell conjugates and trogocytosis as well as a lack of antibodies distinguishing between the closely related isoforms of FcγRII. To generate high-affinity binders specific for FcγRIIA, libraries of designed ankyrin repeat proteins (DARPins) were screened for binding to its extracellular domains by ribosomal display. Counterselection against FcγRIIB eliminated binders cross-reacting with both isoforms. The identified DARPins bound FcγRIIA with no detectable binding for FcγRIIB. Their affinities for FcγRIIA were in the low nanomolar range and could be enhanced by cleavage of the His-tag and dimerization. Interestingly, complex formation between DARPin and FcγRIIA followed a two-state reaction model, and discrimination from FcγRIIB was based on a single amino acid residue. In flow cytometry, DARPin F11 detected FcγRIIA+ cells even when they made up less than 1% of the cell population. Image stream analysis of primary human blood cells confirmed that F11 caused dim but reliable cell surface staining of a small subpopulation of T lymphocytes. When incubated with platelets, F11 inhibited their aggregation equally efficient as antibodies unable to discriminate between both FcγRII isoforms. The selected DARPins are unique novel tools for platelet aggregation studies as well as the role of FcγRIIA for the latent HIV-1 reservoir

An outbreak of norovirus infection in a long-term care facility in Brazil

ABSTRACT Objective: To describe a norovirus outbreak in a Brazilian long-term care facility from July 8 to 29, 2005. Methods: In the first 48 to 72 hours after onset of symptoms in inpatients and employees, the main infection control strategies were staff education, emphasis on hand washing, implementing contact precautions up to 48-72 hours after resolution of symptoms, complete cleaning of the rooms and exclusion of symptomatic employees from work until 48-72 hours after resolution of their symptoms. Epidemiological and clinical characteristics of the norovirus infections were described based on chart review. Results: The incidence among inpatients and employees was 41.3% and 16.25%, respectively. The main symptom was diarrhea, affecting 100% of inpatients and employees. Forty-four percent of specimens were positive by RIDASCREEN® Norovirus analyses, and identified as norovirus genogroup GII. Seventy percent of inpatients were women and their age range was 51-98 years. Inpatients had in average two comorbid conditions – 87.3% with cardiovascular or chronic pulmonary condition and 47.6% with dementia. There was not relapse or death. Conclusions: The early infection-control measures associated to surveillance are required to keep long-term care facilities free of noroviruses and to protect those who are most vulnerable