Quench Cooled Ice Crystal Imprint Size: A Micro-Method for Study of Macromolecular Hydration

Quench cooling (rate \u3e 4000°C/sec) of biological specimens limits growth of ice crystals by processes different from slow cooling methods. Quench cooling in liquid propane cooled in liquid nitrogen induced ice crystal segregation compartments, as imaged by scanning transmission electron micrographs of freeze-dried cryosections of tissues and protein solutions. The observed imprints of ice crystals were relatively small and roughly spherical. The size of these ice crystal imprints increased with distance from the specimen/quenchant surface. Beyond a depth of 150 microns the size of the imprints was constant but differed among subcellular compartments. The size of the imprints was found to be dependent on: water content, extent of hydration water and the degree of protein aggregation. Determination of extent of hydration water and degree of protein aggregation in protein solutions by measurements on the size of ice crystal imprints yields data in agreement with macroscopic methods. Thus ice crystal imprints give information about the interactions of macromolecules and water at a subcellular level of resolution

Evidence that a Major Portion of Cellular Potassium is Bound

In this report we briefly review recent evidence which shows that a substantial proportion of intracellular K+ is bound or perturbed from the physicochemical properties expected in dilute aqueous solutions. In addition, we present evidence from electron probe x-ray microanalysis of thin cryosections of cells which indicates that the binding of K+ to anionic groups either carboxyl groups (HCO2) on proteins or to phosphate groups in creatine phosphate (CrP) , in adenosine triphosphate, (ATP), in protein and in nucleic acids, are the main determinants of the maintenance of (as differentiated from the generated of) the well known intra- to extracellular K+ concentration difference. The collective evidence suggests that much of cellular K+ is reduced in its mobility and in its chemical activity due to association with negative charge groups (e.g. carboxyl and phosphates). This fact forces abandonment of the misleading assumption that the majority of intracellular K+ and other inorganic ions are as free as would be expected under ideal solution conditions. This realization should have far reaching consequences toward understanding transmembrane movement of water and solutes in cells

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia

Biomedical imaging research opportunities workshop IV: A white paper

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134967/1/mp5838.pd

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60])