Optical approaches for neurocritical care: Toward non-invasive recording of cerebral physiology in acute brain injury.

Acute brain injury (ABI) is a complex disease process that begins with an initial insult followed by secondary injury resulting from disturbances in cerebral physiology. In the metabolically active brain, early recognition of physiologic derangements is critical in enabling clinicians with the insight to adjust therapeutic interventions and reduce risk of ischemia and permanent injury. Current established approaches for monitoring cerebral physiology include the neurologic physical examination, traditional brain imaging such as computed tomography (CT) and magnetic resonance imaging (MRI), electroencephalography (EEG), and bedside modalities such as invasive parenchymal probes and transcranial doppler ultrasound.

High-resolution transcranial optical imaging of in vivo neural activity.

Rapid sub-nanometer neuronal deformations have been shown to occur as a consequence of action potentials in vitro, allowing for optical registration of discrete axonal and synaptic depolarizations. Such optically-measured deformations are a novel signature for recording neural activity. We demonstrate this signature can be extended to in vivo measurements through recording of rapid neuronal deformations on the population level with holographic, optical phase-based recordings.

Restructuring and serving web-accessible streamflow data from the NOAA National Water Model historic simulations.

In 2016, the National Oceanic and Atmospheric Administration deployed the first iteration of an operational National Water Model (NWM) to forecast the water cycle in the continental United States. With many versions, an hourly, multi-decadal historic simulation is made available to the public. In all released to date, the files containing simulated streamflow contain a snapshot of model conditions across the entire domain for a single timestep which makes accessing  time series a technical and resource-intensive challenge.

Prehospital Detection of Life-Threatening Intracranial Pathology: An Unmet Need for Severe TBI in Austere, Rural, and Remote Areas.

Severe traumatic brain injury (TBI) is a leading cause of death and disability worldwide, especially in low- and middle-income countries, and in austere, rural, and remote settings. The purpose of this Perspective is to challenge the notion that accurate and actionable diagnosis of the most severe brain injuries should be limited to physicians and other highly-trained specialists located at hospitals. Further, we aim to demonstrate that the great opportunity to improve severe TBI care is in the prehospital setting.

Attitudes and knowledge about cannabis and cannabis-based therapies among US neurologists, nurses, and pharmacists.

Use of cannabinoid therapies is on the rise in the United States, but responses of healthcare professionals and their knowledge of these therapies have been mixed. More information is needed about factors associated with healthcare professionals' attitudes and knowledge about medical cannabis. We conducted an online survey of US-based neurologists, nurse practitioners (NPs)/nurses, and pharmacists in August-September of 2018 (n = 451).

Recovery of viable endocrine-specific cells and transcriptomes from human pancreatic islet-engrafted mice.

Human pancreatic islets engrafted into immunodeficient mice serve as an important model for in vivo human diabetes studies. Following engraftment, islet function can be monitored in vivo by measuring circulating glucose and human insulin; however, it will be important to recover viable cells for more complex graft analyses. Moreover, RNA analyses of dissected grafts have not distinguished which hormone-specific cell types contribute to gene expression.

HLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of Islet β-Cells From Donors With Type 1 Diabetes.

Type 1 diabetes studies consistently generate data showing islet β-cell dysfunction and T cell-mediated anti-β-cell-specific autoimmunity. To explore the pathogenesis, we interrogated the β-cell transcriptomes from donors with and without type 1 diabetes using both bulk-sorted and single β-cells. Consistent with immunohistological studies, β-cells from donors with type 1 diabetes displayed increased Class I transcripts and associated mRNA species.

α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes.

Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion.

Snake fungal disease: an emerging threat to wild snakes.

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused by Ophidiomyces ophiodiicola, a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV).

Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes.

A major therapeutic goal for type 1 diabetes (T1D) is to induce autoantigen-specific tolerance of T cells. This could suppress autoimmunity in those at risk for the development of T1D, as well as in those with established disease who receive islet replacement or regeneration therapy. Because functional studies of human autoreactive T cell responses have been limited largely to peripheral blood-derived T cells, it is unclear how representative the peripheral T cell repertoire is of T cells infiltrating the islets.

Surprising Heterogeneity of Pancreatic Islet Cell Subsets.

Two studies clearly demonstrate that pancreatic islets and, more specifically, their cellular constituents, display a much greater complexity than previously appreciated.

End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data.

RNA-seq protocols that focus on transcript termini are well suited for applications in which template quantity is limiting. Here we show that, when applied to end-sequencing data, analytical methods designed for global RNA-seq produce computational artifacts. To remedy this, we created the End Sequence Analysis Toolkit (ESAT).

Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β.

Individuals with schizophrenia and their first-degree relatives have higher rates of type 2 diabetes (T2D) than the general population (18-30 vs. 1.2-6.

Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.

Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic α- and β-cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase β-cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify α-, β-, and δ-cells from human fetal and adult pancreata by intracellular staining for the cell-specific hormone content, sorting the subpopulations by flow cytometry, and, using next-generation RNA sequencing, we report the detailed transcriptomes of fetal and adult α- and β-cells. We observed that human islet composition was not influenced by age, sex, or BMI, and transcripts for inflammatory gene products were noted in fetal β-cells.

Liver enzymes in White Leghorns selected for the sheep red blood cell immune response.

Liver enzymes are essential to xenobiotic metabolism. Expression of these enzymes is dependent upon factors such as age and sex. The objective of this study was to determine basal liver enzyme levels in male and female White Leghorn chickens to provide reference values for future studies.

Disease allele-dependent small-molecule sensitivities in blood cells from monogenic diabetes.

Even as genetic studies identify alleles that influence human disease susceptibility, it remains challenging to understand their functional significance and how they contribute to disease phenotypes. Here, we describe an approach to translate discoveries from human genetics into functional and therapeutic hypotheses by relating human genetic variation to small-molecule sensitivities. We use small-molecule probes modulating a breadth of targets and processes to reveal disease allele-dependent sensitivities, using cells from multiple individuals with an extreme form of diabetes (maturity onset diabetes of the young type 1, caused by mutation in the orphan nuclear receptor HNF4α).

Phalaris arundinacea (reed canarygrass) grass staggers in beef cattle.

Four adult mixed-breed beef cows from a cow-calf operation in West Virginia were referred to the Virginia-Maryland Regional College of Veterinary Medicine in March 2009 with weakness, ataxia, hind limb paresis progressing to lateral recumbency, and death within 2-3 days. Histologically, there was accumulation of light brown, granular pigment in neurons of the ventral gray horns of the spinal cord (more severe in thoracic and lumbar sections), brain stem, and pons, resulting in distortion and bulging of the cell body and displacement of the Nissl substance, suggestive of Phalaris sp. grass toxicosis.

Effects of silymarin on gossypol toxicosis in divergent lines of chickens.

Gossypol, a pigment of cotton, is a hepatic toxin for chickens. Thus, despite its high protein content, inclusion of cottonseed meal in poultry diets is problematic. Silymarin, an extract from milk thistle, has hepatoprotective qualities and could potentially serve as a feed additive to offset the toxicity of gossypol.

Analysis of glucose transporter topology and structural dynamics.

Homology modeling and scanning cysteine mutagenesis studies suggest that the human glucose transport protein GLUT1 and its distant bacterial homologs LacY and GlpT share similar structures. We tested this hypothesis by mapping the accessibility of purified, reconstituted human erythrocyte GLUT1 to aqueous probes. GLUT1 contains 35 potential tryptic cleavage sites.

Influence of endophyte consumption and heat stress on intravaginal temperatures, plasma lipid oxidation, blood selenium, and glutathione redox of mononuclear cells in heifers grazing tall fescue.

A grazing experiment was conducted to assess the effects of wild-type endophyte-infected (E+) tall fescue consumption and elevated ambient temperatures on intravaginal temperatures, plasma lipid peroxidation, and glutathione redox of peripheral blood mononuclear cells. Angus heifers (n = 34) were allotted by BW to 4 blocks consisting of E+ and endophyte-free (E-) fescue pastures. Monthly, in June, July, and August, temperature loggers were fixed into blank controlled internal drug releasers and inserted into a subsample of heifers (n = 16) for 2 d.

Structural basis of GLUT1 inhibition by cytoplasmic ATP.

Cytoplasmic ATP inhibits human erythrocyte glucose transport protein (GLUT1)-mediated glucose transport in human red blood cells by reducing net glucose transport but not exchange glucose transport (Cloherty, E.K., D.