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.

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.

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.

The pancreatic β-cell transcriptome and integrated-omics.

Purpose Of Review: β Cells represent one of many cell types in heterogeneous pancreatic islets and play the central role in maintaining glucose homeostasis, such that disrupting β-cell function leads to diabetes. This review summarizes the methods for isolating and characterizing β cells, and describes integrated 'omics' approaches used to define the β cell by its transcriptome and proteome.

Recent Findings: RNA sequencing and mass spectrometry-based protein identification have now identified RNA and protein profiles for mouse and human pancreatic islets and β cells, and for β-cell lines.

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).

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.

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.

Understanding radiologic and nuclear terrorism as public health threats: preparedness and response perspectives.

Terrorism dates back to antiquity, but our understanding of it as a public health threat is still in its nascent stages. Focusing on radiation and nuclear terrorism, we apply a public health perspective to explore relevant physical health and psychosocial impacts, the evolving national response infrastructure created to address terrorism, and the potential roles of nuclear medicine professionals in preparing for and responding to radiologic and nuclear terrorism.

Modeling of the frequency- and temperature-dependent absorption coefficient of long-wave-infrared (2-25 microm) transmitting materials.

A semiempirical multiphonon model based on quantum-mechanical oscillators under a Morse potential is applied to the absorption coefficient of far-infrared transmitting materials. Known material properties are combined with absorption coefficient data to fit the empirical parameters of the model. This provides an accurate means of predicting the intrinsic absorption of the materials in their multiphonon regions.

The Road Map to Preparedness: a competency-based approach to all-hazards emergency readiness training for the public health workforce.

Facing limited time and budgetary resources, state and local health departments need a practical, competency-based training approach to meet the all-hazards readiness requirements of their employees. The Road Map to Preparedness is a training tool designed to assist health departments in providing comprehensive, agency-tailored readiness instruction to their employees. This tool uses an incentive-based, game-like, experiential learning approach to meet the Centers for Disease Control and Prevention's nine core competencies for all public health workers while facilitating public health employees' understanding and acceptance of their emergency response roles.

Applying risk perception theory to public health workforce preparedness training.

Since 9/11, public health has seen a progressive culture change toward a 24/7 emergency response organizational model. This transition entails new expectations for public health workers, including (1) a readiness and willingness to report to duty in emergencies and (2) an ability to effectively communicate risk to an anxious public about terrorism or naturally occurring disasters. To date, however, research on readiness education for health department workers has focused little attention upon the risk perceptions that may influence their willingness to report to duty during disasters, as well as their ability to provide effective emergency risk communication to the public.

The application of the Haddon matrix to public health readiness and response planning.

State and local health departments continue to face unprecedented challenges in preparing for, recognizing, and responding to threats to the public's health. The attacks of 11 September 2001 and the ensuing anthrax mailings of 2001 highlighted the public health readiness and response hurdles posed by intentionally caused injury and illness. At the same time, recent natural disasters have highlighted the need for comparable public health readiness and response capabilities.

Quench-flow analysis reveals multiple phases of GluT1-mediated sugar transport.

Standard models for carrier-mediated nonelectrolyte transport across cell membranes do not explain sugar uptake by human red blood cells. This means that either (1) the models for sugar transport are incorrect or (2) measurements of sugar transport are flawed. Most measurements of red cell sugar transport have been made over intervals of 10 s or greater, a range which may be too long to measure transport accurately.

Conventional transport assays underestimate sugar transport rates in human red cells.

The time course of protein-mediated 3-O-methylglucose uptake by human red cells and by red cell ghosts containing or lacking 4 mM MgATP was measured at ice temperature and sub-saturating sugar levels by conventional sampling procedures and at 20 degrees C by use of a quench-flow apparatus. The temporal resolution of the quench-flow apparatus (as fast as 5-ms sample times) was confirmed by analysis of alkaline hydrolysis of dinitrophenolacetate. Red cell sugar uptake at 4 degrees C is consistent with two processes [fast (tau = 120 s) and slow (tau = 1100 s)] that occur in series.