Widespread loss of safe lake ice access in response to a warming climate.

Millions of people rely on lake ice for safe winter recreation. Warming air temperatures impact the phenology (timing of formation and breakup) and quality (ratio of black to white ice) of lake ice cover, both critical components of ice safety. Later formation and earlier breakup of lake ice lead to overall shorter periods of use.

Analysis of electrode arrangements for brain stroke diagnosis via electrical impedance tomography through numerical computational models.

Rapid stroke-type classification is crucial for improved prognosis. However, current methods for classification are time-consuming, require expensive equipment, and can only be used in the hospital. One method that has demonstrated promise in a rapid, low-cost, non-invasive approach to stroke diagnosis is electrical impedance tomography (EIT).

Adaptive changes in tumor cells in response to reductive stress.

Reductive stress is characterized by an excess of cellular electron donors and can be linked with various human pathologies including cancer. We developed melanoma cell lines resistant to reductive stress agents: rotenone (ROT), n-acetyl-L-cysteine, (NAC), or dithiothreitol (DTT). Resistant cells divided more rapidly and had intracellular homeostatic redox-couple ratios that were shifted towards the reduced state.

Applied machine learning for stroke differentiation by electrical impedance tomography with realistic numerical models.

Electrical impedance tomography (EIT) may have potential to overcome existing limitations in stroke differentiation, enabling low-cost, rapid, and mobile data collection. Combining bioimpedance measurement technologies such as EIT with machine learning classifiers to support decision-making can avoid commonly faced reconstruction challenges due to the nonlinear and ill-posed nature of EIT imaging. Therefore, in this work, we advance this field through a study integrating realistic head models with clinically relevant test scenarios, and a robust architecture consisting of nested cross-validation and principal component analysis.

A role for microsomal glutathione transferase 1 in melanin biosynthesis and melanoma progression.

Recent advancements in the treatment of melanoma are encouraging, but there remains a need to identify additional therapeutic targets. We identify a role for microsomal glutathione transferase 1 (MGST1) in biosynthetic pathways for melanin and as a determinant of tumor progression. Knockdown (KD) of MGST1 depleted midline-localized, pigmented melanocytes in zebrafish embryos, while in both mouse and human melanoma cells, loss of MGST1 resulted in a catalytically dependent, quantitative, and linear depigmentation, associated with diminished conversion of L-dopa to dopachrome (eumelanin precursor).

Leveraging Metal and Ligand Reactive Sites for One Pot Reactions: Ligand-Centered Borenium Ions for Tandem Catalysis with Palladium.

Tandem catalysts that perform two different organic transformations in a single pot are highly desirable because they enable rapid and efficient assembly of simple organic building blocks into more complex molecules. Many examples of tandem catalysis rely on metal-catalyzed reactions involving one or more metal complexes. Remarkably, despite surging interest in the development of chemically reactive (i.

Fluorination and hydrolytic stability of water-soluble platinum complexes with a borane-bridged diphosphoramidite ligand.

The high fluorophilicity of borane-containing ligands offers promise for accessing new metallodrug candidates capable of bifunctional [F]-positron emission tomography (PET) imaging, but this requires water soluble and hydrolytically stable ligands that can be fluorinated under mild conditions. Toward this goal, here we report the synthesis and characterization of water-soluble Pt(II) complexes containing a triaminoborane-bridged diphosphoramidite ligand called TBDPhos that can be fluorinated using simple fluoride salts. NMR and XRD studies show that (TBDPhos)PtCl (1) dissolves in water with cooperative H-OH addition across the bridgehead N-B bond to form 1-H2O.

Impact of Local Electrodes on Brain Stroke Type Differentiation using Electrical Impedance Tomography.

Electrical impedance tomography (EIT) of the head has the potential to provide rapid characterization of brain stroke. This study builds on previous work by implementing a more anatomically complex head model, contrasting results of bleed and clot simulations, and by establishing the electrodes which dominate in voltage difference measurements. This work provides the basis for machine learning with clusters of small numbers of electrodes as unique features for stroke-type detection and differentiation.

A Multidisciplinary Diabetes Clinic Improves Clinical and Behavioral Outcomes in a Primary Care Setting.

The percentage of adults achieving hemoglobin A1c goals less than 7% remains a challenge. The study objective was to evaluate effects of a multidisciplinary approach on behavioral outcomes and mean change in A1c in immediate start (intervention) versus 6-month delay (control) groups at 6 months. The study assessed 111 patients recruited from a safety-net primary care clinic with a pharmacist-led multidisciplinary team and found that the intervention improved mean A1c outcomes for patients with type 2 diabetes.

Smoke from regional wildfires alters lake ecology.

Wildfire smoke often covers areas larger than the burned area, yet the impacts of smoke on nearby aquatic ecosystems are understudied. In the summer of 2018, wildfire smoke covered Castle Lake (California, USA) for 55 days. We quantified the influence of smoke on the lake by comparing the physics, chemistry, productivity, and animal ecology in the prior four years (2014-2017) to the smoke year (2018).

Altered redox regulation and S-glutathionylation of BiP contribute to bortezomib resistance in multiple myeloma.

Multiple myeloma (MM) cells have high rates of secretion of proteins rich in disulfide bonds and depend upon compartmentalized redox balance for accurate protein folding. The proteasome inhibitor bortezomib (Btz) is a successful frontline treatment for the disease, but its long-term efficacy is restricted by the acquisition of resistance. We found that MM cell lines resistant to Btz maintain high levels of oxidative stress and are cross resistant to endoplasmic reticulum (ER) stress-inducing agents thapsigargin (ThG), and tunicamycin (TuM).

Reduction of PCE and TCE by magnetite revisited.

Here we revisit whether the common mixed-valent Fe mineral, magnetite, is a viable reductant for the abiotic natural attenuation of perchloroethylene (PCE) and trichloroethylene (TCE) in anoxic groundwater plumes. We measured PCE and TCE reduction by stoichiometric magnetite as a function of pH and Fe(ii) concentration. In the absence of added Fe(ii), stoichiometric magnetite does not reduce PCE and TCE over a three month period under anoxic conditions.

Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group.

The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported.

Stroke survivors with severe mental illness: Are they at-risk for increased non-psychiatric hospitalizations?

Background: This study examined outcomes for two groups of stroke survivors treated in Veteran Health Administration (VHA) hospitals, those with a severe mental illness (SMI) and those without prior psychiatric diagnoses, to examine risk of non-psychiatric medical hospitalizations over five years after initial stroke.

Methods: This retrospective cohort study included 523 veterans who survived an initial stroke hospitalization in a VHA medical center during fiscal year 2003. The survivors were followed using administrative data documenting inpatient stroke treatment, patient demographics, disease comorbidities, and VHA hospital admissions.

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests.

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as "radical cure"), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine.

The specialized wound care center: a 7-year experience at a tertiary care hospital.

Multidisciplinary wound care centers have proliferated as a result of an increasing need for care of nonhealing wounds. Information regarding types of wounds treated, length of treatment, compliance with treatment, and rates of healing was collected from a tertiary care hospital-based wound center over a 7-year period. Venous stasis ulcers were the most common type of wound treated (21%) and were also the most likely to heal.

From information management to protein annotation: preparing protein structures for drug discovery.

In contrast to academic pursuits of structural genomics, Structural GenomiX (SGX) solves protein structures at high throughput for the main purpose of enhancing drug-discovery projects, either internally or in partnership with pharmaceutical/biotechnology companies. This involves a radical redesign of the pipeline of methods that turn a gene sequence into a three-dimensional protein structure. The various processes all report electronically to a Laboratory Information Management System (LIMS) to make sure all the parameters of the experiment are recorded in an accessible and 'mineable' form, helping guarantee reproducibility of results.

Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation.

Chemokines are small secreted proteins that stimulate the directional migration of leukocytes and mediate inflammation. During screening of a murine choroid plexus complementary DNA library, we identified a new chemokine, designated neurotactin. Unlike other chemokines, neurotactin has a unique cysteine pattern, Cys-X-X-X-Cys, and is predicted to be a type 1 membrane protein.

Biochemical and genetic characterization of multiple splice variants of the Flt3 ligand.

We have performed a comprehensive analysis of cell lines and tissues to compare and contrast the expression patterns of Flt3 ligand (FL), c-Kit ligand (KL), and macrophage colony-stimulating factor as well as their receptors, Flt3, c-Kit, and c-Fms. The message for FL is unusually ubiquitous, whereas that of its receptor is quite restricted, apparently limiting the function of the ligand to fetal development and early hematopoiesis. We have also sequenced a mouse FL genomic clone, revealing how the three splice variant FL mRNAs that we have isolated arise.

Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.

The mutated gene responsible for the tubby obesity phenotype has been identified by positional cloning. A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript. The consequence of this mutation is the substitution of the carboxy-terminal 44 amino acids with 24 intron-encoded amino acids.

Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice.

OB-R is a high affinity receptor for leptin, an important circulating signal for the regulation of body weight. We identified an alternatively spliced transcript that encodes a form of mouse OB-R with a long intracellular domain. db/db mice also produce this alternatively spliced transcript, but with a 106 nt insertion that prematurely terminates the intracellular domain.

Identification and expression cloning of a leptin receptor, OB-R.

The ob gene product, leptin, is an important circulating signal for the regulation of body weight. To identify high affinity leptin-binding sites, we generated a series of leptin-alkaline phosphatase (AP) fusion proteins as well as [125I]leptin. After a binding survey of cell lines and tissues, we identified leptin-binding sites in the mouse choroid plexus.

Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells.

Dendritic cells are APCs that are unique in their potency to stimulate proliferation of primary Ag-specific responses in vitro and in vivo. In this study, we demonstrate that dendritic cells can produce IL-12, a dominant cytokine involved in the development of IFN-gamma-producing T cells. This finding resulted from our observations that dendritic cell-induced Th1 development from total CD4+ T cells upon neutralization of endogenous levels of IL-4 was IL-12-dependent.