Stac Proteins Suppress Ca2+-Dependent Inactivation of Neuronal L-type Ca2+ Channels

Stac protein (named for its SH3-and cysteine-rich domains) was first identified in brain 20 years ago and is currently known to have three isoforms. Stac2, Stac1, and Stac3 transcripts are found at high, modest, and very low levels, respectively, in the cerebellum and forebrain, but their neuronal functions have been little investigated. Here, we tested the effects of Stac proteins on neuronal, high-voltage-activated Ca2+ channels. Overexpression of the three Stac isoforms eliminated Ca2+-dependent inactivation (CDI) ofL-type current in rat neonatal hippocampal neurons (sex unknown), but not CDI of non-L-type current. Using heterologous expression in tsA201 cells (together with β and α2-δ1 auxiliary subunits), we found that CDI for CaV1.2 and CaV1.3 (the predominant, neuronalL-type Ca2+ channels) was suppressed by all three Stac isoforms, whereas CDI for the P/Q channel, CaV2.1, was not. For CaV1.2, the inhibition of CDI by the Stac proteins appeared to involve their direct interaction with the channel’s C terminus. Within the Stac proteins, a weakly conserved segment containing ~100 residues and linking the structurally conserved PKC C1 and SH3_1 domains was sufficient to fully suppress CDI. The presence of CDI forL-type current in control neonatal neurons raised the possibility that endogenous Stac levels are low in these neurons and Western blotting indicated that the expression of Stac2 was substantially increased in adult forebrain and cerebellum compared with neonate. Together, our results indicate that one likely function of neuronal Stac proteins is to tune Ca2+ entry via neuronal L-type channels. © 2018 the authors

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath

BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes

Composite absorbing potentials

The multiple scattering interferences due to the addition of several contiguous potential units are used to construct composite absorbing potentials that absorb at an arbitrary set of incident momenta or for a broad momentum interval.Comment: 9 pages, Revtex, 2 postscript figures. Accepted in Phys. Rev. Let

1935: Abilene Christian College Bible Lectures - Full Text

Delivered in the auditorium of Abilene Christian College, Abilene, Texas, February 193

Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives:A Feasibility Study

Background: Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot–based screening to identify islet autoantibody–positive relatives potentially eligible for inclusion in prevention trials. Materials and Methods: Dried blood spot (DBS) and venous samples were collected from 229 relatives participating in the TrialNet Pathway to Prevention Study. Both samples were tested for glutamic acid decarboxylase, islet antigen 2, and zinc transporter 8 autoantibodies, and venous samples were additionally tested for insulin autoantibodies and islet cell antibodies. We defined multiple autoantibody positive as two or more autoantibodies in venous serum and DBS screen positive if one or more autoantibodies were detected. Participant questionnaires compared the sample collection methods. Results: Of 44 relatives who were multiple autoantibody positive in venous samples, 42 (95.5%) were DBS screen positive, and DBS accurately detected 145 of 147 autoantibody-negative relatives (98.6%). Capillary blood sampling was perceived as more painful than venous blood draw, but 60% of participants would prefer initial screening using home fingerstick with clinic visits only required if autoantibodies were found. Conclusions: Capillary blood sampling could facilitate screening for type 1 diabetes prevention studies.</p

The Impact of Bisphenol A and Triclosan on Immune Parameters in the U.S. Population, NHANES 2003–2006

Background: Exposure to environmental toxicants is associated with numerous disease outcomes, many of which involve underlying immune and inflammatory dysfunction. Objectives: To address the gap between environmental exposures and immune dysfunction, we investigated the association of two endocrine-disrupting compounds (EDCs) with markers of immune function. Methods: Using data from the 2003–2006 National Health and Nutrition Examination Survey, we compared urinary bisphenol A (BPA) and triclosan levels with serum cytomegalovirus (CMV) antibody levels and diagnosis of allergies or hay fever in U.S. adults and children ≥ 6 years of age. We used multivariate ordinary least squares linear regression models to examine the association of BPA and triclosan with CMV antibody titers, and multivariate logistic regression models to investigate the association of these chemicals with allergy or hay fever diagnosis. Statistical models were stratified by age (\u3c 18 years and ≥ 18 years). Results: In analyses adjusted for age, sex, race, body mass index, creatinine levels, family income, and educational attainment, in the ≥ 18-year age group, higher urinary BPA levels were associated with higher CMV antibody titers (p \u3c 0.001). In the \u3c 18-year age group, lower levels of BPA were associated with higher CMV antibody titers (p \u3c 0.05). However, triclosan, but not BPA, showed a positive association with allergy or hay fever diagnosis. In the \u3c 18-year age group, higher levels of triclosan were associated with greater odds of having been diagnosed with allergies or hay fever (p \u3c 0.01). Conclusions: EDCs such as BPA and triclosan may negatively affect human immune function as measured by CMV antibody levels and allergy or hay fever diagnosis, respectively, with differential consequences based on age. Additional studies should be done to investigate these findings

Analysis of the impact of dislocation distribution on the breakdown voltage of GaAs-based power varactor diodes

A synchrotron x-ray topography analysis of the impact of the distribution of defects/dislocations on the electrical performance of GaAs power varactor diodes was carried out. Diodes fabricated on or near Liquid Encapsulated Czochralski cellular dislocation networks in the substrate, which are also known to be rich in As precipitates near these cell walls, were observed to have reduced breakdown voltages (VBR). This is consistent with the possibility that the presence of space-charge cylinders surrounding these dislocations gives rise to reduced VBR if they thread a p-n junction; it is also in accord with the possibility that the As precipitates themselves can act as sites for local field enhancement, thus promoting premature avalanche breakdown

Microbial Iron Cycling in Acidic Geothermal Springs of Yellowstone National Park: Integrating Molecular Surveys, Geochemical Processes, and Isolation of Novel Fe-Active Microorganisms

Geochemical, molecular, and physiological analyses of microbial isolates were combined to study the geomicrobiology of acidic iron oxide mats in Yellowstone National Park. Nineteen sampling locations from 11 geothermal springs were studied ranging in temperature from 53 to 88°C and pH 2.4 to 3.6. All iron oxide mats exhibited high diversity of crenarchaeal sequences from the Sulfolobales, Thermoproteales, and Desulfurococcales. The predominant Sulfolobales sequences were highly similar to Metallosphaera yellowstonensis str. MK1, previously isolated from one of these sites. Other groups of archaea were consistently associated with different types of iron oxide mats, including undescribed members of the phyla Thaumarchaeota and Euryarchaeota. Bacterial sequences were dominated by relatives of Hydrogenobaculum spp. above 65–70°C, but increased in diversity below 60°C. Cultivation of relevant iron-oxidizing and iron-reducing microbial isolates included Sulfolobus str. MK3, Sulfobacillus str. MK2, Acidicaldus str. MK6, and a new candidate genus in the Sulfolobales referred to as Sulfolobales str. MK5. Strains MK3 and MK5 are capable of oxidizing ferrous iron autotrophically, while strain MK2 oxidizes iron mixotrophically. Similar rates of iron oxidation were measured for M. yellowstonensis str. MK1 and Sulfolobales str. MK5. Biomineralized phases of ferric iron varied among cultures and field sites, and included ferric oxyhydroxides, K-jarosite, goethite, hematite, and scorodite depending on geochemical conditions. Strains MK5 and MK6 are capable of reducing ferric iron under anaerobic conditions with complex carbon sources. The combination of geochemical and molecular data as well as physiological observations of isolates suggests that the community structure of acidic Fe mats is linked with Fe cycling across temperatures ranging from 53 to 88°C

Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain

Urban park use during the COVID-19 pandemic:Are socially vulnerable communities disproportionately impacted?

The COVID-19 pandemic altered human behavior around the world. To maintain mental and physical health during periods of lockdown and quarantine, people often engaged in outdoor, physically distanced activities such as visits to parks and greenspace. However, research tracking outdoor recreation patterns during the pandemic has yielded inconsistent results, and few studies have explored the impacts of COVID-19 on park use across diverse neighborhoods. We used a mixed methods approach to examine changes in park use patterns in cities across North Carolina, USA, during the COVID-19 pandemic, with an emphasis on impacts in socially vulnerable communities (based on racial/ethnic composition and socioeconomic status). First, we surveyed a demographically representative sample of 611 urban residents during August 2020 to assess their use of outdoor park spaces before and during the pandemic. Second, we used cell phone location (i.e., geo-tracking) data to document changes in park visits within 605 socioeconomically diverse urban census tracts before (July 2019) and during (July 2020) the pandemic. Data from both methods revealed urban park use declined during the pandemic; 56% of survey respondents said they stopped or reduced park use, and geo-tracked park visits dropped by 15%. Park users also became more homogenous, with visits increasing the most for past park visitors and declining the most in socially vulnerable communities and among individuals who were BIPOC or lower-income. Our results raise concerns about urban park use during the COVID-19 pandemic and suggest pre-existing health disparities in socially vulnerable communities might be exacerbated by inequitable access and utilization of parks and greenspace