Multiplexed assay of variant effect reveals residues of functional importance in the BRCA1 coiled-coil and serine cluster domains.

Delineating functionally normal variants from functionally abnormal variants in tumor suppressor proteins is critical for cancer surveillance, prognosis, and treatment options. BRCA1 is a protein that has many variants of uncertain significance which are not yet classified as functionally normal or abnormal. In vitro functional assays can be used to identify the functional impact of a variant when the variant has not yet been categorized through clinical observation.

Hydrogen-bearing vesicles in space weathered lunar calcium-phosphates.

Water on the surface of the Moon is a potentially vital resource for future lunar bases and longer-range space exploration. Effective use of the resource depends on developing an understanding of where and how within the regolith the water is formed and retained. Solar wind hydrogen, which can form molecular hydrogen, water and/or hydroxyl on the lunar surface, reacts and is retained differently depending on regolith mineral content, thermal history, and other variables.

Interpreting magnitude of change in strength and conditioning: Effect size selection, threshold values and Bayesian updating.

The magnitude of change following strength and conditioning (S&C) training can be evaluated comparing effect sizes to thresholds. This study conducted a series of meta-analyses and compiled results to identify thresholds specific to S&C, and create prior distributions for Bayesian updating. Pre- and post-training data from S&C interventions were translated into standardised mean difference (SMD) and percentage improvement (%Improve) effect sizes.

Transgenerational evidence of increases in dopamine D2 receptor sensitivity in rodents: Impact on sensorimotor gating, the behavioral response to nicotine and BDNF.

Background/aims: Neonatal quinpirole (NQ) treatment to rats increases dopamine D (DAD) receptor sensitivity in adult animals. We investigated if increased DAD sensitivity would be passed to the next (F1) generation, and if these animals demonstrated sensorimotor gating deficits and enhanced behavioral responses to nicotine.

Methods: Male and female rats were intraperitoneal (IP) administered quinpirole (1 mg/kg) or saline (NS) from postnatal day (P)1-21.

The effects of a novel inhibitor of tumor necrosis factor (TNF) alpha on prepulse inhibition and microglial activation in two distinct rodent models of schizophrenia.

Increased neuroinflammation has been shown in individuals diagnosed with schizophrenia (SCHZ). This study evaluated a novel immune modulator (PD2024) that targets the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) to alleviate sensorimotor gating deficits and microglial activation employing two different rodent models of SCHZ. In Experiment 1, rats were neonatally treated with saline or the dopamine D-like agonist quinpirole (NQ; 1 mg/kg) from postnatal day (P) 1-21 which produces increases of dopamine D receptor sensitivity throughout the animal's lifetime.

Short- and long-term diets of the threatened longhorned pygmy devil ray, Mobula eregoodoo determined using stable isotopes.

Most mobulids are listed as near threatened to endangered. Nonetheless, effective conservation measures are hindered by knowledge gaps in their ecology and behaviour. In particular, few studies have assessed diets and trophic ecologies that could inform methods to avoid fishing mortality.

Effects of an adenosine A agonist on the rewarding associative properties of nicotine and neural plasticity in a rodent model of schizophrenia.

Background: Adenosine A receptors form a mutually inhibitory heteromeric complex with dopamine D receptors such that each receptor exhibits lower sensitivity to its agonist after the opposing receptor agonist is bound. This study analyzed the effects of CGS 21680, an adenosine A agonist, on nicotine conditioned place preference (CPP) in adolescence using a rodent model of schizophrenia (SZ).

Methods: Rats were treated from postnatal day (P) 1 to P21 with saline or the dopamine D/D agonist quinpirole (NQ treatment) and raised to P41.

Ciliary neurotrophic factor is a key sex-specific regulator of depressive-like behavior in mice.

Ciliary neurotrophic factor (CNTF) is produced by astrocytes and promotes neurogenesis and neuroprotection. Little is known about the role of CNTF in affective behavior. We investigated whether CNTF affects depressive- and anxiety-like behavior in adult mice as tested in the forced swim, sucrose preference and elevated-T maze tests.

Molecular analysis of endotracheal tube biofilms and tracheal aspirates in the pediatric intensive care unit.

Background: Ventilator-associated pneumonia (VAP) is a known complication of mechanically ventilated children in the pediatric intensive care unit (PICU). Endotracheal tube (ETT) biofilms are often implicated in the development of VAP by providing a conduit for pathogens to the lower respiratory tract.

Methods: A prospective cohort study from April 2010-March 2011 of children 4 weeks to 18 years of age ventilated for greater than 72 hours to determine the microbiota of ETT biofilms and tracheal aspirates.

Effects of Environmental Enrichment on Nicotine Sensitization in Rats Neonatally Treated with Quinpirole: Analyses of Glial Cell Line-Derived Neurotrophic Factor and Implications towards Schizophrenia.

The current study analyzed the effects of environmental enrichment versus isolation housing on the behavioral sensitization to nicotine in the neonatal quinpirole (NQ; dopamine D2-like agonist) model of dopamine D2 receptor supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases dopamine D2 receptor sensitivity throughout the animal's lifetime, consistent with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing or isolated in wire cages throughout the experiment.

Novel signature fatty acid profile of the giant manta ray suggests reliance on an uncharacterised mesopelagic food source low in polyunsaturated fatty acids.

Traditionally, large planktivorous elasmobranchs have been thought to predominantly feed on surface zooplankton during daytime hours. However, the recent application of molecular methods to examine long-term assimilated diets, has revealed that these species likely gain the majority from deeper or demersal sources. Signature fatty acid analysis (FA) of muscle tissue was used to examine the assimilated diet of the giant manta ray Mobula birostris, and then compared with surface zooplankton that was collected during feeding and non-feeding events at two aggregation sites off mainland Ecuador.

Physiological responses to prolonged saturation diving: a field-based pilot study.

This study aimed to assess the effect of extreme environmental exposure during an operational saturation dive on airway inflammation (exhaled nitric oxide (FeNo)), components of fitness (flexibility and aerobic capacity) and blood hematological variables. Six saturation divers, who undertook a 26±0.5 day operational saturation dive were recruited to take part in this study.

Antidepressant-Like Actions of Inhibitors of Poly(ADP-Ribose) Polymerase in Rodent Models.

Background: Many patients suffering from depressive disorders are refractory to treatment with currently available antidepressant medications, while many more exhibit only a partial response. These factors drive research to discover new pharmacological approaches to treat depression. Numerous studies demonstrate evidence of inflammation and elevated oxidative stress in major depression.

Emergency Department Utilization by Native American Children.

Objectives: The aims of this study were to determine differences in emergency department (ED) use by Native American (NA) children in rural and urban settings and identify factors associated with frequent ED visits.

Methods: This cross-sectional, cohort study examined visits to 6 EDs: 2 rural, 2 midsize urban, and 2 large urban EDs from June 2011 to May 2012. Univariate and multiple regression analyses were conducted.

Mobulid rays feed on euphausiids in the Bohol Sea.

Mobulid rays have a conservative life history and are caught in direct fisheries and as by-catch. Their subsequent vulnerability to overexploitation has recently been recognized, but fisheries management can be ineffective if it ignores habitat and prey preferences and other trophic interactions of the target species. Here, we assessed the feeding ecology of four mobulids (, , , ) in the Bohol Sea, Philippines, using stomach contents analysis of fisheries specimens landed between November and May in 2013-2015.

An analysis of the rewarding and aversive associative properties of nicotine in the neonatal quinpirole model: Effects on glial cell line-derived neurotrophic factor (GDNF).

This study analyzed the associative properties of nicotine in a conditioned place preference (CPP) paradigm in adolescent rats neonatally treated with quinpirole (NQ) or saline (NS). NQ produces dopamine D receptor supersensitivity that persists throughout the animal's lifetime, and therefore has relevance towards schizophrenia. In two experiments, rats were ip administered quinpirole (1mg/kg) or saline from postnatal day (P)1-21.

The effects of nicotine in the neonatal quinpirole rodent model of psychosis: Neural plasticity mechanisms and nicotinic receptor changes.

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal's lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine.

Combined laser ultrasonics, laser heating, and Raman scattering in diamond anvil cell system.

We developed a multi-functional in situ measurement system under high pressure equipped with a laser ultrasonics (LU) system, Raman device, and laser heating system (LU-LH) in a diamond anvil cell (DAC). The system consists of four components: (1) a LU-DAC system (probe and pump lasers, photodetector, and oscilloscope) and DAC; (2) a fiber laser, which is designed to allow precise control of the total power in the range from 2 to 100 W by changing the diode current, for heating samples; (3) a spectrometer for measuring the temperature of the sample (using black body radiation), fluorescence spectrum (spectrum of the ruby for pressure measurement), and Raman scattering measurements inside a DAC under high pressure and high temperature (HPHT) conditions; and (4) an optical system to focus laser beams on the sample and image it in the DAC. The system is unique and allows us to do the following: (a) measure the shear and longitudinal velocities of non-transparent materials under HPHT; (b) measure temperature in a DAC under HPHT conditions using Planck's law; (c) measure pressure in a DAC using a Raman signal; and (d) measure acoustical properties of small flat specimens removed from the DAC after HPHT treatment.

Elevated DNA Oxidation and DNA Repair Enzyme Expression in Brain White Matter in Major Depressive Disorder.

Background: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood.

Methods: Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8).

, predator of the deep? Insight into the diet of the giant manta ray through stable isotope analysis.

The characterization of diet for the giant manta ray has been problematic given their large-scale movement patterns and the difficulty in obtaining stomach contents from this species. The large majority of existing information is based on observational data limited to feeding events at the sea surface during daylight. Recently discovered aggregation sites for the giant manta ray off mainland Ecuador are some of the most accessible to date and provide a unique opportunity for researchers to gather much needed information on this elusive species.

Strain Effects in Epitaxial VO Thin Films on Columnar Buffer-Layer TiO/AlO Virtual Substrates.

Epitaxial VO/TiO thin film heterostructures were grown on (100) (m-cut) AlO substrates via pulsed laser deposition. We have demonstrated the ability to reduce the semiconductor-metal transition (SMT) temperature of VO to ∼44 °C while retaining a 4 order of magnitude SMT using the TiO buffer layer. A combination of electrical transport and X-ray diffraction reciprocal space mapping studies help examine the specific strain states of VO/TiO/AlO heterostructures as a function of TiO film growth temperatures.

The physiological effect of a 'climb assist' device on vertical ladder climbing.

'Climb assist' claims to reduce strain when climbing ladders; however, no research has yet substantiated this. The purpose of this study was to assess the physiological and psychophysical effects of climb assist on 30 m ladder climbing at a minimum acceptable speed. Eight participants (six male and two female) climbed a 30 m ladder at 24 rungs per minute with and without climb assist, and were monitored for heart rate (HR), [Formula: see text]O and rate of perceived exertion (RPE).

Emergency Department Utilization for Mental Health in American Indian Children.

Objectives: To examine emergency department (ED) visits for mental health concerns by American Indian children in a multicenter cohort. To analyze demographic and clinical factors, the types of mental health concerns, and repeat mental health visits.

Study Design: Cross-sectional study of children 5-18 years old who visited 1 of 6 EDs in the Upper Midwest from June 2011 to May 2012 and self-identified as white or American Indian.

The Role of Bias by Emergency Department Providers in Care for American Indian Children.

Background: American Indian children have high rates of emergency department (ED) use and face potential discrimination in health care settings.

Objective: Our goal was to assess both implicit and explicit racial bias and examine their relationship with clinical care.

Research Design: We performed a cross-sectional survey of care providers at 5 hospitals in the Upper Midwest.