bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in voltage-sensing of the mitochondrial permeability transition pore in ANT1-deficient cells
Authors: Doczi Judit , Torocsik Beata , Echaniz-Laguna Andoni , Mousson de Camaret Bénédicte , Starkov Anatoly , Starkova Natalia , Gál Aniko , Molnár Mária J , Kawamata Hibiki , Manfredi Giovanni , Adam-Vizi Vera , Chinopoulos Christos 
Published: May 2016

AbstractThe probability of mitochondrial permeability transition (mPT) pore opening is inversely related to the magnitude of the proton electrochemical gradient. The module conferring sensitivity of the pore to this gradient has not been identified. We investigated mPT’s voltage-sensing properties elicited by calcimycin or H2O2 in human fibroblasts exhibiting partial or complete lack of ANT1 and in C2C12 myotubes with knocked-down ANT1 expression. mPT onset was assessed by measuring in situ mitochondrial volume using the ‘thinness ratio’ and the ‘cobalt-calcein’ technique. De-energization hastened calcimycin-induced swelling in control and partially-expressing ANT1 fibroblasts, but not in cells lacking ANT1, despite greater losses of mitochondrial membrane potential. Matrix Ca2+ levels measured by X-rhod-1 or mitochondrially-targeted ratiometric biosensor 4mtD3cpv, or ADP-ATP exchange rates did not differ among cell types. ANT1-null fibroblasts were also resistant to H2O2-induced mitochondrial swelling. Permeabilized C2C12 myotubes with knocked-down ANT1 exhibited higher calcium uptake capacity and voltage-thresholds of mPT opening inferred from cytochrome c release, but intact cells showed no differences in calcimycin-induced onset of mPT, irrespective of energization and ANT1 expression, albeit the number of cells undergoing mPT increased less significantly upon chemically-induced hypoxia than control cells. We conclude that ANT1 confers sensitivity of the pore to the electrochemical gradient.
The minimal amount of starting DNA for Agilent’s hybrid capture-based targeted massively parallel sequencing
Authors: Chung Jongsuk , Son Dae-Soon , Jeon Hyo-Jeong , Kim Kyoung-Mee , Park Gahee , Ryu Gyu Ha , Park Woong-Yang , Park Donghyun 
Published: May 2016

AbstractTargeted capture massively parallel sequencing is increasingly being used in clinical settings, and as costs continue to decline, use of this technology may become routine in health care. However, a limited amount of tissue has often been a challenge in meeting quality requirements. To offer a practical guideline for the minimum amount of input DNA for targeted sequencing, we optimized and evaluated the performance of targeted sequencing depending on the input DNA amount. First, using various amounts of input DNA, we compared commercially available library construction kits and selected Agilent’s SureSelect-XT and KAPA Biosystems’ Hyper Prep kits as the kits most compatible with targeted deep sequencing using Agilent’s SureSelect custom capture. Then, we optimized the adapter ligation conditions of the Hyper Prep kit to improve library construction efficiency and adapted multiplexed hybrid selection to reduce the cost of sequencing. In this study, we systematically evaluated the performance of the optimized protocol depending on the amount of input DNA, ranging from 6.25 to 200 ng, suggesting the minimal input DNA amounts based on coverage depths required for specific applications.
Open and closed evolutionary paths for drastic morphological changes, involving serial gene duplication, sub-functionalization and selection
Authors: Abe Gembu , Lee Shu-Hua , Li Ing-Jia , Chang Chun-Ju , Tamura Koji , Ota Kinya G. 
Published: May 2016

AbstractTwin-tail goldfish strains are examples of drastic morphological alterations that emerged through domestication. Although this mutation is known to be caused by deficiency of one of two duplicatedchordingenes, it is unknown why equivalent mutations have not been observed in other domesticated fish species. Here, we compared thechordingene morphant phenotypes of single-tail goldfish and common carp (close relatives, both of which underwentchordingene duplication and domestication). Morpholino-induced knockdown depletedchordingene expression in both species; however, while knockdown reproduced twin-tail morphology in single-tail goldfish, it had no effect on common carp morphology. This difference can be explained by the observation that expression patterns of the duplicatedchordingenes overlap completely in common carp, but are sub-functionalized in goldfish. Our finding implies that goldfish drastic morphological changes might be enhanced by the subsequent occurrence of three different types of evolutionary event (duplication, sub-functionalization and selection) in a certain order.
Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment
Authors: Mellon S H , Wolkowitz O M , Schonemann M D , Epel E S , Rosser R , Burke H B , Mahan L , Reus V I , Stamatiou D , Liew C -C , Cole S W 
Published: May 2016

AbstractMajor depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1–4 (EGR1–4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators.
Angler Returns of Channel Catfish Stocked in Arkansas Lakes and Streams
Authors: Quinn Jeffrey W. , Andrews Diana 
Published: May 2016

Abstract
Stocking is the primary fisheries management tool used to enhance fisheries for Channel Catfish Ictalurus punctatus throughout the United States, but the technique has not been thoroughly evaluated for large reservoirs (e.g., &gt;5,000 ha) and small rivers. We compared angler return rates of catchable-sized fish (316-456 mm TL) stocked in 16 water bodies of three types: large U.S. Army Corps of Engineers (COE) lakes (5,425–18,381 ha), Arkansas Game and Fish Commission (AGFC) lakes (81–2,716 ha), and small rivers. We tagged and stocked 400–500 fish per water body with standard Carlin dangler reward tags (US$10–$100), and 10 fish per water body were stocked with a $100 high-reward tag to assess nonreporting. A total of 1,210 anglers reported catching 1,964 of the 6,800 fish (29%) stocked with standard tags. Anglers reported catching 82 of the 160 high-reward fish (51%). The 95% CI around the mean angler reporting rate was 0.61 ± 0.14. The mean adjusted 3-year return rate ± SD among stockings was 0.59 ± 0.26, and AGFC lakes had higher return rates than COE lakes or rivers. Anglers with the greatest reported catch on average caught 12 fish. Nearly all fish stocked were caught at three AGFC lakes, so the management of these fisheries may benefit from periodic population assessments. This study provides evidence that 3-year return rates for put-and-take Channel Catfish fisheries in large reservoirs and streams can approach or exceed 0.70. However, return rates were highly variable within and among water body types, which indicated stocking rates should be determined for each water body.
Received October 30, 2015; accepted January 28, 2016 Published online May 24, 2016
Use of Polymerase Chain Reaction for Bivalve Pathogen Surveillance in the Yellow Clam Mesodesma mactroides
Authors: Carvalho Yuri Bovi Morais , Silva Santos Juan Jethro , Raibenberg Fernando C. , Poersch Luis Henrique , Romano Luis Alberto 
Published: May 2016

Abstract
The yellow clam Mesodesma mactroides is a valuable shellfish occurring from the southeastern coast of Brazil to the northern coast of Argentina. Populations of yellow clams are disappearing from their entire range, and the cause is still unknown. The objective of this paper was to search for World Organisation for Animal Health (OIE)–listed pathogens and their relatives in the genera Marteilia, Bonamia, and Perkinsus as well as Mikrocytos mackini and the virus OsHV-1 μ var the yellow clam population in southern Brazil using molecular techniques and classic histology protocols. A total of 180 clams were manually collected in the intertidal region at six sampling points covering the entire coast of Rio Grande do Sul State (length, 622 km) in 2013. Tissue samples were tested by OIE-recommended single-step conventional polymerase chain reaction assays. The screening showed no evidence of the specific sequences of the protistan parasites and viral pathogens at any site within the six zones under study. We recommend continuous monitoring of the mollusks in the region.
Received July 3, 2015; accepted February 3, 2016
How does reading direction modulate perceptual asymmetry effects?
Authors: Chung Harry K. S. , Liu Joyce Y. W. , Hsiao Janet H. 
Published: May 2016

Left-side bias effects refer to a bias towards the left side of the stimulus/space in perceptual/visuospatial judgments, and are argued to reflect dominance of right hemisphere processing. It remains unclear whether reading direction can also account for the bias effect. Previous studies comparing readers of languages read from left to right with those read from right to left (e.g., French vs. Hebrew) have obtained inconsistent results. As a language that can be read from left to right or from right to left, Chinese provides a unique opportunity for a within-culture examination of reading direction effects. Chinese participants performed a perceptual judgment task (with both face and Chinese character stimuli; Experiment 1) and two visuospatial attention tasks (the greyscales and line bisection tasks; Experiment 2) once before and once after a reading task, in which they read Chinese passages either from left to right or from right to left for about 20 min. After reading from right to left, participants showed significantly reduced left-side bias in Chinese character perceptual judgments but not in the other three tasks. This effect suggests that the role of reading direction on different forms of left-side bias may differ, and its modulation may be stimulus-specific.
Characterisation of the properties of a negative hydrogen ion beam by several beam diagnostic techniques
Authors: Maurizio R. , Fantz U. , Bonomo F. , Serianni G. 
Published: May 2016

Abstract
The beam properties of the BATMAN negative ion source, which is the prototype of one module of the source for the ITER neutral beam injection system, are characterised by means of three diagnostic techniques: beam emission spectroscopy (BES), the experimental calorimeter mini-STRIKE and a copper calorimeter. The main beam parameters—beam divergence, homogeneity and top–bottom asymmetries—are studied in different operational scenarios: with different magnetic filter field setups, source settings and with different gases (hydrogen or deuterium). Among all dependences, the influence of the magnetic field configuration on the beam and the evolution of the beam features during some conditioning days are investigated in detail. Data show that the stronger the filter field in the beam region, the higher the beam top–bottom asymmetry—likely a

v
×
B

effect. During the conditioning of the source, such vertical beam asymmetry increases as well, suggesting an inhomogeneous H
−production at the first grid of the extraction system.
Comparative Study of the Efficacy of Olmesartan/Amlodipine vs. Perindopril/Amlodipine in Peripheral and Central Blood Pressure Parameters After Missed Dose in Type 2 Diabetes
Authors: Redon Josep , Pichler Gernot 
Published: May 2016

Abstract

BACKGROUND
Central aortic blood pressure (CBP) and CBP-derived parameters are independent predictors of cardiovascular risk. Angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors plus calcium channel blockers are the recommended first-line treatments in hypertensive diabetic patients; however, the effect in reducing CBP when a dose is skipped has not been established yet. The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine (OLM/AML) provides equal efficacy and safety as the perindopril/AML (PER/AML) combination in reducing CBP, augmentation index (AIx), and pulse wave velocity (PWV) when a drug dose is missed.

METHODS
In this noninferiority, randomized, double-blind, double-dummy parallel group, controlled design trial, 88 patients received either OLM 20–40mg/AML 5–10mg (41 patients) or PER 4–8mg/AML 5–10mg (47 patients) for 24 weeks. The main endpoint was the aortic systolic BP (SBP) after 24 weeks of treatment at 48 hours from the last administration.

RESULTS
The OLM/AML combination reached the noninferiority criteria in reducing central systolic BP after 24 weeks of treatment and after the missed dose, compared to the PER/AML combination (−17 and −8mm Hg, respectively). Peripheral BP, AIx, and PWV were significantly lower in both groups after 24 weeks of treatment and 48 hours after the missed dose, observing a trend to a greater reduction in CBP-derived parameters in the OLM/AML group.

CONCLUSIONS
The OLM/AML combination is safe, well tolerated, and not inferior to the combination of PER/AML in lowering CBP and CBP-derived parameters in diabetic patients. OLM/AML provides longer-lasting efficacy in terms of CBP reduction compared to PER/AML.
Measuring Diversity of the National Institutes of Health–Funded Workforce
Authors: Heggeness Misty L. , Evans Lisa , Pohlhaus Jennifer Reineke , Mills Sherry L. 
Published: May 2016

Purpose
To measure diversity within the National Institutes of Health (NIH)-funded workforce. The authors use a relevant labor market perspective to more directly understand what the NIH can influence in terms of enhancing diversity through NIH policies.

Method
Using the relevant labor market (defined as persons with advanced degrees working as biomedical scientists in the United States) as the conceptual framework, and informed by accepted economic principles, the authors used the American Community Survey and NIH administrative data to calculate representation ratios of the NIH-funded biomedical workforce from 2008 to 2012 by race, ethnicity, sex, and citizenship status, and compared this against the pool of characteristic individuals in the potential labor market.

Results
In general, the U.S. population during this time period was an inaccurate comparison group for measuring diversity of the NIH-funded scientific workforce. Measuring accurately, we found the representation of women and traditionally underrepresented groups in NIH-supported postdoc fellowships and traineeships and mentored career development programs was greater than their representation in the relevant labor market. The same analysis found these demographic groups are less represented in the NIH-funded independent investigator pool.

Conclusions
Although these findings provided a picture of the current NIH-funded workforce and a foundation for understanding the federal role in developing, maintaining, and renewing diverse scientific human resources, further study is needed to identify whether junior- and early-stage investigators who are part of more diverse cohorts will naturally transition into independent NIH-funded investigators, or whether they will leave the workforce before achieving independent researcher status.
A Big Data and Learning Analytics Approach to Process-Level Feedback in Cognitive Simulations
Authors: Pecaric Martin , Boutis Kathy , Beckstead Jason , Pusic Martin 
Published: May 2016

Collecting and analyzing large amounts of process data for the purposes of education can be considered a big data/learning analytics (BD/LA) approach to improving learning. However, in the education of health care professionals, the application of BD/LA is limited to date. The authors discuss the potential advantages of the BD/LA approach for the process of learning via cognitive simulations. Using the lens of a cognitive model of radiograph interpretation with four phases (orientation, searching/scanning, feature detection, and decision making), they reanalyzed process data from a cognitive simulation of pediatric ankle radiography where 46 practitioners from three expertise levels classified 234 cases online. To illustrate the big data component, they highlight the data available in a digital environment (time-stamped, click-level process data). Learning analytics were illustrated using algorithmic computer-enabled approaches to process-level feedback.For each phase, the authors were able to identify examples of potentially useful BD/LA measures. For orientation, the trackable behavior of re-reviewing the clinical history was associated with increased diagnostic accuracy. For searching/scanning, evidence of skipping views was associated with an increased false-negative rate. For feature detection, heat maps overlaid on the radiograph can provide a metacognitive visualization of common novice errors. For decision making, the measured influence of sequence effects can reflect susceptibility to bias, whereas computer-generated path maps can provide insights into learners’ diagnostic strategies.In conclusion, the augmented collection and dynamic analysis of learning process data within a cognitive simulation can improve feedback and prompt more precise reflection on a novice clinician’s skill development.
Outcomes From the NIH Clinical Research Training Program: A Mentored Research Experience to Enhance Career Development of Clinician–Scientists
Authors: Ognibene Frederick P. , Gallin John I. , Baum Bruce J. , Wyatt Richard G. , Gottesman Michael M. 
Published: May 2016

Purpose
Clinician–scientists are considered an endangered species for many reasons, including challenges with establishing and maintaining a career pipeline. Career outcomes from yearlong medical and dental students’ research enrichment programs have not been well determined. Therefore, the authors assessed career and research outcome data from a cohort of participants in the National Institutes of Health (NIH) Clinical Research Training Program (CRTP).

Method
The CRTP provided a yearlong mentored clinical or translational research opportunity for 340 medical and dental students. Of these, 135 completed their training, including fellowships, from 1997 to January 2014. Data for 130 of 135 were analyzed: time conducting research, types of public funding (NIH grants), and publications from self-reported surveys that were verified via the NIH Research Portfolio Online Reporting Tools Web site and PubMed.

Results
Nearly two-thirds (84 of 130) indicated that they were conducting research, and over half of the 84 (approximately one-third of the total cohort) spent more than 25% of time conducting research. Of those 84, over 25% received grant support from the NIH, and those further in their careers published more scholarly manuscripts.

Conclusions
Data suggest that the CRTP helped foster the careers of research-oriented medical and dental students as measured by time conducting research, successful competition for federal funding, and the publication of their research. Longer follow-up is warranted to assess the impact of these mentored research experiences. Investments in mentored research programs for health professional students are invaluable to support the dwindling pipeline of biomedical researchers and clinician–scientists.
Group II mGluRs suppress hyperexcitability in mouse and human nociceptors
Authors: Davidson Steve , Golden Judith P. , Copits Bryan A. , Ray Pradipta R. , Vogt Sherri K. , Valtcheva Manouela V. , Schmidt Robert E. , Ghetti Andrea , Price Theodore J. , Gereau Robert W. 
Published: May 2016

Abstract
We introduce a strategy for preclinical research wherein promising targets for analgesia are tested in rodent and subsequently validated in human sensory neurons. We evaluate group II metabotropic glutamate receptors, the activation of which is efficacious in rodent models of pain. Immunohistochemical analysis showed positive immunoreactivity for mGlu2 in rodent dorsal root ganglia (DRG), peripheral fibers in skin, and central labeling in the spinal dorsal horn. We also found mGlu2-positive immunoreactivity in human neonatal and adult DRG. RNA-seq analysis of mouse and human DRG revealed a comparative expression profile between species for group II mGluRs and for opioid receptors. In rodent sensory neurons under basal conditions, activation of group II mGluRs with a selective group II agonist produced no changes to membrane excitability. However, membrane hyperexcitability in sensory neurons exposed to the inflammatory mediator prostaglandin E2 (PGE2) was prevented by (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC). In human sensory neurons from donors without a history of chronic pain, we show that PGE2 produced hyperexcitability that was similarly blocked by group II mGluR activation. These results reveal a mechanism for peripheral analgesia likely shared by mice and humans and demonstrate a translational research strategy to improve preclinical validation of novel analgesics using cultured human sensory neurons.