bluuebunny/crossref_metadata_2025_split huggingface dataset:
X-Linked Hearing Loss: Two Gene Mutation Examples Provide Generalizable Implications for Clinical Care
Authors: Stanton Susan G. , Griffin Anne , Stockley Tracy L. , Brown Christine , Young Terry-Lynn , Benteau Tammy , Abdelfatah Nelly 
Published: March 2014

Purpose

To describe the inheritance patterns and auditory phenotype features of 3 Canadian families with mutations in 2 X-linked “deafness” genes (
DFNX
).

Method

Audiological, medical, and family histories were collected and family members interviewed to compare hearing thresholds and case histories between cases with mutations in
SMPX
versus
POU3F4
.

Results

The family pedigrees reveal characteristic X-linked inheritance patterns. Phenotypic features associated with the
SMPX
(
DFNX4
) mutation include early onset in males with rapid progression from mild and flat to sloping sensorineural loss, with highly variable onset and hearing loss severity in females. In contrast, phenotypic features associated with the
POU3F4 (DFNX2)
mutation are characterized by an early onset, mixed hearing loss with fluctuation in males, and a normal hearing phenotype reported for females.

Conclusions
The study shows how this unique inheritance pattern and both gender and mutation-specific phenotype variations can alert audiologists to the presence of X-linked genetic etiologies in their clinical practice. By incorporating this knowledge into clinical decision making, audiologists can facilitate the early identification of X-linked hearing loss and contribute to the effective team management of affected families.
Supporting Narrative Retells for People With Aphasia Using Augmentative and Alternative Communication: Photographs or Line Drawings? Text or No Text?
Authors: Griffith Julie , Dietz Aimee , Weissling Kristy 
Published: March 2014

Purpose
The purpose of this study was to examine how the interface design of an augmentative and alternative communication (AAC) device influences the communication behaviors of people with aphasia during a narrative retell task.

Method
A case-series design was used. Four narratives were created on an AAC device with combinations of personally relevant (PR) photographs, line drawings (LDs), and text for each participant. The narrative retells were analyzed to describe the expressive modality units (EMUs) used, trouble sources experienced, and whether trouble sources were repaired. The researchers also explored the participants' perceived helpfulness of the interface features.

Results
The participants primarily used spoken EMUs to retell their narratives. They relied on PR photographs more frequently than LDs; however, they reported both picture types to be equally helpful. Text was frequently used and reported as helpful by all 4 people with aphasia. Participants experienced similar rates of trouble sources across conditions; however, they displayed unique trends for successful repairs of trouble sources.

Conclusion
For narrative retells, LDs may serve as an effective visual support when PR photographs are unavailable. Individual assessment is necessary to determine the optimum combination of supports in AAC systems for people with aphasia.
Reliability‐centred maintenance for circuit breakers in transmission networks
Authors: Abbasghorbani Morteza , Rajabi Mashhadi Habib , Damchi Yaser 
Published: March 2014

Reliability of power system can be influenced by the maintenance strategy adopted for the system's equipments. This study focuses on power circuit breakers maintenance planning based on the concept of reliability‐centered maintenance (RCM) and applies the proposed approach on the 400 kV transmission network in Khorasan province in Iran. The RCM strategy takes into account the technical condition and importance of each circuit breaker from the network's perspective. The technical condition index of a specific circuit breaker is a numerical representation of the physical health of the breaker and can be evaluated by some criteria. To determine this index, the performance of the circuit breakers during interval 2007–2012 is considered. The importance of each circuit breaker is related to the consequence of its failure on the network. As the main drawback of the available researches in this area is the lack of a generic tool to determine the importance of the circuit breakers, this study proposes a three‐stage procedure to accurately evaluate the importance of the circuit breakers. The main idea in the proposed approach is to analyse all failure modes of the circuit breakers and simulate the effect of each failure mode on the overall expected energy not served. The obtained results show the efficiency of the proposed approach.
Suppressing unwanted memories reduces their unconscious influence via targeted cortical inhibition
Authors: Gagnepain Pierre , Henson Richard N. , Anderson Michael C. 
Published: March 2014

Significance
After a trauma, people often suppress intrusive visual memories. We used functional MRI to understand how healthy participants suppress the visual content of memories to overcome intrusions, and whether suppressed content continues to exert unconscious influences. Effective connectivity, representational similarity, and computational analyses revealed a frontally mediated mechanism that suppresses intrusive visual memories by reducing activity in the visual cortex. This reduction disrupted neural and behavioral expressions of implicit memory during a later perception test. Thus, our findings indicate that motivated forgetting mechanisms, known to disrupt conscious retention, also reduce unconscious expressions of memory, pointing to a neurobiological model of this process.
Genome-wide activity of unliganded estrogen receptor-α in breast cancer cells
Authors: Caizzi Livia , Ferrero Giulio , Cutrupi Santina , Cordero Francesca , Ballaré Cecilia , Miano Valentina , Reineri Stefania , Ricci Laura , Friard Olivier , Testori Alessandro , Corà Davide , Caselle Michele , Di Croce Luciano , De Bortoli Michele 
Published: March 2014

Significance
Estrogen receptor-α (ERα) is a key protein in breast cancer and treatments targeting ERα are among the most widely used and effective in clinics. Although the role of estrogen-stimulated ERα in breast cancer has been exhaustively described, the functions of ERα in the absence of estrogen is hill-defined. In this work, we show that ERα binds extensively to the genome of breast cancer cells in the absence of estrogen, where it regulates the expression of hundreds of genes endowed with developmental functions. Our data suggest that ERα has a fundamental role in the homeostasis of luminal epithelial cells also when estrogen is ablated physiologically or pharmacologically.
Global patterns of marine mammal, seabird, and sea turtle bycatch reveal taxa-specific and cumulative megafauna hotspots
Authors: Lewison Rebecca L. , Crowder Larry B. , Wallace Bryan P. , Moore Jeffrey E. , Cox Tara , Zydelis Ramunas , McDonald Sara , DiMatteo Andrew , Dunn Daniel C. , Kot Connie Y. , Bjorkland Rhema , Kelez Shaleyla , Soykan Candan , Stewart Kelly R. , Sims Michelle , Boustany Andre , Read Andrew J. , Halpin Patrick , Nichols W. J. , Safina Carl 
Published: March 2014

SignificanceLoss of megafauna, termed trophic downgrading, has been found to affect biotic interactions, disturbance regimes, species invasions, and nutrient cycling. One recognized cause in air-breathing marine megafauna is incidental capture or bycatch by fisheries. Characterizing megafauna bycatch patterns across large ocean regions is limited by data availability but essential to direct conservation and management resources. We use empirical data to identify the global distribution and magnitude of seabird, marine mammal, and sea turtle bycatch in three widely used fishing gears. We identify taxa-specific hotspots and find evidence of cumulative impacts. This analysis provides an unprecedented global assessment of the distribution and magnitude of air-breathing megafauna bycatch, highlighting its cumulative nature and the urgent need to build on existing mitigation successes.
Reprogrammed and transmissible intestinal microbiota confer diminished susceptibility to induced colitis in TMF
−/−
mice
Authors: Bel Shai , Elkis Yoav , Elifantz Hila , Koren Omry , Ben-Hamo Rotem , Lerer-Goldshtein Tal , Rahimi Roni , Ben Horin Shomron , Nyska Abraham , Shpungin Sally , Nir Uri 
Published: March 2014

Significance
Our data demonstrate that a knockout of a single gene (tmf1) leads to the beneficial reprogramming of the gut resident microbiota. This reprogramming results in a diminished susceptibility of the genetically modified animals to induced colitis. Notably, the reprogrammed bacterial profile is transmissible, thereby conferring altered microbiome and reduced susceptibility to induced colitis in wild-type mice, when cohoused. Our findings open previously unreported avenues for unraveling regulatory factors that affect the gut homeostasis and mammalian sensitivity to the onset of inflammatory bowel diseases.
Unexpected trapping of particles at a T junction
Authors: Vigolo Daniele , Radl Stefan , Stone Howard A. 
Published: March 2014

Significance
Most flow systems we encounter in everyday life, such as cardiovascular blood flow in our body or the flow in typical domestic or industrial piping systems, present T junctions that split the flow into two streams. Another characteristic that these systems often have in common is the presence of a dispersed phase made of low-density particles or air bubbles. In this paper we present evidence that in these situations particles can get trapped at the junction, accumulate, and ultimately change the flow distribution. The unanticipated trapping mechanism can affect health and diagnostics in human beings or create malfunctions, and consequently unexpected dangers, in industrial environments. Nonetheless, the same effect can also be exploited to design new particle separation devices.
Therapeutic vaccine against DPP4 improves glucose metabolism in mice
Authors: Pang Zhengda , Nakagami Hironori , Osako Mariana K. , Koriyama Hiroshi , Nakagami Futoshi , Tomioka Hideki , Shimamura Munehisa , Kurinami Hitomi , Takami Yoichi , Morishita Ryuichi , Rakugi Hiromi 
Published: March 2014

Significance
Type 2 diabetes mellitus (T2DM) has become a common disease, and long-term effective drugs have become a necessity. In recent years, dipeptidyl peptidase 4 (DPP4) inhibitors have been commercialized due to its ability to inhibit glucagon-like peptide 1 degradation, a hormone important for enhancing insulin secretion. Despite the availability of efficient drugs, the success of treatment is limited by patients’ inconsistent drug intake and the economic burden included in a lifelong treatment required for T2DM. To alleviate these limitations, in this study an affordable and effective immunotherapeutic method was developed and assessed for T2DM treatment. We selected and designed the appropriate peptide sequences that induce the anti-DPP4 antibody that effectively improves the diabetic phenotype without an adverse autoimmune response.
Transient but Not Genetic Loss of miR‐451 is Protective in the Development of Pulmonary Arterial Hypertension
Authors: Grant Jennifer S. , Morecroft Ian , Dempsie Yvonne , van Rooij Eva , MacLean Margaret R. , Baker Andrew H. 
Published: March 2014

MicroRNAs are small noncoding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work has established that miR‐451 is upregulated in rodent models of PAH. The role of miR‐451 in the pulmonary circulation is unknown. We therefore sought to assess the involvement of miR‐451 in the development of PAH. Silencing of miR‐451 was performed in vivo using miR‐451 knockout mice and an anti‐miR targeting mature miR‐451 in rats. Coupled with exposure to hypoxia, indices of PAH were assessed. The effect of modulating miR‐451 on human pulmonary artery smooth muscle cell proliferation and migration was analyzed. We observed a reduction in systolic right ventricular pressure in hypoxic rats pretreated with anti‐miR‐451 compared with hypoxia alone (47.7 ± 1.36 mmHg and 56.0 ± 2.03 mmHg, respectively; P <. 01). In miR‐451 knockout mice, compared with wild‐type hypoxic mice, no significant differences were observed following exposure to chronic hypoxia. In vitro analysis demonstrated that overexpression of miR‐451 in human pulmonary artery smooth muscle cells promoted migration under serum‐free conditions. No effect on cellular proliferation was observed. In conclusion, transient inhibition of miR‐451 attenuated the development of PAH in hypoxia‐exposed rats. Genetic deletion of miR‐451 had no beneficial effect on indices of PAH, potentially because of pathway redundancy compensating for the loss of miR‐451.
Nitrosation‐Dependent Caveolin 1 Phosphorylation, Ubiquitination, and Degradation and its Association with Idiopathic Pulmonary Arterial Hypertension
Authors: Bakhshi Farnaz R. , Mao Mao , Shajahan Ayesha N. , Piegeler Tobias , Chen Zhenlong , Chernaya Olga , Sharma Tiffany , Elliott W. Mark , Szulcek Robert , Bogaard Harm Jan , Comhair Suzy , Erzurum Serpil , van Nieuw Amerongen Geerten P. , Bonini Marcelo G. , Minshall Richard D. 
Published: March 2014

In the present study, we tested the hypothesis that chronic inflammation and oxidative/nitrosative stress induce caveolin 1 (Cav‐1) degradation, providing an underlying mechanism of endothelial cell activation/dysfunction and pulmonary vascular remodeling in patients with idiopathic pulmonary arterial hypertension (IPAH). We observed reduced Cav‐1 protein despite increased Cav‐1 messenger RNA expression and also endothelial nitric oxide synthase (eNOS) hyperphosphorylation in human pulmonary artery endothelial cells (PAECs) from patients with IPAH. In control human lung endothelial cell cultures, tumor necrosis factor α–induced nitric oxide (NO) production and S‐nitrosation (SNO) of Cav‐1 Cys‐156 were associated with Src displacement and activation, Cav‐1 Tyr‐14 phosphorylation, and destabilization of Cav‐1 oligomers within 5 minutes that could be blocked by eNOS or Src inhibition. Prolonged stimulation (72 hours) with NO donor DETANONOate reduced oligomerized and total Cav‐1 levels by 40%–80%, similar to that observed in IPAH patient–derived PAECs. NO donor stimulation of endothelial cells for >72 hours, which was associated with sustained Src activation and Cav‐1 phosphorylation, ubiquitination, and degradation, was blocked by NOS inhibitor L‐NAME, Src inhibitor PP2, and proteosomal inhibitor MG132. Thus, chronic inflammation, sustained eNOS and Src signaling, and Cav‐1 degradation may be important causal factors in the development of IPAH by promoting PAEC dysfunction/activation via sustained oxidative/nitrosative stress.
Iloprost Improves Ventricular Function in the Hypertrophic and Functionally Impaired Right Heart by Direct Stimulation
Authors: Holmboe Sarah , Andersen Asger , Vildbrad Mads D. , Nielsen Jan M. , Ringgaard Steffen , Nielsen‐Kudsk Jens E. 
Published: March 2014

Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure‐overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; n = 8), pulmonary trunk banding (PTB; n = 8), or a sham operation (n = 8). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a 12% ± 4% (P = 0.022) increase in stroke volume in the sham group and a 12% ± 3% (P = 0.005) increase in the PTB group. RV dP=dtmax was elevated by 11% ± 5% (P = 0.039) in the sham group and by 12% ± 3% (P = 0.016) in the PTB group. An elevation in cardiac output of 14% ±3% (P = 0.0008) and an 11% ± 2% (P = 0.0021) increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.
Dysregulation of Ubiquitin‐Proteasome Pathway and Apolipoprotein a Metabolism in Sickle Cell Disease–Related Pulmonary Arterial Hypertension
Authors: Anjum Fatima , Lazar Jason , Soh James , Albitar Maher , Gowda Satish , Hussain M. Mahmood , Wadgaonkar Raj 
Published: March 2014

Pulmonary arterial hypertension (PAH) is a major complication of sickle cell disease (SCD). Low levels of apolipoprotein A1 (Apo‐A1) have been implicated in the development of PAH in SCD. We speculate that lower levels of Apo‐A1 are related to dysregulation of the ubiquitin‐proteasome pathway (UPP). Of 36 recruited patients with SCD, 14 were found to have PAH on the basis of right heart catheterization. Levels of Apo‐A1 and Apo‐B, polyubiquitin, total protease, and specific and normalized activity of chymotrypsin‐like, trypsin‐like, and caspase‐like proteases in plasma were measured. Levels of Apo‐A1 were found to be lower and polyubiquitin levels were found to be significantly higher in the PAH group (P < 0.05) in SCD. Apo‐A levels were inversely correlated with polyubiquitin levels (r = −0.499, P = 0.009). These results indicate that lower levels of Apo‐A1 in SCD patients with PAH are likely related to enhance degradation by UPP, potentially contributing to pulmonary vascular pathology. These findings may provide significant insight in identifying suitable therapeutic targets in these patients.
Quotidian Changes of Genital Tract Cytokines in Human Immunodeficiency Virus-1-Infected Women During the Menstrual Cycle
Authors: Cortez Valerie , Odem-Davis Katherine , Lehman Dara A. , Mabuka Jennifer , Overbaugh Julie 
Published: March 2014

Abstract
The role of hormonal changes throughout the menstrual cycle on genital tract inflammation during chronic human immunodeficiency virus (HIV) infection is not well defined, but it has implications for HIV prevention. We assessed daily levels of 26 vaginal cytokines and chemokines from 15 women infected with HIV-1. Taking into account coexisting sexually transmitted infections, behavioral factors, and menstruation, this study illustrates cyclic patterns of granulocyte macrophage colony-stimulating factor, interferon-α2, interleukin (IL)-6, IL-10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and tumor necrosis factor (TNF)-α. Progesterone was associated with levels of granulocyte colony-stimulating factor, IL-1α, and monocyte chemoattractant protein-1. Interferon-α2, IL-6, MIP-1α, MIP-1β, and TNF-α levels predicted HIV shedding, but these associations were heavily influenced by the menstrual cycle.
Cystatin C-Based Renal Function Changes After Antiretroviral Initiation: A Substudy of a Randomized Trial
Authors: Gupta Samir K. , Kitch Douglas , Tierney Camlin , Daar Eric S. , Sax Paul E. , Melbourne Kathleen , Ha Belinda , McComsey Grace A. ,   for the AIDS Clinical Trials Group Study A5224s Team
Published: March 2014

Abstract
Background.  The effects of antiretrovirals on cystatin C-based renal function estimates are unknown.
Methods.  We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz.
Results.  Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P &lt; .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were −8.3 (−14.0, −2.6) mL/min with Cockcroft-Gault; −14.9 (−19.7, −10.1) mL/min per 1.732 with Modification of Diet in Renal Disease; −12.8 (−16.5, −9.0) mL/min per 1.732 with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.732 with 2012 CKD-EPI cystatin C; and −1.2 (−5.1, 2.6) mL/min per 1.732 with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation.
Conclusions.  Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used.
Measuring error rates in genomic perturbation screens: gold standards for human functional genomics
Authors: Hart Traver , Brown Kevin R. , Sircoulomb Fabrice , Rottapel Robert , Moffat Jason 
Published: March 2014

AbstractTechnological advancement has opened the door to systematic genetics in mammalian cells. Genome-scale loss-of-function screens can assay fitness defects induced by partial gene knockdown, using RNA interference, or complete gene knockout, using new CRISPR techniques. These screens can reveal the basic blueprint required for cellular proliferation. Moreover, comparing healthy to cancerous tissue can uncover genes that are essential only in the tumor; these genes are targets for the development of specific anticancer therapies. Unfortunately, progress in this field has been hampered by offtarget effects of perturbation reagents and poorly quantified error rates in large-scale screens. To improve the quality of information derived from these screens, and to provide a framework for understanding the capabilities and limitations of CRISPR technology, we derive gold-standard reference sets of essential and nonessential genes, and provide a Bayesian classifier of gene essentiality that outperforms current methods on both RNAi and CRISPR screens. Our results indicate that CRISPR technology is more sensitive than RNAi, and that both techniques have nontrivial false discovery rates that can be mitigated by rigorous analytical methods.
The Arabidopsis LYSIN MOTIF-CONTAINING RECEPTOR-LIKE KINASE3 Regulates the Cross Talk between Immunity and Abscisic Acid Responses
Authors: Paparella Chiara , Savatin Daniel Valentin , Marti Lucia , De Lorenzo Giulia , Ferrari Simone 
Published: March 2014

AbstractTransmembrane receptor-like kinases characterized by the presence of one or more lysin motif (LysM) domains in the extracytoplasmic portion (LysM-containing receptor-like kinases [LYKs]) mediate recognition of symbiotic and pathogenic microorganisms in plants. The Arabidopsis (Arabidopsis thaliana) genome encodes five putative LYKs; among them, AtLYK1/CHITIN ELICITOR RECEPTOR KINASE1 is required for response to chitin and peptidoglycan, and AtLYK4 contributes to chitin perception. More recently, AtLYK3 has been shown to be required for full repression, mediated by Nod factors, of Arabidopsis innate immune responses. In this work, we show that AtLYK3 also negatively regulates basal expression of defense genes and resistance to Botrytis cinerea and Pectobacterium carotovorum infection. Enhanced resistance of atlyk3 mutants requires PHYTOALEXIN-DEFICIENT3, which is crucial for camalexin biosynthesis. The expression of AtLYK3 is strongly repressed by elicitors and fungal infection and is induced by the hormone abscisic acid (ABA), which has a negative impact on resistance against B. cinerea and P. carotovorum. Plants lacking a functional AtLYK3 also show reduced physiological responses to ABA and are partially resistant to ABA-induced inhibition of PHYTOALEXIN-DEFICIENT3 expression. These results indicate that AtLYK3 is important for the cross talk between signaling pathways activated by ABA and pathogens.