bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy
Authors: Nikopoulos Konstantinos , Avila-Fernandez Almudena , Corton Marta , Lopez-Molina Maria Isabel , Perez-Carro Raquel , Bontadelli Lara , Di Gioia Silvio Alessandro , Zurita Olga , Garcia-Sandoval Blanca , Rivolta Carlo , Ayuso Carmen 
Published: September 2015

AbstractInherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients’ molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision, reduced or absent ERG responses, macular atrophy and pigmentary deposits in the peripheral retina. Genetic investigation included autozygosity mapping coupled with exome sequencing in the first family, whereas autozygome-guided candidate gene screening was performed by means of Sanger DNA sequencing in the second family. Our approach revealed nucleotide changes in CDHR1; a homozygous missense variant (c.1720C > G, p.P574A) and a homozygous single base transition (c.1485 + 2T > C) affecting the canonical 5’ splice site of intron 13, respectively. Both changes co-segregated with the disease and were absent among cohorts of unrelated control individuals. To date, only five mutations in CDHR1 have been identified, all resulting in premature stop codons leading to mRNA nonsense mediated decay. Our work reports two previously unidentified homozygous mutations in CDHR1 further expanding the mutational spectrum of this gene.
Structural basis of redox-dependent substrate binding of protein disulfide isomerase
Authors: Yagi-Utsumi Maho , Satoh Tadashi , Kato Koichi 
Published: September 2015

AbstractProtein disulfide isomerase (PDI) is a multidomain enzyme, operating as an essential folding catalyst, in which the b′ and a′ domains provide substrate binding sites and undergo an open–closed domain rearrangement depending on the redox states of the a′ domain. Despite the long research history of this enzyme, three-dimensional structural data remain unavailable for its ligand-binding mode. Here we characterize PDI substrate recognition using α-synuclein (αSN) as the model ligand. Our nuclear magnetic resonance (NMR) data revealed that the substrate-binding domains of PDI captured the αSN segment Val37–Val40 only in the oxidized form. Furthermore, we determined the crystal structure of an oxidized form of the b′–a′ domains in complex with an undecapeptide corresponding to this segment. The peptide-binding mode observed in the crystal structure with NMR validation, was characterized by hydrophobic interactions on the b′ domain in an open conformation. Comparison with the previously reported crystal structure indicates that the a′ domain partially masks the binding surface of the b′ domain, causing steric hindrance against the peptide in the reduced form of the b′–a′ domains that exhibits a closed conformation. These findings provide a structural basis for the mechanism underlying the redox-dependent substrate binding of PDI.
Manganese powder promoted highly efficient and selective synthesis of fullerene mono- and biscycloadducts at room temperature
Authors: Si Weili , Zhang Xuan , Lu Shirong , Yasuda Takeshi , Asao Naoki , Han Liyuan , Yamamoto Yoshinori , Jin Tienan 
Published: September 2015

AbstractDiscovery of an efficient, practical and flexible synthetic method to produce various important electron acceptors for low-cost organic photovoltaics (OPVs) is highly desirable. Although the most commonly used acceptor materials, such as PC61BM, PC71BM, IC60BA, bisPC61BM have been proved to be promising for the OPVs, they are still very expensive mainly due to their low production yields and limited synthetic methods. Herein, we report an unprecedented and innovative synthetic method of a variety of fullerene mono- and biscycloadducts by using manganese powder as a promotor. The reaction of fullerenes with various dibromides proceeds efficiently and selectively under very mild conditions to give the corresponding cycloadducts in good to excellent yields. The combination of manganese power with DMSO additive is crucial for the successful implementation of the present cycloaddition. Notably, the standard OPV acceptors, such as PCBMs, have been obtained in extraordinarily high yields, which cannot be achieved under the previously reported methods.
Rapid Bacterial Identification, Resistance, Virulence and Type Profiling using Selected Reaction Monitoring Mass Spectrometry
Authors: Charretier Yannick , Dauwalder Olivier , Franceschi Christine , Degout-Charmette Elodie , Zambardi Gilles , Cecchini Tiphaine , Bardet Chloe , Lacoux Xavier , Dufour Philippe , Veron Laurent , Rostaing Hervé , Lanet Veronique , Fortin Tanguy , Beaulieu Corinne , Perrot Nadine , Dechaume Dominique , Pons Sylvie , Girard Victoria , Salvador Arnaud , Durand Géraldine , Mallard Frédéric , Theretz Alain , Broyer Patrick , Chatellier Sonia , Gervasi Gaspard , Van Nuenen Marc , Ann Roitsch Carolyn , Van Belkum Alex , Lemoine Jérôme , Vandenesch François , Charrier Jean-Philippe 
Published: September 2015

AbstractMass spectrometry (MS) in Selected Reaction Monitoring (SRM) mode is proposed for in-depth characterisation of microorganisms in a multiplexed analysis. Within 60–80 minutes, the SRM method performs microbial identification (I), antibiotic-resistance detection (R), virulence assessment (V) and it provides epidemiological typing information (T). This SRM application is illustrated by the analysis of the human pathogen Staphylococcus aureus, demonstrating its promise for rapid characterisation of bacteria from positive blood cultures of sepsis patients.
BACOM2.0 facilitates absolute normalization and quantification of somatic copy number alterations in heterogeneous tumor
Authors: Fu Yi , Yu Guoqiang , Levine Douglas A. , Wang Niya , Shih Ie-Ming , Zhang Zhen , Clarke Robert , Wang Yue 
Published: September 2015

AbstractMost published copy number datasets on solid tumors were obtained from specimens comprised of mixed cell populations, for which the varying tumor-stroma proportions are unknown or unreported. The inability to correct for signal mixing represents a major limitation on the use of these datasets for subsequent analyses, such as discerning deletion types or detecting driver aberrations. We describe the BACOM2.0 method with enhanced accuracy and functionality to normalize copy number signals, detect deletion types, estimate tumor purity, quantify true copy numbers and calculate average-ploidy value. While BACOM has been validated and used with promising results, subsequent BACOM analysis of the TCGA ovarian cancer dataset found that the estimated average tumor purity was lower than expected. In this report, we first show that this lowered estimate of tumor purity is the combined result of imprecise signal normalization and parameter estimation. Then, we describe effective allele-specific absolute normalization and quantification methods that can enhance BACOM applications in many biological contexts while in the presence of various confounders. Finally, we discuss the advantages of BACOM in relation to alternative approaches. Here we detail this revised computational approach, BACOM2.0 and validate its performance in real and simulated datasets.
Assessment of electricity price uncertainty impact on the operation of multi‐carrier energy systems
Authors: Zarif Mahdi , Khaleghi Sadegh , Javidi Mohammad Hossein 
Published: September 2015

Today, there are serious trends to use all potentials of the available energy carriers through the concept of energy hubs. However, different types of inherent uncertainties in these systems are the main challenge for utilisation of energy hubs. Furthermore, a framework is presented to analyse the multi‐carrier energy systems under five zones of uncertainty in order to achieve the maximum electricity profits. For example, it is shown that the profit of the system is <8.5% despite the 50% of uncertainty in the state without combined heat and power (CHP) while system earns a profit of at least 12.8 in the state with CHP. The Monte Carlo simulation method has used to generate different scenarios. The proposed design methodology decides on which model is suitable for hub. It includes detailed models for transducer performance and hub using the mean and variance of profits and assess of their impact individually. The model also considers information on energy products used as per‐unit form. Price and electricity markets have intended as in the day‐ahead and real‐time pricing with three types of tariffs during the day.
Improved single‐phase transformerless inverter with high power density and high efficiency for grid‐connected photovoltaic systems
Authors: Cho Yong‐Won , Cha Woo‐Jun , Kwon Jung‐Min , Kwon Bong‐Hwan 
Published: September 2015

This study proposes an improved single‐phase transformerless inverter with high power density and high efficiency for grid‐connected photovoltaic systems. The proposed inverter is comprised of the dual‐paralleled‐buck inverter and two auxiliary circuits for the zero‐current switching turn‐off of the diodes. The dual‐paralleled‐buck inverter and auxiliary circuits are joined by two coupled inductors. To achieve high power density, the proposed inverter operates at high switching frequency of 40 kHz. This leads to lower filter inductors and lower conduction losses of the filter inductors than conventional full‐bridge inverters. Moreover, two auxiliary circuits reduce the switching losses caused by high switching frequency operation. Furthermore, the proposed inverter provides the low common‐mode leakage current, which satisfies the criteria given by VDE‐0126‐1‐1. Thus, the proposed inverter achieves the maximum efficiency of 99%. The operation principle of the proposed inverter is analysed and verified. Experimental results for a 1 kW prototype are obtained to show the performance of the proposed inverter.
Management of Typical and Atypical Hangman's Fractures
Authors: Al-Mahfoudh Rafid , Beagrie Christopher , Woolley Ele , Zakaria Rasheed , Radon Mark , Clark Simon , Pillay Robin , Wilby Martin 
Published: September 2015

Study Design Retrospective study of a prospectively maintained database. Objective Our aim was to retrospectively review management and outcomes of patients with low-grade hangman's fractures, specifically looking at differences in outcomes between collars and halo immobilization. We also studied fracture patterns and their treatment outcomes. Methods Forty-one patients with hangman's fractures were identified from 105 patients with axis fractures between 2007 and 2013. Typical hangman's fractures were defined as traumatic spondylolisthesis of the axis causing a bilateral pars interarticularis fracture. Fractures involving the posterior cortex of C2 on one or both sides or an asymmetrical pattern were defined as atypical. Results There were 41 patients with a mean age of 59 years, with 13 (31.7%) typical and 28 (68.2%) atypical fractures. There were 22 (53.6%) type 1 fractures, 7 (41.4%) type 2 fractures, and 2 (4.9%) type 2a fractures in this series. Cervical collars were used to manage 11 patients (27% of all patients with hangman's fractures) and halo orthosis was used in 27 (65.8%). Three (7.3%) patients underwent surgical fixation of the fracture. Bony union was achieved in all patients on radiologic follow-up. Permanent neurologic deficit occurred in one patient due to associated injuries. Neck pain and stiffness were reported more commonly in the atypical group, but this finding was not statistically significant. Conclusions The majority of hangman type fractures can be treated nonoperatively. We found no difference in outcomes between a rigid collar or halo immobilization for treatment of low-grade fractures. Radiologic follow-up is essential to identify cases of nonunion.
Does Transforaminal Lumbar Interbody Fusion Have Advantages over Posterolateral Lumbar Fusion for Degenerative Spondylolisthesis?
Authors: Fujimori Takahito , Le Hai , Schairer William W. , Berven Sigurd H. , Qamirani Erion , Hu Serena S. 
Published: September 2015

The author regrets an error in the Conclusion of the above article, published in the Global Spine Journal, Volume 5, Number 2, 2015 (DOI: 10.1055/s-0034-1396432). The word “reduction” was inadvertently omitted. The corrected Conclusion appears below. Conclusion The TLIF group demonstrated significantly greater improvement in low back pain and unilateral leg pain compared with the PLF group. However, no differences in improvement in either ODI or PCS were noted between the groups. The postoperative slippage reduction and disk height were significantly greater in the TLIF group, but local disk lordosis, lumbar lordosis, and pelvic parameters were similar between the groups.
Freshwater discharges drive high levels of methylmercury in Arctic marine biota
Authors: Schartup Amina T. , Balcom Prentiss H. , Soerensen Anne L. , Gosnell Kathleen J. , Calder Ryan S. D. , Mason Robert P. , Sunderland Elsie M. 
Published: September 2015

Significance
Estuaries are the predominant hunting and fishing territory for northern indigenous populations whose way of life is threatened by both climate change and industrial development. Direct measurements and modeling conducted as part of this study show enhanced production of methylmercury, a potent neurotoxin, and uptake by plankton in stratified oxic seawater. Enhanced climate-driven stratification of ocean margin areas with sea-ice melt will likely elevate biological methylmercury concentrations in the Arctic. Elevated biological methylmercury levels will be exacerbated by hydroelectric development planned throughout many northern regions. Our experimental measurements indicate that, over the next decade, regional increases in methylmercury concentrations resulting from flooding associated with hydroelectric development will be greater than those expected from climate change.
Biochemical isolation of Argonaute protein complexes by Ago-APP
Authors: Hauptmann Judith , Schraivogel Daniel , Bruckmann Astrid , Manickavel Sudhir , Jakob Leonhard , Eichner Norbert , Pfaff Janina , Urban Marc , Sprunck Stefanie , Hafner Markus , Tuschl Thomas , Deutzmann Rainer , Meister Gunter 
Published: September 2015

Significance
Small RNA-guided gene-silencing pathways regulate fundamental cellular processes. Small RNAs such as microRNAs (miRNAs) directly bind to a member of the Argonaute (Ago) protein family. In animals, Ago proteins interact with a member of the GW protein family (referred to as TNRC6A-C). Based on an Ago-interacting TNRC6 peptide, we have developed a method allowing for the efficient isolation and characterization of Ago protein complexes from any animal organism. We refer to this method as “Ago protein Affinity Purification by Peptides.” Our approach also allows for the identification of Ago-bound small RNAs as well as mRNAs. Expression of this peptide in living cells leads to global miRNA inactivation, thus providing a powerful tool to study miRNA function on various levels.
Piezo1 regulates mechanotransductive release of ATP from human RBCs
Authors: Cinar Eyup , Zhou Sitong , DeCourcey James , Wang Yixuan , Waugh Richard E. , Wan Jiandi 
Published: September 2015

Significance
Mechanotransductive release of ATP from RBCs participates in the regulation of microvascular tone and plays essential roles in vascular physiopathology. The mechanism responsible for the release of ATP, however, is poorly understood. We show for the first time, to our knowledge, that Piezo1, the recently identified mechanically activated cation channel, regulates the mechanotransductive release of ATP from RBCs. In particular, we uncover the link between Piezo1, calcium influx, and ATP release and propose a previously unidentified mechanotransductive pathway that modulates the release of ATP from RBCs. The outcome of this study will allow the development of much needed approaches to regulate the release of ATP from RBCs and thus, impact significantly the fields of red cell research, cellular mechanosensing, and Piezo1 channels.
Single quantum dot controls a plasmonic cavity’s scattering and anisotropy
Authors: Hartsfield Thomas , Chang Wei-Shun , Yang Seung-Cheol , Ma Tzuhsuan , Shi Jinwei , Sun Liuyang , Shvets Gennady , Link Stephan , Li Xiaoqin 
Published: September 2015

Significance
We experimentally demonstrate that a single semiconductor quantum dot placed in close proximity to a plasmonic cavity (i.e., a spherical metallic nanoparticle) can be used to control the scattering spectrum and anisotropy of the latter. The scattering spectrum of the hybrid structure features a Fano resonance mediated by single photon absorption/scattering. This result is highly counterintuitive because the scattering cross sections of these two nanoparticles differ by four orders of magnitude. Our work represents a critical step toward realizing quantum plasmonic nanostructures that are capable of producing scattered light, which, depending on its polarization state, obeys either quantum or classical statistics. Furthermore, our work enables a hybrid orientation sensor unaffected by photobleaching of quantum dots.
Ancient genomes link early farmers from Atapuerca in Spain to modern-day Basques
Authors: Günther Torsten , Valdiosera Cristina , Malmström Helena , Ureña Irene , Rodriguez-Varela Ricardo , Sverrisdóttir Óddny Osk , Daskalaki Evangelia A. , Skoglund Pontus , Naidoo Thijessen , Svensson Emma M. , Bermúdez de Castro José María , Carbonell Eudald , Dunn Michael , Storå Jan , Iriarte Eneko , Arsuaga Juan Luis , Carretero José-Miguel , Götherström Anders , Jakobsson Mattias 
Published: September 2015

Significance
The transition from a foraging subsistence strategy to a sedentary farming society is arguably the greatest innovation in human history. Some modern-day groups—specifically the Basques—have been argued to be a remnant population that connect back to the Paleolithic. We present, to our knowledge, the first genome-wide sequence data from eight individuals associated with archaeological remains from farming cultures in the El Portalón cave (Atapuerca, Spain). These individuals emerged from the same group of people as other Early European farmers, and they mixed with local hunter–gatherers on their way to Iberia. The El Portalón individuals showed the greatest genetic affinity to Basques, which suggests that Basques and their language may be linked with the spread of agriculture across Europe.
Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer’s disease pathogenesis
Authors: Zhu Li , Zhong Minghao , Elder Gregory A. , Sano Mary , Holtzman David M. , Gandy Sam , Cardozo Christopher , Haroutunian Vahram , Robakis Nikolaos K. , Cai Dongming 
Published: September 2015

Significance
The apolipoprotein E4 (ApoE4) genotype is the strongest genetic risk factor for developing Alzheimer’s disease (AD). However, the mechanisms that underlie this link between ApoE4 genotype and AD are not well understood. Our data in this paper are the first mechanistic studies to our knowledge that link ApoE4 genotype-specific changes in brain phospholipid homeostasis to ApoE4-increased susceptibility to develop AD. Our studies indicate previously unidentified therapeutic options for the treatment of AD, targeting ApoE4’s pathogenic nature.
Gut DNA viromes of Malawian twins discordant for severe acute malnutrition
Authors: Reyes Alejandro , Blanton Laura V. , Cao Song , Zhao Guoyan , Manary Mark , Trehan Indi , Smith Michelle I. , Wang David , Virgin Herbert W. , Rohwer Forest , Gordon Jeffrey I. 
Published: September 2015

Significance
Childhood malnutrition is a global health problem not attributable to food insecurity alone. Sequencing DNA viruses present in fecal microbiota serially sampled from 0- to 3-y-old Malawian twin pairs, we identify age-discriminatory viruses that define a “program” of assembly of phage and eukaryotic components of the gut “virome” within and across pairs where both cotwins manifest healthy growth. This program is perturbed (delayed) in both members of discordant pairs where one cotwin develops severe acute malnutrition and the other appears healthy by anthropometry. This developmental delay is not repaired by therapeutic foods. These age- and disease-discriminatory viruses may help define familial risk for childhood malnutrition and provide a viral dimension for characterizing the developmental biology of our gut microbial “organ.”
Transcellular spreading of huntingtin aggregates in theDrosophilabrain
Authors: Babcock Daniel T. , Ganetzky Barry 
Published: September 2015

SignificancePropagation of protein aggregates throughout the nervous system is thought to play a significant role in the pathology of neurodegenerative diseases. Thus, understanding how this propagation is regulated is crucial for identifying potential therapeutic interventions. Here we use experimental advantages ofDrosophilato investigate aggregate spreading. We demonstrate that huntingtin, containing an expanded polyglutamine tract of 138 repeats, but not an unexpanded form, aggregates and spreads rapidly throughout the brain, resulting in loss of vulnerable neurons. Aggregate spreading and neuronal loss are impaired by blocking synaptic exocytosis in releasing cells or endocytic uptake in target cells. These studies enable screens for genetic and pharmacological modifiers that could ameliorate the deleterious effects of spreading in neurodegenerative diseases.
BMix: probabilistic modeling of occurring substitutions in PAR-CLIP data
Authors: Golumbeanu Monica , Mohammadi Pejman , Beerenwinkel Niko 
Published: September 2015

Abstract
Motivation : Photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) is an experimental method based on next-generation sequencing for identifying the RNA interaction sites of a given protein. The method deliberately inserts T-to-C substitutions at the RNA-protein interaction sites, which provides a second layer of evidence compared with other CLIP methods. However, the experiment includes several sources of noise which cause both low-frequency errors and spurious high-frequency alterations. Therefore, rigorous statistical analysis is required in order to separate true T-to-C base changes, following cross-linking, from noise. So far, most of the existing PAR-CLIP data analysis methods focus on discarding the low-frequency errors and rely on high-frequency substitutions to report binding sites, not taking into account the possibility of high-frequency false positive substitutions.
Results : Here, we introduce BMix , a new probabilistic method which explicitly accounts for the sources of noise in PAR-CLIP data and distinguishes cross-link induced T-to-C substitutions from low and high-frequency erroneous alterations. We demonstrate the superior speed and accuracy of our method compared with existing approaches on both simulated and real, publicly available human datasets.
Availability and implementation : The model is freely accessible within the BMix toolbox at www.cbg.bsse.ethz.ch/software/BMix , available for Matlab and R.
Supplementary information: Supplementary data is available at Bioinformatics online.
Contact : niko.beerenwinkel@bsse.ethz.ch