bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Resistance-Associated NS5A Mutations in Hepatitis C Virus on Viral Production and Susceptibility to Antiviral Reagents
Authors: Nitta Sayuri , Asahina Yasuhiro , Matsuda Mami , Yamada Norie , Sugiyama Ryuichi , Masaki Takahiro , Suzuki Ryosuke , Kato Nobuyuki , Watanabe Mamoru , Wakita Takaji , Kato Takanobu 
Published: October 2016

AbstractDirect-acting antivirals (DAAs) for hepatitis C virus (HCV) have potent anti-HCV effects but may provoke resistance-associated variants (RAVs). In this study, we assessed the characteristics of these RAVs and explored efficacious anti-HCV reagents using recombinant HCV with NS5A from a genotype 1b strain. We replaced the NS5A of JFH1 with that of Con1 (JFH1/5ACon1) and introduced known NS5A inhibitor resistance mutations (L31M, L31V, L31I and Y93H) individually or in combination. Susceptibilities against anti-HCV reagents were also investigated. RAVs with Y93H exhibited high extracellular core antigen levels and infectivity titers. Variants with any single mutation showed mild to moderate resistance against NS5A inhibitors, whereas variants with double mutations at both L31 and Y93 showed severe resistance. The variants with mutations exhibited similar levels of susceptibility to interferon (IFN)-α, IFN-λ1, IFN-λ3 and Ribavirin. Variants with the Y93H mutation were more sensitive to protease inhibitors compared with JFH1/5ACon1. In conclusion, the in vitro analysis indicated that the Y93H mutation enhanced infectious virus production, suggesting advantages in the propagation of RAVs with this mutation. However, these RAVs were susceptible to protease inhibitors. Thus, a therapeutic regimen that includes these reagents is a promising means to eradicate these RAVs.
Unravelling the low-temperature metastable state in perovskite solar cells by noise spectroscopy
Authors: Barone C. , Lang F. , Mauro C. , Landi G. , Rappich J. , Nickel N. H. , Rech B. , Pagano S. , Neitzert H. C. 
Published: October 2016

AbstractThe hybrid perovskite methylammonium lead iodide CH3NH3PbI3 recently revealed its potential for the manufacturing of low-cost and efficient photovoltaic cells. However, many questions remain unanswered regarding the physics of the charge carrier conduction. In this respect, it is known that two structural phase transitions, occurring at temperatures near 160 and 310 K, could profoundly change the electronic properties of the photovoltaic material, but, up to now, a clear experimental evidence has not been reported. In order to shed light on this topic, the low-temperature phase transition of perovskite solar cells has been thoroughly investigated by using electric noise spectroscopy. Here it is shown that the dynamics of fluctuations detect the existence of a metastable state in a crossover region between the room-temperature tetragonal and the low-temperature orthorhombic phases of the perovskite compound. Besides the presence of a noise peak at this transition, a saturation of the fluctuation amplitudes is observed induced by the external DC current or, equivalently, by light exposure. This noise saturation effect is independent on temperature, and may represent an important aspect to consider for a detailed explanation of the mechanisms of operation in perovskite solar cells.
Preparation of cross-linked hen-egg white lysozyme crystals free of cracks
Authors: Yan Er-Kai , Lu Qin-Qin , Zhang Chen-Yan , Liu Ya-Li , He Jin , Chen Da , Wang Bo , Zhou Ren-Bin , Wu Ping , Yin Da-Chuan 
Published: October 2016

AbstractCross-linked protein crystals (CLPCs) are very useful materials in applications such as biosensors, catalysis, and X-ray crystallography. Hence, preparation of CLPCs is an important research direction. During the preparation of CLPCs, an often encountered problem is that cracks may appear in the crystals, which may finally lead to shattering of the crystals into small pieces and cause problem in practical applications. To avoid cross-link induced cracking, it is necessary to study the cracking phenomenon in the preparation process. In this paper, we present an investigation on how to avoid cracking during preparation of CLPCs. An orthogonal experiment was designed to study the phenomenon of cross-link induced cracking of hen-egg white lysozyme (HEWL) crystals against five parameters (temperature, solution pH, crystal growth time, glutaraldehyde concentration, and cross-linking time). The experimental results showed that, the solution pH and crystal growth time can significantly affect cross-link induced cracking. The possible mechanism was studied, and optimized conditions for obtaining crack-free CLPCs were obtained and experimentally verified.
Optogenetic activation of septal GABAergic afferents entrains neuronal firing in the medial habenula
Authors: Choi Kyuhyun , Lee Youngin , Lee Changwoo , Hong Seokheon , Lee Soonje , Kang Shin Jung , Shin Ki Soon 
Published: October 2016

AbstractThe medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (γ -aminobutyric acid) is a major inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors. Depending on intracellular chloride concentration, however, GABAA receptors also function in an excitatory manner. In the absence of various synaptic inputs, we found that MHb neurons displayed spontaneous tonic firing at a rate of about ~4.4 Hz. Optogenetic stimulation of MS/DB inputs to the MHb evoked GABAA receptor-mediated synaptic currents, which produced stimulus-locked neuronal firing. Subsequent delayed yet lasting activation of GABAB receptors attenuated the intrinsic tonic firing. Consequently, septal GABAergic input alone orchestrates both excitatory GABAA and inhibitory GABAB receptors, thereby entraining the firing of MHb neurons.
OAHG: an integrated resource for annotating human genes with multi-level ontologies
Authors: Cheng Liang , Sun Jie , Xu Wanying , Dong Lixiang , Hu Yang , Zhou Meng 
Published: October 2016

AbstractOAHG, an integrated resource, aims to establish a comprehensive functional annotation resource for human protein-coding genes (PCGs), miRNAs, and lncRNAs by multi-level ontologies involving Gene Ontology (GO), Disease Ontology (DO), and Human Phenotype Ontology (HPO). Many previous studies have focused on inferring putative properties and biological functions of PCGs and non-coding RNA genes from different perspectives. During the past several decades, a few of databases have been designed to annotate the functions of PCGs, miRNAs, and lncRNAs, respectively. A part of functional descriptions in these databases were mapped to standardize terminologies, such as GO, which could be helpful to do further analysis. Despite these developments, there is no comprehensive resource recording the function of these three important types of genes. The current version of OAHG, release 1.0 (Jun 2016), integrates three ontologies involving GO, DO, and HPO, six gene functional databases and two interaction databases. Currently, OAHG contains 1,434,694 entries involving 16,929 PCGs, 637 miRNAs, 193 lncRNAs, and 24,894 terms of ontologies. During the performance evaluation, OAHG shows the consistencies with existing gene interactions and the structure of ontology. For example, terms with more similar structure could be associated with more associated genes (Pearson correlation γ2 = 0.2428, p < 2.2e–16).
Cross-inhibition of pathogenic agents and the host proteins they exploit
Authors: Zilbermintz Leeor , Leonardi William , Tran Sharon H. , Zozaya Josue , Mathew-Joseph Alyssa , Liem Spencer , Levitin Anastasia , Martchenko Mikhail 
Published: October 2016

AbstractThe major limitations of pathogen-directed therapies are the emergence of drug-resistance and their narrow spectrum of coverage. A recently applied approach directs therapies against host proteins exploited by pathogens in order to circumvent these limitations. However, host-oriented drugs leave the pathogens unaffected and may result in continued pathogen dissemination. In this study we aimed to discover drugs that could simultaneously cross-inhibit pathogenic agents, as well as the host proteins that mediate their lethality. We observed that many pathogenic and host-assisting proteins belong to the same functional class. In doing so we targeted a protease component of anthrax toxin as well as host proteases exploited by this toxin. We identified two approved drugs, ascorbic acid 6-palmitate and salmon sperm protamine, that effectively inhibited anthrax cytotoxic protease and demonstrated that they also block proteolytic activities of host furin, cathepsin B, and caspases that mediate toxin’s lethality in cells. We demonstrated that these drugs are broad-spectrum and reduce cellular sensitivity to other bacterial toxins that require the same host proteases. This approach should be generally applicable to the discovery of simultaneous pathogen and host-targeting inhibitors of many additional pathogenic agents.
Repeatability of cortisol stress response in the European sea bass (Dicentrarchus labrax) and transcription differences between individuals with divergent responses
Authors: Samaras A. , Dimitroglou A. , Sarropoulou E. , Papaharisis L. , Kottaras L. , Pavlidis M. 
Published: October 2016

AbstractUnderstanding the stress responses of organisms is of importance in the performance and welfare of farmed animals, including fish. Especially fish in aquaculture commonly face stressors, and better knowledge of their responses may assist in proper husbandry and selection of breeding stocks. European sea bass (Dicentrarchus labrax), a species with high cortisol concentrations, is of major importance in this respect. The main objectives of the present study were to assess the repeatability and consistency of cortisol stress response and to identify differences in liver transcription profiles of European sea bass individuals, showing a consistent low (LR) or high (HR) cortisol response. The progeny of six full sib families was used, and sampled for plasma cortisol after an acute stress challenge once per month, for four consecutive months. Results suggest that cortisol responsiveness was a repeatable trait with LR and HR fish showing low or high resting, free and post-stress cortisol concentrations respectively. Finally, the liver transcription profiles of LR and HR fish showed some important differences, indicating differential hepatic regulation between these divergent phenotypes. These transcription differences were related to various metabolic and immunological processes, with 169 transcripts being transcribed exclusively in LR fish and 161 exclusively in HR fish.
Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload
Authors: Li Wei-ming , Zhao Yi-fan , Zhu Guo-fu , Peng Wen-hui , Zhu Meng-yun , Yu Xue-jing , Chen Wei , Xu Da-chun , Xu Ya-wei 
Published: October 2016

Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the dual specific phosphatase (DUSP) family, which is characterized by its DUSP activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in hypertrophic hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we demonstrated that DUSP12 deficiency apparently aggravated pressure overload-induced cardiac hypertrophy and fibrosis as well as impaired cardiac function, whereas cardiac-specific overexpression of DUPS12 was capable of reversing this hypertrophic and fibrotic phenotype and improving contractile function. Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38 activity was increased in the DUSP12 deficient group and decreased in the DUSP12 overexpression group both in vitro and in vivo under hypertrophic stress conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12 overexpression can alleviate this hypertrophic phenotype with improved cardiac function. Further study demonstrated that DUSP12 inhibited JNK activity to attenuate pathological cardiac hypertrophy.
No‐load performance study of 1200 kV Indian UHVAC transmission system
Authors: Bharti Satyadharma , Dubey Satya Prakash 
Published: October 2016

Major load centres of India are located at northern part and western–southern part of country, whereas most of the generating units are concentrated at eastern and North‐eastern parts. Economic transmission of bulk power over a long distance is a basic requirement for which ultra‐high voltage AC (UHVAC) transmission system is identified as a feasible solution resulting in reduced transmission loss and reduced corridor width (right of way), protection of precious flora and fauna. For this, Powergrid Corporation of India along with Central Power Research Institute had made a call for indigenous development of UHVAC technology. As a result, 1200 kV UHVAC National Test Station is developed in India at Bina. One 400/1200 kV bay is successfully charged, along with one 1200 kV single circuit and one 1200 kV double‐circuit test transmission line. This study deals with the study of on‐site acceptance test such as sweep frequency response analysis, frequency‐domain spectroscopy (FDS), along with inrush current measurement, voltage withstand test, corona measurement, thermo‐vision scanning conducted on‐site at no load, to ensure the performance of transmission system. A brief review of technical studies related to UHVAC technology developed throughout the World is also presented. The power transmission at 1200 kV is a feasible and viable option but further research is required in this area to make UHV transmission a global success.
Historische Entwicklung von Wollproben- und Farbtafeltests für das Screening von Farbsehstörungen im deutschsprachigen Raum
Authors: Kuchenbecker J. 
Published: October 2016

ZusammenfassungDas Farbensehen ist eine komplexe visuelle Funktion, die durch angeborene und/oder erworbene Störungen beeinträchtigt sein kann. Insbesondere ab den 70er-Jahren des 19. Jahrhunderts wurden durch planmäßige Untersuchungen insbesondere von Eisenbahn- und Marinepersonal die Verbreitung von angeborenen Störungen des Farbensehens erkannt und zahlreiche Untersuchungsverfahren entwickelt. So kamen u. a. Wollprobentests, Florkontrasttests und Farbtafeltests zur Anwendung. Bis in die heutige Zeit wird ein Farbtafeltest auf der Grundlage der Stillingʼschen pseudoisochromatischen Tafeln kombiniert mit einem Florkontrasttest als Screeningmethode für die Farbsehtestung im deutschen Sprachraum publiziert. Ziel des Tests ist es, angeborene und erworbene Farbsehstörungen einfach und zuverlässig aufzudecken. Dabei können bereits heute und in Zukunft auch die modernen Möglichkeiten wie Internet und Tablet-PC, trotz ihrer technischen Limitationen, ergänzend für das Screening von Farbsehstörungen genutzt werden.
Label-free imaging of the native, living cellular nanoarchitecture using partial-wave spectroscopic microscopy
Authors: Almassalha Luay M. , Bauer Greta M. , Chandler John E. , Gladstein Scott , Cherkezyan Lusik , Stypula-Cyrus Yolanda , Weinberg Samuel , Zhang Di , Thusgaard Ruhoff Peder , Roy Hemant K. , Subramanian Hariharan , Chandel Navdeep S. , Szleifer Igal , Backman Vadim 
Published: October 2016

Significance
Chromatin is one of the most critical structures within the cell because it houses most genetic information. Its structure is well understood at the nucleosomal (<20-nm) and chromosomal (>200-nm) levels; however, due to the lack of quantitative imaging modalities to study this organization, little is known about the higher-order structure between these length scales in live cells. We present a label-free technique, live-cell partial-wave spectroscopic (PWS) microscopy, with sensitivity to structures between 20 and 200 nm that can quantify the nanoarchitecture in live cells. With this technique, we can detect DNA fragmentation and expand on the link between metabolic function and higher-order chromatin structure. Live-cell PWS allows high-throughput study of the relationship between nanoscale organization and molecular function.
Palliative Pelvic Exenteration: Clinical Outcomes and Quality of Life
Authors: Quyn Aaron J. , Solomon Michael J. , Lee Peter M. , Badgery-Parker Tim , Masya Lindy M. , Young Jane M. 
Published: October 2016

BACKGROUND:
Locally advanced pelvic malignancy can be associated with disabling symptoms and reduced quality of life. If resectable with clear margins, a pelvic exenteration can offer long-term survival and improved quality of life. Its role in the palliation of symptoms has been described; however, the clinical outcomes and surgical indication are poorly defined.

OBJECTIVE:
This study describes the clinical and quality-of-life outcomes after palliative pelvic exenteration for advanced pelvic malignancy.

DESIGN:
Clinical data and patient-reported outcomes were collected for patients undergoing pelvic exenteration for symptom palliation.

SETTINGS:
This study was conducted at a tertiary referral center for pelvic exenteration.

PATIENTS:
All of the patients undergoing palliative pelvic exenteration for advanced primary rectal or recurrent cancer were included in our analysis.

MAIN OUTCOME MEASURES:
Patient-reported quality of life and physical and mental health status were measured. Quality-of-life trajectories were modeled over the 12 months from the date of surgery using linear mixed models.

RESULTS:
A total of 39 patients underwent pelvic exenteration for symptom palliation. Although there were no in-hospital deaths, 34% experienced significant morbidity. Patient-reported quality of life reduced postoperatively and gradually declined thereafter. Overall median survival was 24 months, with a 1-year mortality rate of 31%. There was a significant survival difference for the 39 patients undergoing pelvic exenteration compared with those patients who only had a debulking/bypass procedure or were closed without definitive treatment (overall median survival = 24 versus 9 months; p = <0.02).

LIMITATIONS:
Disease and patient heterogeneity limit the interpretation of these results.

CONCLUSIONS:
Palliative pelvic exenteration is a technically demanding operation that can be performed safely in a dedicated exenteration center. However, no durable palliation of symptoms with associated improved or sustained quality of life was observed, and the role of palliation therefore remains highly controversial in this complex group of patients.
Closing the Generational Gap in Surgery: Why So Angry?
Authors: Zbar Ross I.S. 
Published: October 2016

Summary:
Significant and rapid changes in healthcare delivery are forcing surgeons into collaborative teams. Additionally, surgeons are faced with new bureaucratic requirements that do not directly impact patient care, but nevertheless require allocation of time and attention. Surgeons are required to communicate with an expanding group of individuals at various professional levels, adding further stress to daily tasks. Even the method of communication is undergoing rapid transformation. Some surgeons, especially those who are members of the Boomer or X Generation, find this revolution difficult to manage; whereas those who are members of the Y Generation may in fact be better equipped. Surgeons who either refuse to acknowledge these changes or simply lack emotional self-awareness run the risk of being labeled as disruptive. Behavioral techniques are explored which may help those surgeons who are having difficulty.
Congenital Sucrase‐isomaltase Deficiency
Authors: Haberman Yael , Di Segni Ayelet , Loberman‐Nachum Nurit , Barel Ortal , Kunik Vered , Eyal Eran , Kol Nitzan , Hout‐Siloni Goni , Kochavi Brigitte , Avivi Camila , Schvimer Michael , Rechavi Gideon , Anikster Yair , Barshack Iris , Weiss Batia 
Published: October 2016

ABSTRACTObjectives:Congenital diarrheal disorders is a group of inherited enteropathies presenting in early life and requiring parenteral nutrition. In most cases, genetics may be the key for precise diagnosis. We present an infant girl with chronic congenital diarrhea that resolved after introduction of fructose‐based formula but had no identified mutation in the SLC5A1 gene. Using whole exome sequencing (WES) we identified other mutations that better dictated dietary adjustments.Methods:WES of the patient and her parents was performed. The analysis focused on recessive model including compound heterozygous mutations. Sanger sequencing was used to validate identified mutations and to screen the patient's newborn sister and grandparents. Expression and localization analysis were performed in the patient's duodenal biopsies using immunohistochemistry.Results:Using WES we identified a new compound heterozygote mutation in sucrase‐isomaltase (SI) gene; a maternal inherited known V577G mutation, and a novel paternal inherited C1531W mutation. Importantly, the newborn offspring carried similar compound heterozygous mutations. Computational predictions suggest that both mutations highly destabilize the protein. SI expression and localization studies determined that the mutated SI protein was not expressed on the brush border membrane in the patient's duodenal biopsies, verifying the diagnosis of congenital sucrase‐isomaltase deficiency (CSID).Conclusions:The novel compound heterozygote V577G/C1531W SI mutations lead to lack of SI expression in the duodenal brush border, confirming the diagnosis of CSID. These cases of CSID extend the molecular spectrum of this condition, further directing a more adequate dietary intervention for the patient and newborn sibling.