bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa
Authors: Ikeda Hanako Ohashi , Sasaoka Norio , Koike Masaaki , Nakano Noriko , Muraoka Yuki , Toda Yoshinobu , Fuchigami Tomohiro , Shudo Toshiyuki , Iwata Ayana , Hori Seiji , Yoshimura Nagahisa , Kakizuka Akira 
Published: August 2014

AbstractNeuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell. Surprisingly, KUSs did not significantly impair reported cellular functions of VCP but nonetheless suppressed the VCP-dependent decrease of cellular ATP levels. Moreover, KUSs, as well as exogenous ATP or ATP-producing compounds, e.g. methylpyruvate, suppressed endoplasmic reticulum stress and demonstrably protected various types of cultured cells from death, including several types of retinal neuronal cells. We then examined theirin vivoefficacies in rd10, a mouse model of retinitis pigmentosa. KUSs prevented photoreceptor cell death and preserved visual function. These results reveal an unexpected, crucial role of ATP consumption by VCP in determining cell fate in this pathological context and point to a promising new neuroprotective strategy for currently incurable retinitis pigmentosa.
Mode division multiplexing over 19‐cell hollow‐core photonic bandgap fibre by employing integrated mode multiplexer
Authors: Chen Haoshuo , van Uden R.G.H. , Okonkwo C.M. , Jung Yongmin , Wheeler N.V. , Fokoua E.N. , Baddela N. , Petrovich M.N. , Poletti F. , Richardson D.J. , Raz O. , de Waardt H. , Koonen A.M.J. 
Published: August 2014

A photonic integrated mode coupler based on silicon‐on‐insulator is employed for mode division multiplexing (MDM) over a 193 m 19‐cell hollow‐core photonic bandgap fibre (HC‐PBGF) with a −3 dB bandwidth >120 nm. Robust MDM transmissions using LP01 and LP11 modes, and two degenerate LP11 modes (LP11a and LP11b) are both experimentally verified.
Spliceostatin hemiketal biosynthesis in
Burkholderia
spp. is catalyzed by an iron/α-ketoglutarate–dependent dioxygenase
Authors: Eustáquio Alessandra S. , Janso Jeffrey E. , Ratnayake Anokha S. , O’Donnell Christopher J. , Koehn Frank E. 
Published: August 2014

Significance
Spliceostatins are bacterial natural products that show promising anticancer activity. Understanding how the bacterium makes spliceostatins will aid efforts toward a sustainable route for their production. Moreover, altering the chemical structure of a natural product is usually necessary to improve its pharmaceutical properties. For example, the parent spliceostatin molecule contains an unstable hemiketal chemical group. Contrary to previous hypotheses, we report on the identification of a dioxygenase enzyme responsible for hemiketal biosynthesis. Deletion of the corresponding dioxygenase gene led to a strain that produces exclusively spliceostatin congeners that are more stable than, and as active as, the parent compound, when derivatized to increase cell permeability. The strain generated in this study will be the basis for future development.
Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential
Authors: Ohnuki Mari , Tanabe Koji , Sutou Kenta , Teramoto Ito , Sawamura Yuka , Narita Megumi , Nakamura Michiko , Tokunaga Yumie , Nakamura Masahiro , Watanabe Akira , Yamanaka Shinya , Takahashi Kazutoshi 
Published: August 2014

Significance
In this study, we found that human endogenous retoriviruses type-H (HERV-Hs) are transiently hyperactivated during reprogramming toward induced pluripotent stem cells (iPSCs) and play important roles in this process. However, when reprogramming is complete and cells acquire full pluripotency, HERV-H activity should decrease to levels comparable with those in embryonic stem cells because failure to resilence this activity leads to the differentiation-defective phenotype in neural lineage. We also found that during reprogramming, reprogramming factors, including POU class 5 homeobox 1 (OCT3/4), sex determining region Y-box 2 (SOX2), and Krüppel-like factor 4 (KLF4) (OSK) bind to and activate long-terminal repeats of HERV-Hs. KLF4 possibly precludes Tripartite motif containing 28 and recruits not only OCT3/4 and SOX2, but also E1A binding protein p300 (p300) histone acethyltransferase on HERV-H loci. Therefore, OKSM-induced HERV-H activation constitutes an unanticipated and critical mechanism for iPSC formation.
Tracking global changes induced in the CD4 T-cell receptor repertoire by immunization with a complex antigen using short stretches of CDR3 protein sequence
Authors: Thomas Niclas , Best Katharine , Cinelli Mattia , Reich-Zeliger Shlomit , Gal Hilah , Shifrut Eric , Madi Asaf , Friedman Nir , Shawe-Taylor John , Chain Benny 
Published: August 2014

Abstract
Motivation: The clonal theory of adaptive immunity proposes that immunological responses are encoded by increases in the frequency of lymphocytes carrying antigen-specific receptors. In this study, we measure the frequency of different T-cell receptors (TcR) in CD4 + T cell populations of mice immunized with a complex antigen, killed Mycobacterium tuberculosis , using high throughput parallel sequencing of the TcR β chain. Our initial hypothesis that immunization would induce repertoire convergence proved to be incorrect, and therefore an alternative approach was developed that allows accurate stratification of TcR repertoires and provides novel insights into the nature of CD4 + T-cell receptor recognition.
Results: To track the changes induced by immunization within this heterogeneous repertoire, the sequence data were classified by counting the frequency of different clusters of short (3 or 4) continuous stretches of amino acids within the antigen binding complementarity determining region 3 (CDR3) repertoire of different mice. Both unsupervised (hierarchical clustering) and supervised (support vector machine) analyses of these different distributions of sequence clusters differentiated between immunized and unimmunized mice with 100% efficiency. The CD4 + TcR repertoires of mice 5 and 14 days postimmunization were clearly different from that of unimmunized mice but were not distinguishable from each other. However, the repertoires of mice 60 days postimmunization were distinct both from naive mice and the day 5/14 animals. Our results reinforce the remarkable diversity of the TcR repertoire, resulting in many diverse private TcRs contributing to the T-cell response even in genetically identical mice responding to the same antigen. However, specific motifs defined by short stretches of amino acids within the CDR3 region may determine TcR specificity and define a new approach to TcR sequence classification.
Availability and implementation: The analysis was implemented in R and Python, and source code can be found in Supplementary Data .
Contact: b.chain@ucl.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
DNAApp: a mobile application for sequencing data analysis
Authors: Nguyen Phi-Vu , Verma Chandra Shekhar , Gan Samuel Ken-En 
Published: August 2014

Abstract
Summary: There have been numerous applications developed for decoding and visualization of ab1 DNA sequencing files for Windows and MAC platforms, yet none exists for the increasingly popular smartphone operating systems. The ability to decode sequencing files cannot easily be carried out using browser accessed Web tools. To overcome this hurdle, we have developed a new native app called DNAApp that can decode and display ab1 sequencing file on Android and iOS. In addition to in-built analysis tools such as reverse complementation, protein translation and searching for specific sequences, we have incorporated convenient functions that would facilitate the harnessing of online Web tools for a full range of analysis. Given the high usage of Android/iOS tablets and smartphones, such bioinformatics apps would raise productivity and facilitate the high demand for analyzing sequencing data in biomedical research.
Availability and implementation: The Android version of DNAApp is available in Google Play Store as ‘DNAApp’, and the iOS version is available in the App Store. More details on the app can be found at www.facebook.com/APDLab ; www.bii.a-star.edu.sg/research/trd/apd.php
The DNAApp user guide is available at http://tinyurl.com/DNAAppuser , and a video tutorial is available on Google Play Store and App Store, as well as on the Facebook page.
Contact: samuelg@bii.a-star.edu.sg
Thresher: an improved algorithm for peak height thresholding of microbial community profiles
Authors: Starke Verena , Steele Andrew 
Published: August 2014

AbstractMotivation: This article presents Thresher, an improved technique for finding peak height thresholds for automated rRNA intergenic spacer analysis (ARISA) profiles. We argue that thresholds must be sample dependent, taking community richness into account. In most previous fragment analyses, a common threshold is applied to all samples simultaneously, ignoring richness variations among samples and thereby compromising cross-sample comparison. Our technique solves this problem, and at the same time provides a robust method for outlier rejection, selecting for removal any replicate pairs that are not valid replicates.Results : Thresholds are calculated individually for each replicate in a pair, and separately for each sample. The thresholds are selected to be the ones that minimize the dissimilarity between the replicates after thresholding. If a choice of threshold results in the two replicates in a pair failing a quantitative test of similarity, either that threshold or that sample must be rejected. We compare thresholded ARISA results with sequencing results, and demonstrate that the Thresher algorithm outperforms conventional thresholding techniques.Availability and Implementation : The software is implemented in R, and the code is available at http://verenastarke.wordpress.com or by contacting the author.Contact : vstarke@ciw.edu or http://verenastarke.wordpress.comSupplementary information: Supplementary data are available at Bioinformatics online.
A method for calculating a meta-analytical prior for the natural mortality rate using multiple life history correlates
Authors: Hamel Owen S. 
Published: August 2014

Abstract
The natural mortality rate M is an important parameter for understanding population dynamics, and is extraordinarily difficult to estimate for many fish species. The uncertainty associated with M translates into increased uncertainty in fishery stock assessments. Estimation of M within a stock assessment model is complicated by its confounding with other life history and fishery parameters which are also uncertain, some of which are typically estimated within the model. Ageing error and variation in growth, which may not be fully modelled, can also affect estimation of M, as can various assumptions, including the form of the stock–recruitment function (e.g. Beverton–Holt, Ricker) and the level of compensation (or steepness), which may be fixed (or limited by a prior) in the model. To avoid these difficulties, stock assessors often assume point estimates for M derived from meta-analytical relationships between M and more easily measured life history characteristics, such as growth rate or longevity. However, these relationships depend on estimates of M for a great number of species, and those estimates are also subject to errors and biases (as are, to a lesser extent, the other life history parameters). Therefore, at the very least, some measure of uncertainty in M should be calculated and used for evaluating uncertainty in stock assessments and management strategy evaluations. Given error-free data on M and the covariate(s) for a meta-analysis, prediction intervals would provide the appropriate measure of uncertainty in M. In contrast, if the relationship between the covariate(s) and M is exact and the only error is in the estimates of M used for the meta-analysis, confidence intervals would appropriate. Using multiple published meta-analyses of M’s relationship with various life history correlates, and beginning with the uncertainty interval calculations, I develop a method for creating combined priors for M for use in stock assessment.
ERAP1 functions override the intrinsic selection of specific antigens as immunodominant peptides, thereby altering the potency of antigen-specific cytolytic and effector memory T-cell responses
Authors: Rastall David P. W. , Aldhamen Yasser A. , Seregin Sergey S. , Godbehere Sarah , Amalfitano Andrea 
Published: August 2014

Abstract
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a critical component of the adaptive immune system that has been shown to increase or decrease the presentation of specific peptides on MHC class I molecules. Here, we have demonstrated that ERAP1 functions are not only important during the presentation of antigen-derived peptides, but these functions can also completely change which antigen-derived peptides ultimately become selected as immunodominant T-cell epitopes. Our results suggest that ERAP1 may do this by destroying epitopes that would otherwise become immunodominant in the absence of adequate ERAP1 functionality. We further establish that ERAP1-mediated influences on T-cell functions are both qualitative and quantitative, by demonstrating that loss of ERAP1 function redirects CTL killing toward a different set of antigen-derived epitopes and increases the percent of antigen-specific memory T cells elicited by antigen exposure. As a result, our studies suggest that normal ERAP1 activity can act to suppress the numbers of T effector memory cells that respond to a given antigen. This unique finding may shed light on why certain ERAP1 single nucleotide polymorphisms are associated with several autoimmune diseases, for example, by significantly altering the robustness and quality of CD8+ T-cell memory responses to antigen-derived peptides.
Responses of macrophages to the danger signals released from necrotic cells
Authors: Kimura Toshifumi , Kobayashi Shuhei , Hanihara-Tatsuzawa Fumito , Sayama Aoi , MaruYama Takashi , Muta Tatsushi 
Published: August 2014

Abstract
The immune system maintains homeostasis by recognizing and responding to cell death caused by various stresses. The immune response is considered to be elicited by ‘danger signals’ released from necrotic cells. However, the identity of the danger signals remains elusive. In this study, we focused on the expression of chemokines by macrophages stimulated with necrotic cells. In mouse bone-marrow-derived macrophages, the chemokine monocyte chemoattractant protein (MCP)-3 was induced at both the mRNA and protein levels in response to heat-killed murine cells. The induction of MCP-3 was also observed in MyD88-deficient macrophages, indicating that Toll-like receptors and the IL-1 receptor are not involved in this response. Consistent with this observation, the activation of NF-κB was not detected in RAW264.7 macrophages stimulated with necrotic cells. Treatments with proteinase K, DNaseI or RNaseA did not affect the ‘stimulating activity’ of necrotic cells. In contrast, treatment with apyrase, which removes phosphates from nucleoside tri- and di-phosphates, abolished the inducing activity. Purified UDP at 30 µM concentration elicited similar induction of MCP-3 in RAW264.7 macrophages. Small interfering RNA-mediated knock-down of the UDP receptor P2Y6 in RAW264.7 cells significantly reduced the induction of MCP-3 in response to necrotic cells, but not its induction by lipopolysaccharide. Furthermore, ectopic expression of the P2Y6 receptor in HEK293 cells conferred responsiveness to necrotic cells. These results suggest that UDP released by necrotic cells plays a critical role as an endogenous danger signal and that P2Y6 is required for the induction of MCP-3 in response to necrotic cells.
REVIEW: Properties of Cereal Brans: A Review
Authors: Chinma Chiemela Enyinnaya , Ramakrishnan Yogeshini , Ilowefah Muna , Hanis‐Syazwani Mat , Muhammad Kharidah 
Published: August 2014

ABSTRACTCereal brans are functional ingredients with high nutritive value and enormous health properties. Cereal brans have not been fully utilized in food systems despite their health benefits. This review presents an overview on the physical, chemical, microbiological, functional, and sensory properties of cereal brans for possible comparisons and selection to enhance the utilization of this underutilized milling fraction.
Associations Between Body Mass and Revision Surgical Outcomes in Adult Scoliosis
Authors: Fu Lingjie , Chang Michael S. , Crandall Dennis G. , Revella Jan 
Published: August 2014

Study Design:
Retrospective cohort study.

Objective:
To determine whether an association exists between high body mass index (BMI>25 kg/m2) and surgical outcomes in revision adult scoliosis patients.

Summary of Background Data:
Obesity is thought to be associated with increased surgical complications and inferior clinical outcomes in adults. There are no studies analyzing the effect of obesity on surgical outcomes in revision patients for adult scoliosis.

Methods:
Forty-five consecutive revision adult scoliosis patients (35 women and 10 men; mean age, 62.7±9.3 y) with a minimum follow-up of 2 years were included in this study. Patients were divided into 2 groups according to BMI: overweight (BMI≥25 kg/m2, n=27) and nonoverweight (<25 kg/m2, n=18). Radiographic measures, Oswestry Disability Index (ODI), Visual Analog Scale (VAS), as well as comorbidities and complications were reviewed and compared at preoperative and 2-year follow-up.

Results:
No significant differences in surgical methods, complication rates, or radiographic measures were found between the 2 groups except for the greater preoperative and final follow-up thoracic kyphosis in the overweight group (P<0.05). A higher comorbidity rate of circulatory disorders (33.3% vs. 0%, P=0.018) and diabetes (25.9% vs. 0%, P=0.053) was observed in the overweight group, as well as a higher preoperative VAS score (7.1±1.7 vs. 5.2±2.9, P=0.031). At 2-year follow-up, VAS and ODI improvements for both groups showed significant and similar improvement from preoperative (P<0.01).

Conclusions:
Overweight revision adult scoliosis patients had higher thoracic kyphosis and more significant preoperative pain compared with normal-weight individuals. Overweight patients also had significantly higher rates of medical comorbidities. However, BMI did not affect the functional outcome of surgical correction or perioperative complication rates. Overweight patients benefited from surgery just as much as nonoverweight patients at 2-year follow-up.
Auxin Perception Is Required for Arbuscule Development in Arbuscular Mycorrhizal Symbiosis
Authors: Etemadi Mohammad , Gutjahr Caroline , Couzigou Jean-Malo , Zouine Mohamed , Lauressergues Dominique , Timmers Antonius , Audran Corinne , Bouzayen Mondher , Bécard Guillaume , Combier Jean-Philippe 
Published: August 2014

Abstract
Most land plant species live in symbiosis with arbuscular mycorrhizal fungi. These fungi differentiate essential functional structures called arbuscules in root cortical cells from which mineral nutrients are released to the plant. We investigated the role of microRNA393 (miR393), an miRNA that targets several auxin receptors, in arbuscular mycorrhizal root colonization. Expression of the precursors of the miR393 was down-regulated during mycorrhization in three different plant species: Solanum lycopersicum, Medicago truncatula, and Oryza sativa. Treatment of S. lycopersicum, M. truncatula, and O. sativa roots with concentrations of synthetic auxin analogs that did not affect root development stimulated mycorrhization, particularly arbuscule formation. DR5-GUS, a reporter for auxin response, was preferentially expressed in root cells containing arbuscules. Finally, overexpression of miR393 in root tissues resulted in down-regulation of auxin receptor genes (transport inhibitor response1 and auxin-related F box) and underdeveloped arbuscules in all three plant species. These results support the conclusion that miR393 is a negative regulator of arbuscule formation by hampering auxin perception in arbuscule-containing cells.
The role of predation and food limitation on claims for compensation, reindeer demography and population dynamics
Authors: Tveraa Torkild , Stien Audun , Brøseth Henrik , Yoccoz Nigel G. 
Published: August 2014

Summary

A major challenge in biodiversity conservation is to facilitate viable populations of large apex predators in ecosystems where they were recently driven to ecological extinction due to resource conflict with humans.

Monetary compensation for losses of livestock due to predation is currently a key instrument to encourage human–carnivore coexistence. However, a lack of quantitative estimates of livestock losses due to predation leads to disagreement over the practice of compensation payments. This disagreement sustains the human–carnivore conflict.

The level of depredation on year‐round, free‐ranging, semi‐domestic reindeer by large carnivores in Fennoscandia has been widely debated over several decades. In Norway, the reindeer herders claim that lynx and wolverine cause losses of tens of thousands of animals annually and cause negative population growth in herds. Conversely, previous research has suggested that monetary predator compensation can result in positive population growth in the husbandry, with cascading negative effects of high grazer densities on the biodiversity in tundra ecosystems.

We utilized a long‐term, large‐scale data set to estimate the relative importance of lynx and wolverine predation and density‐dependent and climatic food limitation on claims for losses, recruitment and population growth rates in Norwegian reindeer husbandry.

Claims of losses increased with increasing predator densities, but with no detectable effect on population growth rates. Density‐dependent and climatic effects on claims of losses, recruitment and population growth rates were much stronger than the effects of variation in lynx and wolverine densities.

Synthesis and applications. Our analysis provides a quantitative basis for predator compensation and estimation of the costs of reintroducing lynx and wolverine in areas with free‐ranging semi‐domestic reindeer. We outline a potential path for conflict management which involves adaptive monitoring programmes, open access to data, herder involvement and development of management strategy evaluation (MSE) models to disentangle complex responses including multiple stakeholders and individual harvester decisions.