bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide RNAi screen identifies the Parkinson disease GWAS risk locusSREBF1as a regulator of mitophagy
Authors: Ivatt Rachael M. , Sanchez-Martinez Alvaro , Godena Vinay K. , Brown Stephen , Ziviani Elena , Whitworth Alexander J. 
Published: May 2014

SignificanceThis study presents the first results, to our knowledge, of a whole-genome RNAi screen to identify factors that promote Parkin-mediated mitophagy, which have been validated for conservation across species. Top hits comprise several components of thesterol regulatory element binding transcription factor(SREBF) lipogenesis pathway, and we show that provision of exogenous lipids can promote the mitophagy pathway. BecauseSREBF1has been identified as a risk locus for sporadic Parkinson disease (PD) through genome-wide association studies, the identification ofSREBF1in our screen provides evidence for mechanistic insight into the pathogenesis of sporadic PD. Thus, our functional studies provide the first insight, to our knowledge, into why the master regulator for lipogenesis,SREBF1, may contribute to sporadic PD and further underscore the impact of dysfunctional mitophagy on pathogenesis.
Hedgehog signaling mediates adaptive variation in a dynamic functional system in the cichlid feeding apparatus
Authors: Hu Yinan , Albertson R. Craig 
Published: May 2014

Significance
Although evolutionary developmental biology has traditionally focused on linking genes to simple shifts in morphology, adaptation to new environments involves divergence in resource use, which often involves variation in complex functional systems. Thus, for evo-devo research to explain broad evolutionary processes, we must examine more dynamic traits within this context. Here we combine traditional quantitative trait locus mapping, population genetics, and experimental embryology to show how differences in gene expression during larval development lead to adaptive morphological variation in adults. By functional modeling of the skull, we show further how such anatomical shifts in response to genetic variation predict discrete differences in feeding mechanics in African cichlids.
Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses
Authors: Gideons Erinn S. , Kavalali Ege T. , Monteggia Lisa M. 
Published: May 2014

Significance
Ketamine is an NMDA receptor (NMDAR) antagonist that elicits rapid antidepressant responses in patients with treatment-resistant depression. However, ketamine can also produce adverse side effects, which raised interest in whether the clinically tolerated NMDAR antagonist memantine can elicit similar fast antidepressant action. Rather surprisingly, clinical data have shown that memantine does not trigger rapid antidepressant effects for reasons that have yet to be elucidated. Here, we reconstitute the ketamine and memantine clinical findings in animal models and, combined with the analysis of synaptic function and subsequent intracellular signaling, demonstrate significant differences between the efficacies of ketamine and memantine on NMDAR-mediated neurotransmission and downstream intracellular signaling. These findings suggest a potential mechanism to explain the earlier clinical observations.
Molecular determinants of Hv1 proton channel inhibition by guanidine derivatives
Authors: Hong Liang , Kim Iris H. , Tombola Francesco 
Published: May 2014

Significance
The activity of the Hv1 proton channel has been shown to exacerbate neuronal death after cerebral hypoxia and promote tumor formation by highly metastatic breast cancer cells. Compounds able to inhibit excessive Hv1 activity could find applications as neuroprotective agents in ischemic stroke or anticancer drugs. In this work, we investigate how guanidine derivatives, like 2-guanidinobenzimidazole (2GBI), interact with Hv1 and inhibit proton conduction. We identify the binding site for 2GBI and determine the most likely orientation of the inhibitor inside the channel. We also show that a simple modification of 2GBI eliminates the requirement for the inhibitor to have direct access to the intracellular side of the channel to block the proton current.
Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis
Authors: Triviai Ioanna , Ziegler Marion , Bergholz Ulla , Oler Andrew J. , Stübig Thomas , Prassolov Vladimir , Fehse Boris , Kozak Christine A. , Kröger Nicolaus , Stocking Carol 
Published: May 2014

Significance
Immunodeficient mice are important tools to define stem cells that drive malignancies (cancers). Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm that can progress to malignant leukemia. In a study to define PMF stem cells in transplanted mice, we observed a high incidence of mouse leukemia. We show that endogenous retrovirus (ERV), whose replication is unrestricted in immunodeficient mice, are pathogenic in the PMF-xenograft microenvironment, likely because of increased numbers of proliferating mouse cells stimulated by PMF-derived cells. Proliferating cells are targets of retroviral transformation and spontaneous mutations, and thus susceptible to leukemia induction. These results substantiate the importance of paracrine mechanisms in PMF disease and expose the presence of replicating ERVs in mice commonly used to model human diseases.
Loss of the death receptor CD95 (Fas) expression by dendritic cells protects from a chronic viral infection
Authors: Varanasi Vineeth , Khan Aly Azeem , Chervonsky Alexander V. 
Published: May 2014

Significance
Chronic viral infections evolved to avoid destruction by the immune system. Lymphocytic choriomeningitis virus (LCMV) clone 13, which causes a chronic infection, induces expression of Fas death receptor protein by antigen-presenting cells, such as dendritic cells (DCs). When Fas is ligated by Fas ligand expressed by T cells, DCs die. This event blocks further T-cell activation. To break this mechanism and to sustain antiviral T-cell responses, we used mice that lost Fas from DCs. These animals cleared the infection, whereas Fas-sufficient mice did not. Moreover, a transfer of Fas-negative DCs into infected mice supported the clearance of LCMV infection. Thus, we suggest a novel strategy for stimulation of T cells to achieve the clearance of persistent viruses in infected animals and humans.
Father's brain is sensitive to childcare experiences
Authors: Abraham Eyal , Hendler Talma , Shapira-Lichter Irit , Kanat-Maymon Yaniv , Zagoory-Sharon Orna , Feldman Ruth 
Published: May 2014

Significance
Brain, oxytocin, and parenting behavior were measured in primary-caregiving mothers, secondary-caregiving fathers, and primary-caregiving homosexual fathers raising infants without maternal involvement. Parenting integrated functioning of two neural networks: subcortical-paralimbic structures implicated in emotional processing and cortical circuits involved in social understanding. Mothers showed greater activation in the emotional processing network and fathers in the socio-cognitive circuits, which were differentially linked with oxytocin and behavior. Primary-caregiving fathers exhibited high amygdala activation similar to mothers, alongside high superior temporal sulcus (STS) activation comparable to fathers, and functional connectivity between amygdala and STS. Among all fathers, time spent in childcare correlated with amygdala-STS connectivity. Findings describe mechanisms of brain malleability with caregiving experiences in human fathers.
Structural and functional characterization of a conserved pair of bacterial cellulose-oxidizing lytic polysaccharide monooxygenases
Authors: Forsberg Zarah , Mackenzie Alasdair K. , Sørlie Morten , Røhr Åsmund K. , Helland Ronny , Arvai Andrew S. , Vaaje-Kolstad Gustav , Eijsink Vincent G. H. 
Published: May 2014

Significance
The discovery of lytic polysaccharide monooxygenases (LPMOs) has profoundly changed our understanding of the enzymatic conversion of recalcitrant polysaccharides, such as cellulose. Although in-depth studies of fungal cellulolytic LPMOs have been reported, the structures and functions of their bacterial counterparts with no detectable sequence similarity remain largely elusive. We present the structures of a conserved pair of bacterial cellulose-active LPMOs supplemented with extensive functional characterization. The structural data allow a thorough comparative assessment of fungal and bacterial LPMOs, providing insight into the structural basis of substrate specificity and the oxidative mechanism (C1/C4 oxidation). Importantly, we show that this LPMO pair acts synergistically when degrading cellulose, a finding that may help explain the occurrence of multiple LPMOs in a single microbe.
PipX, the coactivator of NtcA, is a global regulator in cyanobacteria
Authors: Espinosa Javier , Rodríguez-Mateos Francisco , Salinas Paloma , Lanza Val F. , Dixon Ray , de la Cruz Fernando , Contreras Asuncion 
Published: May 2014

SignificancePII, a signal transduction protein involved in nitrogen control in bacteria and plants, and NtcA, the transcriptional nitrogen regulator of cyanobacteria, can form complexes with PIIinteracting protein X (PipX). We demonstrate by a combination of genetic, transcriptomic, and multivariate analyses that PipX is involved in a much wider interaction network affecting nitrogen assimilation, translation, and photosynthesis. Two groups of genes differentially regulated bypipXprovided further insights into the function of NtcA–PipX complexes and an improved definition of the consensus NtcA binding motif. The other four groups suggested the involvement of PipX in NtcA-independent regulatory pathways. Our results pave the way to uncover new regulatory interactions and mechanisms in the control of gene expression in cyanobacteria.
Scalable production of mechanically tunable block polymers from sugar
Authors: Xiong Mingyong , Schneiderman Deborah K. , Bates Frank S. , Hillmyer Marc A. , Zhang Kechun 
Published: May 2014

Significance
In recent years there has been extensive research toward the development of sustainable polymeric materials. However, environmentally benign, bioderived polymers still represent a woefully small fraction of plastics and elastomers on the market today. To displace the widely useful oil-based polymers that currently dominate the industry, a bioderived synthetic polymer must be both cost and performance competitive. In this paper we address this challenge by combining the efficient bioproduction of β-methyl-δ-valerolactone with controlled polymerization techniques to produce economically viable block polymer materials with mechanical properties akin to commercially available thermoplastics and elastomers.
Nonequilibrium dynamics and ultraslow relaxation of confined DNA during viral packaging
Authors: Berndsen Zachary T. , Keller Nicholas , Grimes Shelley , Jardine Paul J. , Smith Douglas E. 
Published: May 2014

Significance
The high-density packaging of DNA in many viruses is a process that requires the action of powerful molecular motor complexes. Besides being a key step in viral assembly, DNA packaging is a general model for understanding the physics of tightly confined polymers. A fundamental question raised in the literature is whether packaging can be modeled as a quasistatic thermodynamic process, in which the DNA relaxes quickly to equilibrium, or whether it involves nonequilibrium dynamics. In this study, we show that the confined DNA undergoes nonequilibrium dynamics with an extremely long relaxation time and this slows the motor, causes significant heterogeneity in packaging rates of individual viruses, and causes frequent pausing in DNA translocation by the motor.
IL-15.IL-15Rα complex shedding followingtrans-presentation is essential for the survival of IL-15 responding NK and T cells
Authors: Tamzalit Fella , Barbieux Isabelle , Plet Ariane , Heim Julie , Nedellec Steven , Morisseau Sébastien , Jacques Yannick , Mortier Erwan 
Published: May 2014

SignificanceInterleukin (IL)-15 plays a role in diverse functions of cells involved in the protection against cancer and infections. IL-15 signal is delivered via a mechanism calledtrans-presentation, in which IL-15 expressed at the surface of presenting cells via the membrane-bound IL-15Rα chain, is presented during the interaction with responding cells expressing the transducing receptor. IL-15Rα can be cleaved from the surface of presenting cells and we wondered whether such a mechanism could participate in the regulation of IL-15trans-presentation. By generating an uncleavable form of IL-15Rα, we found an unprecedented cytokine pathway in which the IL-15.IL-15Rα complex cleaved from presenting cells allows responding cells to internalize, store and use IL-15.IL-15Rα complex for their own proliferation and survival.
Accounting for a mirror-image conformation as a subtle effect in protein folding
Authors: Kachlishvili Khatuna , Maisuradze Gia G. , Martin Osvaldo A. , Liwo Adam , Vila Jorge A. , Scheraga Harold A. 
Published: May 2014

Significance
Numerous diseases, including neurodegenerative diseases, are caused by misfolding of proteins; therefore, understanding the mechanism by which a protein folds to its native conformation is one of the most important problems of biophysics. This task becomes more complicated for proteins with a high degree of symmetry that, in addition to the native structure, allows the existence of another, energetically competitive conformation with the native one, a native-like “mirror-image” structure, which has not yet been detected experimentally. By investigating one of the representatives of such symmetrical proteins, reasons for formation of the mirror-image conformation are provided.
Pivotal role for the ubiquitin Y59-E51 loop in lysine 48 polyubiquitination
Authors: Chong Robert A. , Wu Kenneth , Spratt Donald E. , Yang Yingying , Lee Chan , Nayak Jaladhi , Xu Ming , Elkholi Rana , Tappin Inger , Li Jessica , Hurwitz Jerard , Brown Brian D. , Chipuk Jerry Edward , Chen Zhijian J. , Sanchez Roberto , Shaw Gary S. , Huang Lan , Pan Zhen-Qiang 
Published: May 2014

Significance
Our identification and characterization of the ubiquitin (Ub) Y59-E51 loop have uncovered a pivotal determinant for lysine 48 (K48) linkage-specific Ub chain synthesis catalyzed by Cdc34 E2 Ub-conjugating enzyme. The Ub Y59-E51 loop appears to anchor a Cdc34 E2-engaging zone, allowing the landing of E2 and enabling it to gain access to the receptor K48. These findings will provide a strong starting point for future biochemical and structural studies aiming to elucidate the detailed interactions between Ub and E2/E3 enzymes that produce the K48 linkage. In addition, the observed global impact of the Ub Y59-E51 loop in cellular K48-polyubiquitination and apoptosis will stimulate investigations for exploring new therapeutic strategies to induce cell killing through pharmacological perturbation of K48-polyubiquitination.
Identification of interacting proteins for calcium-dependent protein kinase 8 by a novel screening system based on bimolecular fluorescence complementation
Authors: Kamimura Mayu , Han Yulong , Kito Nobuki , Che Fang-Sik 
Published: May 2014

Abstract
Protein kinases are key regulators of cell function that constitute one of the largest and most functionally diverse gene families. We developed a novel assay system, based on the bimolecular fluorescence complementation (BiFC) technique in Escherichia coli, for detecting transient interactions such as those between kinases and their substrates. This system detected the interaction between OsMEK1 and its direct target OsMAP1. By contrast, BiFC fluorescence was not observed when OsMAP2 or OsMAP3, which are not substrates of OsMEK1, were used as prey proteins. We also screened for interacting proteins of calcium-dependent protein kinase 8 (OsCPK8), a regulator of plant immune responses, and identified three proteins as interacting molecules of OsCPK8. The interaction between OsCPK8 and two of these proteins (ARF-GEF and peptidyl prolyl isomerase) was confirmed in rice cells by means of BiFC technology. These results indicate that our new assay system has the potential to screen for protein kinase target molecules.
Phylogenetic relationship of Paenibacillus species based on putative replication origin regions and analysis of an yheCD-like sequence found in this region
Authors: Iiyama Kazuhiro , Otao Masahiro , Mori Kazuki , Mon Hiroaki , Lee Jae Man , Kusakabe Takahiro , Tashiro Kousuke , Asano Shin-Ichiro , Yasunaga-Aoki Chisa 
Published: May 2014

Abstract
To determine the phylogenetic relationship among Paenibacillus species, putative replication origin regions were compared. In the rsmG-gyrA region, gene arrangements in Paenibacillus species were identical to those of Bacillus species, with the exception of an open reading frame (orf14) positioned between gyrB and gyrA, which was observed only in Paenibacillus species. The orf14 product was homologous to the endospore-associated proteins YheC and YheD of Bacillus subtilis. Phylogenetic analysis based on the YheCD proteins suggested that Orf14 could be categorized into the YheC group. In the Paenibacillus genome, DnaA box clusters were found in rpmH-dnaA and dnaA-dnaN intergenic regions, known as box regions C and R, respectively; this localization was similar to that observed in B. halodurans. A phylogenetic tree based on the nucleotide sequences of the whole replication origin regions suggested that P. popilliae, P. thiaminolyticus, and P. dendritiformis are closely related species.
Thiol modification by bioactivated polyphenols and its potential role in skin inflammation
Authors: Nakamura Yoshimasa , Ishii Takeshi , Abe Naomi , Murata Yoshiyuki 
Published: May 2014

Abstract
In the present study, we evaluated the modifying behavior of simple phenolic compounds on the sulfhydryl groups of glutathione and proteins. The catechol-type polyphenols, including protocatechuic acid, but neither the monophenols nor O-methylated catechol, can modify the sulfhydryl groups in a phenol oxidase-dependent manner. The possible involvement of polyphenol bioactivation in the enhancement of skin inflammation was also suggested.
Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats
Authors: Kobayashi Misato , Hoshinaga Yukiko , Miura Natsuko , Tokuda Yuki , Shigeoka Shigeru , Murai Atsushi , Horio Fumihiko 
Published: May 2014

Abstract
The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.
Dynamic changes in genes related to glucose uptake and utilization during pig skeletal and cardiac muscle development
Authors: Guo Yanqin , Jin Long , Wang Fengjiao , He Mengnan , Liu Rui , Li Mingzhou , Shuai Surong 
Published: May 2014

Abstract
Skeletal and cardiac muscle have important roles in glucose uptake and utilization. However, changes in expression of protein coding genes and miRNAs that participate in glucose metabolism during development are not fully understood. In this study, we investigated the expression of genes related to glucose metabolism during muscle development. We found an age-dependent increase in gene expression in cardiac muscle, with enrichment in heart development- and energy-related metabolic processes. A subset of genes that were up-regulated until 30 or 180 days postnatally, and then down-regulated in psoas major muscle was significantly enriched in mitochondrial oxidative-related processes, while genes that up-regulated in longissimus doris muscle was significantly enriched in glycolysis-related processes. Meanwhile, expression of energy-related microRNAs decreased with increasing age. In addition, we investigated the correlation between microRNAs and mRNAs in three muscle types across different stages of development and found many potential microRNA–mRNA pairs involved in regulating glucose metabolism.
CWig: compressed representation of Wiggle/BedGraph format
Authors: Huy Hoang Do , Sung Wing-Kin 
Published: May 2014

Abstract
Motivation: BigWig, a format to represent read density data, is one of the most popular data types. They can represent the peak intensity in ChIP-seq, the transcript expression in RNA-seq, the copy number variation in whole genome sequencing, etc. UCSC Encode project uses the bigWig format heavily for storage and visualization. Of 5.2 TB Encode hg19 database, 1.6 TB (31% of the total space) is used to store bigWig files. BigWig format not only saves a lot of space but also supports fast queries that are crucial for interactive analysis and browsing. In our benchmark, bigWig often has similar size to the gzipped raw data, while is still able to support ∼5000 random queries per second.
Results: Although bigWig is good enough at the moment, both storage space and query time are expected to become limited when sequencing gets cheaper. This article describes a new method to store density data named CWig. The format uses on average one-third of the size of existing bigWig files and improves random query speed up to 100 times.
Availability and implementation: http://genome.ddns.comp.nus.edu.sg/∼cwig
Contact: ksung@comp.nus.edu.sg
Supplementary information: Supplementary data are available at Bioinformatics online.
MIPgen: optimized modeling and design of molecular inversion probes for targeted resequencing
Authors: Boyle Evan A. , O’Roak Brian J. , Martin Beth K. , Kumar Akash , Shendure Jay 
Published: May 2014

Abstract
Summary Molecular inversion probes (MIPs) enable cost-effective multiplex targeted gene resequencing in large cohorts. However, the design of individual MIPs is a critical parameter governing the performance of this technology with respect to capture uniformity and specificity. MIPgen is a user-friendly package that simplifies the process of designing custom MIP assays to arbitrary targets. New logistic and SVM-derived models enable in silico predictions of assay success, and assay redesign exhibits improved coverage uniformity relative to previous methods, which in turn improves the utility of MIPs for cost-effective targeted sequencing for candidate gene validation and for diagnostic sequencing in a clinical setting.
Availability and implementation: MIPgen is implemented in C++. Source code and accompanying Python scripts are available at http://shendurelab.github.io/MIPGEN/ .
Contact: shendure@uw.edu or boylee@uw.edu
Supplementary information: Supplementary data are available at Bioinformatics online.