bluuebunny/crossref_metadata_2025_split huggingface dataset:
Honey bee microRNAs respond to infection by the microsporidian parasite Nosema ceranae
Authors: Huang Qiang , Chen Yanping , Wang Rui Wu , Schwarz Ryan S. , Evans Jay D. 
Published: December 2015

AbstractIn order to study the effects ofNosema ceranaeinfection on honey bee microRNA (miRNA) expression, we deep-sequenced honey bee miRNAs daily across a full 6-day parasite reproduction cycle. Seventeen miRNAs were differentially expressed in honey bees infected byN. ceranaethat potentially target over 400 genes predicted to primarily involve ion binding, signaling, the nucleus, transmembrane transport and DNA binding. Based on Enzyme Code analysis, nine biological pathways were identified by screening target genes against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, seven of which involved metabolism. Our results suggest that differentially expressed miRNAs regulate metabolism related genes of host honey bees in response toN. ceranaeinfection.
Transcriptomes reveal the genetic mechanisms underlying ionic regulatory adaptations to salt in the crab-eating frog
Authors: Shao Yong , Wang Li-Jun , Zhong Li , Hong Mei-Ling , Chen Hong-Man , Murphy Robert W. , Wu Dong-Dong , Zhang Ya-Ping , Che Jing 
Published: December 2015

AbstractThe crab-eating frog,Fejervarya cancrivora, is the only frog that lives near seas. It tolerates increased environmental concentrations of sodium, chloride and potassium partly by raising ion and urea levels in its blood plasma. The molecular mechanism of the adaptation remains rarely documented. Herein, we analyze transcriptomes of the crab-eating frog and its closely related saline-intolerant species,F. limnocharis, to explore the molecular basis of adaptations to such extreme environmental conditions. Analyses reveal the potential genetic mechanism underlying the adaptation to salinity for the crab-eating frog. Genes in categories associated with ion transport appear to have evolved rapidly inF. cancrivora. Both positively selected and differentially expressed genes exhibit enrichment in the GO category regulation of renal sodium excretion. In this category, the positively selected sites ofANPEPandAVPR2encode CD13 and V2 receptors, respectively; they fall precisely on conserved domains. More differentially expressed rapidly evolved genes occur in the kidney ofF. cancrivorathan inF. limnocharis. Four genes involved in the regulation of body fluid levels show signs of positive selection and increased expression. Significant up-regulation occurs in several genes ofF. cancrivoraassociated with renin-angiotensin system and aldosterone-regulated sodium reabsorption pathways, which relate to osmotic regulation.
Delivery of miR-34a by chitosan/PLGA nanoplexes for the anticancer treatment of multiple myeloma
Authors: Cosco Donato , Cilurzo Felisa , Maiuolo Jessica , Federico Cinzia , Di Martino Maria Teresa , Cristiano Maria Chiara , Tassone Pierfrancesco , Fresta Massimo , Paolino Donatella 
Published: December 2015

AbstractThe encapsulation of miR-34a into chitosan/PLGA nanoparticles in order to obtain nanoplexes useful for the modulation of the biopharmaceutical features of the active compound was studied. The nanoplexes were obtained through nanoprecipitation and were characterized by a mean diameter of ~160 nm, a good size distribution and a positive surface charge. The structure of the nanoparticles allowed a high level of entrapment efficiency of the miR-34a and provided protection of the genetic material from the effects of RNase. A high degree of transfection efficiency of the nanoplexes and a significant in vitro antitumor effect against multiple myeloma cells was demonstrated. The therapeutic properties of the nanoplexes were evaluated in vivo against human multiple myeloma xenografts in NOD-SCID mice. The systemic injection of miR-34a mimic-loaded nanoparticles significantly inhibited tumor growth and translated into improved survival of the laboratory mice. RT-PCR analysis carried out on retrieved tumors demonstrated the presence of a high concentration of miR-34a mimics. The integrity of the nanoplexes remained intact and no organ toxicity was observed in treated animals.
Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr−/− mouse model
Authors: Kuba Motoko , Matsuzaka Takashi , Matsumori Rie , Saito Ryo , Kaga Naoko , Taka Hikari , Ikehata Kei , Okada Naduki , Kikuchi Takuya , Ohno Hiroshi , Han Song-iee , Takeuchi Yoshinori , Kobayashi Kazuto , Iwasaki Hitoshi , Yatoh Shigeru , Suzuki Hiroaki , Sone Hirohito , Yahagi Naoya , Arakawa Yoji , Fujimura Tsutomu , Nakagawa Yoshimi , Yamada Nobuhiro , Shimano Hitoshi 
Published: December 2015

AbstractNonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can develop into liver cirrhosis and cancer. Elongation of very long chain fatty acids (ELOVL) family member 6 (Elovl6) is a microsomal enzyme that regulates the elongation of C12–16 saturated and monounsaturated fatty acids (FAs). We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition. Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH. In the present study, we further investigated the role of Elovl6 in the progression of lithogenic diet (LD)-induced steatohepatitis. We showed that the absence of Elovl6 suppresses hepatic lipid accumulation, plasma total cholesterol and total bile acid (BA) levels in LDL receptor-deficient (Ldlr−/−) mice challenged with a LD. The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder. These findings suggest that Elovl6-mediated changes in hepatic FA composition, especially oleic acid (C18:1n-9), control handling of hepatic cholesterol and BA, which protects against hepatotoxicity and steatohepatitis, but promotes gallstone formation in LD-fed Ldlr−/− mice.
An integrated network of Arabidopsis growth regulators and its use for gene prioritization
Authors: Sabaghian Ehsan , Drebert Zuzanna , Inzé Dirk , Saeys Yvan 
Published: December 2015

AbstractElucidating the molecular mechanisms that govern plant growth has been an important topic in plant research and current advances in large-scale data generation call for computational tools that efficiently combine these different data sources to generate novel hypotheses. In this work, we present a novel, integrated network that combines multiple large-scale data sources to characterize growth regulatory genes in Arabidopsis, one of the main plant model organisms. The contributions of this work are twofold: first, we characterized a set of carefully selected growth regulators with respect to their connectivity patterns in the integrated network, and, subsequently, we explored to which extent these connectivity patterns can be used to suggest new growth regulators. Using a large-scale comparative study, we designed new supervised machine learning methods to prioritize growth regulators. Our results show that these methods significantly improve current state-of-the-art prioritization techniques and are able to suggest meaningful new growth regulators. In addition, the integrated network is made available to the scientific community, providing a rich data source that will be useful for many biological processes, not necessarily restricted to plant growth.
Synchrotron FTIR micro-spectroscopy for structural analysis of Lewy bodies in the brain of Parkinson’s disease patients
Authors: Araki Katsuya , Yagi Naoto , Ikemoto Yuka , Yagi Hisashi , Choong Chi-Jing , Hayakawa Hideki , Beck Goichi , Sumi Hisae , Fujimura Harutoshi , Moriwaki Taro , Nagai Yoshitaka , Goto Yuji , Mochizuki Hideki 
Published: December 2015

AbstractLewy bodies (LBs), which mainly consist of α-synuclein (α-syn), are neuropathological hallmarks of patients with Parkinson’s disease (PD). The fine structure of LBs is unknown and LBs cannot be made artificially. Nevertheless, many studies have described fibrillisation using recombinant α-syn purified from E. coli. An extremely fundamental problem is whether the structure of LBs is the same as that of recombinant amyloid fibrils. Thus, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to analyse the fine structure of LBs in the brain of PD patients. Our results showed a shift in the infrared spectrum that indicates abundance of a β-sheet-rich structure in LBs. Also, 2D infrared mapping of LBs revealed that the content of the β-sheet structure is higher in the halo than in the core and the core contains a large amount of proteins and lipids.
Soluble CD109 binds TGF-β and antagonizes TGF-β signalling and responses
Authors: Li Carter , Hancock Mark A. , Sehgal Priyanka , Zhou Shufeng , Reinhardt Dieter P. , Philip Anie 
Published: December 2015

Transforming growth factor-β (TGF-β) is a multifunctional cytokine implicated in many diseases, including tissue fibrosis and cancer. TGF-β mediates diverse biological responses by signalling through type I and II TGF-β receptors (TβRI and TβRII). We have previously identified CD109, a glycosylphosphatidylinositol (GPI)-anchored protein, as a novel TGF-β co-receptor that negatively regulates TGF-β signalling and responses and demonstrated that membrane-anchored CD109 promotes TGF-β receptor degradation via a SMAD7/Smurf2-mediated mechanism. To determine whether CD109 released from the cell surface (soluble CD109 or sCD109) also acts as a TGF-β antagonist, we determined the efficacy of recombinant sCD109 to interact with TGF-β and inhibit TGF-β signalling and responses. Our results demonstrate that sCD109 binds TGF-β with high affinity as determined by surface plasmon resonance (SPR) and cell-based radioligand binding and affinity labelling competition assays. SPR detected slow dissociation kinetics between sCD109 and TGF-β at low concentrations, indicating a stable and effective interaction. In addition, sCD109 antagonizes TGF-β-induced Smad2/3 phosphorylation, transcription and cell migration. Together, our results suggest that sCD109 can bind TGF-β, inhibit TGF-β binding to its receptors and decrease TGF-β signalling and TGF-β-induced cellular responses.
Hydrogel-laden paper scaffold system for origami-based tissue engineering
Authors: Kim Su-Hwan , Lee Hak Rae , Yu Seung Jung , Han Min-Eui , Lee Doh Young , Kim Soo Yeon , Ahn Hee-Jin , Han Mi-Jung , Lee Tae-Ik , Kim Taek-Soo , Kwon Seong Keun , Im Sung Gap , Hwang Nathaniel S. 
Published: December 2015

SignificanceThis work describes an intriguing strategy for the formation of hydrogel-laden multiform structures utilizing paper sheets and suggests a route for trachea tissue engineering. It combines concepts extracted from paper origami, functional thin polymer coating, and thin hydrogel layering on top of the paper scaffolds. A computer-aided design-based lock-and-key arrangement was used for folding the sheets into multiform structures with spatial arrangements. With encapsulating cells in hydrogel-laden paper, the scaffold system was able to deliver biological cues in vivo. In this work, we have successfully applied an origami-based tissue engineering approach to the trachea regeneration model.
Networks of energetic and metabolic interactions define dynamics in microbial communities
Authors: Embree Mallory , Liu Joanne K. , Al-Bassam Mahmoud M. , Zengler Karsten 
Published: December 2015

Significance
Microbial communities are critical to global carbon cycling and particularly important in oxygen-limited environments, such as sediments and parts of the human microbiome. However, the uncultured members of these communities often hinder the study of community composition and interspecies interactions at a deeper level. Here, we integrate metagenomic binning, metatranscriptomic analysis, and metabolic modeling to obtain quantitative information about interspecies interactions between individual species present in methanogenic communities. We found that these communities are defined by not only metabolic interactions but also additional interdependencies, such as amino acid auxotrophies. Strategic usage of antimicrobials by specific community members further reinforces this intricate interspecies network, thereby enforcing strong collaboration among community members.
Origin of information-limiting noise correlations
Authors: Kanitscheider Ingmar , Coen-Cagli Ruben , Pouget Alexandre 
Published: December 2015

Significance
Populations of neurons encode information in activity patterns that vary across repeated presentation of the same input and are correlated across neurons (noise correlations). Such noise correlations can limit information about sensory stimuli and therefore limit behavioral performance in tasks such as discrimination between two similar stimuli. Therefore it is important to understand where and how noise correlations are generated. Most previous accounts focused on sources of variability inside the brain. Here we focus instead on noise that is injected at the sensory periphery and propagated to the cortex: We show that this simple framework accounts for many known properties of noise correlations and explains behavioral performance in discrimination tasks, without the need to assume further sources of information loss.
Universal brain signature of proficient reading: Evidence from four contrasting languages
Authors: Rueckl Jay G. , Paz-Alonso Pedro M. , Molfese Peter J. , Kuo Wen-Jui , Bick Atira , Frost Stephen J. , Hancock Roeland , Wu Denise H. , Mencl William Einar , Duñabeitia Jon Andoni , Lee Jun-Ren , Oliver Myriam , Zevin Jason D. , Hoeft Fumiko , Carreiras Manuel , Tzeng Ovid J. L. , Pugh Kenneth R. , Frost Ram 
Published: December 2015

Significance
Using functional MRI, we examined reading and speech perception in four highly contrasting languages: Spanish, English, Hebrew, and Chinese. With three complementary analytic approaches, we demonstrate that in spite of striking dissimilarities among writing systems, successful literacy acquisition results in a convergence of the speech and orthographic processing systems onto a common network of neural structures. These findings have the major theoretical implication that the reading network has evolved to be universally constrained by the organization of the brain network underlying speech.
Neofunction of ACVR1 in fibrodysplasia ossificans progressiva
Authors: Hino Kyosuke , Ikeya Makoto , Horigome Kazuhiko , Matsumoto Yoshihisa , Ebise Hayao , Nishio Megumi , Sekiguchi Kazuya , Shibata Mitsuaki , Nagata Sanae , Matsuda Shuichi , Toguchida Junya 
Published: December 2015

SignificanceBy utilizing patient-specific induced pluripotent stem cells (iPSCs) of fibrodysplasia ossificans progressiva (FOP) and gene-corrected (rescued) FOP-iPSCs, we discovered a novel mechanism in ectopic bone formation: The disease-causing mutation endows ACVR1 with the ability to transmit the signal of an unexpected ligand, Activin-A. We believe this is a milestone study for FOP research and provides a novel platform for searching therapeutic targets of this intractable disease.
Augmented Binary Substitution: Single-pass CDR germ-lining and stabilization of therapeutic antibodies
Authors: Townsend Sue , Fennell Brian J. , Apgar James R. , Lambert Matthew , McDonnell Barry , Grant Joanne , Wade Jason , Franklin Edward , Foy Niall , Ní Shúilleabháin Deirdre , Fields Conor , Darmanin-Sheehan Alfredo , King Amy , Paulsen Janet E. , Hickling Timothy P. , Tchistiakova Lioudmila , Cunningham Orla , Finlay William J. J. 
Published: December 2015

SignificanceImmunized animals are a key source of monoclonal antibodies used to treat human diseases. Before clinical use, animal antibodies are typically “humanized” by laborious and suboptimal methods that transfer their full target binding loops (a.k.a. CDRs) into human frameworks. We report an optimal method, where the CDRs from species such as rodents and chickens can be adapted to fit human frameworks in which we have clinical and manufacturing confidence. The Augmented Binary Substitution (ABS) process exploits the fundamental plasticity of antibody CDRs to ultrahumanize antibodies from key species in a single pass. ABS results in a final antibody that is much closer to human germ line in the frameworks and CDRs, minimizing immunogenicity risks in man and maximizing the therapeutic potential of the antibody.
Mitochondrial function in the brain links anxiety with social subordination
Authors: Hollis Fiona , van der Kooij Michael A. , Zanoletti Olivia , Lozano Laura , Cantó Carles , Sandi Carmen 
Published: December 2015

Significance
Within a dominance hierarchy, low social status strongly reduces individual well-being. In socially living species, rank in a hierarchy is determined through competitive encounters. Despite the numerous health consequences, the ability of personality traits to predispose individuals to a particular social rank remains largely unclear. Our work identifies trait anxiety as a predisposing factor to a subordinate rank. We demonstrate that mitochondrial function in the nucleus accumbens, a brain region relevant for motivation and depression, is a critical mediating factor in the subordinate status displayed by high-anxious rats. These findings highlight a role for cerebral energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for mood disorders.
Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior
Authors: Li Jun , Chai Anping , Wang Lifang , Ma Yuanlin , Wu Zhiliu , Yu Hao , Mei Liwei , Lu Lin , Zhang Chen , Yue Weihua , Xu Lin , Rao Yi , Zhang Dai 
Published: December 2015

SignificanceImpairments in social behavior and behavioral flexibility have been found in autistic people. However, the genetic mechanism that may contribute to these symptoms is unknown. Here we identified a previously unreported autism-associated gene that regulates synaptic plasticity. The mice lacking this gene exhibit deficits in AMPA receptor endocytosis and synaptic depression because of the blockade of a postsynaptic signaling pathway, leading to autism-like social recognition deficit and behavioral inflexibility. These findings provide new insights into the mechanisms underlying social recognition behavior and suggest that the synaptic depression-related signaling pathway might represent a new therapeutic target for treatment of social recognition deficit disorders such as autism spectrum disorders.
HSV targeting of the host phosphatase PP1α is required for disseminated disease in the neonate and contributes to pathogenesis in the brain
Authors: Wilcox Douglas R. , Muller William J. , Longnecker Richard 
Published: December 2015

Significance
The increased severity of herpes simplex virus (HSV) disease in the newborn compared with the adult is a result of complex interactions between the virus and the host response. We studied viral targeting of host-mediated shutoff of protein synthesis during HSV disease in a murine model and found that HSV-1 targeting of the host phosphatase PP1α was required for disseminated disease in the newborn and contributed to HSV encephalitis. Additionally, this report demonstrates that the host response resulting in translational arrest is tissue-specific and also reveals a tissue-specific reliance on the type I IFN response for control of HSV-1. These results provide important insight into the mechanisms of severe HSV disease in the newborn compared with the adult.
Rotational diffusion affects the dynamical self-assembly pathways of patchy particles
Authors: Newton Arthur C. , Groenewold Jan , Kegel Willem K. , Bolhuis Peter G. 
Published: December 2015

Significance
Recent experiments show that the rotational diffusion of proteins and patchy colloids does not always follow the Stokes–Einstein relation, especially in crowded environments or with the use of external fields. Because cellular cytoplasm is very crowded, this finding can have consequences for protein complex formation such as viruses. We study the kinetic network of simple models for proteins and patchy colloids and find that their dynamical self-assembly pathways change with varying the rotational diffusion constant. In particular, lowering the rotational diffusion avoids frustrated intermediate states. Such control of kinetic networks would also benefit the design of new self-assembled functional materials.
Production of functional small interfering RNAs by an amino-terminal deletion mutant of human Dicer
Authors: Kennedy Edward M. , Whisnant Adam W. , Kornepati Anand V. R. , Marshall Joy B. , Bogerd Hal P. , Cullen Bryan R. 
Published: December 2015

Significance
Although RNA interference (RNAi) is an important antiviral innate-immune response in plants and invertebrates, whether mammals mount effective RNAi responses remains controversial. Using human cells lacking functional Dicer and protein kinase RNA-activated genes, we examined whether wild-type or a deletion mutant of Dicer, lacking the helicase domain, could induce RNAi when presented with double-stranded RNAs derived from plasmids or generated during viral infections. Overexpression of the truncated Dicer mutant resulted in the production of siRNAs in both cases, and these were sufficient to inhibit the expression of cognate mRNAs. Whether the latent ability of human Dicer to induce RNAi will ever be unmasked in vivo remains unclear.
Angptl4 links α-cell proliferation following glucagon receptor inhibition with adipose tissue triglyceride metabolism
Authors: Ben-Zvi Danny , Barrandon Ornella , Hadley Stephanie , Blum Barak , Peterson Quinn P. , Melton Douglas A. 
Published: December 2015

Significance
Hyperactivity of the hormone glucagon plays an important role in the pathophysiology of type 2 diabetes, but the factors that affect glucagon levels and α-cell proliferation are not entirely understood. This is particularly important for the development diabetes drugs based on glucagon receptor inhibition, which increase glucagon levels in plasma and α-cell mass. Here we show that increased levels of Angiopoietin-like 4 (Angptl4) in adipose tissue and plasma are sufficient to induce α-cell proliferation. Angptl4 is a conserved, secreted lipoprotein lipase inhibitor expressed by many tissues that is regulated by exercise and feeding. Moreover, Angptl4 is required for the compensatory hyperglucagonemia and α-cell proliferation following treatment with glucagon receptor antagonists.
Autotetraploid rice methylome analysis reveals methylation variation of transposable elements and their effects on gene expression
Authors: Zhang Jie , Liu Yuan , Xia En-Hua , Yao Qiu-Yang , Liu Xiang-Dong , Gao Li-Zhi 
Published: December 2015

Significance
Whole genome duplication (WGD) has long been recognized as a major force in angiosperm evolution. DNA methylation variation is known to be involved in polyploidization events. We synthesized autotetraploid rice that may rule out disturbances from hybridization and investigated the scope and scale of DNA methylation variation in response to WGD in neopolyploid rice. We found that WGD prompts increased methylation in class II transposable elements, which then suppress the genome-wide expression level of nearby genes. Hypermethylation of these transposable elements inhibits their transposition, stabilizing the integrity of chromosomes, and decreases nearby gene expression, potentially reducing deleterious genome-dosage effects. Our results indicate that DNA methylation plays an important role in assisting plant neopolyploids rapidly adapt to WGD.