bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression
Authors: Franz André , Pirson Paul A. , Pilger Domenic , Halder Swagata , Achuthankutty Divya , Kashkar Hamid , Ramadan Kristijan , Hoppe Thorsten 
Published: February 2016

AbstractThe coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in bothCaenorhabditis elegansand humans, which is relevant to oncogenesis and aging.
Analysis of genetic admixture in Uyghur using the 26 Y-STR loci system
Authors: Bian Yingnan , Zhang Suhua , Zhou Wei , Zhao Qi , Siqintuya  , Zhu Ruxin , Wang Zheng , Gao Yuzhen , Hong Jie , Lu Daru , Li Chengtao 
Published: February 2016

AbstractThe Uyghur population has experienced extensive interaction with European and Eastern Asian populations historically. A set of high-resolution genetic markers could be useful to infer the genetic relationships between the Uyghur population and European and Asian populations. In this study we typed 100 unrelated Uyghur males living in southern Xinjiang at 26 Y-STR loci. Using the high-resolution 26 Y-STR loci system, we investigated genetic and phylogenetic relationship between the Uyghur population and 23 reference European or Asian populations. We found that the Uyghur population exhibited a genetic admixture of Eastern Asian and European populations and had a slightly closer relationship with the selected European populations than the Eastern Asian populations. We also demonstrated that the 26 Y-STR loci system was potentially useful in forensic sciences because it has a large power of discrimination and rarely exhibits common haplotypes. However, ancestry inference of Uyghur samples could be challenging due to the admixed nature of the population.
Clonal Complex 17 Group B Streptococcus strains causing invasive disease in neonates and adults originate from the same genetic pool
Authors: Teatero Sarah , Ramoutar Erin , McGeer Allison , Li Aimin , Melano Roberto G. , Wasserscheid Jessica , Dewar Ken , Fittipaldi Nahuel 
Published: February 2016

AbstractA significant proportion of group B Streptococcus (GBS) neonatal disease, particularly late-onset disease, is associated with strains of serotype III, clonal complex (CC) 17. CC17 strains also cause invasive infections in adults. Little is known about the phylogenetic relationships of isolates recovered from neonatal and adult CC17 invasive infections. We performed whole-genome-based phylogenetic analysis of 93 temporally and geographically matched CC17 strains isolated from both neonatal and adult invasive infections in the metropolitan region of Toronto/Peel, Canada. We also mined the whole-genome data to reveal mobile genetic elements carrying antimicrobial resistance genes. We discovered that CC17 GBS strains causing neonatal and adult invasive disease are interspersed and cluster tightly in a phylogenetic tree, signifying that they are derived from the same genetic pool. We identified limited variation due to recombination in the core CC17 genome. We describe that loss of Pilus Island 1 and acquisition of different mobile genetic elements carrying determinants of antimicrobial resistance contribute to CC17 genetic diversity. Acquisition of some of these mobile genetic elements appears to correlate with clonal expansion of the strains that possess them. Our results provide a genome-wide portrait of the population structure and evolution of a major disease-causing clone of an opportunistic pathogen.
A Dual Target-directed Agent against Interleukin-6 Receptor and Tumor Necrosis Factor α ameliorates experimental arthritis
Authors: Kim Youngkyun , Yi Hyoju , Jung Hyerin , Rim Yeri Alice , Park Narae , Kim Juryun , Jung Seung Min , Park Sung-Hwan , Park Young Woo , Ju Ji Hyeon 
Published: February 2016

AbstractA considerable proportion of patients with rheumatoid arthritis (RA) do not respond to monospecific agents. The purpose of our study was to generate a hybrid form of biologics, targeting tumor-necrosis factor alpha (TNFα) and interleukin-6 receptor (IL-6R) and determine its anti-arthritic propertiesin vitroandin vivo. A novel dual target-directed agent (DTA(A7/sTNFR2)) was generated by conjugating soluble TNF receptor 2 (sTNFR2) to the Fc region of A7, a new anti-IL-6R antibody obtained by screening the phage display human antibody library. DTA(A7/sTNFR2) inhibited the proliferation and migration of fibroblast-like synoviocytes from patients with RA (RA-FLS) more efficiently than single target-directed agents. DTA(A7/sTNFR2) also blocked osteoclastogenesis from bone marrow cells. The arthritis severity scores of the experimental arthritis mice with DTA(A7/sTNFR2) tended to be lower than those of mice with IgG, A7, or sTNFR2. Histological data suggested that DTA(A7/sTNFR2) is more efficient than single-target drugs in preventing joint destruction and bone loss. These results were confirmedin vivousing the minicircle system. Taken together, the results show that DTA(A7/sTNFR2) may be a promising therapeutic agent for the treatment of RA.
Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets
Authors: Muller Laurent , Mitsuhashi Masato , Simms Patricia , Gooding William E. , Whiteside Theresa L. 
Published: February 2016

AbstractTumor cell-derived exosomes (TEX) suppress functions of immune cells. Here, changes in the gene profiles of primary human T lymphocytes exposed in vitro to exosomes were evaluated. CD4+ Tconv, CD8+ T or CD4+ CD39+ Treg were isolated from normal donors’ peripheral blood and co-incubated with TEX or exosomes isolated from supernatants of cultured dendritic cells (DEX). Expression levels of 24–27 immune response-related genes in these T cells were quantified by qRT-PCR. In activated T cells, TEX and DEX up-regulated mRNA expression levels of multiple genes. Multifactorial data analysis of ΔCt values identified T cell activation and the immune cell type, but not exosome source, as factors regulating gene expression by exosomes. Treg were more sensitive to TEX-mediated effects than other T cell subsets. In Treg, TEX-mediated down-regulation of genes regulating the adenosine pathway translated into high expression of CD39 and increased adenosine production. TEX also induced up-regulation of inhibitory genes in CD4+ Tconv, which translated into a loss of CD69 on their surface and a functional decline. Exosomes are not internalized by T cells, but signals they carry and deliver to cell surface receptors modulate gene expression and functions of human T lymphocytes.
Transcriptional comparison of human induced and primary midbrain dopaminergic neurons
Authors: Xia Ninuo , Zhang Pengbo , Fang Fang , Wang Zhengyuan , Rothstein Megan , Angulo Benjamin , Chiang Rosaria , Taylor James , Reijo Pera Renee A. 
Published: February 2016

AbstractGeneration of induced dopaminergic (iDA) neurons may provide a significant step forward towards cell replacement therapy for Parkinson’s disease (PD). To study and compare transcriptional programs of induced cells versus primary DA neurons is a preliminary step towards characterizing human iDA neurons. We have optimized a protocol to efficiently generate iDA neurons from human pluripotent stem cells (hPSCs). We then sequenced the transcriptomes of iDA neurons derived from 6 different hPSC lines and compared them to that of primary midbrain (mDA) neurons. We identified a small subset of genes with altered expression in derived iDA neurons from patients with Parkinson’s Disease (PD). We also observed that iDA neurons differ significantly from primary mDA neurons in global gene expression, especially in genes related to neuron maturation level. Results suggest iDA neurons from patient iPSCs could be useful for basic and translational studies, including in vitro modeling of PD. However, further refinement of methods of induction and maturation of neurons may better recapitulate full development of mDA neurons from hPSCs.
A SPION-eicosane protective coating for water soluble capsules: Evidence for on-demand drug release triggered by magnetic hyperthermia
Authors: Che Rose Laili , Bear Joseph C. , McNaughter Paul D. , Southern Paul , Piggott R. Ben , Parkin Ivan P. , Qi Sheng , Mayes Andrew G. 
Published: February 2016

AbstractAn orally-administered system for targeted, on-demand drug delivery to the gastrointestinal (GI) tract is highly desirable due to the high instances of diseases of that organ system and harsh mechanical and physical conditions any such system has to endure. To that end, we present an iron oxide nanoparticle/wax composite capsule coating using magnetic hyperthermia as a release trigger. The coating is synthesised using a simple dip-coating process from pharmaceutically approved materials using a gelatin drug capsule as a template. We show that the coating is impervious to chemical conditions within the GI tract and is completely melted within two minutes when exposed to an RF magnetic field under biologically-relevant conditions. The overall simplicity of action, durability and non-toxic and inexpensive nature of our system demonstrated herein are key for successful drug delivery systems.
Multipartite entanglement indicators based on monogamy relations of n-qubit symmetric states
Authors: Liu Feng , Gao Fei , Qin Su-Juan , Xie Shu-Cui , Wen Qiao-Yan 
Published: February 2016

AbstractConstructed from Bai-Xu-Wang-class monogamy relations, multipartite entanglement indicators can detect the entanglement not stored in pairs of the focus particle and the other subset of particles. We investigate the k-partite entanglement indicators related to the αth power of entanglement of formation (αEoF) for k ≤ n, αϵ"Equation missing" and n-qubit symmetric states. We then show that (1) The indicator based on αEoF is a monotonically increasing function of k. (2) When n is large enough, the indicator based on αEoF is a monotonically decreasing function of α and then the n-partite indicator based on "Equation missing" works best. However, the indicator based on 2 EoF works better when n is small enough.
The Prevalence of Atherosclerosis in Those with Inflammatory Connective Tissue Disease by Race, Age and Traditional Risk Factors
Authors: Alenghat Francis J. 
Published: February 2016

AbstractSystemic inflammation promotes cardiovascular disease. Inflammatory connective tissue diseases (CTD) like lupus and rheumatoid arthritis associate with cardiovascular risk, but it is unknown whether particular groups of patients have enhanced propensity for atherosclerotic cardiovascular disease (ASCVD) associated with their CTD. Analysis of aggregate health record data at a large U.S. academic center identified CTD and ASCVD status for 287,467 African American and white adults. ASCVD prevalence in those with CTD was 29.7% for African Americans and 14.7% for white patients with prevalence ratios, compared to those without CTD, of 3.1 and 1.8, respectively. When different types of CTD were analyzed individually (rheumatoid arthritis; lupus; scleroderma; Sjögren Syndrome; dermatomyositis/polymyositis; unspecified/mixed CTD; other inflammatory arthropathy), increased ASCVD rates were found in nearly all subsets, always with higher prevalence ratios in African Americans. The prevalence ratio of ASCVD was particularly high in young African Americans. Furthermore, individuals lacking traditional cardiovascular risk factors had more ASCVD if they had CTD (prevalence ratio 2.9). Multivariate analysis confirmed a positive interaction between CTD and African-American race and a negative interaction between CTD and age. The factors driving the observed disproportionate CTD-associated ASCVD in African Americans, young adults and those without traditional risk factors warrant further study.
A Porous Aromatic Framework Constructed from Benzene Rings Has a High Adsorption Capacity for Perfluorooctane Sulfonate
Authors: Luo Qin , Zhao Changwei , Liu Guixia , Ren Hao 
Published: February 2016

AbstractA low-cost and easily constructed porous aromatic framework (PAF-45) was successfully prepared using the Scholl reaction. PAF-45 was, for the first time, used to remove perfluorooctane sulfonate (PFOS) from aqueous solution. Systematic experiments were performed to determine the adsorption capacity of PAF-45 for PFOS and to characterize the kinetics of the adsorption process. The adsorption of PFOS onto PAF-45 reached equilibrium in 30 min and the adsorption capacity of PAF-45 for PFOS was excellent (5847 mg g−1 at pH 3). The amount of PFOS adsorbed by PAF-45 increased significantly as the cation (Na+, Mg2+, or Fe3+) concentration increased, which probably occurred because the cations enhanced the interactions between the negatively charged PFOS molecules and the positively charged PAF-45 surface. The cations Na+, Mg2+ and Fe3+ were found to form complexes with PFOS anions in solution. Density functional theory was used to identify the interactions between PFOS and Na+, Mg2+ and Fe3+. We expect that materials of the same type as PAF-45 could be useful adsorbents for removing organic pollutants from industrial wastewater and contaminated surface water.
Human oral isolate Lactobacillus fermentum AGR1487 induces a pro-inflammatory response in germ-free rat colons
Authors: Anderson Rachel C. , Ulluwishewa Dulantha , Young Wayne , Ryan Leigh J. , Henderson Gemma , Meijerink Marjolein , Maier Eva , Wells Jerry M. , Roy Nicole C. 
Published: February 2016

AbstractLactobacilli are thought to be beneficial for human health, with lactobacilli-associated infections being confined to immune-compromised individuals. However, Lactobacillus fermentum AGR1487 negatively affects barrier integrity in vitro so we hypothesized that it caused a pro-inflammatory response in the host. We compared germ-free rats inoculated with AGR1487 to those inoculated with another L. fermentum strain, AGR1485, which does not affect in vitro barrier integrity. We showed that rats inoculated with AGR1487 had more inflammatory cells in their colon, higher levels of inflammatory biomarkers and increased colonic gene expression of pro-inflammatory pathways. In addition, our in vitro studies showed that AGR1487 had a greater capacity to activate TLR signaling and induce pro-inflammatory cytokines in immune cells. This study indicates the potential of strains of the same species to differentially elicit inflammatory responses in the host and highlights the importance of strain characterization in probiotic approaches to treat inflammatory disorders.
Role of transcription factor-mediated nucleosome disassembly in PHO5 gene expression
Authors: Kharerin Hungyo , Bhat Paike J. , Marko John F. , Padinhateeri Ranjith 
Published: February 2016

AbstractStudying nucleosome dynamics in promoter regions is crucial for understanding gene regulation. Nucleosomes regulate gene expression by sterically occluding transcription factors (TFs) and other non–histone proteins accessing genomic DNA. How the binding competition between nucleosomes and TFs leads to transcriptionally compatible promoter states is an open question. Here, we present a computational study of the nucleosome dynamics and organization in the promoter region of PHO5 gene in Saccharomyces cerevisiae. Introducing a model for nucleosome kinetics that takes into account ATP-dependent remodeling activity, DNA sequence effects and kinetics of TFs (Pho4p), we compute the probability of obtaining different “promoter states” having different nucleosome configurations. Comparing our results with experimental data, we argue that the presence of local remodeling activity (LRA) as opposed to basal remodeling activity (BRA) is crucial in determining transcriptionally active promoter states. By modulating the LRA and Pho4p binding rate, we obtain different mRNA distributions—Poisson, bimodal and long-tail. Through this work we explain many features of the PHO5 promoter such as sequence-dependent TF accessibility and the role of correlated dynamics between nucleosomes and TFs in opening/coverage of the TATA box. We also obtain possible ranges for TF binding rates and the magnitude of LRA.
Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics
Authors: Cervera Javier , Alcaraz Antonio , Mafe Salvador 
Published: February 2016

AbstractBioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects in small multicellular ensembles, ignoring slow diffusional processes. The spatio-temporal patterns obtained for the local map of cell electric potentials illustrate the normalization of regions with abnormal cell electrical states. The effects of intercellular coupling and blocking of specific channels on the electrical patterns are described. These patterns can regulate the electrically-induced redistribution of charged nanoparticles over small regions of a model tissue. The inclusion of bioelectrical signals provides new insights for the modeling of cancer biophysics because collective multicellular states show electrical coupling mechanisms that are not readily deduced from biochemical descriptions at the individual cell level.
Cofilin-induced cooperative conformational changes of actin subunits revealed using cofilin-actin fusion protein
Authors: Umeki Nobuhisa , Hirose Keiko , Uyeda Taro Q. P. 
Published: February 2016

AbstractTo investigate cooperative conformational changes of actin filaments induced by cofilin binding, we engineered a fusion protein made of Dictyostelium cofilin and actin. The filaments of the fusion protein were functionally similar to actin filaments bound with cofilin in that they did not bind rhodamine-phalloidin, had quenched fluorescence of pyrene attached to Cys374 and showed enhanced susceptibility of the DNase loop to cleavage by subtilisin. Quantitative analyses of copolymers made of different ratios of the fusion protein and control actin further demonstrated that the fusion protein affects the structure of multiple neighboring actin subunits in copolymers. Based on these and other recent related studies, we propose a mechanism by which conformational changes induced by cofilin binding is propagated unidirectionally to the pointed ends of the filaments and cofilin clusters grow unidirectionally to the pointed ends following this path. Interestingly, the fusion protein was unable to copolymerize with control actin at pH 6.5 and low ionic strength, suggesting that the structural difference between the actin moiety in the fusion protein and control actin is pH-sensitive.
Decline in intertidal biota after the 2011 Great East Japan Earthquake and Tsunami and the Fukushima nuclear disaster: field observations
Authors: Horiguchi Toshihiro , Yoshii Hiroshi , Mizuno Satoshi , Shiraishi Hiroaki 
Published: February 2016

AbstractIn 2011, 2012 and 2013, in the intertidal zones of eastern Japan, we investigated the ecological effects of the severe accident at the Fukushima Daiichi Nuclear Power Plant that accompanied the 2011 Great East Japan Earthquake and Tsunami. The number of intertidal species decreased significantly with decreasing distance from the power plant and no rock shell (Thais clavigera) specimens were collected near the plant, from Hirono to Futaba Beach (a distance of approximately 30 km) in 2012. The collection of rock shell specimens at many other sites hit by the tsunami suggests that the absence of rock shells around the plant in 2012 might have been caused by the nuclear accident in 2011. Quantitative surveys in 2013 showed that the number of species and population densities in the intertidal zones were much lower at sites near, or within several kilometers south of, the plant than at other sites and lower than in 1995, especially in the case of Arthropoda. There is no clear explanation for these findings, but it is evident that the intertidal biota around the power plant has been affected since the nuclear accident.
Linking suckling biomechanics to the development of the palate
Authors: Li Jingtao , Johnson Chelsey A. , Smith Andrew A. , Hunter Daniel J. , Singh Gurpreet , Brunski John B. , Helms Jill A. 
Published: February 2016

AbstractSkulls are amongst the most informative documents of evolutionary history but a complex geometry, coupled with composite material properties and complicated biomechanics, have made it particularly challenging to identify mechanical principles guiding the skull’s morphogenesis. Despite this challenge, multiple lines of evidence, for example the relationship between masticatory function and the evolution of jaw shape, nonetheless suggest that mechanobiology plays a major role in skull morphogenesis. To begin to tackle this persistent challenge, cellular, molecular and tissue-level analyses of the developing mouse palate were coupled with finite element modeling to demonstrate that patterns of strain created by mammalian-specific oral behaviors produce complementary patterns of chondrogenic gene expression in an initially homogeneous population of cranial neural crest cells. Neural crest cells change from an osteogenic to a chondrogenic fate, leading to the materialization of cartilaginous growth plate-like structures in the palatal midline. These growth plates contribute to lateral expansion of the head but are transient structures; when the strain patterns associated with suckling dissipate at weaning, the growth plates disappear and the palate ossifies. Thus, mechanical cues such as strain appear to co-regulate cell fate specification and ultimately, help drive large-scale morphogenetic changes in head shape.
Plasmon-assisted trapping of nanoparticles using a silver-nanowire-embedded PMMA nanofiber
Authors: Cheng Chang , Xu Xiaohao , Lei Hongxiang , Li Baojun 
Published: February 2016

AbstractThe integration of surface plasmon with waveguide is a strategy for lab-on-a-chip compatible optical trapping. Here, we report a method for trapping of nanoparticles using a silver nanowire (AgNW) embedded poly(methyl methacrylate) (PMMA) nanofiber with the assistance of surface plasmon polaritons (SPPs). The nanoparticles (polystyrene, 700 nm diameter) are transported along the nanofiber and ultimately trapped at the AgNW embedded region because of the enhanced optical gradient force towards the nanofiber exerted on the nanoparticles and optical potential well generated by the excitation of SPPs. The low optical power requirement and the easy fabrication of the AgNW-embedded nanofiber with broad range of wavelength for SPPs are advantageous to the applications in optofluidics and plasmofluidics.