bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variety of shapes of solar wind ion flux spectra: Spektr-R measurements
Authors: Riazantseva Maria , Budaev V. , Rakhmanova L. , Zastenker G. , Yermolaev Yu. , Lodkina I. , Šafránková J. , Němeček Z. , Přech L. 
Published: August 2017

The paper is devoted to the shapes of the solar wind ion flux fluctuation spectrum at the transition between the inertial and the kinetic range usingin situhigh-resolution measurements of the Russian mission Spektr-R. We analyse the variability of the transition region and select five typical types of spectral shapes: (i) spectra with two slopes and one break, (ii) spectra characterized by a nonlinear steepening in the kinetic range, (iii) spectra with flattening in the vicinity of the break, (iv) spectra with a bump in the vicinity of the break and (v) spectra without any steepening in the kinetic range. The most popular is the well-known type (i) observed in approximately half of the cases. The second most popular type of spectra is type (iii) occurring in approximately one third of the cases. The other three types are observed less often: type (ii) – in approximately 6 %; type (iv) in 3 % and type (v) in 6 % of cases. An analysis of typical plasma conditions for different types of spectra revealed that the last two type of spectra (iv) and (v) are generally observed in a very slow solar wind with a low proton density, (i) and (iii) are observed in the solar wind with rather typical conditions and (ii) is usually observed in high-speed streams. The effect of nonlinear steepening of the spectra in the kinetic range increases with the solar wind speed. We present also the analysis of statistical properties of the observed events and compare them with the predictions of several statistical turbulence models. We show that intermittency is always observed in the solar wind flow despite the presence of one or another shape of spectra. The log-Poisson model with a dominant contribution of filament-like structures shows the best parameterization of the experimentally observed scaling.
Genotyping ofBartonellabacteria and their animal hosts: current status and perspectives
Authors: KOSOY M. , MCKEE C. , ALBAYRAK L. , FOFANOV Y. 
Published: August 2017

SUMMARYGrowing evidence demonstrates that bacterial species diversity is substantial, and many of these species are pathogenic in some contexts or hosts. At the same time, laboratories and museums have collected valuable animal tissue and ectoparasite samples that may contain substantial novel information on bacterial prevalence and diversity. However, the identification of bacterial species is challenging, partly due to the difficulty in culturing many microbes and the reliance on molecular data. Although the genomics revolution will surely add to our knowledge of bacterial systematics, these approaches are not accessible to all researchers and rely predominantly on cultured isolates. Thus, there is a need for comprehensive molecular analyses capable of accurately genotyping bacteria from animal tissues or ectoparasites using common methods that will facilitate large-scale comparisons of species diversity and prevalence. To illustrate the challenges of genotyping bacteria, we focus on the genusBartonella, vector-borne bacteria common in mammals. We highlight the value and limitations of commonly used techniques for genotyping bartonellae and make recommendations for researchers interested in studying the diversity of these bacteria in various samples. Our recommendations could be applicable to many bacterial taxa (with some modifications) and could lead to a more complete understanding of bacterial species diversity.
Regional organisations and enduring defective democratic members
Authors: Davies Mathew 
Published: August 2017

AbstractInstead of asking whether regional organisations can promote democracy, a well-established conclusion, this article asks what type of democracy regional organisations can promote. Where their commitments to democracy are weak, regional organisations can promote the transition away from authoritarianism but cannot drive that process to completion with the creation of embedded liberal democracies. Under such circumstances regional organisations serve as regimes of bounded toleration, and can provide regional linkages that sustain defective democracies. Through examining the relationship between the Association of Southeast Asian Nations and Myanmar, three supporting roles are identified; regional legitimacy, defence from external pressure, and future-oriented accommodation. The presence of these linkages between defective democracies and regional organisations provides a caveat to the positive assessments of regional organisations as socialisers of democracy.
Why is terrorism a man’s business?
Authors: Möller-Leimkühler Anne Maria 
Published: August 2017

Terrorism, whether it is group-related or performed as lone actor terrorism, is a predominantly male phenomenon. Generally and throughout history, young males have been the main protagonists of criminal and political violence.This article aims to contribute, from different perspecives, to the question of what makes young men violent. These include neurobiological aspects, such as sex differences in the brain that predispose males to physical aggression and violence; gender role aspects, with regard to aggression and violence being basic components for demonstrating and reconstructing masculinity; demographic aspects of male youth bulges as potential breeding grounds for terrorism; aspects of group dynamics and identity fusion in the process of radicalization; and psychosocial characteristics of lone actor terrorists, which differ from group-related terrorists.It is concluded that in addition to ideological, political, economic, regional, demographic, or psychosocial causes, experiences of threatened masculinity may be an underlying factor and driving force for terrorism.
Evolution of new regulatory functions on biophysically realistic fitness landscapes
Authors: Friedlander Tamar , Prizak Roshan , Barton Nicholas H. , Tkačik Gašper 
Published: August 2017

AbstractGene expression is controlled by networks of regulatory proteins that interact specifically with external signals and DNA regulatory sequences. These interactions force the network components to co-evolve so as to continually maintain function. Yet, existing models of evolution mostly focus on isolated genetic elements. In contrast, we study the essential process by which regulatory networks grow: the duplication and subsequent specialization of network components. We synthesize a biophysical model of molecular interactions with the evolutionary framework to find the conditions and pathways by which new regulatory functions emerge. We show that specialization of new network components is usually slow, but can be drastically accelerated in the presence of regulatory crosstalk and mutations that promote promiscuous interactions between network components.
Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling
Authors: Petersen Julian , Wright Shane C. , Rodríguez David , Matricon Pierre , Lahav Noa , Vromen Aviv , Friedler Assaf , Strömqvist Johan , Wennmalm Stefan , Carlsson Jens , Schulte Gunnar 
Published: August 2017

AbstractG protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors. They can exist and act as dimers, but the requirement of dimers for agonist-induced signal initiation and structural dynamics remains largely unknown. Frizzled 6 (FZD6) is a member of Class F GPCRs, which bind WNT proteins to initiate signaling. Here, we show that FZD6 dimerizes and that the dimer interface of FZD6 is formed by the transmembrane α-helices four and five. Most importantly, we present the agonist-induced dissociation/re-association of a GPCR dimer through the use of live cell imaging techniques. Further analysis of a dimerization-impaired FZD6 mutant indicates that dimer dissociation is an integral part of FZD6 signaling to extracellular signal-regulated kinases1/2. The discovery of agonist-dependent dynamics of dimers as an intrinsic process of receptor activation extends our understanding of Class F and other dimerizing GPCRs, offering novel targets for dimer-interfering small molecules.
RETRACTED ARTICLE:Endocrine disruptors induce perturbations in endoplasmic reticulum and mitochondria of human pluripotent stem cell derivatives
Authors: Rajamani Uthra , Gross Andrew R. , Ocampo Camille , Andres Allen M. , Gottlieb Roberta A. , Sareen Dhruv 
Published: August 2017

AbstractPersistent exposure to man-made endocrine disrupting chemicals during fetal endocrine development may lead to disruption of metabolic homeostasis contributing to childhood obesity. Limited cellular platforms exist to test endocrine disrupting chemical-induced developmental abnormalities in human endocrine tissues. Here we use an human-induced pluripotent stem cell-based platform to demonstrate adverse impacts of obesogenic endocrine disrupting chemicals in the developing endocrine system. We delineate the effects upon physiological low-dose exposure to ubiquitous endocrine disrupting chemicals including, perfluoro-octanoic acid, tributyltin, and butylhydroxytoluene, in endocrine-active human-induced pluripotent stem cell-derived foregut epithelial cells and hypothalamic neurons. Endocrine disrupting chemicals induce endoplasmic reticulum stress, perturb NF-κB, and p53 signaling, and diminish mitochondrial respiratory gene expression, spare respiratory capacity, and ATP levels. As a result, normal production and secretion of appetite control hormones, PYY, α-MSH, and CART, are hampered. Blocking NF-κB rescues endocrine disrupting chemical-induced aberrant mitochondrial phenotypes and endocrine dysregulation, but not ER-stress and p53-phosphorylation changes.
Evolutionary conservation of a core root microbiome across plant phyla along a tropical soil chronosequence
Authors: Yeoh Yun Kit , Dennis Paul G. , Paungfoo-Lonhienne Chanyarat , Weber Lui , Brackin Richard , Ragan Mark A. , Schmidt Susanne , Hugenholtz Philip 
Published: August 2017

AbstractCulture-independent molecular surveys of plant root microbiomes indicate that soil type generally has a stronger influence on microbial communities than host phylogeny. However, these studies have mostly focussed on model plants and crops. Here, we examine the root microbiomes of multiple plant phyla including lycopods, ferns, gymnosperms, and angiosperms across a soil chronosequence using 16S rRNA gene amplicon profiling. We confirm that soil type is the primary determinant of root-associated bacterial community composition, but also observe a significant correlation with plant phylogeny. A total of 47 bacterial genera are associated with roots relative to bulk soil microbial communities, including well-recognized plant-associated genera such as Bradyrhizobium, Rhizobium, and Burkholderia, and major uncharacterized lineages such as WPS-2, Ellin329, and FW68. We suggest that these taxa collectively constitute an evolutionarily conserved core root microbiome at this site. This lends support to the inference that a core root microbiome has evolved with terrestrial plants over their 400 million year history.
A Plasmodium yoelii HECT-like E3 ubiquitin ligase regulates parasite growth and virulence
Authors: Nair Sethu C. , Xu Ruixue , Pattaradilokrat Sittiporn , Wu Jian , Qi Yanwei , Zilversmit Martine , Ganesan Sundar , Nagarajan Vijayaraj , Eastman Richard T. , Orandle Marlene S. , Tan John C. , Myers Timothy G. , Liu Shengfa , Long Carole A. , Li Jian , Su Xin-zhuan 
Published: August 2017

AbstractInfection of mice with strains of Plasmodium yoelii parasites can result in different pathology, but molecular mechanisms to explain this variation are unclear. Here we show that a P. yoelii gene encoding a HECT-like E3 ubiquitin ligase (Pyheul) influences parasitemia and host mortality. We genetically cross two lethal parasites with distinct disease phenotypes, and identify 43 genetically diverse progeny by typing with microsatellites and 9230 single-nucleotide polymorphisms. A genome-wide quantitative trait loci scan links parasite growth and host mortality to two major loci on chromosomes 1 and 7 with LOD (logarithm of ﻿the odds) scores = 6.1 and 8.1, respectively. Allelic exchange of partial sequences of Pyheul in the chromosome 7 locus and modification of the gene expression alter parasite growth and host mortality. This study identifies a gene that may have a function in parasite growth, virulence, and host–parasite interaction, and therefore could be a target for drug or vaccine development.
An early mechanical coupling of planktonic bacteria in dilute suspensions
Authors: Sretenovic Simon , Stojković Biljana , Dogsa Iztok , Kostanjšek Rok , Poberaj Igor , Stopar David 
Published: August 2017

AbstractIt is generally accepted that planktonic bacteria in dilute suspensions are not mechanically coupled and do not show correlated motion. The mechanical coupling of cells is a trait that develops upon transition into a biofilm, a microbial community of self-aggregated bacterial cells. Here we employ optical tweezers to show that bacteria in dilute suspensions are mechanically coupled and show long-range correlated motion. The strength of the coupling increases with the growth of liquid bacterial culture. The matrix responsible for the mechanical coupling is composed of cell debris and extracellular polymer material. The fragile network connecting cells behaves as viscoelastic liquid of entangled extracellular polymers. Our findings point to physical connections between bacteria in dilute bacterial suspensions that may provide a mechanistic framework for understanding of biofilm formation, osmotic flow of nutrients, diffusion of signal molecules in quorum sensing, or different efficacy of antibiotic treatments at low and high bacterial densities.
Single cardiomyocyte nuclear transcriptomes reveal a lincRNA-regulated de-differentiation and cell cycle stress-response in vivo
Authors: See Kelvin , Tan Wilson L. W. , Lim Eng How , Tiang Zenia , Lee Li Ting , Li Peter Y. Q. , Luu Tuan D. A. , Ackers-Johnson Matthew , Foo Roger S. 
Published: August 2017

AbstractCardiac regeneration may revolutionize treatment for heart failure but endogenous progenitor-derived cardiomyocytes in the adult mammalian heart are few and pre-existing adult cardiomyocytes divide only at very low rates. Although candidate genes that control cardiomyocyte cell cycle re-entry have been implicated, expression heterogeneity in the cardiomyocyte stress-response has never been explored. Here, we show by single nuclear RNA-sequencing of cardiomyocytes from both mouse and human failing, and non-failing adult hearts that sub-populations of cardiomyocytes upregulate cell cycle activators and inhibitors consequent to the stress-response in vivo. We characterize these subgroups by weighted gene co-expression network analysis and discover long intergenic non-coding RNAs (lincRNA) as key nodal regulators. KD of nodal lincRNAs affects expression levels of genes related to dedifferentiation and cell cycle, within the same gene regulatory network. Our study reveals that sub-populations of adult cardiomyocytes may have a unique endogenous potential for cardiac regeneration in vivo.
Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus
Authors: Cipriani Valentina , Silva Raquel S. , Arno Gavin , Pontikos Nikolas , Kalhoro Ambreen , Valeina Sandra , Inashkina Inna , Audere Mareta , Rutka Katrina , Puech Bernard , Michaelides Michel , van Heyningen Veronica , Lace Baiba , Webster Andrew R. , Moore Anthony T. 
Published: August 2017

AbstractAutosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development.
Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness
Authors: Gonda Kohsuke , Watanabe Mika , Tada Hiroshi , Miyashita Minoru , Takahashi-Aoyama Yayoi , Kamei Takashi , Ishida Takanori , Usami Shin , Hirakawa Hisashi , Kakugawa Yoichiro , Hamanaka Yohei , Yoshida Ryuichi , Furuta Akihiko , Okada Hisatake , Goda Hideki , Negishi Hiroshi , Takanashi Kensaku , Takahashi Masaru , Ozaki Yuichi , Yoshihara Yuka , Nakano Yasushi , Ohuchi Noriaki 
Published: August 2017

AbstractThe quantitative sensitivity and dynamic range of conventional immunohistochemistry (IHC) with 3,3′-diaminobenzidine (IHC-DAB) used in pathological diagnosis in hospitals are poor, because enzyme activity can affect the IHC-DAB chromogenic reaction. Although fluorescent IHC can effectively increase the quantitative sensitivity of conventional IHC, tissue autofluorescence interferes with the sensitivity. Here, we created new fluorescent nanoparticles called phosphor-integrated dots (PIDs). PIDs have 100-fold greater brightness and a more than 300-fold greater dynamic range than those of commercially available fluorescent nanoparticles, quantum dots, whose fluorescence intensity is comparable to tissue autofluorescence. Additionally, a newly developed image-processing method enabled the calculation of the PID particle number in the obtained image. To quantify the sensitivity of IHC using PIDs (IHC-PIDs), the IHC-PIDs method was compared with fluorescence-activated cell sorting (FACS), a method well suited for evaluating total protein amount, and the two values exhibited strong correlation (R = 0.94). We next applied IHC-PIDs to categorize the response to molecular target-based drug therapy in breast cancer patients. The results suggested that the PID particle number estimated by IHC-PIDs of breast cancer tissues obtained from biopsy before chemotherapy can provide a score for predicting the therapeutic effect of the human epidermal growth factor receptor 2-targeted drug trastuzumab.
KDM4B-mediated reduction of H3K9me3 and H3K36me3 levels improves somatic cell reprogramming into pluripotency
Authors: Wei Jingwei , Antony Jisha , Meng Fanli , MacLean Paul , Rhind Rebekah , Laible Götz , Oback Björn 
Published: August 2017

AbstractCorrect reprogramming of epigenetic marks is essential for somatic cells to regain pluripotency. Repressive histone (H) lysine (K) methylation marks are known to be stable and difficult to reprogram. In this study, we generated transgenic mice and mouse embryonic fibroblasts (MEFs) for the inducible expression of KDM4B, a demethylase that removes H3 K9 and H3K36 trimethylation (me3) marks (H3K9/36me3). Upon inducing Kdm4b, H3K9/36me3 levels significantly decreased compared to non-induced controls. Concurrently, H3K9me1 levels significantly increased, while H3K9me2 and H3K27me3 remained unchanged. The global transcriptional impact of Kdm4b-mediated reduction in H3K9/36me3 levels was examined by comparative microarray analysis and mRNA-sequencing of three independent transgenic MEF lines. We identified several commonly up-regulated targets, including the heterochromatin-associated zinc finger protein 37 and full-length endogenous retrovirus repeat elements. Following optimized zona-free somatic nuclear transfer, reduced H3K9/36me3 levels were restored within hours. Nevertheless, hypo-methylated Kdm4b MEF donors reprogrammed six-fold better into cloned blastocysts than non-induced donors. They also reprogrammed nine-fold better into induced pluripotent stem cells that gave rise to teratomas and chimeras. In summary, we firmly established H3K9/36me3 as a major roadblock to somatic cell reprogramming and identified transcriptional targets of derestricted chromatin that could contribute towards improving this process in mouse.
Unraveling heme detoxification in the malaria parasite by in situ correlative X-ray fluorescence microscopy and soft X-ray tomography
Authors: Kapishnikov Sergey , Grolimund Daniel , Schneider Gerd , Pereiro Eva , McNally James G. , Als-Nielsen Jens , Leiserowitz Leslie 
Published: August 2017

AbstractA key drug target for malaria has been the detoxification pathway of the iron-containing molecule heme, which is the toxic byproduct of hemoglobin digestion. The cornerstone of heme detoxification is its sequestration into hemozoin crystals, but how this occurs remains uncertain. We report new results of in vivo rate of heme crystallization in the malaria parasite, based on a new technique to measure element-specific concentrations at defined locations in cell ultrastructure. Specifically, a high resolution correlative combination of cryo soft X-ray tomography has been developed to obtain 3D parasite ultrastructure with cryo X-ray fluorescence microscopy to measure heme concentrations. Our results are consistent with a model for crystallization via the heme detoxification protein. Our measurements also demonstrate the presence of considerable amounts of non-crystalline heme in the digestive vacuole, which we show is most likely contained in hemoglobin. These results suggest a tight coupling between hemoglobin digestion and heme crystallization, highlighting a new link in the crystallization pathway for drug development.
RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency
Authors: Jin Jianliang , Tao Jianguo , Gu Xin , Yu Zhenzhen , Wang Rong , Zuo Guoping , Li Qing , Lv Xianhui , Miao Dengshun 
Published: August 2017

Abstract
To determine whether p16

INK4a
deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1
−/−) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16

INK4a
double-knockout, and Bmi-1
−/− and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-β1. Our results demonstrated that p16

INK4a
deletion largely rescued renal aging phenotypes caused by Bmi-1 deficiency, including impaired renal structure and function, decreased proliferation, increased apoptosis, senescence and SASP, DNA damage, NF-κB and TGF-β1/Smad signal activation, inflammatory cell infiltration, and tubulointerstitial fibrosis and tubular atrophy. P16

INK4a
deletion also promoted proliferation, reduced senescence and SASP of RIFs and subsequently inhibited EMT of Bmi-1-knockdown HK2 cells. TGF-β1 further induced the EMT of Bmi-1-knockdown HK2 cells. Thus, p16

INK4a
positive senescent cells would be a therapeutic target for preventing renal tubulointerstitial injury.