bluuebunny/crossref_metadata_2025_split huggingface dataset:
The V-ATPase a2 isoform controls mammary gland development through Notch and TGF-β signaling
Authors: Pamarthy Sahithi , Mao Liquin , Katara Gajendra K , Fleetwood Sara , Kulshreshta Arpita , Gilman-Sachs Alice , Beaman Kenneth D 
Published: November 2016

AbstractAmong all tissues and organs, the mammary gland is unique because most of its development occurs in adulthood. Notch signaling has a major role in mammary gland development and has been implicated in breast cancer. The vacuolar-ATPase (V-ATPase) is a proton pump responsible for the regulation and control of pH in intracellular vesicles and the extracellular milieu. We have previously reported that a2V-ATPase (a2V), an isoform of ‘a’ subunit of V-ATPase, regulates processing of Notch receptor and alters Notch signaling in breast cancer. To study the role of a2V in mammary gland development, we generated an a2V-KO model (conditional mammary knockout a2V mouse strain). During normal mammary gland development, the basal level expression of a2V increased from puberty, virginity, and pregnancy through the lactation stage and then decreased during involution. Litters of a2V-KO mice weighed significantly less when compared with litters from wild-type mice and showed reduced expression of the lactation marker β-casein. Whole-mount analysis of mammary glands demonstrated impaired ductal elongation and bifurcation in a2V-KO mice. Consequently, we found disintegrated mammary epithelium as seen by basal and luminal epithelial staining, although the rate of proliferation remained unchanged. Delayed mammary morphogenesis in a2V-KO mice was associated with aberrant activation of Notch and TGF-β (transforming growth factor-β) pathways. Notably, Hey1 (hairy/enhancer-of-split related with YRPW motif) and Smad2, the key downstream mediators of Notch and TGF-β pathways, respectively, were upregulated in a2V-KO mice and also in human mammary epithelial cells treated with a2V siRNA. Taken together, our results show that a2V deficiency disrupts the endolysosomal route in Notch and TGF signaling, thereby impairing mammary gland development. Our findings have broader implications in developmental and oncogenic cellular environments where V-ATPase, Notch and TGF-β are crucial for cell survival.
Integration and segregation of large-scale brain networks during short-term task automatization
Authors: Mohr Holger , Wolfensteller Uta , Betzel Richard F. , Mišić Bratislav , Sporns Olaf , Richiardi Jonas , Ruge Hannes 
Published: November 2016

AbstractThe human brain is organized into large-scale functional networks that can flexibly reconfigure their connectivity patterns, supporting both rapid adaptive control and long-term learning processes. However, it has remained unclear how short-term network dynamics support the rapid transformation of instructions into fluent behaviour. Comparing fMRI data of a learning sample (N=70) with a control sample (N=67), we find that increasingly efficient task processing during short-term practice is associated with a reorganization of large-scale network interactions. Practice-related efficiency gains are facilitated by enhanced coupling between the cingulo-opercular network and the dorsal attention network. Simultaneously, short-term task automatization is accompanied by decreasing activation of the fronto-parietal network, indicating a release of high-level cognitive control, and a segregation of the default mode network from task-related networks. These findings suggest that short-term task automatization is enabled by the brain’s ability to rapidly reconfigure its large-scale network organization involving complementary integration and segregation processes.
Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death
Authors: Thurston Teresa L. M. , Matthews Sophie A. , Jennings Elliott , Alix Eric , Shao Feng , Shenoy Avinash R. , Birrell Mark A. , Holden David W. 
Published: November 2016

AbstractSensing bacterial products in the cytosol of mammalian cells by NOD-like receptors leads to the activation of caspase-1 inflammasomes, and the production of the pro-inflammatory cytokines interleukin (IL)-18 and IL-1β. In addition, mouse caspase-11 (represented in humans by its orthologs, caspase-4 and caspase-5) detects cytosolic bacterial LPS directly. Activation of caspase-1 and caspase-11 initiates pyroptotic host cell death that releases potentially harmful bacteria from the nutrient-rich host cell cytosol into the extracellular environment. Here we use single cell analysis and time-lapse microscopy to identify a subpopulation of host cells, in which growth of cytosolic Salmonella Typhimurium is inhibited independently or prior to the onset of cell death. The enzymatic activities of caspase-1 and caspase-11 are required for growth inhibition in different cell types. Our results reveal that these proteases have important functions beyond the direct induction of pyroptosis and proinflammatory cytokine secretion in the control of growth and elimination of cytosolic bacteria.
DNA looping mediates nucleosome transfer
Authors: Brennan Lucy D. , Forties Robert A. , Patel Smita S. , Wang Michelle D. 
Published: November 2016

AbstractProper cell function requires preservation of the spatial organization of chromatin modifications. Maintenance of this epigenetic landscape necessitates the transfer of parental nucleosomes to newly replicated DNA, a process that is stringently regulated and intrinsically linked to replication fork dynamics. This creates a formidable setting from which to isolate the central mechanism of transfer. Here we utilized a minimal experimental system to track the fate of a single nucleosome following its displacement, and examined whether DNA mechanics itself, in the absence of any chaperones or assembly factors, may serve as a platform for the transfer process. We found that the nucleosome is passively transferred to available dsDNA as predicted by a simple physical model of DNA loop formation. These results demonstrate a fundamental role for DNA mechanics in mediating nucleosome transfer and preserving epigenetic integrity during replication.
First maintenance therapy for COPD in the UK between 2009 and 2012: a retrospective database analysis
Authors: Price David , Miravitlles Marc , Pavord Ian , Thomas Mike , Wedzicha Jadwiga , Haughney John , Bichel Katsiaryna , West Daniel 
Published: November 2016

AbstractClinical guidelines recommend long-acting bronchodilators as first maintenance therapy for chronic obstructive pulmonary disease (COPD), with inhaled corticosteroids (ICS) reserved for patients with more severe disease and exacerbations. The aim of this analysis was to examine real-life prescribing of first maintenance therapy for COPD in the UK. Data were extracted from the UK Optimum Patient Care Research Database for patients with a first prescription for COPD maintenance therapy between 2009 and 2012 and a diagnosis of COPD at or before the date of the first prescription for COPD maintenance therapy. Routine clinical data including demographics, disease history and symptoms, comorbidities, therapy, hospitalisation rate and exacerbation rate were collected and used to characterise patients stratified by disease severity and Global Initiative for Chronic Obstructive Lung Disease (GOLD) group (A–D). The analysis population included 2,217 individuals (55.4% male, 45.2% smokers). Long-acting muscarinic antagonists (LAMA) as monotherapy were prescribed as first maintenance therapy for 40.2% of patients. ICS were prescribed as ICS/long-acting beta-agonists combination for 29.1% of patients or as monotherapy for 15.5%. ICS (alone or in combination) were prescribed to >40% of patients in each GOLD group. ICS-containing regimens were prescribed to patients with a history of pneumonia and comorbid conditions for whom the risks of ICS therapy may outweigh the benefits. The clinical reality of prescribing indicates that ICS are often prescribed outside current guideline recommendations for many patients newly diagnosed with COPD in the UK. Encouragingly, LAMAs are increasingly being prescribed as first maintenance therapy for these patients.
The formation of the ocean’s anthropogenic carbon reservoir
Authors: Iudicone Daniele , Rodgers Keith B. , Plancherel Yves , Aumont Olivier , Ito Takamitsu , Key Robert M. , Madec Gurvan , Ishii Masao 
Published: November 2016

AbstractThe shallow overturning circulation of the oceans transports heat from the tropics to the mid-latitudes. This overturning also influences the uptake and storage of anthropogenic carbon (Cant). We demonstrate this by quantifying the relative importance of ocean thermodynamics, circulation and biogeochemistry in a global biochemistry and circulation model. Almost 2/3 of the Cant ocean uptake enters via gas exchange in waters that are lighter than the base of the ventilated thermocline. However, almost 2/3 of the excess Cant is stored below the thermocline. Our analysis shows that subtropical waters are a dominant component in the formation of subpolar waters and that these water masses essentially form a common Cant reservoir. This new method developed and presented here is intrinsically Lagrangian, as it by construction only considers the velocity or transport of waters across isopycnals. More generally, our approach provides an integral framework for linking ocean thermodynamics with biogeochemistry.
Molecular Characterization of A Novel Effector Expansin-like Protein from Heterodera avenae that Induces Cell Death in Nicotiana benthamiana
Authors: Liu Jing , Peng Huan , Cui Jiangkuan , Huang Wenkun , Kong Lingan , Clarke Jihong Liu , Jian Heng , Wang Guo Liang , Peng Deliang 
Published: November 2016

AbstractCereal cyst nematodes are sedentary biotrophic endoparasites that maintain a complex interaction with their host plants. Nematode effector proteins are synthesized in the oesophageal glands and are secreted into plant tissues through the stylet. To understand the function of nematode effectors in parasitic plants, we cloned predicted effectors genes from Heterodera avenae and transiently expressed them in Nicotiana benthamiana. Infiltration assays showed that HaEXPB2, a predicted expansin-like protein, caused cell death in N. benthamiana. In situ hybridization showed that HaEXPB2 transcripts were localised within the subventral gland cells of the pre-parasitic second-stage nematode. HaEXPB2 had the highest expression levels in parasitic second-stage juveniles. Subcellular localization assays revealed that HaEXPB2 could be localized in the plant cell wall after H. avenae infection.This The cell wall localization was likely affected by its N-terminal and C-terminal regions. In addition, we found that HaEXPB2 bound to cellulose and its carbohydrate-binding domain was required for this binding. The infectivity of H. avenae was significantly reduced when HaEXPB2 was knocked down by RNA interference in vitro. This study indicates that HaEXPB2 may play an important role in the parasitism of H. avenae through targeting the host cell wall.
Future C loss in mid-latitude mineral soils: climate change exceeds land use mitigation potential in France
Authors: Meersmans Jeroen , Arrouays Dominique , Van Rompaey Anton J. J. , Pagé Christian , De Baets Sarah , Quine Timothy A. 
Published: November 2016

AbstractMany studies have highlighted significant interactions between soil C reservoir dynamics and global climate and environmental change. However, in order to estimate the future soil organic carbon sequestration potential and related ecosystem services well, more spatially detailed predictions are needed. The present study made detailed predictions of future spatial evolution (at 250 m resolution) of topsoil SOC driven by climate change and land use change for France up to the year 2100 by taking interactions between climate, land use and soil type into account. We conclude that climate change will have a much bigger influence on future SOC losses in mid-latitude mineral soils than land use change dynamics. Hence, reducing CO2 emissions will be crucial to prevent further loss of carbon from our soils.
An improved d-band model of the catalytic activity of magnetic transition metal surfaces
Authors: Bhattacharjee Satadeep , Waghmare Umesh V. , Lee Seung-Cheol 
Published: November 2016

AbstractThe d-band center model of Hammer and Nørskov is widely used in understanding and predicting catalytic activity on transition metal (TM) surfaces. Here, we demonstrate that this model is inadequate for capturing the complete catalytic activity of the magnetically polarized TM surfaces and propose its generalization. We validate the generalized model through comparison of adsorption energies of the NH3 molecule on the surfaces of 3d TMs (V, Cr, Mn, Fe, Co, Ni, Cu and Zn) determined with spin-polarized density functional theory (DFT)-based methods with the predictions of our model. Compared to the conventional d-band model, where the nature of the metal-adsorbate interaction is entirely determined through the energy and the occupation of the d-band center, we emphasize that for the surfaces with high spin polarization, the metal-adsorbate system can be stabilized through a competition of the spin-dependent metal-adsorbate interactions.
Analysis of codon usage patterns in Ginkgo biloba reveals codon usage tendency from A/U-ending to G/C-ending
Authors: He Bing , Dong Hui , Jiang Cong , Cao Fuliang , Tao Shentong , Xu Li-an 
Published: November 2016

AbstractAs one of the most ancient tree species, the codon usage pattern analysis of Ginkgo biloba is a useful way to understand its evolutionary and genetic mechanisms. Several studies have been conducted on angiosperms, but seldom on gymnosperms. Based on RNA-Seq data of the G. biloba transcriptome, amount to 17,579 unigenes longer than 300 bp were selected and analyzed from 68,547 candidates. The codon usage pattern tended towards more frequently use of A/U-ending codons, which showed an obvious gradient progressing from gymnosperms to dicots to monocots. Meanwhile, analysis of high/low-expression unigenes revealed that high-expression unigenes tended to use G/C-ending codons together with more codon usage bias. Variation of unigenes with different functions suggested that unigenes involving in environment adaptation use G/C-ending codons more frequently with more usage bias, and these results were consistent with the conclusion that the formation of G. biloba codon usage bias was dominated by natural selection.
β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces
Authors: Brown James W. P. , Buell Alexander K. , Michaels Thomas C. T. , Meisl Georg , Carozza Jacqueline , Flagmeier Patrick , Vendruscolo Michele , Knowles Tuomas P. J. , Dobson Christopher M. , Galvagnion Céline 
Published: November 2016

Abstractα-Synuclein is an intrinsically disordered protein that is associated with the pathogenesis of Parkinson’s disease through the processes involved in the formation of amyloid fibrils. α and β-synuclein are homologous proteins found at comparable levels in presynaptic terminals but β-synuclein has a greatly reduced propensity to aggregate and indeed has been found to inhibit α-synuclein aggregation. In this paper, we describe how sequence differences between α- and β-synuclein affect individual microscopic processes in amyloid formation. In particular, we show that β-synuclein strongly suppresses both lipid-induced aggregation and secondary nucleation of α-synuclein by competing for binding sites at the surfaces of lipid vesicles and fibrils, respectively. These results suggest that β-synuclein can act as a natural inhibitor of α-synuclein aggregation by reducing both the initiation of its self-assembly and the proliferation of its aggregates.
C2-domain mediated nano-cluster formation increases calcium signaling efficiency
Authors: Bonny Mike , Hui Xin , Schweizer Julia , Kaestner Lars , Zeug André , Kruse Karsten , Lipp Peter 
Published: November 2016

AbstractConventional protein kinase Cs (cPKCs) are key signaling proteins for transducing intracellular Ca2+ signals into downstream phosphorylation events. However, the lifetime of individual membrane-bound activated cPKCs is an order of magnitude shorter than the average time needed for target-protein phosphorylation. Here, we employed intermolecular Förster resonance energy transfer (FRET) in living cells combined with computational analysis to study the spatial organization of cPKCs bound to the plasma membrane. We discovered Ca2+-dependent cPKC nano-clusters that significantly extend cPKC’s plasma-membrane residence time. These protein patterns resulted from self-assembly mediated by Ca2+-binding C2-domains, which are widely used for membrane-targeting of Ca2+-sensing proteins. We also established clustering of other unrelated C2-domain containing proteins, suggesting that nano-cluster formation is a key step for efficient cellular Ca2+-signaling.
Human vision is determined based on information theory
Authors: Delgado-Bonal Alfonso , Martín-Torres Javier 
Published: November 2016

AbstractIt is commonly accepted that the evolution of the human eye has been driven by the maximum intensity of the radiation emitted by the Sun. However, the interpretation of the surrounding environment is constrained not only by the amount of energy received but also by the information content of the radiation. Information is related to entropy rather than energy. The human brain follows Bayesian statistical inference for the interpretation of visual space. The maximization of information occurs in the process of maximizing the entropy. Here, we show that the photopic and scotopic vision absorption peaks in humans are determined not only by the intensity but also by the entropy of radiation. We suggest that through the course of evolution, the human eye has not adapted only to the maximum intensity or to the maximum information but to the optimal wavelength for obtaining information. On Earth, the optimal wavelengths for photopic and scotopic vision are 555 nm and 508 nm, respectively, as inferred experimentally. These optimal wavelengths are determined by the temperature of the star (in this case, the Sun) and by the atmospheric composition.
Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions
Authors: Hebecker Betty , Vlaic Sebastian , Conrad Theresia , Bauer Michael , Brunke Sascha , Kapitan Mario , Linde Jörg , Hube Bernhard , Jacobsen Ilse D. 
Published: November 2016

AbstractCandida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses.
Think global, act local: Preserving the global commons
Authors: Hauser Oliver P. , Hendriks Achim , Rand David G. , Nowak Martin A. 
Published: November 2016

AbstractPreserving global public goods, such as the planet’s ecosystem, depends on large-scale cooperation, which is difficult to achieve because the standard reciprocity mechanisms weaken in large groups. Here we demonstrate a method by which reciprocity can maintain cooperation in a large-scale public goods game (PGG). In a first experiment, participants in groups of on average 39 people play one round of a Prisoner’s Dilemma (PD) with their two nearest neighbours on a cyclic network after each PGG round. We observe that people engage in “local-to-global” reciprocity, leveraging local interactions to enforce global cooperation: Participants reduce PD cooperation with neighbours who contribute little in the PGG. In response, low PGG contributors increase their contributions if both neighbours defect in the PD. In a control condition, participants do not know their neighbours’ PGG contribution and thus cannot link play in the PD to the PGG. In the control we observe a sharp decline of cooperation in the PGG, while in the treatment condition global cooperation is maintained. In a second experiment, we demonstrate the scalability of this effect: in a 1,000-person PGG, participants in the treatment condition successfully sustain public contributions. Our findings suggest that this simple “local-to-global” intervention facilitates large-scale cooperation.
Mitochondrial genomes and comparative genomics of Aphanomyces astaci and Aphanomyces invadans
Authors: Makkonen Jenny , Vesterbacka Arto , Martin Frank , Jussila Japo , Diéguez-Uribeondo Javier , Kortet Raine , Kokko Harri 
Published: November 2016

AbstractThe genus Aphanomyces (Saprolegniales, Oomycetes) includes species with a variety of ecologies from saprotrophs to plant and animal parasites. Two important species in this genus are A. astaci, the cause of crayfish plague and its close relative, A. invadans, which causes the epizootic ulcerative syndrome on fish. In this study, we have assembled and annotated the mitochondrial (mt) genomes of A. astaci and A. invadans from the whole genome shotgun sequence reads (PRJNA187372; PRJNA258292, respectively). The assembly was generated from A. astaci Pc-genotype strain APO3 and A. invadans strain NJM9701. The sizes of the mtDNAs were 49,489 bp and 49,061 bp for A. astaci and A. invadans, respectively. The species shared similar genetic content and organization encoding 35 proteins, two ribosomal RNAs, three putative open reading frames and 33 transfer RNAs of 19 amino acids for peptide synthesis. Both species also had a large inverted repeat region (LIR) of approximately 12 kb, the LIR contained large and small ribosomal RNAs and eight protein coding genes. These annotated mt genomes serve as a valuable genetic backbone for further development of diagnostic methods and phylogenetic and migration studies of the animal parasitic species of Aphanomyces.