bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral health in China: from vision to action
Authors: Zhou Xuedong , Xu Xin , Li Jiyao , Hu Deyu , Hu Tao , Yin Wei , Fan Yujiang , Zhang Xingdong 
Published: January 2018

AbstractChinese president Xi Jinping made clear at the National Health and Wellness Conference that health is the prerequisite for people’s all-around development and a precondition for the sustainable development of China. Oral health is an indispensable component of overall health in humans. However, the long neglect of oral health in overall health agendas has made oral diseases an increasing concern. With this perspective, we described the global challenges of oral diseases, with an emphasis on the challenges faced by China. We also described and analyzed the recently released health policies of the Chinese government, which aim to guide mid-term and long-term oral health promotion in China. More importantly, we called for specific actions to fulfill the larger goal of oral health for the nation. The implementation of primordial prevention efforts against oral diseases, the integration of oral health into the promotion of overall health, and the management of oral diseases in conjunction with other chronic non-communicable diseases with shared risk factors were highly recommended. In addition, we suggested the reform of standard clinical residency training, the development of domestic manufacturing of dental equipment and materials, the revitalization traditional Chinese medicine for the prevention and treatment of oral diseases, and integration of oral health promotion into the Belt and Road Initiative. We look forward to seeing a joint effort from all aspects of the society to fulfill the goal of Healthy China 2030 and ensure the oral health of the nation.
Expression profiling of host and virus during a coccolithophore bloom provides insights into the role of viral infection in promoting carbon export
Authors: Sheyn Uri , Rosenwasser Shilo , Lehahn Yoav , Barak-Gavish Noa , Rotkopf Ron , Bidle Kay D , Koren Ilan , Schatz Daniella , Vardi Assaf 
Published: January 2018

Abstract
The cosmopolitan coccolithophore Emiliania huxleyi is a unicellular eukaryotic alga that forms vast blooms in the oceans impacting large biogeochemical cycles. These blooms are often terminated due to infection by the large dsDNA virus, E. huxleyi virus (EhV). It was recently established that EhV-induced modulation of E. huxleyi metabolism is a key factor for optimal viral infection cycle. Despite the huge ecological importance of this host–virus interaction, the ability to assess its spatial and temporal dynamics and its possible impact on nutrient fluxes is limited by current approaches that focus on quantification of viral abundance and biodiversity. Here, we applied a host and virus gene expression analysis as a sensitive tool to quantify the dynamics of this interaction during a natural E. huxleyi bloom in the North Atlantic. We used viral gene expression profiling as an index for the level of active infection and showed that the latter correlated with water column depth. Intriguingly, this suggests a possible sinking mechanism for removing infected cells as aggregates from the E. huxleyi population in the surface layer into deeper waters. Viral infection was also highly correlated with induction of host metabolic genes involved in host life cycle, sphingolipid, and antioxidant metabolism, providing evidence for modulation of host metabolism under natural conditions. The ability to track and quantify defined phases of infection by monitoring co-expression of viral and host genes, coupled with advance omics approaches, will enable a deeper understanding of the impact that viruses have on the environment.
Infection dynamics of insecticide-degrading symbionts from soil to insects in response to insecticide spraying
Authors: Itoh Hideomi , Hori Tomoyuki , Sato Yuya , Nagayama Atsushi , Tago Kanako , Hayatsu Masahito , Kikuchi Yoshitomo 
Published: January 2018

Abstract
Insecticide resistance is a serious concern in modern agriculture, and an understanding of the underlying evolutionary processes is pivotal to prevent the problem. The bean bug Riptortus pedestris, a notorious pest of leguminous crops, acquires a specific Burkholderia symbiont from the environment every generation, and harbors the symbiont in the midgut crypts. The symbiont’s natural role is to promote insect development but the insect host can also obtain resistance against the insecticide fenitrothion (MEP) by acquiring MEP-degrading Burkholderia from the environment. To understand the developing process of the symbiont-mediated MEP resistance in response to the application of the insecticide, we investigated here in parallel the soil bacterial dynamics and the infected gut symbionts under different MEP-spraying conditions by culture-dependent and culture-independent analyses, in conjunction with stinkbug rearing experiments. We demonstrate that MEP application did not affect the total bacterial soil population but significantly decreased its diversity while it dramatically increased the proportion of MEP-degrading bacteria, mostly Burkholderia. Moreover, we found that the infection of stinkbug hosts with MEP-degrading Burkholderia is highly specific and efficient, and is established after only a few times of insecticide spraying at least in a field soil with spraying history, suggesting that insecticide resistance could evolve in a pest bug population more quickly than was thought before.
Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank
Authors: Hall Lynsey S. , Adams Mark J. , Arnau-Soler Aleix , Clarke Toni-Kim , Howard David M. , Zeng Yanni , Davies Gail , Hagenaars Saskia P. , Maria Fernandez-Pujals Ana , Gibson Jude , Wigmore Eleanor M. , Boutin Thibaud S. , Hayward Caroline , Scotland Generation ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Porteous David J. , Deary Ian J. , Thomson Pippa A. , Haley Chris S. , McIntosh Andrew M. 
Published: January 2018

AbstractFew replicable genetic associations for Major Depressive Disorder (MDD) have been identified. Recent studies of MDD have identified common risk variants by using a broader phenotype definition in very large samples, or by reducing phenotypic and ancestral heterogeneity. We sought to ascertain whether it is more informative to maximize the sample size using data from all available cases and controls, or to use a sex or recurrent stratified subset of affected individuals. To test this, we compared heritability estimates, genetic correlation with other traits, variance explained by MDD polygenic score, and variants identified by genome-wide meta-analysis for broad and narrow MDD classifications in two large British cohorts - Generation Scotland and UK Biobank. Genome-wide meta-analysis of MDD in males yielded one genome-wide significant locus on 3p22.3, with three genes in this region (CRTAP,GLB1, andTMPPE) demonstrating a significant association in gene-based tests. Meta-analyzed MDD, recurrent MDD and female MDD yielded equivalent heritability estimates, showed no detectable difference in association with polygenic scores, and were each genetically correlated with six health-correlated traits (neuroticism, depressive symptoms, subjective well-being, MDD, a cross-disorder phenotype and Bipolar Disorder). Whilst stratified GWAS analysis revealed a genome-wide significant locus for male MDD, the lack of independent replication, and the consistent pattern of results in other MDD classifications suggests that phenotypic stratification using recurrence or sex in currently available sample sizes is currently weakly justified. Based upon existing studies and our findings, the strategy of maximizing sample sizes is likely to provide the greater gain.
Enrichment of schizophrenia heritability in both neuronal and glia cell regulatory elements
Authors: Tansey Katherine E. , Hill Matthew J. 
Published: January 2018

AbstractGenome-wide association studies have identified over 100 robust risk loci for schizophrenia with thousands of variants mediating genetic heritability, the majority of which reside in non-coding regions. Analytical approaches have shown this heritability is strongly enriched at variants within regulatory elements identified from human post-mortem brain tissue. However, bulk post-mortem brain tissue has a heterogeneous cell composition, making biological interpretations difficult. We sought to refine the cell types mediating schizophrenia heritability by separating neuronal and glial signals using data from: (1) NeuN-sorted post-mortem brain and (2) cell culture systems. Schizophrenia heritability was partitioned using linkage disequilbrium (LD) score regression. Variants within genomic regions marked by H3K4me3 (marker of active promoters) from NeuN-positive (neuronal) and NeuN-negative (non-neuronal) cells explained a significant amount of schizophrenia heritability (P = 1.38 × 10−10 and P = 7.97 × 10−10). However, variants located in H3K4me3 sites specific to NeuN-positive (neuronal) cells were enriched (P = 3.13 × 10−4), while those specific to NeuN-negative (non-neuronal) cells were not (P = 0.470). Data from cell culture systems mimicked this pattern of association. We show the previously observed enrichment of heritability from variants at brain H3K4me3 sites is mediated by both neuronal and non-neuronal brain cell types. However, only neuronal cell populations showed a unique contribution driven by cell-type specific regulatory elements. Cell culture systems recapitulate disease relevant gene-regulatory landscapes, validating them as a tool for future investigation of genetic mechanisms underlying schizophrenia. Identifying the cell types in which risk variants operate will greatly increase our understanding of schizophrenia pathobiology and aid in the development of novel model systems and therapies.
Non-invasive modulation reduces repetitive behavior in a rat model through the sensorimotor cortico-striatal circuit
Authors: Edemann-Callesen Henriette , Habelt Bettina , Wieske Franziska , Jackson Mark , Khadka Niranjan , Mattei Daniele , Bernhardt Nadine , Heinz Andreas , Liebetanz David , Bikson Marom , Padberg Frank , Hadar Ravit , Nitsche Michael A. , Winter Christine 
Published: January 2018

AbstractInvoluntary movements as seen in repetitive disorders such as Tourette Syndrome (TS) results from cortical hyperexcitability that arise due to striato-thalamo-cortical circuit (STC) imbalance. Transcranial direct current stimulation (tDCS) is a stimulation procedure that changes cortical excitability, yet its relevance in repetitive disorders such as TS remains largely unexplored. Here, we employed the dopamine transporter-overexpressing (DAT-tg) rat model to investigate behavioral and neurobiological effects of frontal tDCS. The outcome of tDCS was pathology dependent, as anodal tDCS decreased repetitive behavior in the DAT-tg rats yet increased it in wild-type (wt) rats. Extensive deep brain stimulation (DBS) application and computational modeling assigned the response in DAT-tg rats to the sensorimotor pathway. Neurobiological assessment revealed cortical activity changes and increase in striatal inhibitory properties in the DAT-tg rats. Our findings show that tDCS reduces repetitive behavior in the DAT-tg rat through modulation of the sensorimotor STC circuit. This sets the stage for further investigating the usage of tDCS in repetitive disorders such as TS.
Rare loss of function mutations in N-methyl-d-aspartate glutamate receptors and their contributions to schizophrenia susceptibility
Authors: Yu Yanjie , Lin Yingni , Takasaki Yuto , Wang Chenyao , Kimura Hiroki , Xing Jingrui , Ishizuka Kanako , Toyama Miho , Kushima Itaru , Mori Daisuke , Arioka Yuko , Uno Yota , Shiino Tomoko , Nakamura Yukako , Okada Takashi , Morikawa Mako , Ikeda Masashi , Iwata Nakao , Okahisa Yuko , Takaki Manabu , Sakamoto Shinji , Someya Toshiyuki , Egawa Jun , Usami Masahide , Kodaira Masaki , Yoshimi Akira , Oya-Ito Tomoko , Aleksic Branko , Ohno Kinji , Ozaki Norio 
Published: January 2018

AbstractIn schizophrenia (SCZ) and autism spectrum disorder (ASD), the dysregulation of glutamate transmission through N-methyl-d-aspartate receptors (NMDARs) has been implicated as a potential etiological mechanism. Previous studies have accumulated evidence supporting NMDAR-encoding genes' role in etiology of SCZ and ASD. We performed a screening study for exonic regions of GRIN1, GRIN2A, GRIN2C, GRIN2D, GRIN3A, and GRIN3B, which encode NMDAR subunits, in 562 participates (370 SCZ and 192 ASD). Forty rare variants were identified including 38 missense, 1 frameshift mutation in GRIN2C and 1 splice site mutation in GRIN2D. We conducted in silico analysis for all variants and detected seven missense variants with deleterious prediction. De novo analysis was conducted if pedigree samples were available. The splice site mutation in GRIN2D is predicted to result in intron retention by minigene assay. Furthermore, the frameshift mutation in GRIN2C and splice site mutation in GRIN2D were genotyped in an independent sample set comprising 1877 SCZ cases, 382 ASD cases, and 2040 controls. Both of them were revealed to be singleton. Our study gives evidence in support of the view that ultra-rare variants with loss of function (frameshift, nonsense or splice site) in NMDARs genes may contribute to possible risk of SCZ.
Intrinsic apoptotic pathway activation increases response to anti-estrogens in luminal breast cancers
Authors: Williams Michelle M. , Lee Linus , Werfel Thomas , Joly Meghan M. Morrison , Hicks Donna J. , Rahman Bushra , Elion David , McKernan Courtney , Sanchez Violeta , Estrada Monica V. , Massarweh Suleiman , Elledge Richard , Duvall Craig , Cook Rebecca S. 
Published: January 2018

AbstractEstrogen receptor-α positive (ERα+) breast cancer accounts for approximately 70–80% of the nearly 25,0000 new cases of breast cancer diagnosed in the US each year. Endocrine-targeted therapies (those that block ERα activity) serve as the first line of treatment in most cases. Despite the proven benefit of endocrine therapies, however, ERα+ breast tumors can develop resistance to endocrine therapy, causing disease progression or relapse, particularly in the metastatic setting. Anti-apoptotic Bcl-2 family proteins enhance breast tumor cell survival, often promoting resistance to targeted therapies, including endocrine therapies. Herein, we investigated whether blockade of anti-apoptotic Bcl-2 family proteins could sensitize luminal breast cancers to anti-estrogen treatment. We used long-term estrogen deprivation (LTED) of human ERα+ breast cancer cell lines, an established model of sustained treatment with and acquired resistance to aromatase inhibitors (AIs), in combination with Bcl-2/Bcl-xL inhibition (ABT-263), finding that ABT-263 induced only limited tumor cell killing in LTED-selected cells in culture and in vivo. Interestingly, expression and activity of the Bcl-2-related factor Mcl-1 was increased in LTED cells. Genetic Mcl-1 ablation induced apoptosis in LTED-selected cells, and potently increased their sensitivity to ABT-263. Increased expression and activity of Mcl-1 was similarly seen in clinical breast tumor specimens treated with AI + the selective estrogen receptor downregulator fulvestrant. Delivery of Mcl-1 siRNA loaded into polymeric nanoparticles (MCL1 si-NPs) decreased Mcl-1 expression in LTED-selected and fulvestrant-treated cells, increasing tumor cell death and blocking tumor cell growth. These findings suggest that Mcl-1 upregulation in response to anti-estrogen treatment enhances tumor cell survival, decreasing response to therapeutic treatments. Therefore, strategies blocking Mcl-1 expression or activity used in combination with endocrine therapies would enhance tumor cell death.
Volcanic crystals as time capsules of eruption history
Authors: Ubide Teresa , Kamber Balz S. 
Published: January 2018

AbstractCrystals formed prior to a volcanic event can provide evidence of processes leading to and timing of eruptions. Clinopyroxene is common in basaltic to intermediate volcanoes, however, its ability as a recorder of pre-eruptive histories has remained comparatively underexplored. Here we show that novel high-resolution trace element images of clinopyroxene track eruption triggers and timescales at Mount Etna (Sicily, Italy). Chromium (Cr) distribution in clinopyroxene from 1974 to 2014 eruptions reveals punctuated episodes of intrusion of primitive magma at depth. Magma mixing efficiently triggered volcanism (success rate up to 90%), within only 2 weeks of arrival of mafic intrusions. Clinopyroxene zonations distinguish between injections of mafic magma and regular recharges with more evolved magma, which often fail to tip the system to erupt. High Cr zonations can therefore be used to reconstruct past eruptions and inform responses to geophysical signals of volcano unrest, potentially offering an additional approach to volcano hazard monitoring.
Characterizing the dynamics underlying global spread of epidemics
Authors: Wang Lin , Wu Joseph T. 
Published: January 2018

AbstractOver the past few decades, global metapopulation epidemic simulations built with worldwide air-transportation data have been the main tool for studying how epidemics spread from the origin to other parts of the world (e.g., for pandemic influenza, SARS, and Ebola). However, it remains unclear how disease epidemiology and the air-transportation network structure determine epidemic arrivals for different populations around the globe. Here, we fill this knowledge gap by developing and validating an analytical framework that requires only basic analytics from stochastic processes. We apply this framework retrospectively to the 2009 influenza pandemic and 2014 Ebola epidemic to show that key epidemic parameters could be robustly estimated in real-time from public data on local and global spread at very low computational cost. Our framework not only elucidates the dynamics underlying global spread of epidemics but also advances our capability in nowcasting and forecasting epidemics.
Epsin and Sla2 form assemblies through phospholipid interfaces
Authors: Garcia-Alai Maria M. , Heidemann Johannes , Skruzny Michal , Gieras Anna , Mertens Haydyn D. T. , Svergun Dmitri I. , Kaksonen Marko , Uetrecht Charlotte , Meijers Rob 
Published: January 2018

AbstractIn clathrin-mediated endocytosis, adapter proteins assemble together with clathrin through interactions with specific lipids on the plasma membrane. However, the precise mechanism of adapter protein assembly at the cell membrane is still unknown. Here, we show that the membrane–proximal domains ENTH of epsin and ANTH of Sla2 form complexes through phosphatidylinositol 4,5-bisphosphate (PIP2) lipid interfaces. Native mass spectrometry reveals how ENTH and ANTH domains form assemblies by sharing PIP2 molecules. Furthermore, crystal structures of epsin Ent2 ENTH domain from S. cerevisiae in complex with PIP2 and Sla2 ANTH domain from C. thermophilum illustrate how allosteric phospholipid binding occurs. A comparison with human ENTH and ANTH domains reveal only the human ENTH domain can form a stable hexameric core in presence of PIP2, which could explain functional differences between fungal and human epsins. We propose a general phospholipid-driven multifaceted assembly mechanism tolerating different adapter protein compositions to induce endocytosis.
Streamlined sensory motor communication through cortical reciprocal connectivity in a visually guided eye movement task
Authors: Itokazu Takahide , Hasegawa Masashi , Kimura Rui , Osaki Hironobu , Albrecht Urban-Raphael , Sohya Kazuhiro , Chakrabarti Shubhodeep , Itoh Hideaki , Ito Tetsufumi , Sato Tatsuo K. , Sato Takashi R. 
Published: January 2018

AbstractCortical computation is distributed across multiple areas of the cortex by networks of reciprocal connectivity. However, how such connectivity contributes to the communication between the connected areas is not clear. In this study, we examine the communication between sensory and motor cortices. We develop an eye movement task in mice and combine it with optogenetic suppression and two-photon calcium imaging techniques. We identify a small region in the secondary motor cortex (MOs) that controls eye movements and reciprocally connects with a rostrolateral part of the higher visual areas (VRL/A/AL). These two regions encode both motor signals and visual information; however, the information flow between the regions depends on the direction of the connectivity: motor information is conveyed preferentially from the MOs to the VRL/A/AL, and sensory information is transferred primarily in the opposite direction. We propose that reciprocal connectivity streamlines information flow, enhancing the computational capacity of a distributed network.
Sequence-regulated copolymerization based on periodic covalent positioning of monomers along one-dimensional nanochannels
Authors: Mochizuki Shuto , Ogiwara Naoki , Takayanagi Masayoshi , Nagaoka Masataka , Kitagawa Susumu , Uemura Takashi 
Published: January 2018

AbstractThe design of monomer sequences in polymers has been a challenging research subject, especially in making vinyl copolymers by free-radical polymerization. Here, we report a strategy to obtain sequence-regulated vinyl copolymers, utilizing the periodic structure of a porous coordination polymer (PCP) as a template. Mixing of Cu2+ ion and styrene-3,5-dicarboxylic acid (S) produces a PCP, [Cu(styrene-3,5-dicarboxylate)]
n
, with the styryl groups periodically immobilized along the one-dimensional channels. After the introduction of acrylonitrile (A) into the host PCP, radical copolymerization between A and the immobilized S is performed inside the channel, followed by decomposing the PCP to isolate the resulting copolymer. The predominant repetitive SAAA sequence in the copolymer is confirmed by monomer composition, NMR spectroscopy and theoretical calculations. Copolymerization using methyl vinyl ketone also provides the same type of sequence-regulated copolymer, showing that this methodology has a versatility to control the copolymer sequence via transcription of PCP periodicity at the molecular level.
Structure of a MacAB-like efflux pump from Streptococcus pneumoniae
Authors: Yang Hong-Bo , Hou Wen-Tao , Cheng Meng-Ting , Jiang Yong-Liang , Chen Yuxing , Zhou Cong-Zhao 
Published: January 2018

AbstractThe spr0693-spr0694-spr0695 operon of Streptococcus pneumoniae encodes a putative ATP-binding cassette (ABC)-type efflux pump involved in the resistance of antibiotics and antimicrobial peptides. Here we report the crystal structures of Spr0694–0695 at 3.3 Å and Spr0693 at 3.0 Å resolution, revealing a MacAB-like efflux pump. The dimeric Spr0694–0695 adopts a non-canonical fold of ABC transporter, the transmembrane domain of which consists of eight tightly packed transmembrane helices with an insertion of extracellular domain between the first and second helices, whereas Spr0693 forms a nanotube channel docked onto the ABC transporter. Structural analyses combined with ATPase activity and antimicrobial susceptibility assays, enable us to propose a putative substrate-entrance tunnel with a lateral access controlled by a guard helix. Altogether, our findings provide structural insights and putative transport mechanism of a MacAB-like efflux pump in Gram-positive bacteria.