bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neotoma Paleoecology Database, a multiproxy, international, community-curated data resource
Authors: Williams John W. , Grimm Eric C. , Blois Jessica L. , Charles Donald F. , Davis Edward B. , Goring Simon J. , Graham Russell W. , Smith Alison J. , Anderson Michael , Arroyo-Cabrales Joaquin , Ashworth Allan C. , Betancourt Julio L. , Bills Brian W. , Booth Robert K. , Buckland Philip I. , Curry B. Brandon , Giesecke Thomas , Jackson Stephen T. , Latorre Claudio , Nichols Jonathan , Purdum Timshel , Roth Robert E. , Stryker Michael , Takahara Hikaru
Published: January 2018

The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, theneotomaR package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.
Intergenerational land conflict in northern Uganda: children, customary law and return migration
Authors: Joireman Sandra F.
Published: January 2018

Northern Uganda is in transition after the conflict that ended in 2006. While its cities are thriving and economic opportunities abound, the social institutions governing land access are contested, the land administration system is changing, and the mechanisms available to address conflicts over resources have themselves become a venue for authority claims. This article examines the intergenerational nature of land conflicts in northern Uganda, focusing on the interplay of customary law, return migration and the development of a market in land. There are three contributions to existing literature: (1) a discussion of children's property rights under customary and statute law in Uganda; (2) the identification of the dual nature of children during complex emergencies as both victims and agents; and (3) an addition to knowledge on post-conflict return and community reconstruction. Evidence comes from several sources, the most important of which are a set of interviews conducted in Gulu and Kampala in May and June 2015. Secondary sources augment the field research, particularly survey research conducted in northern Uganda after the conflict.
‘The dead are just to drink from’: recycling ideas of revenge among the western Dinka, South Sudan
Authors: Pendle Naomi R.
Published: January 2018

Governments in South Sudan have long built their authority on their ability to fashion changing regimes of revenge and compensation, war and peace. Governments’ capture of these regimes has resulted in the secularization of compensation despite the ongoing spiritual consequences of lethal violence. This article explores these issues by focusing on the western Dinka of Greater Gogrial. In recent years, they have been closely linked to the highest levels of government through familial networks and comradeship. Violent revenge among the western Dinka is best understood not as revealing the absence of institutions of government, but as a consequence of the projection of government power over the details of local, normative codes and sanctions. In this age of post-state violence with automatic weapons, oil-wealthy elites and ambiguous rights, government authority and intention have often been erratic. As government authority now backs up these regimes of compensation and revenge, governments’ shifting nature has reshaped their meaning. In the last decade, the declining political space for peace and the disruption of the cattle economy has undermined the current value of compensation and its ability to appease the spiritual and moral demands for revenge. It has even distorted regimes to the extent that children become legitimate targets for revenge. The article is informed by archival sources and based on ethnographic research among the western Dinka (South Sudan) between 2010 and 2013, and further research in South Sudan until 2015.
Saturation of energetic-particle-driven geodesic acoustic modes due to wave–particle nonlinearity
Authors: Biancalani A. , Chavdarovski I. , Qiu Z. , Bottino A. , Del Sarto D. , Ghizzo A. , Gürcan Ö. , Morel P. , Novikau I.
Published: January 2018

The nonlinear dynamics of energetic-particle (EP) driven geodesic acoustic modes (EGAM) is investigated here. A numerical analysis with the global gyrokinetic particle-in-cell code ORB5 is performed, and the results are interpreted with the analytical theory, in close comparison with the theory of the beam-plasma instability. Only axisymmetric modes are considered, with a nonlinear dynamics determined by wave–particle interaction. Quadratic scalings of the saturated electric field with respect to the linear growth rate are found for the case of interest. As a main result, the formula for the saturation level is provided. Near the saturation, we observe a transition from adiabatic to non-adiabatic dynamics, i.e. the frequency chirping rate becomes comparable to the resonant EP bounce frequency. The numerical analysis is performed here with electrostatic simulations with circular flux surfaces, and kinetic effects of the electrons are neglected.
Ceratomyxa gracillima n. sp. (Cnidaria: Myxosporea) provides evidence of panmixia and ceratomyxid radiation in the Amazon basin
Authors: Zatti Suellen A. , Atkinson Stephen D. , Maia Antônio A. M. , Bartholomew Jerri L. , Adriano Edson A.
Published: January 2018

We describe a new freshwater myxosporean species Ceratomyxa gracillima n. sp. from the gall bladder of the Amazonian catfish Brachyplatystoma rousseauxii; the first myxozoan recorded in this host. The new Ceratomyxa was described on the basis of its host, myxospore morphometry, ssrDNA and internal transcribed spacer region (ITS-1) sequences. Infected fish were sampled from geographically distant localities: the Tapajós River, Pará State, the Amazon River, Amapá State and the Solimões River, Amazonas State. Immature and mature plasmodia were slender, tapered at both ends, and exhibited vermiform motility. The ribosomal sequences from parasite isolates from the three localities were identical, and distinct from all other Ceratomyxa sequences. No population-level genetic variation was observed, even in the typically more variable ITS-1 region. This absence of genetic variation in widely separated parasite samples suggests high gene flow as a result of panmixia in the parasite populations. Maximum likelihood and maximum parsimony analyses placed C. gracillima n. sp. sister to Ceratomyxa vermiformis in a subclade together with Ceratomyxa brasiliensis and Ceratomyxa amazonensis, all of which have Amazonian hosts. This subclade, together with other Ceratomyxa from freshwater hosts, formed an apparently early diverging lineage. The Amazonian freshwater Ceratomyxa species may represent a radiation that originated during marine incursions into the Amazon basin that introduced an ancestral lineage in the late Oligocene or early Miocene.
Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis
Authors: Padula Maria Carmela , Schaer Marie , Armando Marco , Sandini Corrado , Zöller Daniela , Scariati Elisa , Schneider Maude , Eliez Stephan
Published: January 2018

Background

Patients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile.

Methods

In this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach.

Results

Our results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS.

Conclusions

These results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.
Generation, transport, and efficient extraction of a large cross-section electron beam into an air in an accelerator with a mesh plasma cathode
Authors: Vorobyov Maxim S. , Koval Tamara V. , Koval Nikolay N. , Hung Nguyen Bao
Published: January 2018

The paper presents experimental and theoretical research data on the generation, transport, and extraction of a large cross-section (750 × 150 mm2) electron beam into the air through a thin metal foil in an accelerator with a mesh plasma cathode on the bases of a low-pressure arc and with a multi-aperture two-electrode electron-optical system. When the burning conditions of the arc discharge, responsible for the generation of the emission plasma, is changed, the characteristics of this plasma were investigated, including under the conditions of the selection of electrons from it. Our experiments show that at an accelerating voltage of 200 kV, current in the accelerating gap of up to 30 A, and full width at half maximum of up to 100 µm, the average extracted power is ≈4 kW and the extracted beam current is ≈85% from the common current into the accelerating gap. Our numerical estimates give a good correlation between the arc and emission plasma parameters depending on the electrode configuration in the discharge system and on the mechanism of electron beam generation. Analysis of the emission plasma parameters under different arc conditions and of the mechanisms responsible for the beam energy loss suggests that most of the energy in the accelerator is lost at the support grid and at the output foil due to defocusing of the beam and partial electron reflection from the foil. Other mechanisms that decrease the extracted beam energy are discussed.
HARNESSING HEURISTICS FOR ECONOMIC POLICY
Authors: Mabsout Ramzi , Mourad Jana G.
Published: January 2018

The effectiveness of heuristics has received contradicting interpretations in the behavioural sciences. We study the policy implications of two programmes that dispute the effectiveness of heuristics – the biases and heuristics and the fast and frugal heuristics programmes. While the first blames heuristics for most errors in judgement, the second posits heuristics as simple mental algorithms that work well in a range of environments. We argue that the fast and frugal programme is less paternalistic insofar as it models humans as effective decision-makers in a range of environments. However, in the rapidly changing environments of the 21st century, both are needed to inform evidence-based policies.
Association between Falls and Caregiving Tasks among Informal Caregivers: Canadian Community Health Survey Data
Authors: Vaughon Wendy , Lee Yeonjung , Gallo William , Kaufman Jennifer , Unuigbe Aig
Published: January 2018

Les chutes constituent une cause de morbidité et de mortalité fréquente chez les personnes âgées. Bien que plusieurs études aient exploré les liens entre les chutes des bénéficiaires de soins plus âgés et la santé de leurs aidants, peu de recherches ont abordé les liens entre les tâches effectuées par les aidants âgés et leurs propres chutes. La présente étude a évalué les rapports entre, d’une part, les chutes des aidants et, d’autre part, la fréquence et le type de tâches assumées par des aidants naturels plus âgés. Les données, tirées de l’Enquête sur la santé des collectivités canadiennes - Vieillissement en santé (ESCC 2008-2009; N=2934), ont été examinées à l’aide d’analyses descriptives et de régressions logistiques. Les fréquences de prestation de soins plus élevées étaient positivement associées, chez les aidants, avec un plus grand nombre de chutes subies au cours de la dernière année, tandis que les aidants effectuant des tâches ménagères rapportaient moins de chutes. Ces résultats indiquent qu’il pourrait y avoir une relation entre des facteurs associés aux soins fournis et les chutes, chez les aidants plus âgés. De plus amples recherches, utilisant des données longitudinales et expérimentales, sont nécessaires pour mieux comprendre les liens entre les tâches assumées par l’aidant âgé et ses risques de chute.
Crystal structure of methylprednisolone acetate form II, C24H32O6
Authors: Wheatley Austin M. , Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: January 2018

The crystal structure of methylprednisolone acetate form II, C24H32O6, has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Methylprednisolone acetate crystallizes in space group P212121 (#19) with a = 8.17608(2), b = 9.67944(3), c = 26.35176(6) Å, V = 2085.474(6) Å3, and Z = 4. Both hydroxyl groups act as hydrogen bond donors, resulting in a two-dimensional hydrogen bond network in the ab plane. C–H⋯O hydrogen bonds also contribute to the crystal energy. The powder pattern is included in the Powder Diffraction File™ as entry 00-065-1412.
THE BUSINESS CYCLE WITH NOMINAL CONTRACTS AND SEARCH FRICTIONS
Authors: Moon Weh-Sol
Published: January 2018

Macroeconomic models of the economy with rigid wage structures tend to predict unrealistically volatile labor hours and countercyclical productivity. This study extends the Cho–Cooley model by incorporating labor market frictions and efficient bargaining as an alternative contracting scheme in which contracts are forward-looking and specify labor hours and wage rates. By accounting for search frictions and realistic contractual schemes, the extended model overcomes two counterfactual predictions: (1) excess volatility of employment and output and (2) countercyclical productivity. However, the extended model fails to produce the Beveridge curve.
Aphid–Buchnera–Ant symbiosis; or why are aphids rare in the tropics and very rare further south?
Authors: Perkovsky Evgeny , Wegierek Piotr
Published: January 2018

At least since the Cretaceous Terrestrial Revolution, the geographical distribution of aphids, particularly in the Northern Hemisphere, has been strongly affected by the low thermal tolerance of their obligatory bacterial symbiont,Buchnera aphidicola, which was why the aphids switched to obligate parthenogenesis in low latitudes. Hormaphidids and greenideids penetrated into the tropics only after the Oligocene strengthening of climate seasonality, and specialisations of the tropical representatives of these families did not allow them to spread further south (in the case of cerataphidines), or only allowed in few cases (in the case of greenideids).

Aphids suffered from the Mesozoic–Cenozoic boundary extinction event much more strongly than other insects. The extinction was roughly coincidental with the establishment of the tight symbiosis of aphids with formicine and dolichoderine ants, which was accompanied by the flourishing of all three groups.

In the Cretaceous, all of the representatives of extant and subfamilies occupied positions that were subordinate to Armaniinae and Sphecomyrminae. Prior to large ant colonies evolving their efficient ant–aphid mutualism, the aphids remained unprotected before the growing ant predation. The origin of the aphid trophobiosis with large colonies of Formicinae and Dolichoderinae has resulted in the steep decline of aphids left beyond that ant–aphid symbiotic network. By at least the basal Eocene (unlike the Late Cretaceous), ant proportions in the entomofauna increased sharply, and evident dominants emerged. Even now, aphid milkers from small colonies (hundreds of specimens) never protect their symbionts, and homopteran-tending ants are more likely to be dominant, with large colonies of 104–105workers.

The mutualistic ant–aphid system failed to cross the tropical belt during the Cenozoic because ofBuchnera's low heat tolerance. As a result, the native southern temperate aphid fauna consists now of seven genera only, five of which are Late Cretaceous relicts. Some of them had relatives in Late Cretaceous amber of the Northern Hemisphere.
The fossil record of the planthopper family Achilidae, with particular reference to those in Baltic amber (Hemiptera: Fulgoromorpha)
Authors: Brysz Alicja Magdalena , Szwedo Jacek
Published: January 2018

The family Achilidae (Hemiptera, Fulgoromorpha, commonly called planthoppers) is one of the least known and least understood groups, due to their cryptic lifestyle. They appear in the fossil record in the Lower Cretaceous, with a single genus and two species from the Crato Formation of Brazil. The oldest amber inclusion is reported from the earliest Late Cretaceous amber of Burma. Surprisingly, Achilidae are relatively common among the larger inclusions that can be found in Eocene Baltic amber. The first description of a fossil species was in the mid-19thCentury. Currently, there are 13 genera and 16 species known from fossils, of which nine genera and 11 species are from Baltic amber. However, many of them need reconsideration, revisionary studies and placement in the phylogenetic context of the family. Former studies on inclusions in this amber revealed several unique forms (extinct tribes Ptychoptilini and Waghildini), or taxa ascribable to the sparse Recent tribe Achilini. This paper provides an overview of the knowledge of fossil Achilidae, particularly those from Baltic amber. The Eocene appears to be the heyday of the family; however, this hypothesis should be tested with further detailed studies.
Akuter Schwindel: zentral versus peripher
Authors: Diener Suzie
Published: January 2018

Zusammenfassung. Schwindel ist nach Kopfschmerzen eines der häufigsten Symptome, die zu einem Arztbesuch führen. Ausgehend von dieser Tatsache stellen sich ca. 25 % der Patienten mit akuten Schwindelbeschwerden in einer Notfallaufnahme vor. Die Herausforderung der betreuenden Kollegen besteht darin, ein akut zentral-vestibuläres Syndrom nicht zu übersehen, was verheerende Folgen mit sich bringen könnte. Eine sorgfältige und strukturierte Anamneseerhebung zusammen mit der klinischen Untersuchung trägt bereits zu ca. 90 % zur Diagnosestellung bei und ist sensitiver als die diffusionsgewichtete Kernspintomografie. Der Fokus der Anamnese liegt bei der Dauer der Symptome und deren Triggerfaktoren. Ein Bedside-Test, bestehend aus Kopfimpulstest, Nystagmusprüfung, Test auf Skew und zusätzliche Hörprüfung mittels Fingerreiben, hilft bei der differenzialdiagnostischen Eingrenzung im Hinblick auf die Differenzierung zwischen akutem zentralen und peripheren Schwindelsyndrom.
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

Chinese 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

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

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

Few 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

Genome-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

Involuntary 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

In 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

Estrogen 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

Crystals 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

Over 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

In 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.
Author Correction: Signatures of the topological s+− superconducting order parameter in the type-II Weyl semimetal T
d
-MoTe2
Authors: Guguchia Z. , von Rohr F. , Shermadini Z. , Lee A. T. , Banerjee S. , Wieteska A. R. , Marianetti C. A. , Frandsen B. A. , Luetkens H. , Gong Z. , Cheung S. C. , Baines C. , Shengelaya A. , Taniashvili G. , Pasupathy A. N. , Morenzoni E. , Billinge S. J. L. , Amato A. , Cava R. J. , Khasanov R. , Uemura Y. J.
Published: January 2018

The original version of this article omitted the following from the Acknowledgements: “CAM and AL were supported by the NSF MRSEC program through Columbia in the Center for Precision Assembly of Superstratic and Superatomic Solids (DMR-1420634). Additionally, this research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under ‘Contract No. DE-AC02-05CH11231’.” This has now been corrected in both the PDF and HTML versions of the article.
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

Cortical 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

The 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

The 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.
Gamma-interferon exerts a critical early restriction on replication and dissemination of yellow fever virus vaccine strain 17D-204
Authors: Lam L. K. Metthew , Watson Alan M. , Ryman Kate D. , Klimstra William B.
Published: January 2018

Live attenuated viruses are historically among the most effective viral vaccines. Development of a safe vaccine requires the virus to be less virulent, a phenotype that is historically arrived by empirical evaluation often leaving the mechanisms of attenuation unknown. The yellow fever virus 17D live attenuated vaccine strain has been developed as a delivery vector for heterologous antigens; however, the mechanisms of attenuation remain elusive. The successful and safe progress of 17D as a vaccine vector and the development of live attenuated vaccines (LAVs) to related flaviviruses requires an understanding of the molecular mechanisms leading to attenuation. Using subcutaneous infection of interferon-deficient mouse models of wild type yellow fever virus (WT YFV) pathogenesis and 17D-mediated immunity, we found that, in the absence of type I IFN (IFN-α/β), type II interferon (IFN-γ) restricted 17D replication, but not that of WT YFV, by 1–2 days post-infection. In this context, IFN-γ responses protected 17D-infected animals from mortality, largely restricted the virus to lymphoid organs, and eliminated viscerotropic disease signs such as steatosis in the liver and inflammatory cell infiltration into the spleen. However, WT YFV caused a disseminated infection, gross liver pathology, and rapid death of the animals. In vitro, IFN-γ treatment of myeloid cells suppressed the replication of 17D significantly more than that of WT YFV, suggesting a direct differential effect on 17D virus replication. Together these data indicate that an important mechanism of 17D attenuation in vivo is increased sensitivity to IFN-γ stimulated responses elicited early after infection.
Microbial Competition of Rhodotorula mucilaginosa UANL-001L and E. coli increase biosynthesis of Non-Toxic Exopolysaccharide with Applications as a Wide-Spectrum Antimicrobial
Authors: Vazquez-Rodriguez Augusto , Vasto-Anzaldo Ximena G , Barboza Perez Daniel , Vázquez-Garza Eduardo , Chapoy-Villanueva Héctor , García-Rivas Gerardo , Garza-Cervantes Javier A. , Gómez-Lugo Jéssica J. , Gomez-Loredo Alma Elizabeth , Garza Gonzalez Maria Teresa , Zarate Xristo , Morones-Ramirez Jose Ruben
Published: January 2018

Bacterial species are able to colonize and establish communities in biotic and abiotic surfaces. Moreover, within the past five decades, incidence of bacterial strains resistant to currently used antibiotics has increased dramatically. This has led to diverse health issues and economical losses for different industries. Therefore, there is a latent need to develop new and more efficient antimicrobials. This work reports an increased production of an exopolysaccharide in a native yeast strain isolated from the Mexican Northeast, Rhodotorula mucilaginosa UANL-001L, when co-cultured with E. coli. The exopolysaccharide produced is chemically and physically characterized and its applications as an antimicrobial and antibiofilm are explored. The exopolysaccharide is capable of inhibiting planktonic growth and biofilm formation in Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, the exopolysaccharide studied here does not exhibit cytotoxic effects when assessed both, in vitro against an H9c2 mammalian cell line, and in vivo in a murine toxicity model. Taken together, the properties of this exopolysaccharide indicate that it has potential applications to inhibit bacterial colonization in medical and industrial settlings.