bluuebunny/crossref_metadata_2025 huggingface dataset:
AMERICAN POWER AND INTERWAR INTERNATIONALISM
Authors: THOMPSON JOHN A.
Published: August 2018

Two central features of global history over the past century have been the pre-eminent power of the United States in world politics and the growth of international organizations. The relationship between these phenomena has been variously interpreted, in ways that reflect theoretical and methodological commitments as well as political perspectives. The Realist school, for whom power relationships are always determinative, have followed Carl Schmitt and E. H. Carr in seeing international institutions, and the norms and laws they uphold, as instruments through which dominant powers seek legitimacy as well as influence. By contrast, liberal theorists have viewed the pursuit of a rule-governed world order, and the development of the idea of a ‘world community’, as a more autonomous and broadly based enterprise, one spurred by increased interdependence and greater concern with matters of common interest to all nations – not least that of avoiding the devastating effects of great power warfare in the modern era. As is usually the case with such analytically sharp distinctions, neither of these positions conveys the whole truth. From the Concert of Europe on, great powers have recognized a collective interest in peace and stability but the growth of international institutions has also been the product of wider ideals and interests. As Mark Mazower has shown in his wide-ranging study, Governing the world, the relationship between the narrower interests of great powers on the one hand and various forms of internationalism on the other has been a complex one, involving elements both of conflict and of congruence. But, Mazower emphasizes, since the Second World War, the structure and activities of the United Nations, the International Monetary Fund, the World Bank, and other international organizations have been largely shaped by Washington. A generation earlier, however, the United States did not even become a member of the League of Nations, making it more possible to distinguish between the role of American power and that of other sources of support for international bodies, and also to assess the relationship and comparative importance of these two novel elements in world politics. It is perhaps not surprising that much of the recent scholarship on the international history of the post-First World War period has focused, in one way or another, on this issue.
European Reconfigurations of Transnational Activism: Solidarity and Human Rights Campaigns on Behalf of Chile during the 1970s and 1980s
Authors: Christiaens Kim
Published: August 2018

The overthrow of the democratically elected socialist president Salvador Allende in Chile and the human rights violations under the military junta of Augusto Pinochet spawned one of the most iconic and sustained human rights campaigns of the Cold War. Human rights scholars have argued that this movement on behalf of Chile signalled the “breakthrough” of human rights as the lingua franca of transnational activism. They have emphasized the global dimensions of these campaigns, which inspired movements mobilizing on behalf of other issues in the Third World. However, such narratives have not been corroborated by research on the campaigns as developed in Europe. Historians have so far focused on the impact of the Chilean crisis in specific countries or on particular organizations, and on the ways in which human rights activism was coloured by local and national contexts. This article aims to shift the scope of the debate by establishing relations with and crossovers from other transnational causes and campaigns, analysing the ways in which campaigns on behalf of Chile became intimately related to campaigns on intra-European issues during the 1970s and 1980s. It explores the so far little-studied connections between campaigns over Chile and simultaneously burgeoning movements on behalf of East–West détente, resistance against authoritarian regimes in Southern Europe, and the plight of dissidents in Eastern Europe. It argues that campaigns on behalf of Chile were reconfigured around European themes, created bonds of solidarity within a divided Europe, and drew on analogies rather than a juxtaposition between Europe and the Third World.
Dietary patterns and components to prevent and treat heart failure: a comprehensive review of human studies
Authors: Kerley Conor P.
Published: August 2018

Growing evidence has emerged about the role of dietary patterns and components in heart failure (HF) incidence and severity. The objective here is to provide a comprehensive summary of the current evidence regarding dietary patterns/components and HF. A comprehensive search of online databases was conducted using multiple relevant keywords to identify relevant human studies. The Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets have consistently been associated with decreased HF incidence and severity. Regarding specific dietary components, fruit, vegetables, legumes and whole grains appear beneficial. Current evidence suggests that red/processed meats, eggs and refined carbohydrates are harmful, while fish, dairy products and poultry remain controversial. However, there is a notable lack of human intervention trials. The existing but limited observational and interventional evidence from human studies suggests that a plant-based dietary pattern high in antioxidants, micronutrients, nitrate and fibre but low in saturated/trans-fat and Na may decrease HF incidence/severity. Potential mechanisms include decreased oxidative stress, homocysteine and inflammation but higher antioxidant defence and NO bioavailability and gut microbiome modulation. Randomised, controlled trials are urgently required.
THE CONTENT-INDEPENDENCE OF POLITICAL OBLIGATION: WHAT IT IS AND HOW TO TEST IT
Authors: Valentini Laura
Published: August 2018

One of the distinctive features of the obligation to obey the law is its content-independence. We ought to do what the law commandsbecausethe law commands it, and not because of the law's content—i.e., the independent merits of the actions it prescribes. Despite its popularity, the notion of content-independence is marked by ambiguity. In this paper, I first clarify what content-independence is. I then develop a simple test—the “content-independence test”—which allows us to establish whether any candidate justification of the obligation to obey the law delivers genuine content-independence. I apply this test to prominent such justifications and conclude that several of them, surprisingly, fail it.
Executive Functions and Their Relation to Sleep Following Mild Traumatic Brain Injury in Preschoolers
Authors: Landry-Roy Catherine , Bernier Annie , Gravel Jocelyn , Beauchamp Miriam H.
Published: August 2018

Objectives:Traumatic brain injury (TBI) sustained during childhood is known to impact children’s executive functioning. However, few studies have focused specifically on executive functioning after preschool TBI. TBI has also been associated with sleep disturbances, which are known to impair executive functions in healthy children. The aim of this study was to investigate executive functions in preschoolers with mild TBI, and to determine the role of sleep in the links between TBI and executive functioning.Methods:The sample was drawn from a longitudinal study and included 167 children, aged 18 to 60 months, divided into 2 groups: children with accidental mild TBI (n=84) and typically developing children (n=83). Children were assessed 6 months post-injury on executive function measures (inhibition and cognitive flexibility) and sleep measures (actigraphy data and parental rating of sleep problems).Results:The two groups did not differ in their executive abilities. However, relative to controls, children with mild TBI and shorter nighttime sleep duration or increased sleep problems exhibited poorer executive functions.Conclusions:These results support a “double hazard” effect, whereby the combination of sleep disturbances and mild TBI results in poorer executive functions. The findings highlight the importance of assessing and monitoring the quality of sleep even after mild head injuries. Poor sleep may place children at risk for increased cognitive difficulties. (JINS, 2018,24, 769–780)
New Yes/No Recognition Memory Analysis on the California Verbal Learning Test-3: Clinical Utility in Alzheimer’s and Huntington’s Disease
Authors: Graves Lisa V. , Holden Heather M. , Van Etten Emily J. , Delano-Wood Lisa , Bondi Mark W. , Salmon David P. , Corey-Bloom Jody , Delis Dean C. , Gilbert Paul E.
Published: August 2018

Objectives: The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington’s disease [HD]). Methods: We compared the performance of individuals with Alzheimer’s disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. Results: Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. Conclusions: Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833–841)
Maternal smoking and low family income during pregnancy as predictors of the relationship between depression and adiposity in young adults
Authors: Bhat S. K. , Beilin L. J. , Robinson M. , Burrows S. , Mori T. A.
Published: August 2018

There is an increasing incidence of overweight/obesity and mental health disorders in young adults and the two conditions often coexist. We aimed to investigate the influence of antenatal and postnatal factors that may underlie this association with a focus on maternal prenatal smoking, socio-economic status and gender. Data from the Western Australian Pregnancy Cohort (Raine) Study (women enrolled 1989–1991) including 1056 offspring aged 20 years (cohort recalled 2010–2012) were analyzed (2015–2016) using multivariable models for associations between offspring depression scores (DASS-21 Depression-scale) and body mass index (BMI), adjusting for pregnancy and early life factors and offspring behaviours. There was a significant positive relationship between offspring depression-score and BMI independent of gender and other psychosocial covariates. There was a significant interaction between maternal prenatal smoking and depression-score (interaction coefficient=0.096; 95% CI: 0.006, 0.19, P=0.037), indicating the relationship between depression-score and BMI differed according to maternal prenatal smoking status. In offspring of maternal prenatal smokers, a positive association between BMI and depression-score (coefficient=0.133; 95% CI: 0.05, 0.21, P=0.001) equated to 1.1 kg/m2 increase in BMI for every 1standard deviation (8 units) increase in depression-score. Substituting low family income during pregnancy for maternal prenatal smoking in the interaction (interaction coefficient=0.091; 95% CI: 0.01, 0.17, P=0.027) showed a positive association between BMI and depression score only among offspring of mothers with a low family income during pregnancy (coefficient=0.118; 95% CI: 0.06, 0.18, P<0.001). There were no significant effects of gender on these associations. Whilst further studies are needed to determine whether these associations are supported in other populations, they suggest potentially important maternal behavioural and socio-economic factors that identify individuals vulnerable to the coexistence of obesity and depression in early adulthood.
Strategies to reduce non-communicable diseases in the offspring: negative and positivein uteroprogramming
Authors: Rodriguez-Caro H. , Williams S. A.
Published: August 2018

Non-communicable diseases (NCDs) are a major problem as they are the leading cause of death and represent a substantial economic cost. The ‘Developmental Origins of Health and Disease Hypothesis’ proposes that adverse stimuli at different life stages can increase the predisposition to these diseases. In fact, adversein uteroprogramming is a major origin of these diseases due to the high malleability of embryonic development. This review provides a comprehensive analysis of the scientific literature onin uteroprogramming and NCDs highlighting potential medical strategies to prevent these diseases based upon this programming. We fully address the concept and mechanisms involved in this programming (anatomical disruptions, epigenetic modifications and microbiota alterations). We also examine the negative role ofin uteroprogramming on the increased predisposition of NCDs in the offspring, which introduces the passive medical approach that consists of avoiding adverse stimuli including an unhealthy diet and environmental chemicals. Finally, we extensively discuss active medical approaches that target the causes of NCDs and have the potential to significantly and rapidly reduce the incidence of NCDs. These approaches can be classified as directin uteroprogramming modifications and personalized lifestyle pregnancy programs; they could potentially provide transgenerational NCDs protection. Active strategies against NCDs constitute a promising tool for the reduction in NCDs.
Sources of confounding in life course epidemiology
Authors: Santos S. , Zugna D. , Pizzi C. , Richiardi L.
Published: August 2018

In epidemiologic analytical studies, the primary goal is to obtain a valid and precise estimate of the effect of the exposure of interest on a given outcome in the population under study. A crucial source of violation of the internal validity of a study involves bias arising from confounding, which is always a challenge in observational research, including life course epidemiology. The increasingly popular approach of meta-analyzing individual participant data from several observational studies also brings up to discussion the problem of confounding when combining data from different populations. In this study, we review and discuss the most common sources of confounding in life course epidemiology: (i) confounding by indication, (ii) impact of baseline selection on confounding, (iii) time-varying confounding and (iv) mediator–outcome confounding. We also discuss the issue of addressing confounding in the context of an individual participant data meta-analysis.
Living in Harmony with Nature? A Critical Appraisal of the Rights of Mother Earth in Bolivia
Authors: Villavicencio Calzadilla Paola , Kotzé Louis J.
Published: August 2018

Juridical protection of the rights of nature is steadily emerging in several legal systems and in public discourse. Building on a recent publication inTransnational Environmental Lawin which we interrogated Ecuador’s constitutional experiment with the rights of nature, we critically reflect in this contribution on Bolivia’s legal regime providing for the rights of Mother Earth. We do so, first, by sketching the juridical-political context within which these statutes were drafted and adopted, and then by analyzing the relevant constitutional provisions that provide the basis for the laws of Mother Earth. The third part forms the bulk of the discussion and details the background and the most relevant provisions of Bolivian statutes with a view to enabling a deeper critique in Part 4, in which we critically evaluate both the symbolic and the theoretical significance of the statutes as well as concerns related to their practical implementation. Insofar as the rights of nature paradigm has now become a truly global debate and a consideration in transnational comparative legal borrowing practices, our analysis aims to reveal the Bolivian experience, which could be instructive for civil society groups, academics, politicians and legislatures in a transnational setting.
Stoichiometric N:P Ratios, Temperature, and Iron Impact Carbon and Nitrogen Uptake by Ross Sea Microbial Communities
Authors: Spackeen Jenna L. , Bronk Deborah A. , Sipler Rachel E. , Bertrand Erin M. , Hutchins David A. , Allen Andrew E.
Published: August 2018

Phytoplankton growth in the seasonally productive Southern Ocean is typically limited by iron (Fe). In the next century, however, Fe inputs and temperature are predicted to increase. Dissolved concentrations of nitrogen (N) and phosphorus (P) may also change due to physical and biological drivers, altering the stoichiometric N:P ratio of the water column. Two separate experiments were conducted to study how these predicted changes will impact nutrient utilization by two natural microbial communities from the Ross Sea, Antarctica. The first investigation focused on a Terra Nova Bay community amended with Fe and grown under a wide range of seven different N:P ratios. Building on the results of the first study, a McMurdo Sound community was incubated under a factorial design at high, medium (ambient), and low N:P ratios, with and without Fe addition, and at ambient versus elevated temperature. In both experiments absolute uptake rates of bicarbonate, nitrate, and amino acids by two size fractions (0.7–5.0 μm and > 5.0 μm) of microorganisms were measured using stable isotopes. For Terra Nova Bay microorganisms, significant differences in nutrient uptake rates occurred when the N:P ratio was elevated, and nitrate uptake rates significantly increased early in the experiment but were not different at the end. For McMurdo Sound microorganisms, changing the N:P supply ratio did not have a clear effect, while temperature elevation and/or Fe addition significantly increased nutrient uptake. Results indicate that changing the dissolved N:P ratio can potentially alter nutrient uptake rates; however, the impact of temperature and Fe are greater.
Brown Carbon from Increased Shipping Could Harm Arctic Ice
Authors: Underwood Emily
Published: August 2018

Brown carbon in future marine engine emissions could have a negative effect on Arctic ice.
The Coupled Dynamic and Thermodynamic Processes for Secondary Eyewall Formation
Authors: Wang Xingbao , Li Qinglan , Davidson Noel E.
Published: August 2018

Using a previously documented successful simulation of secondary eyewall formation (SEF), the coupled dynamic and thermodynamic processes during SEF are investigated from an axisymmetric mean perspective. The budgets of momentum, density potential temperature, and radial pressure gradient force (PGF) with very small residuals reveal that rather than a single process dominating, the SEF is the consequence of tight coupling processes between the hurricane tangential wind, transverse circulation, diabatic heating, mean and eddy fluxes of momentum and heat, and the hurricane boundary layer. The collective actions of these coupling processes generate the following conditions for the SEF: (i) along with slow eyewall contraction, the azimuthal‐mean tangential wind increases on the inner side of the eyewall; (ii) while the regions in the eye and beyond the eyewall are warming, a lesser warming or cooling zone sandwiched between these two warming regions appears near the axis of maximum vertical velocity; (iii) low‐level pressure decreases (increases) with the column‐integrated warming (cooling); the increment in the PGF beyond the eyewall brings about a significant low‐level radial and tangential wind increment at SEF radii, and (iv) the hurricane boundary layer radial flow corresponding to the PGF increment enhances the convergence of moisture and angular momentum within the SEF radii. Eventually, these processes result in the SEF.
Tracing the Impact of Coastal Water Geochemistry on the Re‐Os Systematics of Macroalgae: Insights From the Basaltic Terrain of Iceland
Authors: Sproson Adam D. , Selby David , Gannoun Abdelmouchine , Burton Kevin W. , Dellinger Mathieu , Lloyd Jeremy M.
Published: August 2018

This study presents rhenium (Re) and osmium (Os) elemental and isotope data for macroalgae, dissolved load, and bed load from Icelandic coastal and/or river waters, an environment adjacent to predominantly basaltic terrains, ranging in age from historic to ~12 Ma. Both the Re (0.1 to 88.4 ppb) and Os (3.3 to 254.5 ppt) abundance in macroalgae are shown to be primarily controlled by uptake from the dissolved load of local seawater and are largely dependent on the relative influence of local freshwater inputs. Incorporation of Re and Os into macroalgae appears to be complicated by additional Re and Os uptake from the bed load. The 187Os/188Os (0.16 to 0.99) composition of macroalgae is highly variable and is explained in terms of an unradiogenic 187Os/188Os contribution from rivers draining younger basaltic catchments that have undergone congruent weathering (and/or hydrothermal input) and a radiogenic 187Os/188Os contribution from two distinct sources: rivers draining older catchments that have undergone incongruent weathering of radiogenic primary basaltic minerals and North Atlantic seawater. The 187Re/188Os composition (~65 to 40,320) of macroalgae traces that of water, with higher values associated with higher salinity waters, but far exceeds the 187Re/188Os of water due to the preferential uptake of Re over Os by macroalgae in areas of high dissolved and/or bed load Re abundances. This study substantiates the utility of macroalgae as a proxy for the long‐term (months to years) average 187Os/188Os composition of seawater, which holds the potential to elucidate a range of Earth system and anthropogenic processes.
Association of anxiety with subcortical amyloidosis in cognitively normal older adults
Authors: Hanseeuw Bernard J. , Jonas Victoria , Jackson Jonathan , Betensky Rebecca A. , Rentz Dorene M. , Johnson Keith A. , Sperling Reisa A. , Donovan Nancy J.
Published: August 2018

Late-life anxiety has been associated with increased progression from normal cognition to amnestic MCI, suggesting that anxiety may be a neuropsychiatric symptom of Alzheimer’s disease (AD) pathological changes and a possible marker of anatomical progression in preclinical AD. This study examined whether cortical or subcortical amyloidosis, indicating earlier or later stages of preclinical AD, was associated with greater self-reported anxiety among 118 cognitively normal volunteers, aged 65–90 years, and whether this association was stronger in APOEε4 carriers. Participants underwent Pittsburgh Compound B Positron Emission Tomography (PiB-PET) to assess fibrillar amyloid-β burden in cortical and subcortical regions, and measurement of anxiety using the Hospital Anxiety and Depression Scale-anxiety subscale. Higher PiB-PET measures in the subcortex (striatum, amygdala, and thalamus), but not in the cortex, were associated with greater anxiety, adjusting for demographics, cognition, and depression. Findings were similar using a cortico-striatal staging system and continuous PET measurements. Anxiety was highest in APOEε4 carriers with subcortical amyloidosis. This work supports in vivo staging of amyloid-β deposition in both cortical and subcortical regions as a promising approach to the study of neuropsychiatric symptoms such as anxiety in cognitively normal older individuals. Elevated anxiety symptoms in combination with high-risk biological factors such as APOEε4 and subcortical amyloid-β may identify participants closest to MCI for secondary prevention trials.
Abundance and distribution of Archaea in the subseafloor sedimentary biosphere
Authors: Hoshino Tatsuhiko , Inagaki Fumio
Published: August 2018

Subseafloor sedimentary environments harbor a remarkable number of microorganisms that constitute anaerobic and aerobic microbial ecosystems beneath the ocean margins and open-ocean gyres, respectively. Microbial biomass and diversity richness generally decrease with increasing sediment depth and burial time. However, there has been a long-standing debate over the contribution and distribution of Archaea in the subseafloor sedimentary biosphere. Here we show the global quantification of archaeal and bacterial 16S rRNA genes in 221 sediment core samples obtained from diverse oceanographic settings through scientific ocean drilling using microfluidic digital PCR. We estimated that archaeal cells constitute 37.3% of the total microbial cells (40.0% and 12.8% in the ocean margin and open-ocean sites, respectively), corresponding to 1.1 × 1029 cells on Earth. In addition, the relative abundance of archaeal 16S rRNA genes generally decreased with the depth of water in the overlying sedimentary habitat, suggesting that Archaea may be more sensitive to nutrient quality and quantity supplied from the overlying ocean.
Inter-Kingdom beach warfare: Microbial chemical communication activates natural chemical defences
Authors: Khalil Zeinab G , Cruz-Morales Pablo , Licona-Cassani Cuauhtemoc , Marcellin Esteban , Capon Robert J
Published: August 2018

An inter-kingdom beach warfare between a Streptomyces sp. and Aspergillus sp. co-isolated from shallow water beach sand, collected off Heron Island, Queensland, Australia, saw the bacteriostatic Aspergillus metabolite cyclo-(l-Phe-trans-4-hydroxy-l-Pro) (3) stimulate the Streptomyces to produce nitric oxide (NO), which in turn mediated transcriptional activation of a silent biosynthetic gene cluster (BGC) for fungistatic heronapyrrole B (1). Structure activity relationship studies, coupled with the use of NO synthase inhibitors, donors and scavangers, and both genomic and transcriptomic analyses, confirmed the extraordinary chemical cue specificity of 3, and its NO-mediated mechanism of transcriptional action. Our findings reveal the importance of inter-kingdom (fungal-bacterial) chemical communication in the regulation of silent BGCs coding for chemical defenses. We propose that the detection and characterisation of NO mediated transcriptional activation (NOMETA) of silent chemical defences in the environment, may inspire broader application in the field of microbial biodiscovery.
Adiporon, an adiponectin receptor agonist acts as an antidepressant and metabolic regulator in a mouse model of depression
Authors: Nicolas Sarah , Debayle Delphine , Béchade Catherine , Maroteaux Luc , Gay Anne-Sophie , Bayer Pascale , Heurteaux Catherine , Guyon Alice , Chabry Joëlle
Published: August 2018

Major depression is a psychiatric disorder with complex etiology. About 30% of depressive patients are resistant to antidepressants that are currently available, likely because they only target the monoaminergic systems. Thus, identification of novel antidepressants with a larger action spectrum is urgently required. Epidemiological data indicate high comorbidity between metabolic and psychiatric disorders, particularly obesity and depression. We used a well-characterized anxiety/depressive-like mouse model consisting of continuous input of corticosterone for seven consecutive weeks. A panel of reliable behavioral tests were conducted to assessing numerous facets of the depression-like state, including anxiety, resignation, reduced motivation, loss of pleasure, and social withdrawal. Furthermore, metabolic features including weight, adiposity, and plasma biological parameters (lipids, adipokines, and cytokines) were investigated in corticosterone-treated mice. Our data show that chronic administration of corticosterone induced the parallel onset of metabolic and behavioral dysfunctions in mice. AdipoRon, a potent adiponectin receptor agonist, prevented the corticosterone-induced early onset of moderate obesity and metabolic syndromes. Moreover, in all the behavioral tests, daily treatment with AdipoRon successfully reversed the corticosterone-induced depression-like state in mice. AdipoRon exerted its pleiotropic actions on various systems including hippocampal neurogenesis, serotonergic neurotransmission, neuroinflammation, and the tryptophan metabolic pathway, which can explain its antidepressant properties. Our study highlights the pivotal role of the adiponergic system in the development of both metabolic and psychiatric disorders. AdipoRon may constitute a promising novel antidepressant.
Proteomics for blood biomarker exploration of severe mental illness: pitfalls of the past and potential for the future
Authors: Comes Ashley L. , Papiol Sergi , Mueller Thorsten , Geyer Philipp E. , Mann Matthias , Schulze Thomas G.
Published: August 2018

Recent improvements in high-throughput proteomic approaches are likely to constitute an essential advance in biomarker discovery, holding promise for improved personalized care and drug development. These methodologies have been applied to study multivariate protein patterns and provide valuable data of peripheral tissues. To highlight findings of the last decade for three of the most common psychiatric disorders, namely schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD), we queried PubMed. Here we delve into the findings from thirty studies, which used proteomics and multiplex immunoassay approaches for peripheral blood biomarker exploration. In an explorative approach, we ran enrichment analyses in peripheral blood according to these results and ascertained the overlap between proteomic findings and genetic loci identified in genome-wide association studies (GWAS). The studies we appraised demonstrate that proteomics for psychiatric research has been heterogeneous in aims and methods and limited by insufficient sample sizes, poorly defined case definitions, methodological inhomogeneity, and confounding results constraining the conclusions that can be extracted from them. Here, we discuss possibilities for overcoming methodological challenges for the implementation of proteomic signatures in psychiatric diagnosis and offer an outlook for future investigations. To fulfill the promise of proteomics in mental disease diagnostics, future research will need large, well-defined cohorts in combination with state-of-the-art technologies.
Chiral symmetry breaking yields the I-Au60 perfect golden shell of singular rigidity
Authors: Mullins S.-M. , Weissker H.-Ch. , Sinha-Roy R. , Pelayo J. J. , Garzón I. L. , Whetten R. L. , López-Lozano X.
Published: August 2018

The combination of profound chirality and high symmetry on the nm-scale is unusual and would open exciting avenues, both fundamental and applied. Here we show how the unique electronic structure and bonding of quasi-2D gold makes this possible. We report a chiral symmetry breaking, i.e., the spontaneous formation of a chiral-icosahedral shell (I−Au60) from achiral (Ih) precursor forms, accompanied by a contraction in the Au–Au bonding and hence the radius of this perfect golden sphere, in which all 60 sites are chemically equivalent. This structure, which resembles the most complex of semi-regular (Archimedean) polyhedra (34.5*), may be viewed as an optimal solution to the topological problem: how to close a 60-vertex 2D (triangular) net in 3D. The singular rigidity of the I−Au60 manifests in uniquely discrete structural, vibrational, electronic, and optical signatures, which we report herein as a guide to its experimental detection and ultimately its isolation in material forms.
JMJD3 facilitates C/EBPβ-centered transcriptional program to exert oncorepressor activity in AML
Authors: Yu Shan-He , Zhu Kang-Yong , Chen Juan , Liu Xiang-Zhen , Xu Peng-Fei , Zhang Wu , Yan Li , Guo He-Zhou , Zhu Jiang
Published: August 2018

JMJD3, a stress-inducible H3K27 demethylase, plays a critical regulatory role in the initiation and progression of malignant hematopoiesis. However, how this histone modifier affects in a cell type-dependent manner remains unclear. Here, we show that in contrast to its oncogenic effect in preleukemia state and lymphoid malignancies, JMJD3 relieves the differentiation-arrest of certain subtypes (such as M2 and M3) of acute myeloid leukemia (AML) cells. RNA sequencing and ChIP−PCR analyses revealed that JMJD3 exerts anti-AML effect by directly modulating H3K4 and H3K27 methylation levels to activate the expression of a number of key myelopoietic regulatory genes. Mechanistic exploration identified a physical and functional association of JMJD3 with C/EBPβ that presides the regulatory network of JMJD3. Thus, the leukemia regulatory role of JMJD3 varies in a disease phase- and lineage-dependent manner, and acts as a potential oncorepressor in certain subsets of AML largely by coupling to C/EBPβ-centered myelopoietic program.
HIF-2α-pVHL complex reveals broad genotype-phenotype correlations in HIF-2α-driven disease
Authors: Tarade Daniel , Robinson Claire M. , Lee Jeffrey E. , Ohh Michael
Published: August 2018

It is definitively established that mutations in transcription factor HIF-2α are causative of both neuroendocrine tumors (class 1 disease) and polycythemia (class 2 disease). However, the molecular mechanism that underlies this emergent genotype–phenotype relationship has remained unclear. Here, we report the structure of HIF-2α peptide bound to pVHL-elongin B-elongin C (VBC) heterotrimeric complex, which shows topographical demarcation of class 1 and 2 mutations affecting residues predicted, and demonstrated via biophysical analyses, to differentially impact HIF-2α-pVHL interaction interface stability. Concordantly, biochemical experiments showed that class 1 mutations disrupt pVHL affinity to HIF-2α more adversely than class 2 mutations directly or indirectly via impeding PHD2-mediated hydroxylation. These findings suggest that neuroendocrine tumor pathogenesis requires a higher HIF-2α dose than polycythemia, which requires only a mild increase in HIF-2α activity. These biophysical data reveal a structural basis that underlies, and can be used to predict de novo, broad genotype-phenotype correlations in HIF-2α-driven disease.
ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response
Authors: Lian Huan , Wei Jin , Zang Ru , Ye Wen , Yang Qing , Zhang Xia-Nan , Chen Yun-Da , Fu Yu-Zhi , Hu Ming-Ming , Lei Cao-Qi , Luo Wei-Wei , Li Shu , Shu Hong-Bing
Published: August 2018

Cyclic GMP-AMP synthase (cGAS) senses double-strand (ds) DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the adaptor MITA/STING to initiate innate antiviral response. How cGAS activity is regulated remains enigmatic. Here, we identify ZCCHC3, a CCHC-type zinc-finger protein, as a positive regulator of cytosolic dsDNA- and DNA virus-triggered signaling. We show that ZCCHC3-deficiency inhibits dsDNA- and DNA virus-triggered induction of downstream effector genes, and that ZCCHC3-deficient mice are more susceptible to lethal herpes simplex virus type 1 or vaccinia virus infection. ZCCHC3 directly binds to dsDNA, enhances the binding of cGAS to dsDNA, and is important for cGAS activation following viral infection. Our results suggest that ZCCHC3 is a co-sensor for recognition of dsDNA by cGAS, which is important for efficient innate immune response to cytosolic dsDNA and DNA virus.
Co-crystallization of atomically precise metal nanoparticles driven by magic atomic and electronic shells
Authors: Yan Juanzhu , Malola Sami , Hu Chengyi , Peng Jian , Dittrich Birger , Teo Boon K. , Häkkinen Hannu , Zheng Lansun , Zheng Nanfeng
Published: August 2018

This paper reports co-crystallization of two atomically precise, different-size ligand-stabilized nanoclusters, a spherical (AuAg)267(SR)80 and a smaller trigonal-prismatic (AuAg)45(SR)27(PPh3)6 in 1:1 ratio, characterized fully by X-ray crystallographic analysis (SR = 2,4-SPhMe2). The larger cluster has a four concentric-shell icosahedral structure of Ag@M12@M42@M92@Ag120(SR)80 (M = Au or Ag) with the inner-core M147 icosahedron observed here for metal nanoparticles. The cluster has an open electron shell of 187 delocalized electrons, fully metallic, plasmonic behavior, and a zero HOMO-LUMO energy gap. The smaller cluster has an 18-electron shell closing, a notable HOMO-LUMO energy gap and a molecule-like optical spectrum. This is the first direct demonstration of the simultaneous presence of competing effects (closing of atom vs. electron shells) in nanocluster synthesis and growth, working together to form a co-crystal of different-sized clusters. This observation suggests a strategy that may be helpful in the design of other nanocluster systems via co-crystallization.
Architecture of the native major royal jelly protein 1 oligomer
Authors: Tian Wenli , Li Min , Guo Huiyuan , Peng Wenjun , Xue Xiaofeng , Hu Yifan , Liu Yang , Zhao Yazhou , Fang Xiaoming , Wang Kai , Li Xiuting , Tong Yufeng , Conlon Michael A. , Wu Wei , Ren Fazheng , Chen Zhongzhou
Published: August 2018

Honeybee caste development is nutritionally regulated by royal jelly (RJ). Major royal jelly protein 1 (MRJP1), the most abundant glycoprotein among soluble royal jelly proteins, plays pivotal roles in honeybee nutrition and larvae development, and exhibits broad pharmacological activities in humans. However, its structure has long remained unknown. Herein, we identify and report a 16-molecule architecture of native MRJP1 oligomer containing four MRJP1, four apisimin, and eight unanticipated 24-methylenecholesterol molecules at 2.65 Å resolution. MRJP1 has a unique six-bladed β-propeller fold with three disulfide bonds, and it interacts with apisimin mainly by hydrophobic interaction. Every four 24-methylenecholesterol molecules are packaged by two MRJP1 and two apisimin molecules. This assembly dimerizes to form an H-shaped MRJP14-apisimin4-24-methylenecholesterol8 complex via apisimin in a conserved and pH-dependent fashion. Our findings offer a structural basis for understanding the pharmacological effects of MRJPs and 24-methylenecholesterol, and provide insights into their unique physiological roles in bees.
Author Correction: A mechanism for CO regulation of ion channels
Authors: Kapetanaki Sofia M. , Burton Mark J. , Basran Jaswir , Uragami Chiasa , Moody Peter C. E. , Mitcheson John S. , Schmid Ralf , Davies Noel W. , Dorlet Pierre , Vos Marten H. , Storey Nina M. , Raven Emma
Published: August 2018

The originally published version of this article contained an error in the subheading ‘Heme is required for CO-dependent channel activation’, which was incorrectly given as ‘Hame is required for CO-dependent channel activation’. This has now been corrected in both the PDF and HTML versions of the Article.
Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration
Authors: Sahoo Pabitra K. , Lee Seung Joon , Jaiswal Poonam B. , Alber Stefanie , Kar Amar N. , Miller-Randolph Sharmina , Taylor Elizabeth E. , Smith Terika , Singh Bhagat , Ho Tammy Szu-Yu , Urisman Anatoly , Chand Shreya , Pena Edsel A. , Burlingame Alma L. , Woolf Clifford J. , Fainzilber Mike , English Arthur W. , Twiss Jeffery L.
Published: August 2018

Critical functions of intra-axonally synthesized proteins are thought to depend on regulated recruitment of mRNA from storage depots in axons. Here we show that axotomy of mammalian neurons induces translation of stored axonal mRNAs via regulation of the stress granule protein G3BP1, to support regeneration of peripheral nerves. G3BP1 aggregates within peripheral nerve axons in stress granule-like structures that decrease during regeneration, with a commensurate increase in phosphorylated G3BP1. Colocalization of G3BP1 with axonal mRNAs is also correlated with the growth state of the neuron. Disrupting G3BP functions by overexpressing a dominant-negative protein activates intra-axonal mRNA translation, increases axon growth in cultured neurons, disassembles axonal stress granule-like structures, and accelerates rat nerve regeneration in vivo.
Structural conservation in a membrane-enveloped filamentous virus infecting a hyperthermophilic acidophile
Authors: Liu Ying , Osinski Tomasz , Wang Fengbin , Krupovic Mart , Schouten Stefan , Kasson Peter , Prangishvili David , Egelman Edward H.
Published: August 2018

Different forms of viruses that infect archaea inhabiting extreme environments continue to be discovered at a surprising rate, suggesting that the current sampling of these viruses is sparse. We describe here Sulfolobus filamentous virus 1 (SFV1), a membrane-enveloped virus infecting Sulfolobus shibatae. The virus encodes two major coat proteins which display no apparent sequence similarity with each other or with any other proteins in databases. We have used cryo-electron microscopy at 3.7 Å resolution to show that these two proteins form a nearly symmetrical heterodimer, which wraps around A-form DNA, similar to what has been shown for SIRV2 and AFV1, two other archaeal filamentous viruses. The thin (∼ 20 Å) membrane of SFV1 is mainly archaeol, a lipid species that accounts for only 1% of the host lipids. Our results show how relatively conserved structural features can be maintained across evolution by both proteins and lipids that have diverged considerably.
Ultra-low damping insulating magnetic thin films get perpendicular
Authors: Soumah Lucile , Beaulieu Nathan , Qassym Lilia , Carrétéro Cécile , Jacquet Eric , Lebourgeois Richard , Ben Youssef Jamal , Bortolotti Paolo , Cros Vincent , Anane Abdelmadjid
Published: August 2018

A magnetic material combining low losses and large perpendicular magnetic anisotropy (PMA) is still a missing brick in the magnonic and spintronic fields. We report here on the growth of ultrathin Bismuth doped Y3Fe5O12 (BiYIG) films on Gd3Ga5O12 (GGG) and substituted GGG (sGGG) (111) oriented substrates. A fine tuning of the PMA is obtained using both epitaxial strain and growth-induced anisotropies. Both spontaneously in-plane and out-of-plane magnetized thin films can be elaborated. Ferromagnetic Resonance (FMR) measurements demonstrate the high-dynamic quality of these BiYIG ultrathin films; PMA films with Gilbert damping values as low as 3 × 10−4 and FMR linewidth of 0.3 mT at 8 GHz are achieved even for films that do not exceed 30 nm in thickness. Moreover, we measure inverse spin hall effect (ISHE) on Pt/BiYIG stacks showing that the magnetic insulator’s surface is transparent to spin current, making it appealing for spintronic applications.
Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis
Authors: Scavuzzo Marissa A. , Hill Matthew C. , Chmielowiec Jolanta , Yang Diane , Teaw Jessica , Sheng Kuanwei , Kong Yuelin , Bettini Maria , Zong Chenghang , Martin James F. , Borowiak Malgorzata
Published: August 2018

Decoding the molecular composition of individual Ngn3 + endocrine progenitors (EPs) during pancreatic morphogenesis could provide insight into the mechanisms regulating hormonal cell fate. Here, we identify population markers and extensive cellular diversity including four EP subtypes reflecting EP maturation using high-resolution single-cell RNA-sequencing of the e14.5 and e16.5 mouse pancreas. While e14.5 and e16.5 EPs are constantly born and share select genes, these EPs are overall transcriptionally distinct concomitant with changes in the underlying epithelium. As a consequence, e16.5 EPs are not the same as e14.5 EPs: e16.5 EPs have a higher propensity to form beta cells. Analysis of e14.5 and e16.5 EP chromatin states reveals temporal shifts, with enrichment of beta cell motifs in accessible regions at later stages. Finally, we provide transcriptional maps outlining the route progenitors take as they make cell fate decisions, which can be applied to advance the in vitro generation of beta cells.
Loss of GCNT2/I-branched glycans enhances melanoma growth and survival
Authors: Sweeney Jenna Geddes , Liang Jennifer , Antonopoulos Aristotelis , Giovannone Nicholas , Kang Shuli , Mondala Tony S. , Head Steven R. , King Sandra L. , Tani Yoshihiko , Brackett Danielle , Dell Anne , Murphy George F. , Haslam Stuart M. , Widlund Hans R. , Dimitroff Charles J.
Published: August 2018

Cancer cells often display altered cell-surface glycans compared to their nontransformed counterparts. However, functional contributions of glycans to cancer initiation and progression remain poorly understood. Here, from expression-based analyses across cancer lineages, we found that melanomas exhibit significant transcriptional changes in glycosylation-related genes. This gene signature revealed that, compared to normal melanocytes, melanomas downregulate I-branching glycosyltransferase, GCNT2, leading to a loss of cell-surface I-branched glycans. We found that GCNT2 inversely correlated with clinical progression and that loss of GCNT2 increased melanoma xenograft growth, promoted colony formation, and enhanced cell survival. Conversely, overexpression of GCNT2 decreased melanoma xenograft growth, inhibited colony formation, and increased cell death. More focused analyses revealed reduced signaling responses of two representative glycoprotein families modified by GCNT2, insulin-like growth factor receptor and integrins. Overall, these studies reveal how subtle changes in glycan structure can regulate several malignancy-associated pathways and alter melanoma signaling, growth, and survival.
Binge Drinking among adolescents is related to the development of Alcohol Use Disorders: results from a Cross-Sectional Study
Authors: Addolorato Giovanni , Vassallo Gabriele A. , Antonelli Giulio , Antonelli Mariangela , Tarli Claudia , Mirijello Antonio , Agyei-Nkansah Adwoa , Mentella Maria C. , Ferrarese Daniele , Mora Vincenzina , Barbàra Marco , Maida Marcello , Cammà Calogero , Gasbarrini Antonio ,   Alcohol Related Disease Consortium*, Bruno Giovanni , D’Angelo Giovanna , Del Zompo Fabio , Di Rienzo Teresa , Feliciani Daniela , Forte Fabrizio , Isoppo Vanessa , Laterza Lucrezia , Mangiola Francesca , Mosoni Carolina , Rando Margherita , Sestito Luisa
Published: August 2018

Binge drinking (BD) is a common pattern of alcohol consumption among adolescents. At present few data are available on the possible relationship between BD and alcohol use disorders (AUD) in adolescents. The aim of this study was to assess the prevalence of BD and relationship between BD behavior and AUD among adolescents. A total of 2704 students attending 10 purposively selected high schools from three Italian provinces were surveyed. Questionnaires regarding socio-demographic data, pattern and amount of alcohol intake, smoking habits, use of illicit drugs, and physical activity were administered. AUD and affective disorders were also evaluated. Alcohol intake was reported by 2126 participants; 1278 reported at least one episode BD in the last year and 715 in the last month. A diagnosis of AUD was made in 165 adolescents. The prevalence of AUD was higher in adolescents that reported BD behavior than in those that did not report BD (11.6% vs 0.9%, respectively; p < 0.0001). Logistic regression showed a positive relationship between a diagnosis of AUD and BD behavior (OR 9.6; 95% CI 4.7–22·9; p < 0.0001). In conclusion alcohol consumption with the pattern of BD among adolescents is highly related to development of AUD.