On the interplay of borderline personality features, childhood trauma severity, attachment types, and social support

Stress and Psychopatholog

On the Potts model partition function in an external field

We study the partition function of Potts model in an external (magnetic) field, and its connections with the zero-field Potts model partition function. Using a deletion-contraction formulation for the partition function Z for this model, we show that it can be expanded in terms of the zero-field partition function. We also show that Z can be written as a sum over the spanning trees, and the spanning forests, of a graph G. Our results extend to Z the well-known spanning tree expansion for the zero-field partition function that arises though its connections with the Tutte polynomial

Self-Consistent Quasi-Particle RPA for the Description of Superfluid Fermi Systems

Self-Consistent Quasi-Particle RPA (SCQRPA) is for the first time applied to a more level pairing case. Various filling situations and values for the coupling constant are considered. Very encouraging results in comparison with the exact solution of the model are obtained. The nature of the low lying mode in SCQRPA is identified. The strong reduction of the number fluctuation in SCQRPA vs BCS is pointed out. The transition from superfluidity to the normal fluid case is carefully investigated.Comment: 23 pages, 18 figures and 1 table, submitted to Phys. Rev.

CETSA-based target engagement of taxanes as biomarkers for efficacy and resistance

The use of taxanes has for decades been crucial for treatment of several cancers. A major limitation of these therapies is inherent or acquired drug resistance. A key to improved outcome of taxane-based therapies is to develop tools to predict and monitor drug efficacy and resistance in the clinical setting allowing for treatment and dose stratification for individual patients. To assess treatment efficacy up to the level of drug target engagement, we have established several formats of tubulin-specific Cellular Thermal Shift Assays (CETSAs). This technique was evaluated in breast and prostate cancer models and in a cohort of breast cancer patients. Here we show that taxanes induce significant CETSA shifts in cell lines as well as in animal models including patient-derived xenograft (PDX) models. Furthermore, isothermal dose response CETSA measurements allowed for drugs to be rapidly ranked according to their reported potency. Using multidrug resistant cancer cell lines and taxane-resistant PDX models we demonstrate that CETSA can identify taxane resistance up to the level of target engagement. An imaging-based CETSA format was also established, which in principle allows for taxane target engagement to be accessed in specific cell types in complex cell mixtures. Using a highly sensitive implementation of CETSA, we measured target engagement in fine needle aspirates from breast cancer patients, revealing a range of different sensitivities. Together, our data support that CETSA is a robust tool for assessing taxane target engagement in preclinical models and clinical material and therefore should be evaluated as a prognostic tool during taxane-based therapies

A Biased Review of Sociophysics

Various aspects of recent sociophysics research are shortly reviewed: Schelling model as an example for lack of interdisciplinary cooperation, opinion dynamics, combat, and citation statistics as an example for strong interdisciplinarity.Comment: 16 pages for J. Stat. Phys. including 2 figures and numerous reference

Positive biodiversity-productivity relationship predominant in global forests

The biodiversity-productivity relationship (BPR) is foundational to our understanding of the global extinction crisis and its impacts on ecosystem functioning. Understanding BPR is critical for the accurate valuation and effective conservation of biodiversity. Using ground-sourced data from 777,126 permanent plots, spanning 44 countries and most terrestrial biomes, we reveal a globally consistent positive concave-down BPR, showing that continued biodiversity loss would result in an accelerating decline in forest productivity worldwide. The value of biodiversity in maintaining commercial forest productivity alone - US$166 billion to 490 billion per year according to our estimation - is more than twice what it would cost to implement effective global conservation. This highlights the need for a worldwide reassessment of biodiversity values, forest management strategies, and conservation priorities.Peer Reviewe

Women with type 1 diabetes exhibit a progressive increase in gut Saccharomyces cerevisiae in pregnancy associated with evidence of gut inflammation.

Aims: Studies of the gut microbiome have focused on its bacterial composition. We aimed to characterize the gut fungal microbiome (mycobiome) across pregnancy in women with and without type 1 diabetes. Methods: Faecal samples (n = 162) were collected from 70 pregnant women (45 with and 25 without type 1 diabetes) across all trimesters. Fungi were analysed by internal transcribed spacer 1 amplicon sequencing. Markers of intestinal inflammation (faecal calprotectin) and intestinal epithelial integrity (serum intestinal fatty acid binding protein; I-FABP), and serum antibodies to Saccharomyces cerevisiae (ASCA) were measured. Results: Women with type 1 diabetes had decreased fungal alpha diversity by the third trimester, associated with an increased abundance of Saccharomyces cerevisiae that was inversely related to the abundance of the anti-inflammatory butyrate-producing bacterium Faecalibacterium prausnitzii. Women with type 1 diabetes had higher concentrations of calprotectin, I-FABP and ASCA. Conclusions: Women with type 1 diabetes exhibit a shift in the gut mycobiome across pregnancy associated with evidence of gut inflammation and impaired intestinal barrier function. The relevance of these findings to the higher rate of pregnancy complications in type 1 diabetes warrants further study.Esther Bandala-Sanchez, Alexandra J. Roth-Schulze, Helena Oakey Megan A.S. Penno, Naiara G. Bediaga, Gaetano Naselli, Katrina M. Ngui, Alannah D. Smith, Dexing Huang, Enrique Zozaya-Valdes, Rebecca L. Thomson, James D. Brown, Peter J. Vuillermin, Simon C. Barry, Maria E. Craig, William D. Rawlinson, Elizabeth A. Davis, Mark Harris, Georgia Soldatos, Peter G. Colman, John M. Wentworth, Aveni Haynes, Grant Morahan, Richard O. Sinnott, Anthony T. Papenfuss, Jennifer J. Couper, Leonard C. Harrison, on behalf of the ENDIA Study Grou

Polarized deep-inelastic scattering from nuclei: a relativistic approach.

We discuss spin-dependent, deep-inelastic scattering from nuclei within a covariant framework. In the relativistic impulse approximation this is described in terms of the amplitude for forward, virtual-photon scattering from an off-mass-shell nucleon. The general structure of the off-shell nucleon hadronic tensor is derived, and the leading behavior of the off-shell nucleon structure functions computed in the Bjorken limit. The formalism, which is valid for nucleons bound inside nuclei with spin 1/2 or 1, is applied to the case of the deuteron.Piller, G. ; Melnitchouk, W. ; Thomas, A.W

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe