Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.

This is the final version. Available from Nature Research via the DOI in this record. Data availability: The UK Biobank phenotype and WES data described here are publicly available to registered researchers through the UK Biobank data access protocol. Information about registration for access to the data is available at https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access. Data for this study were obtained under resource applications 26041 and 9905. The MCPS welcomes open-access and collaboration data requests from bona fide researchers. For more details on accessibility, the study’s data and sample sharing policy can be downloaded (in English or Spanish) from https://www.ctsu.ox.ac.uk/research/mcps. Available study data can be examined in detail through the study’s Data Showcase, available at https://datashare.ndph.ox.ac.uk/mexico/. SCOOP and INTERVAL WES data are accessible from the European Genome-phenome Archive with accession numbers EGAS00001000124 (SCOOP) and EGAS00001000825 (INTERVAL). snRNA-seq data are available from the NCBI Gene Expression Omnibus (GEO), under accession number: GSE243112. Source data are provided with this paper.Code availability: The pipeline code for processing, filtering, annotating and burden testing UK Biobank WES data using the UK Biobank RAP is publicly available (https://github.com/mrcepid-rap). No custom code for analyzing the UK Biobank WES data was developed for this study. The analysis code for single-nucleus sequencing is available on GitHub (https://github.com/mariachukanova1/BSN_paper) and has been deposited on Zenodo at https://doi.org/10.5281/zenodo.10687754.Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN protein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSN PTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity.Medical Research CouncilMedical Research CouncilMedical Research CouncilMedical Research CouncilWellcome TrustMedical Research CouncilWellcome TrustWellcome Trust and Royal SocietyChan Zuckerberg InitiativeBiotechnology and Biological Sciences Research Council (BBSRC)Mexican Health MinistryNational Council of Science and Technology for MexicoCancer Research UKBritish Heart FoundationNational Institute for Health ResearchCambridge Biomedical Research CentreBotnar FoundationBernard Wolfe Health Neuroscience EndowmentResearch Englan

Thermal boundary resistance of a granular film-substrate interface

The results of measurements of the thermal boundary resistance (RFS) of the interface between a one-layer granular film on a substrate are presented, which reveal the relationship between the RFS value and the grain size in the film material. For a 10-nm-thick nanocrystalline (Fe0.5Co0.5)0.4Cu0.6 film deposited on a silicon substrate with a 50-nm-thick SiO2 oxide layer (interlayer), RFS is increased by almost two orders of magnitude compared to the minimum reported value (10 –7(m2K)/W). The thermal boundary resistance of a La0.65Ca0.35MnO3 film with a microcrystalline structure, which was deposited over a YBa2Cu3O7 –δinterlayer on a SrTiO3 substrate, is RFS = 10–6(m2K)/W

PSYCHOSOMATIC MEDICINE: A KEY TO EFFECTIVE REHABILITATION IN ONCOLOGY PATIENTS

Malignant tumors are still a challenging problem of contemporary medicine. The incidence of malignant diseases and patient mortality is increasing with time while there is no significant growth in long-term survival. Oncological diseases affect the quality of patient’s life more than any other medical conditions. In this regard, medical professionals are expected to pay a special attention to the psychosomatic aspects of patient management. It is important to realize that social and psychological maladaptation have a negative impact on the immune defense, which may trigger the onset or relapse of the major disease. Psychotherapy can improve the patient’s response to oncological treatment; the best way is to start using psychotherapy at the time of diagnosis. For the optimal effect, it is advisable to transfer the patients to specialized rehabilitation centers

Inelastic Relaxation of Oxygen and Low-Field Magnetoresistance in La0.65\text{}_{0.65}Ca0.35\text{}_{0.35}MnO3\text{}_{3} Films on Ferroelectric Ceramics Substrates

Galvanomagnetic properties of polycrystalline La$\text{}_{0.65}$Ca$\text{}_{0.35}$MnO$\text{}_{3}$ films with a thickness of 0.2~μm deposited onto Pb$\text{}_{2.9}$Ba$\text{}_{0.05}$Sr$\text{}_{0.05}$(Zr$\text{}_{0.4}$Ti$\text{}_{0.6}$)O$\text{}_{3}$ ferroelectric ceramics substrates were investigated. We discovered an irreversible increase in film resistance after numerous inversions of substrate polarization. This phenomenon was investigated several times for three film structures. The typical duration of the process of a monotonic 3-5 times increase in film resistance was 3-6 hours. The long-time relaxation of macroscopic film resistance is explained by dielectrization of film intercrystallite boundaries. The typical size of crystallites of both the film and the substrate is 3-10μm. Such small size explains the fact of macroscopic homogeneity of film conductivity, when the specific resistance increases from 1.8×10$\text{}^{-2}$ to 1.8Ω cm. A growth in resistance of narrow (10 nm) regions of film is explained by the redistribution of oxygen anions under the action of inhomogeneous mechanical stress. The stress between crystallites appears due to inverse piezoelectric effect of ferroelectric substrate. The magnitude of diffusion coefficient of oxygen is estimated to be D≥10$\text{}^{-20}$ m$\text{}^{2}$ s$\text{}^{-1}$

ANALYSIS OF THE SERT AND TPH2 GENES POLYMORPHISM RELATIONSHIP WITH SIDE EFFECTS DURING TOPIRAMATE THERAPY TAKING INTO ACCOUNT GENDER FEATURES

We examined the clinical and genetic evaluation of SERT and TPH2 genes SNP polymorphisms role in the development of side effects during topiramate therapy taking into account gender features. Found significant differences in the severity of topiramate side effects in the nervous system and psycho-emotional sphere in patient groups with different variants of alleles, and identified gender features in elaboration of depression and emotional labilit

Ni-sepiolite-falcondoite in garnierite mineralization from the Falcondo Ni-laterite deposit, Dominican Republic

New chemical and structural data on sepiolite-falcondoite in garnierite veins from the Falcondo Ni-laterite deposits, central Dominican Republic, are reported. Samples of Ni-sepiolitefalcondoite vary in colour from whitish green to green depending on the NiO content (wt.%) and the amount of silica present. The texture is normally schistose and friable but samples with considerable quartz and/or amorphous silica are compact and hard. Back-scattered electron images indicate that the samples are composed of at least three generations of Ni-sepiolite-falcondoite. The extreme refined cell parameters for Ni-sepiolite-falcondoite vary from 13.400(2), 27.006(4), 5.273(1) A˚ to 13.340(3), 27.001(6), 5.267(1) A˚ (space group Pncn). As the Ni content increases there is a small reduction in the a parameter. Chemical compositions determined by electron probe microanalysis cover a large interval of the Ni-sepiolite-falcondoite solid solution (Fal3 and Fal77). Individual samples show a considerable range in composition with the widest range determined in one sample from 4.63 to 22.40 wt.% NiO