GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Effect of laser powers on the mechanical properties 27SiMn steel with Inconel 718 cladding coatings

In order to know the influence of laser power on the steel (27SiMn) used for repairing the column with Inconel 718 powder materials, and to obtain the optimal laser power parameters with the best mechanical properties of cladding layer, the microstructure, tensile properties and fracture morphology of the Inconel 718 alloy under three laser powers (1800 W, 2100 W and 2400 W) were investigated by using the single-factor variable method, keeping the scanning speed, powder feeding amount and spot diameter unchanged. The results show that with increase of laser power the mechanical properties of the Inconel 718 alloy coating prepared on the surface for the column steel gradually decreased, and the mechanical properties were the best when the laser power is 1800 W. The yield strength of Inconel 718 alloy coating prepared at 1800 W was 61.7% higher than that of the substrate, and its value is 970 MPa. The elongation is reduced by 50% compared with the substrate, and its value is 7%. The microstructure of 27SiMn steel with cladding coating is (Ni, Fe, Cr) phase and Ni _3 Fe phase, and the microstructure of the coating is mainly composed of uniform cellular crystals. This study provides a valuable reference for the additive manufacturing of industrial materials of 27SiMn steel with laser-cladding coating

LRH-1 senses signaling from phosphatidylcholine to regulate the expansion growth of digestive organs via synergy with Wnt/beta-catenin signaling in zebrafish

Liver receptor homolog-1 (LRH-1) is an orphan nuclear receptor that is critical for the growth and proliferation of cancer cells and other biological processes, including lipid transportation and metabolism, sexual determination and steroidogenesis. However, because homozygous lrh-1(-/-) mice die in utero, the regulatory mechanisms involved in embryonic development mediated by this receptor are poorly understood. In the present study, we performed transcription activator-like effector nuclease (TALEN)-mediated loss-of-function assays, taking advantage of zebrafish external fertilization, to investigate the function of lrh-1. The digestive organs were affected by lrh-1 depletion as a result of cell-cycle arrest (at the checkpoint of G1 to S phase), but not cell apoptosis. Biochemical analysis revealed that LRH-1 augments the transcriptional activity of beta-catenin 1 and 2 via physical interactions. Screening the specific ligand(s) sensed by LRH-1 during organogenesis revealed that phosphatidylcholine (PC), a potential ligand, is the upstream target of LRH-1 during endoderm development. These data provide evidence for the crosstalk between the PC/LRH-1 and Wnt/beta-catenin signaling pathways during the expansion growth of endoderm organs. Copyright (C) 2017, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved

Automatic Interpretation of Potential Field Data Based on Euler Deconvolution with Linear Background

Euler deconvolution is a popular technique used for analyzing potential field data because it requires little prior information. However, the reliability of Euler solutions can be impacted by interference from adjacent field sources, or background fields. In this manuscript, we present an effective Euler deconvolution algorithm that accounts for linear background fields. Our algorithm, called improved finite-difference Euler deconvolution, builds upon the finite-difference method and is less susceptible to interference from nearby sources. We use this algorithm to achieve a joint estimation of the coefficients of the source coordinates, the structure index, and the linear background trend. Compared to Euler deconvolution methods based on differential similarity transformations, which also account for linear background fields, our method is easier to understand and implement programmatically and is faster. We tested our method using both 2D and 3D synthetic data, and the results indicate that our algorithm has better computational accuracy than the finite-difference algorithm and is comparable to the Euler deconvolution algorithm based on differential similarity transformations. In addition, our method was shown to be effective when tested on real data

State of the Art of Non-Invasive Electrode Materials for Brain–Computer Interface

The brain–computer interface (BCI) has emerged in recent years and has attracted great attention. As an indispensable part of the BCI signal acquisition system, brain electrodes have a great influence on the quality of the signal, which determines the final effect. Due to the special usage scenario of brain electrodes, some specific properties are required for them. In this study, we review the development of three major types of EEG electrodes from the perspective of material selection and structural design, including dry electrodes, wet electrodes, and semi-dry electrodes. Additionally, we provide a reference for the current chaotic performance evaluation of EEG electrodes in some aspects such as electrochemical performance, stability, and so on. Moreover, the challenges and future expectations for EEG electrodes are analyzed

Compound C Inhibits Ovarian Cancer Progression via PI3K-AKT-mTOR-NFκB Pathway

Epithelial Ovarian cancer (OvCa) is the leading cause of death from gynecologic malignancies in the United States, with most patients diagnosed at late stages. High-grade serous cancer (HGSC) is the most common and lethal subtype. Despite aggressive surgical debulking and chemotherapy, recurrence of chemo-resistant disease occurs in ~80% of patients. Thus, developing therapeutics that not only targets OvCa cell survival, but also target their interactions within their unique peritoneal tumor microenvironment (TME) is warranted. Herein, we report therapeutic efficacy of compound C (also known as dorsomorphin) with a novel mechanism of action in OvCa. We found that CC not only inhibited OvCa growth and invasiveness, but also blunted their reciprocal crosstalk with macrophages, and mesothelial cells. Mechanistic studies indicated that compound C exerts its effects on OvCa cells through inhibition of PI3K-AKT-NFκB pathways, whereas in macrophages and mesothelial cells, CC inhibited cancer-cell-induced canonical NFκB activation. We further validated the specificity of the PI3K-AKT-NFκB as targets of compound C by overexpression of constitutively active subunits as well as computational modeling. In addition, real-time monitoring of OvCa cellular bioenergetics revealed that compound C inhibits ATP production, mitochondrial respiration, and non-mitochondrial oxygen consumption. Importantly, compound C significantly decreased tumor burden of OvCa xenografts in nude mice and increased their sensitivity to cisplatin-treatment. Moreover, compound C re-sensitized patient-derived resistant cells to cisplatin. Together, our findings highlight compound C as a potent multi-faceted therapeutic in OvCa

Turpanopitys taoshuyuanense gen. et sp. nov., a novel woody branch discovered in Early Triassic deposits of the Turpan Basin, Northwest China, and its palaeoecological and palaeoclimate implications

International audienceA novel well-preserved woody branch, Turpanopitys taoshuyuanense gen. et sp. nov. was collected in the early Triassic terrestrial deposits in the Turpan Basin, Northwest China. The permineralized wood is characterized by a heterogeneous pith, endarch primary xylem and Protophyllocladoxylon-type secondary xylem. The pith consists of parenchyma cells and supporting diaphragms formed by brick-like sclerenchyma cells. The quantitative growth-ring analyses of T. taoshuyuanense indicate that the species was evergreen, the leaf longevity being comprised between 3 to 15 years. T. taoshuyuanense might indicate a warm humid climate with short dry periods in the Turpan basin in the Early Triassic. The Protophyllocladoxylon-type woods were widely distributed in different climate zone in both southern and northern hemispheres during the Palaeozoic and Early Triassic. The growth rings of the woods with Protophyllocladoxylon-type secondary xylem are good indicator for the palaeoclimate. The new specimen indicates that a warm humid climate with irregularly distributed short dry periods in the Early Triassic Turpan basin

A dual-mode NADH biosensor based on gold nanostars decorated CoFe₂ metal–organic frameworks to reveal dynamics of cell metabolism

Nicotinamide adenine dinucleotide (NADH) is central to metabolism and implicated in various diseases. Herein, nanohybrids of gold nanostars and metal-organic frameworks are devised and demonstrated as a dual-mode NADH sensor, for which colorimetric detection is enabled by its peroxidase-like nanozyme property and Raman detection is realized by its surface-enhanced Raman scattering property with the detection limit as low as 28 pM. More importantly, this probe enables real-time SERS monitoring in living cells, providing a unique tool to investigate dynamic cellular processes involving NADH. Our experiments reveal that metabolism dynamics is accelerated by glucose and is much higher in cancerous cells. The SERS results can also be verified by the colorimetric detection. This sensor provides a new potential to detect biomarkers and their dynamics in situ.Ministry of Education (MOE)This work was supported by the National Natural Science Foundation of China (21674085), National Postdoctoral Program for Innovative Talent (BX20190277), the Natural Science Basic Research Plan in Shaanxi Province of China (2020JZ-01), the China Postdoctoral Science Foundation (2020M673387, 2021M702557), the Key Laboratory Construction Program of Xi’an Municipal Bureau of Science and Technology (201805056ZD7CG40), the youth talent support program of Xi’an Jiaotong University (HX6J016) and Singapore Ministry of Education under its Academic Research Fund (AcRF) Tier-1 grants (RG110/20 and RT02/20) and AcRF Tier-2 grant (MOE2019-T2-2-004)