26 research outputs found
Growth Pattern in Chinese Children With 5α-Reductase Type 2 Deficiency: A Retrospective Multicenter Study
Background5α-reductase type 2 deficiency (5αRD) is an autosomal recessive hereditary disease of the group of 46, XY disorders of sex development (DSD).ObjectiveTo study the growth pattern in Chinese pediatric patients with 5αRD.SubjectsData were obtained from 141 patients with 5αRD (age: 0–16 years old) who visited eight pediatric endocrine centers from January 2010 to December 2017.MethodsIn this retrospective cohort study, height, weight, and other relevant data were collected from the multicenter hospital registration database. Baseline luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) after human chorionic gonadotropin (HCG) stimulation test were measured by enzyme enhanced chemiluminescence assay. Bone age (BA) was assessed using the Greulich-Pyle (G-P) atlas. Growth curve was constructed based on λ-median-coefficient of variation method (LMS).ResultsThe height standard deviation scores (HtSDS) and weight standard deviation scores (WtSDS) in 5αRD children were in the normal range as compared to normal boys. Significantly higher HtSDS was observed in patients with 5αRD who were <1 year old (t = 3.658, 2.103, P = 0.002, 0.048, respectively), and higher WtSDS in those <6 months old (t = 2.756, P = 0.012). Then HtSDS and WtSDS decreased gradually and fluctuated near the median of the same age until 13 years. WtSDS in 5αRD children from northern China were significantly higher than those from the south (Z = -2.670, P = 0.008). The variation tendency of HtSDS in Chinese 5αRDs was consistent with the trend of stimulating T. HtSDS and stimulating T in the external masculinization score (EMS) <7 group were slightly higher than those in EMS ≥ 7 group without significant difference. Additionally, the ratio of BA over chronological age (BA/CA) was significantly <1 in children with 5αRD.ConclusionChildren with 5αRD had a special growth pattern that was affected by high levels of T, while DHT played a very small role in it. Their growth accelerated at age <1 year, followed by slowing growth and fluctuating height near normal median boys’ height. The BA was delayed in 5αRD children. Androgen treatment, which may be considered anyway for male 5αRD patients with a micropenis, may also be beneficial for growth
Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis.
Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis
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Analyses of non-coding somatic drivers in 2,658Â cancer whole genomes.
The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
Asiatic acid improves high-fat-diet-induced osteoporosis in mice via regulating SIRT1/FOXO1 signaling and inhibiting oxidative stress
Asiatic acid can attenuate osteoporosis
through suppressing adipogenic differentiation and
osteoclastic differentiation. Oxidative stress enhances
osteoclastic differentiation but represses osteogenic
differentiation to promote osteoporosis. However, the
role and mechanism of asiatic acid in osteoporosis have
not been reported. Firstly, mice were fed with high-fatdiet (HFD) with or without asiatic acid for 16 weeks.
Data from an automatic biochemical analyzer showed
that HFD induced down-regulation of high-density
lipoprotein (HDL) and an increase of serum levels of
triglyceride (TG), total cholesterol (TC) and low-density
lipoprotein (LDL). However, asiatic acid administration
attenuated the decrease of HDL and increase of serum
TG, TC and LDL in osteoporotic mice. Secondly, HFD
induced high levels of malondialdehyde (MDA) and
reactive oxygen species (ROS), low levels of superoxide
dismutase (SOD) and glutathione peroxidase (GSH-Px)
in osteoporotic mice. However, the levels of MDA,
ROS, SOD and GSH-Px in osteoporotic mice were
reversed by asiatic acid administration. (this section is
unclear and requires revision) Asiatic acid
administration reduced expression of c-telopeptide of
type 1 collagen (CTX-1), enhanced alkaline phosphatase
(ALP) and procollagen type 1 N-terminal propeptide
(P1NP) in HFD-induced osteoporotic mice. (this section
is unclear and requires revision) Thirdly, asiatic acid
promoted calcium deposition in bone marrow cells and
osteogenic differentiation in osteoporotic mice, but
decreased ALP in bone marrow cells. Lastly, asiatic acid
enhanced SIRT1 and nuclear FOXO1 (Nu-FOXO1)
expression, while it reduced Acetyl FOXO1 (AcFOXO1) in osteoporotic mice. In conclusion, asiatic acid
might inhibit oxidative stress and promote osteogenic
differentiation through activating SIRT1/FOXO1 to
attenuate HFD-induced osteoporosis in mice
INFLUENCE OF BEARING CONFIGURATION ON SPINDLE MODAL CHARACTERISTICS
ABSTRACT Since bearing configuration has significant influence on the spindle modal characteristics which can reflect the dynamic performance of spindle system in machine tools, so it would be of extraordinary importance and necessity to analyze the spindle modal characteristics through simulation and experiment when it comes to designing spindle system. In this paper, the number and span of bearings, the spacer of bearing set and the overhang of spindle are considered as the main designing parameters of the spindle system. Firstly, a coupled spindle-bearing model is established considering the radial deformation of the bearing inner ring caused by interference fits of spindle assembly, as well as the centrifugal and thermal deformations. Based on the model, the modal characteristics of different bearing configurations are analyzed. Secondly, a spindle test bench is designed and constructed. Finally, modal characteristics of the spindle system are tested with different bearing configurations. From the simulation and experimental results, it's indicated that there is a correlation between the natural frequency and the number of bearings. The using of short spacer inside the bearing set can increase spindle natural frequency slightly. Besides, the first natural frequency of the spindle system rises with the bearing span, whereas the second one tends to decrease. And shortening the overhang of spindle can also increase its natural frequencies, which can be taken into account in spindle design
The complete mitochondrial genome and phylogenetic analysis of Yanglong yak (Bos grunniens)
In this study, we assembled the complete mitochondrial genome of Yanglong yak (Bos grunniens) from Illumina sequencing reads. The mitochondrial genome is 16,323 bp long with an A + T-biased nucleotide composition, and encodes 13 protein-coding, 22 tRNA, and two rRNA genes along with a noncoding control region. In addition, its gene order is identical to those of the previously published mitochondrial genomes of its congeners. Phylogenetic analysis indicates that this breed is closely related to Datong yak, Pamir yak, Tianjun yak, polled yak, Seron yak, Sunnan yak, a series of Domestic Yak and wild yak, followed by Jinchuan yak and Gannan yak, and slightly far away from Bison and Bos taurus
Ultrahigh Performance Triboelectric Nanogenerator Enabled by Charge Transmission in Interfacial Lubrication and Potential Decentralization Design
Triboelectric nanogenerator (TENG) is a promising strategy for harvesting low frequency mechanical energy. However, the bottlenecks of limited electric output by air/dielectric breakdown and poor durability by material abrasion seriously restrict its further improvement. Herein, we propose a liquid lubrication promoted sliding mode TENG to address both issues. Liquid lubrication greatly reduces interface material abrasion, and its high breakdown strength and charge transmission effect further enhance device charge density. Besides, the potential decentralization design by the voltage balance bar effectively suppresses the dielectric breakdown. In this way, the average power density up to 87.26 W·m-2·Hz-1, energy conversion efficiency of 48%, and retention output of 90% after 500,000 operation cycles are achieved, which is the highest average power density and durability currently. Finally, a cell phone is charged to turn on by a palm-sized TENG device at 2 Hz within 25 s. This work has a significance for the commercialization of TENG-based self-powered systems
Changes in Transcriptomic Profiles in Different Reproductive Periods in Yaks
Yak reproductive characteristics have received extensive attention, though the molecular regulation mechanism of its ovarian activity remains to be explored. Therefore, this study initially conducted a comparative analysis of yak ovarian activities in anestrus, estrus, and pregnancy regarding their morphology and histology, followed by implementing RNA sequencing (RNA-seq) technology to detect the overall gene expression and biological mechanism in different reproductive stages. H&E staining showed that there were more growing follicles and mature follicles in ovarian tissue sections during estrus than ovarian tissues during non-estrus. The RNA-seq analysis of yak ovary tissues in three periods showed that DEGs related to follicular development and hormone metabolism were screened in the three comparison groups, such as COL1A2, NR4A1, THBS2, PTGS2, SCARB1, STAR, and WNT2B. Bioinformatics analysis showed that these DEGs are involved in ion binding, cell development, metabolic processes, enriched in ECM–receptor interactions, steroid biosynthesis, together with aldosterone generation/discharge and Wnt/PI3K-Akt signaling pathways. In addition, we speculate alternate splice development events to have important role/s in regulating ovarian functional genomic expression profiles. These results provide essential knowledge aimed at scrutinizing pivotal biomarkers for yak ovarian activity, together with paving the way for enhancing researchers’ focus on improving yak reproductive performance