2,2,4,4-Tetra­phenyl-1,3-bis­(3,3,5,5-tetra­methyl-1,1-diphenyl-5-vinyl­trisilox­an-1-yl)­cyclo­disilazane

The title mol­ecule, C60H70N2O4Si8, lies on an inversion center. In the asymmetric unit, one of the phenyl rings is disordered over two sets of sites with refined occupancies 0.58 (2) and 0.42 (2). In addition, in two substitution sites of the terminal dimeth­yl(vin­yl)silyl unit, a methyl group and the vinyl group are disordered over the same site with refined occupancies 0.523 (13) and 0.477 (13)

Realization of multiple charge density waves in NbTe2 at the monolayer limit

Abstract: Layered transition-metal dichalcogenides (TMDCs) down to the monolayer (ML) limit provide a fertile platform for exploring charge-density waves (CDWs). Though bulk NbTe2 is known to harbor a single axis 3*1 CDW coexisting with non-trivial quantum properties, the scenario in the ML limit is still experimentally unknown. In this study, we unveil the richness of the CDW phases in ML NbTe2, where not only the theoretically predicted 4*4 and 4*1 phases, but also two unexpected sqrt(28)*sqrt(28) and sqrt(19)*sqrt(19) phases, can be realized. For such a complex CDW system, we establish an exhaustive growth phase diagram via systematic efforts in the material synthesis and scanning tunneling microscope characterization. Moreover, we report that the energetically stable phase is the larger scale order (sqrt(19)*sqrt(19)), which is surprisingly in contradiction to the prior prediction (4*4). These findings are confirmed using two different kinetic pathways, i.e., direct growth at proper growth temperatures (T), and low-T growth followed by high-T annealing. Our results provide a comprehensive diagram of the "zoo" of CDW orders in ML 1T-NbTe2 for the first time and offer a new material platform for studying novel quantum phases in the 2D limit

Vulto-van Silfhout-de Vries syndrome caused by de novo variants of DEAF1 gene: a case report and literature review

Vulto-van Silfhout-de Vries syndrome (VSVS; MIM 615828) is an extremely rare autosomal dominant disorder with unknown incidence. It is always caused by de novo heterozygous pathogenic variants in the DEAF1 gene, which encodes deformed epidermal autoregulatory factor-1 homology. VSVS is characterized by mild to severe intellectual disability (ID) and/or global developmental delay (GDD), seriously limited language expression, behavioral abnormalities, somnipathy, and reduced pain sensitivity. In this study, we present a Chinese boy with moderate GDD and ID, severe expressive language impairment, behavioral issues, autism spectrum disorder (ASD), sleeping dysfunction, high pain threshold, generalized seizures, imbalanced gait, and recurrent respiratory infections as clinical features. A de novo heterozygous pathogenic missense variant was found in the 5th exon of DEAF1 gene, NM_021008.4 c.782G>C (p. Arg261Pro) variant by whole exome sequencing (WES). c.782G>C had not been previously reported in genomic databases and literature. According to the ACMG criteria, this missense variant was considered to be “Likely Pathogenic”. We diagnosed the boy with VSVS both genetically and clinically. At a follow-up of 2.1 years, his seizures were well controlled after valproic acid therapy. In addition, the child’s recurrent respiratory infections improved at 3.5 years of age, which has not been reported in previous individuals. Maybe the recurrent respiratory infections like sleep problems reported in the literature are not permanent but may improve naturally over time. The literature review showed that there were 35 individuals with 28 different de novo pathogenic variants of DEAF1-related VSVS. These variants were mostly missense and the clinical manifestations were similar to our patient. Our study expands the genotypic and phenotypic profiles of de novo DEAF1

Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

© 2018 The Author(s). Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αvβ6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD

Analytical methods for inferring functional effects of single base pair substitutions in human cancers

Cancer is a genetic disease that results from a variety of genomic alterations. Identification of some of these causal genetic events has enabled the development of targeted therapeutics and spurred efforts to discover the key genes that drive cancer formation. Rapidly improving sequencing and genotyping technology continues to generate increasingly large datasets that require analytical methods to identify functional alterations that deserve additional investigation. This review examines statistical and computational approaches for the identification of functional changes among sets of single-nucleotide substitutions. Frequency-based methods identify the most highly mutated genes in large-scale cancer sequencing efforts while bioinformatics approaches are effective for independent evaluation of both non-synonymous mutations and polymorphisms. We also review current knowledge and tools that can be utilized for analysis of alterations in non-protein-coding genomic sequence

Insights into hominid evolution from the gorilla genome sequence.

Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genomic basis for RNA alterations in cancer.

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer