Amyloid fibrils formed by selective N-, C-terminal sequences of mouse apolipoprotein A-II

In mice, amyloidogenic type C apolipoprotein A-II (apoA-II) forms amyloid fibrils in age-associated amyloidosis. To understand the mechanism of amyloid fibril formation by apoA-II, we examined the polymerization of synthetic partial peptides of apoA-II in vitro. None of the partial apoA-II peptides polymerized into amyloid fibrils when tested as a single species mixture. We found a unique mechanism in which N- and C-terminal peptides associated into amyloid fibrils in a 1:1 ratio at pH 2.5. The 11-residue amino acid sequence (6-16), which is a common sequence of type B apoA-II and type C apoA-II proteins in amyloidosis-resistant mice and amyloidosis-susceptible mice, respectively, was critical for polymerization into amyloid fibrils. The 18-residue-long amino acid sequence (48-65) is also necessary for nucleation, but not for the extension phase. These findings suggest that there may be different mechanisms underlying the nucleation and extension phases of apoA-II amyloid fibril formation. We also found that amino acid substitutions between type B apoA-II (Pro5, Val38) and type C apoA-II (Gln5, Ala38) did not affect either phase. The strategy of using synthetic partial peptides of amyloidogenic proteins in vitro is a useful system for understanding amyloid fibril formation and for the development of novel therapies.ArticleBIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS. 1794(10):1517-1529 (2009)journal articl

DeepStore: an interaction-aware Wide&Deep model for store site recommendation with attentional spatial embeddings

International audienceStore site recommendation is one of the essential business services in smart cities for brick-and-mortar enterprises. In recent years, the proliferation of multisource data in cities has fostered unprecedented opportunities to the data-driven store site recommendation, which aims at leveraging large-scale user-generated data to analyze and mine users' preferences for identifying the optimal location for a new store. However, most works in store site recommendation pay more attention to a single data source which lacks some significant data (e.g., consumption data and user profile data). In this paper, we aim to study the store site recommendation in a fine-grained manner. Specifically, we predict the consumption level of different users at the store based on multisource data, which can not only help the store placement but also benefit analyzing customer behavior in the store at different time periods. To solve this problem, we design a novel model based on the deep neural network, named DeepStore, which learns low-and high-order feature interactions explicitly and implicitly from dense and sparse features simultaneously. In particular, DeepStore incorporates three modules: 1) the cross network; 2) the deep network; and 3) the linear component. In addition, to learn the latent feature representation from multisource data, we propose two embedding methods for different types of data: 1) the filed embedding and 2) attention-based spatial embedding. Extensive experiments are conducted on a real-world dataset including store data, user data, and point-of-interest data, the results demonstrate that DeepStore outperforms the state-of-the-art models

Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB

Hereditary spherocytosis (HS), the most common inherited hemolytic anemia disorder, is characterized by osmotically fragile microspherocytic red cells with a reduced surface area on the peripheral blood smear. Pathogenic variants in five erythrocyte membrane structure-related genes ANK1 (Spherocytosis, type 1; MIM#182900), SPTB (Spherocytosis, type 2; MIM#616649), SPTA1 (Spherocytosis, type 3; MIM#270970), SLC4A1 (Spherocytosis, type 4; MIM#612653) and EPB42 (Spherocytosis, type 5; MIM#612690) have been confirmed to be related to HS. There have been many studies on the pathogenic variants and mechanisms of HS, however, studies on how to manage the transmission of HS to the next-generation have not been reported. In this study, we recruited a patient with HS. Targeted next-generation sequencing with a panel of 208 genes related to blood system diseases detected a novel heterozygous variant in the SPTB: c.300+2dup in the proband. Sanger sequencing of variant alleles and haplotype linkage analysis of single nucleotide polymorphism (SNP) based on next-generation sequencing were performed simultaneously. Five embryos were identified with one heterozygous and four not carrying the SPTB variant. Single-cell amplification and whole genome sequencing showed that three embryos had varying degrees of trisomy mosaicism. One of two normal embryos was transferred to the proband. Ultimately, a healthy boy was born, confirmed by noninvasive prenatal testing for monogenic conditions (NIPT-M) to be disease-free. This confirmed our successful application of PGT in preventing transmission of the pathogenic variant allele in the HS family

Polyphenol-rich oolong tea alleviates obesity and modulates gut microbiota in high-fat diet-fed mice

Obesity is a major public health issue worldwide. Oolong tea (OT), which is partially fermented from Camellia sinensis leaves, has proven health benefits and potential preventive applications in multiple studies. However, research on the role of OT in obesity prevention and potential mechanisms is still limited. The purpose of this study was to investigate the modulatory effects of OT intervention on high-fat diet (HFD)-induced obesity and gut microbiota dysbiosis using an obese mouse model. Our results showed that 8-week OT supplementation with 93.94% polyphenols significantly decreased body weight gain, adipose tissue mass, and serum levels of triglyceride (2.60 mmol/L), cholesterol (5.49 mmol/L), and low-density lipoprotein cholesterol (0.61 mmol/L) in HFD-fed mice. Meanwhile, OT intervention was observed to improve fat accumulation, hepatic damage, glucose intolerance, and endotoxemia and alleviate inflammation by decreasing the levels of pro-inflammatory factors. OT also upregulated the expression of genes including Srebf1, Ppara, Lxra, Pgc1a, and Hsl and downregulated the expression of genes including Leptin, Il-6, and Il-1b. In addition, the gut dysbiosis characterized by decreased flora diversity and increased Firmicutes/Bacteroidetes ratio in obese mice was recovered by OT intervention. Certain differentially abundant microbes caused by HFD feeding, including Enterococcus, Intestinimonas, Blautia, and Bilophila, were also improved by OT treatment. This study demonstrated that OT, as a novel resource of dietary polyphenols, exhibited a protective effect on HFD-induced obesity and gut microbiota disorder

GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×$10^{−19}$) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×$10^{−8}$), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×$10^{−4}$; rs455804: OR = 0.84, P = 6.92×$10^{−3}$). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC

RESEARCH ON THE IMPACT OF FRICTION COEFFICIENT TO SCALE IN COLD ROLL-BEATING FORMING

Scale of forming surface in cold roll-beating forming process is a major defect. Controlling scaly defects is an important method to improve forming surface quality. According to the basic principle of cold roll-beating forming,the reasons and impact factors of scaly generation are analyzed. The finite element model of cold roll-beating forming was established by the finite element analysis software ABAQUS and the red copper was selected as sheet material. Under the up-beating condition and down-beating condition,the effects of friction coefficient to scaly height and scaly interval were studied. The results show that scaly height increases with the increase of friction coefficient in down-beating,while decrease in up-beating,scaly interval almost invariant in both roll-beating ways. Cold roll-beating forming experiment was carried out in refit milling machine and cross section parameters of scale in forming workpiece surface were measured by Leica DCM3D. In terms of actual measurement condition,experiment results with simulation results are uniformly. The correctness of finite element simulation is verified by experiment.Provide reference for inhibiting strip defects by selecting roll-beating methods and process parameters and improving both workpiece surface quality and dimensional precision