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Protein import

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https://www.readbyqxmd.com/read/29454111/combining-rosetta-with-molecular-dynamics-md-a-benchmark-of-the-md-based-ensemble-protein-design
#1
Jan Ludwiczak, Adam Jarmula, Stanislaw Dunin-Horkawicz
Computational protein design is a set of procedures for computing amino acid sequences that will fold into a specified structure. Rosetta Design, a commonly used software for protein design, allows for the effective identification of sequences compatible with a given backbone structure, while molecular dynamics (MD) simulations can thoroughly sample near-native conformations. We benchmarked a procedure in which Rosetta design is started on MD-derived structural ensembles and showed that such a combined approach generates 20 to 30% more diverse sequences than currently available methods with only a slight increase in computation time...
February 14, 2018: Journal of Structural Biology
https://www.readbyqxmd.com/read/29454102/inflammation-as-a-possible-link-between-dyslipidemia-and-alzheimer-s-disease
#2
REVIEW
Bruno Cabral de Lima Oliveira, Paula Maria Quaglio Bellozi, Helton José Reis, Antônio Carlos Pinheiro de Oliveira
Alzheimer's disease (AD) is the leading cause of dementia worldwide. This pathological condition is characterized not only by Aβ and tau accumulation in the central nervous system (CNS), but also by inflammation, processes that can lead to neurodegeneration. Besides that, other factors may contribute to the development of AD, such as dyslipidemias. Changes in lipid levels can either influence the activity of enzymes related to the protein deposition that occurs in this pathological condition, or enhance the peripheral and CNS immune responses...
February 14, 2018: Neuroscience
https://www.readbyqxmd.com/read/29454095/an-esophageal-adenocarcinoma-susceptibility-locus-at-9q22-also-confers-risk-to-esophageal-squamous-cell-carcinoma-by-regulating-the-function-of-barx1
#3
Caiwang Yan, Yong Ji, Tongtong Huang, Fei Yu, Yong Gao, Yayun Gu, Qi Qi, Jiangbo Du, Juncheng Dai, Hongxia Ma, Guangfu Jin
Genome wide association studies (GWAS) have identified a series of genetic variants associated with the risk of esophageal adenocarcinoma (EAC)/Barrett's esophagus (BE), which was different from those loci for esophageal squamous cell carcinoma (ESCC). It is important to evaluate whether these susceptibility loci for EAC/BE are also implicated in ESCC development. In the current study, we analyzed genetic variants at 3p13, 9q22, 16q24 and 19p13 in a case-control study including 2139 ESCC patients and 2463 cancer-free controls in a Chinese population, and further characterized the biological relevance of genetic variants by functional assays...
February 14, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29454088/hsf4-transcriptional-regulates-hmox-1-expression-in-hlecs
#4
Shengjie Liao, Zhen Qu, Linqiang Li, Benwen Zhou, Meng Gao, Mi Huang, Duanzhuo Li
The major causes for cataract formation are free radicals, which are neutralized by the endogenous antioxidants. However, how the human lens clean these harmful free radicals is still unclear. Transcriptional factor heat shock factor 4 (HSF4) is a cataract-causing gene and plays important roles during lens development. Here we show that HMOX-1, an anti-oxidase, is a bona fide transcriptional target gene of HSF4 in HLECs (human lens epithelial cells). HSF4 directly binds to the HSE element in HMOX-1 promoter to mediate its mRNA transcription and protein accumulation...
February 14, 2018: Gene
https://www.readbyqxmd.com/read/29454073/the-accumulation-of-assembly-intermediates-of-the-mitochondrial-complex-i-matrix-arm-is-reduced-by-limiting-glucose-uptake-in-a-neuronal-like-model-of-melas-syndrome
#5
Guillaume Geffroy, Rayane Benyahia, Samuel Frey, Valerie Desquiret-Dumas, Naig Gueguen, Celine Bris, Sophie Belal, Aurore Inisan, Aurelie Renaud, Arnaud Chevrollier, Daniel Henrion, Dominique Bonneau, Franck Letournel, Guy Lenaers, Pascal Reynier, Vincent Procaccio
Ketogenic diet (KD) which combined carbohydrate restriction and the addition of ketone bodies has emerged as an alternative metabolic intervention used as an anticonvulsant therapy or to treat different types of neurological or mitochondrial disorders including MELAS syndrome. MELAS syndrome is a severe mitochondrial disease mainly due to the m.3243A > G mitochondrial DNA mutation. The broad success of KD is due to multiple beneficial mechanisms with distinct effects of very low carbohydrates and ketones...
February 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29454054/genomic-perspectives-of-spider-silk-genes-through-target-capture-sequencing-conservation-of-stabilization-mechanisms-and-homology-based-structural-models-of-spidroin-terminal-regions
#6
Matthew A Collin, Thomas H Clarke, Nadia A Ayoub, Cheryl Y Hayashi
A powerful system for studying protein aggregation, particularly rapid self-assembly, is spider silk. Spider silks are proteinaceous and silk proteins are synthesized and stored within silk glands as liquid dope. As needed, liquid dope is near-instantaneously transformed into solid fibers or viscous adhesives. The dominant constituents of silks are spidroins (spider fibroins) and their terminal domains are vital for the tight control of silk self-assembly. To better understand spidroin termini, we used target capture and deep sequencing to identify spidroin gene sequences from six species representing the araneoid families of Araneidae, Nephilidae, and Theridiidae...
February 14, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29453988/silencing-calreticulin-gene-might-protect-cardiomyocytes-from-angiotensin-ii-induced-apoptosis
#7
Wen Zhang, Zhiyue Liu, Yanmei Zhang, Qinxue Bao, Wenchao Wu, He Huang, Xiaojing Liu
AIMS: Calreticulin (CRT), as a chaperone, contributes to protein folding and quality control cycle. CRT is an important factor regulating Ca 2+ that participates in cell apoptosis. However, the function of CRT in the heart is still controversial. Therefore, we aimed to investigate the potential role of CRT in angiotensin II-induced cardiomyocytes apoptosis. MAIN METHODS: Primary cultured neonatal cardiomyocytes were stimulated with angiotensin II to induce the apoptosis...
February 14, 2018: Life Sciences
https://www.readbyqxmd.com/read/29453986/sterol-o-acyltransferase-1-deficiency-improves-defective-insulin-signaling-in-the-brains-of-mice-fed-a-high-fat-diet
#8
Ning Xu, Hao Meng, Tian-Yi Liu, Ying-Li Feng, Yuan Qi, Dong-Huan Zhang, Hong-Lei Wang
Insulin resistance induced by a high-fat diet (HFD) is related to metabolic diseases, and sterol O-acyltransferase 1 (SOAT1) is a key enzyme for the biosynthesis of cholesteryl ester. In the present study, wild-type (WT) mice and SOAT1-knockout (KO) mice with a C57BL6 background fed a HFD were used to explore the role of SOAT1 in the hypothalamus. The results show that the WT mice exhibited a significant increase in body weight as well as hepatic histologic changes; they also had a lower glucose and insulin tolerance than the WT mice fed a normal diet...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453935/evaluation-of-cerebrospinal-fluid-phosphorylated-tau-231-as-a-biomarker-in-the-differential-diagnosis-of-alzheimer-s-disease-and-vascular-dementia
#9
Spomenka Kiđemet-Piskač, Mirjana Babić Leko, Antonela Blažeković, Lea Langer Horvat, Nataša Klepac, Zdenko Sonicki, Danijela Kolenc, Patrick R Hof, Marina Boban, Ninoslav Mimica, Fran Borovečki, Goran Šimić
BACKGROUND: The diagnosis of either Alzheimer's disease (AD) or vascular dementia (VaD) is still largely based on clinical guidelines and exclusion of other diseases that may lead to dementia. AIMS: In this study, we assessed whether the use of sensitive and specific biomarkers such as phosphorylated tau proteins could contribute to an earlier and more accurate diagnosis of AD and VaD, as well as to their differentiation. MATERIAL AND METHODS: A total of 198 patients, of which 152 had AD, 28 VaD, and 18 were healthy controls (HC), were included in the analyses...
February 17, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29453900/downregulation-of-reticulocalbin-1-differentially-facilitates-apoptosis-and-necroptosis-in-human-prostate-cancer-cells
#10
Xiaofei Liu, Nianzhao Zhang, Dawei Wang, Deyu Zhu, Quan Yuan, Xiulei Zhang, Lilin Qian, Huanmin Niu, Yi Lu, Guijie Ren, Keli Tian, Huiqing Yuan
Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca 2+ -binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with Cyclin B, not Cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively...
February 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29453692/unacylated-ghrelin-and-obestatin-in-pediatric-ckd-are-they-important-in-protein-energy-wasting
#11
EDITORIAL
Zhen Wang, Eduardo A Oliveira, Robert H Mak
No abstract text is available yet for this article.
February 16, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29453635/monitoring-of-erlotinib-in-pancreatic-cancer-patients-during-long-time-administration-and-comparison-to-a-physiologically-based-pharmacokinetic-model
#12
Andrea Gruber, Martin Czejka, Philipp Buchner, Marie Kitzmueller, Nairi Kirchbaumer Baroian, Christian Dittrich, Azra Sahmanovic Hrgovcic
PURPOSE: In this study, a therapeutic drug monitoring (TDM) of erlotinib in pancreatic cancer patients was performed over 50 weeks to reveal possible alterations in erlotinib plasma concentrations. Additionally, a physiologically based pharmacokinetic (PBPK) model was created to assess such variations in silico. METHODS: Patients with advanced pancreatic cancer received a chemotherapeutic combination of 100 mg erlotinib q.d., 500-900 mg capecitabine b.d. and 5 mg/kg bevacizumab q...
February 16, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29453633/comparative-analysis-of-the-mitochondrial-genome-of-the-fungus-colletotrichum-lindemuthianum-the-causal-agent-of-anthracnose-in-common-beans
#13
Casley Borges de Queiroz, Mateus Ferreira Santana, Pedro M Pereira Vidigal, Marisa Vieira de Queiroz
Fungi of the genus Colletotrichum are economically important and are used as models in plant-pathogen interaction studies. In this study, the complete mitochondrial genomes of two Colletotrichum lindemuthianum isolates were sequenced and compared with the mitochondrial genomes of seven species of Colletotrichum. The mitochondrial genome of C. lindemuthianum is a typical circular molecule 37,446 bp (isolate 89 A 2 2-3) and 37,440 bp (isolate 83.501) in length. The difference of six nucleotides between the two genomes is the result of a deletion in the ribosomal protein S3 (rps3) gene in the 83...
February 16, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29453575/regulation-of-blood-testis-barrier-btb-dynamics-role-of-actin-and-microtubule-based-cytoskeletons
#14
Qing Wen, Elizabeth I Tang, Nan Li, Dolores D Mruk, Will M Lee, Bruno Silvestrini, C Yan Cheng
The blood-testis barrier (BTB) is an important ultrastructure in the testis that supports meiosis and postmeiotic spermatid development since a delay in the establishment of a functional Sertoli cell barrier during postnatal development in rats or mice by 17-20 day postpartum (dpp) would lead to a delay of the first wave of meiosis. Furthermore, irreversible disruption of the BTB by toxicants also induces infertility in rodents. Herein, we summarize recent findings that BTB dynamics (i.e., disassembly, reassembly, and stabilization) are supported by the concerted efforts of the actin- and microtubule (MT)-based cytoskeletons...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29453573/gene-silencing-of-human-sertoli-cells-utilizing-small-interfering-rnas
#15
Hong Wang, Qingqing Yuan, Minghui Niu, Liping Wen, Hongyong Fu, Fan Zhou, Weihui Zhang, Zuping He
Sertoli cells, as the unique somatic cells within the seminiferous tubules, play essential roles in regulating normal spermatogenesis. In addition, recent studies have demonstrated that Sertoli cells could have significant applications in regenerative medicine due to their great plasticity. However, the roles of genes in controlling the fate determinations of human Sertoli cells remain largely unknown. Silencing genes of human Sertoli cells utilizing small interfering RNAs (siRNAs) is an important method to explore their functions and mechanisms in human Sertoli cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29453569/assessing-autophagy-in-sertoli-cells
#16
Chao Liu, Jehangir Khan, Wei Li
Autophagy is an important cellular homeostatic process, it degrades most long-lived proteins and some organelles by lysosome to provide raw materials for the survival of the cells during nutrient or energy deprivation condition. Autophagy is active in Sertoli cells and involved in many cellular processes. However, the precise role of autophagy in Sertoli cells is still largely unknown. Thus, the assessment of autophagy in Sertoli cells should be helpful for investigating the functional roles of autophagy in Sertoli cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29453562/preparation-of-testicular-samples-for-histology-and-immunohistochemistry
#17
Barbara Bilinska, Anna Hejmej, Malgorzata Kotula-Balak
One approach to visualize internal structures of the testis is histological sectioning of the material. The use of testicular samples allows a detailed analysis of the structure of both seminiferous tubules and the interstitial space. It is worth noting that key role in the control of germ cell development is assigned to Sertoli cells. Thus, in this chapter the special reference is made on visualization of Sertoli cells in the seminiferous epithelium in which they create a specialized microenvironment to support the germ cell development through the formation of the blood-testis barrier (BTB)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29453542/mechanisms-underlying-neurotoxicity-of-silver-nanoparticles
#18
Lidia Strużyńska, Joanna Skalska
The potent antimicrobial properties of nanoparticulate silver (AgNPs) have led to broad interest in using them in a wide range of commercial and medical applications. Although numerous in vivo and in vitro studies have provided evidence of toxic effects, rapid commercialization of AgNP-based nanomaterials has advanced without characterization of their potential environmental and health hazards. There is evidence that AgNPs can be translocated from the blood to the brain, regardless the route of exposure, and accumulate in the brain over time...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29453539/nanoparticle-protein-interaction-the-significance-and-role-of-protein-corona
#19
Saad Mohammad Ahsan, Chintalagiri Mohan Rao, Md Faiz Ahmad
The physico-chemical properties of nanoparticles, as characterized under idealized laboratory conditions, have been suggested to differ significantly when studied under complex physiological environments. A major reason for this variation has been the adsorption of biomolecules (mainly proteins) on the nanoparticle surface, constituting the so-called "biomolecular corona". The formation of biomolecular corona on the nanoparticle surface has been reported to influence various nanoparticle properties viz...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29453462/gq-11-a-new-ppar-agonist-improves-obesity-induced-metabolic-alterations-in-ldlr-mice
#20
Jacqueline C Silva, Edson M de Oliveira, Walter M Turato, Gustavo H G Trossini, Vinícius G Maltarollo, Marina G R Pitta, Ivan R Pitta, Beatriz de Las Heras, Lisardo Boscá, Martina Rudnicki, Dulcineia S P Abdalla
BACKGROUND: Obesity and insulin resistance/diabetes are important risk factors for cardiovascular diseases and demand safe and efficacious therapeutics. OBJECTIVE: To assess the effects of a new thiazolidine compound-GQ-11-on obesity and insulin resistance induced by a diabetogenic diet in LDL receptor-deficient (LDLr -/- ) mice. METHODS: Molecular docking simulations of GQ-11, PPARα and PPARγ structures were performed. Male C57BL/6J LDLr -/- mice fed a diabetogenic diet for 24 weeks were treated with vehicle, GQ-11 or pioglitazone or (20 mg/kg/day) for 28 days by oral gavage...
January 30, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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