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familial aggregation

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https://www.readbyqxmd.com/read/29168638/homology-modeling-and-molecular-dynamics-simulation-combined-with-x-ray-solution-scattering-defining-protein-structures-of-thromboxane-and-prostacyclin-synthases
#1
Hsiao-Ching Yang, Cheng-Han Yang, Ming Yi Huang, Jyh-Feng Lu, Jinn-Shyan Wang, Yi-Qi Yeh, U-Ser Jeng
A combination of molecular dynamics (MD) simulations and X-ray scattering (SAXS) has emerged as the approach of choice for studying protein structures and dynamics in solution. This approach has potential applications for membrane proteins that neither are soluble nor form crystals easily. We explore the water-coupled dynamic structures of thromboxane synthase (TXAS) and prostacyclin synthase (PGIS) from scanning HPLC-SAXS measurements combined with MD ensemble analyses. Both proteins are heme-containing enzymes in the cytochrome P450 family, known as prostaglandin H2 (PGH2) isomerase, with counter functions in regulation of platelet aggregation...
November 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29166823/foot-and-mouth-disease-virus-capsid-protein-vp2-activates-the-cellular-eif2s1-atf4-pathway-and-induces-autophagy-via-hspb1
#2
Peng Sun, Shumin Zhang, Xiaodong Qin, Xingni Chang, Xiaorui Cui, Haitao Li, Shuaijun Zhang, Huanghuang Gao, Penghua Wang, Zhidong Zhang, Jianxun Luo
Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication...
November 23, 2017: Autophagy
https://www.readbyqxmd.com/read/29164072/a-new-strain-collection-for-improved-expression-of-outer-membrane-proteins
#3
Ina Meuskens, Marcin Michalik, Nandini Chauhan, Dirk Linke, Jack C Leo
Almost all integral membrane proteins found in the outer membranes of Gram-negative bacteria belong to the transmembrane β-barrel family. These proteins are not only important for nutrient uptake and homeostasis, but are also involved in such processes as adhesion, protein secretion, biofilm formation, and virulence. As surface exposed molecules, outer membrane β-barrel proteins are also potential drug and vaccine targets. High production levels of heterologously expressed proteins are desirable for biochemical and especially structural studies, but over-expression and subsequent purification of membrane proteins, including outer membrane proteins, can be challenging...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29163899/design-crystal-structure-and-atomic-force-microscopy-study-of-thioether-ligated-d-l-cyclic-antimicrobial-peptides-against-multidrug-resistant-pseudomonas-aeruginosa
#4
Runze He, Ivan Di Bonaventura, Ricardo Visini, Bee-Ha Gan, Yongchun Fu, Daniel Probst, Alexandre Lüscher, Thilo Köhler, Christian van Delden, Achim Stocker, Wenjing Hong, Tamis Darbre, Jean-Louis Reymond
Here we report a new family of cyclic antimicrobial peptides (CAMPs) targeting MDR strains of Pseudomonas aeruginosa. These CAMPs are cyclized via a xylene double thioether bridge connecting two cysteines placed at the ends of a linear amphiphilic alternating d,l-sequence composed of lysines and tryptophans. Investigations by transmission electron microscopy (TEM), dynamic light scattering and atomic force microscopy (AFM) suggest that these peptide macrocycles interact with the membrane to form lipid-peptide aggregates...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29162515/whole-exome-sequencing-in-a-japanese-family-with-highly-aggregated-diabetes-identifies-a-candidate-susceptibility-mutation-in-adamtsl3
#5
Byambatseren Jambaljav, Daisuke Tanaka, Kazuaki Nagashima, Shin-Ichi Harashima, Norio Harada, Takanari Harada, Yuta Fujiwara, Yu Wang, Yanyan Liu, Yasuharu Tabara, Fumihiko Matsuda, Akio Koizumi, Nobuya Inagaki
AIMS: The aim of this study was to clarify the genetic background of a family with multiple cases of diabetes accompanied by absolute insulin deficiency using whole-exome sequencing (WES). METHODS: In a Japanese family, WES was performed in four affected members with absolute insulin deficiency and two unaffected members. We focused on variants that were predicted to be disease-causing by bioinformatics and were shared by all of the four affected members but were not present in the two unaffected members...
November 18, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29161404/mutation-dependent-aggregation-and-toxicity-in-a-drosophila-model-for-ubqln2-associated-als
#6
Sang Hwa Kim, Shannon G Stiles, Joseph M Feichtmeier, Nandini Ramesh, Lihong Zhan, Mark A Scalf, Lloyd M Smith, Udai Bhan Pandey, Randal S Tibbetts
Members of the conserved ubiquilin (UBQLN) family of ubiquitin (Ub) chaperones harbor an antipodal UBL (Ub-like)-UBA (Ub-associated) domain arrangement and participate in proteasome and autophagosome-mediated protein degradation. Mutations in a proline-rich-repeat region (PRR) of UBQLN2 cause amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD); however, neither the normal functions of the PRR nor impacts of ALS-associated mutations within it are well understood. In this study we show that ALS mutations perturb UBQLN2 solubility and folding in a mutation-specific manner...
November 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29159058/local-and-distant-relationships-between-amyloid-tau-and-neurodegeneration-in-alzheimer-s-disease
#7
Leonardo Iaccarino, Gautam Tammewar, Nagehan Ayakta, Suzanne L Baker, Alexandre Bejanin, Adam L Boxer, Maria Luisa Gorno-Tempini, Mustafa Janabi, Joel H Kramer, Andreas Lazaris, Samuel N Lockhart, Bruce L Miller, Zachary A Miller, James P O'Neil, Rik Ossenkoppele, Howard J Rosen, Daniel R Schonhaut, William J Jagust, Gil D Rabinovici
The relationships between β-amyloid (Aβ), tau and neurodegeneration within Alzheimer's Disease pathogenesis are not fully understood. To explore these associations in vivo, we evaluated 30 Aβ PET-positive patients (mean ± sd age 62.4 ± 8.3) with mild probable AD and 12 Aβ PET-negative healthy controls (HC) (mean ± sd age 77.3 ± 6.9) as comparison. All participants underwent 3 T MRI, (11)C-PiB (Aβ) PET and (18)F-AV1451 (tau) PET. Multimodal correlation analyses were run at both voxel- and region-of-interest levels...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29158857/the-brca2-variant-c-68-7-t-a-is-associated-with-breast-cancer
#8
Pål Møller, Eivind Hovig
Background: BRCA2 c.68-7T>A has been demonstrated to cause aberrant splicing and is possibly pathogenic. The population prevalence of the variant is 0.2%, which higher than usual for pathogenic BRCA2 variants. The pathogenicity of the variant is discussed. Methods: The outpatient genetic clinic at The Norwegian Radium Hospital, part of Oslo University Hospital, has invited breast cancer kindreds for genetic examinations and prospective follow-up of high risk patients since 1988...
2017: Hereditary Cancer in Clinical Practice
https://www.readbyqxmd.com/read/29158413/amyloid-polymorphisms-constitute-distinct-clouds-of-conformational-variants-in-different-etiological-subtypes-of-alzheimer-s-disease
#9
Jay Rasmussen, Jasmin Mahler, Natalie Beschorner, Stephan A Kaeser, Lisa M Häsler, Frank Baumann, Sofie Nyström, Erik Portelius, Kaj Blennow, Tammaryn Lashley, Nick C Fox, Diego Sepulveda-Falla, Markus Glatzel, Adrian L Oblak, Bernardino Ghetti, K Peter R Nilsson, Per Hammarström, Matthias Staufenbiel, Lary C Walker, Mathias Jucker
The molecular architecture of amyloids formed in vivo can be interrogated using luminescent conjugated oligothiophenes (LCOs), a unique class of amyloid dyes. When bound to amyloid, LCOs yield fluorescence emission spectra that reflect the 3D structure of the protein aggregates. Given that synthetic amyloid-β peptide (Aβ) has been shown to adopt distinct structural conformations with different biological activities, we asked whether Aβ can assume structurally and functionally distinct conformations within the brain...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158014/movement-patterns-in-entomopathogenic-nematodes-continuous-vs-temporal
#10
Wei-Bin Ruan, David Shapiro-Ilan, Edwin E Lewis, Fatma Kaplan, Hans Alborn, Xin-Hui Gu, Paul Schliekelman
To exploit resources, animals implement various foraging behaviors to increase their fitness. Entomopathogenic nematodes are obligate parasites of insects in nature. In previous studies, entomopathogenic nematodes were reported to exhibit group movement behavior in the presence and absence of insect hosts. However, it was not determined if group movement is continuous or temporal. For example, nematode movement behavior upon emergence from the host might start out in an independent fashion prior to aggregation, or group movement may be exhibited continuously...
November 17, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/29157189/molecular-dynamics-of-a-far-positioned-sod1-mutant-v14m-reveals-pathogenic-misfolding-behavior
#11
Dharma Rao Tompa, K Saraboji
Human superoxide dismutase (Cu/Zn SOD1) is a homodimeric enzyme. Mutations in Cu/Zn SOD1 causes a familial form of amyotrophic lateral sclerosis (fALS), and aggregation of mutant SOD1 has been proposed to play a role in neurodegeneration. Though a majority of the mutations are point substitutions, there are a few changes that result in amino acid deletions or truncations of the polypeptide. These pathogenic mutations are scattered throughout the three-dimensional structure of the dimeric enzyme, which creates a puzzling pattern to investigate the molecular determinants of fALS...
November 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29156781/toxoplasma-gondii-clp-family-protein-tgclpb1-plays-a-crucial-role-in-thermotolerance
#12
Shinuo Cao, Nali Du, Heming Chen, Yu Pang, Zhaoxia Zhang, Jun Zheng, Honglin Jia
Caseinolytic peptidase B (ClpB) plays a pivotal role in suppressing and reversing protein aggregation. Toxoplasma gondii is an intracellular parasitic protozoan that infects a wide variety of mammals and birds and therefore is exposed to a broad range of living condition. We screened ToxoDB (http://ToxoDB.org) and identified 10 putative T. gondii genes encoding members of the Clp superfamily of caseinolytic proteases and chaperones. Of these, we focused on characterizing the Class I ATP-dependent molecular chaperones TgClpB1, TgClpB2, and TgClpB3...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156055/analysis-of-an-adtkd-family-with-a-novel-frameshift-mutation-in-muc1-reveals-characteristic-features-of-mutant-muc1-protein
#13
Satoko Yamamoto, Jun-Ya Kaimori, Takuji Yoshimura, Tomoko Namba, Atsuko Imai, Kaori Kobayashi, Ryoichi Imamura, Naotsugu Ichimaru, Kazuto Kato, Akihiro Nakaya, Shiro Takahara, Yoshitaka Isaka
Background: Medullary cystic kidney disease Type 1 is an autosomal dominant tubulointerstitial kidney disease (ADTKD). Recently, mucin 1 ( MUC1 ) was identified as a causal gene of medullary cystic kidney disease (ADTKD-MUC1). However, the MUC1 mutation was found to be a single cytosine insertion in a single copy of the GC-rich variable number of tandem repeats (VNTRs), which are very difficult to analyze by next-generation sequencing. To date, other mutations have not been detected in ADTKD-MUC1, and the mutant MUC1 protein has not been analyzed because of the difficulty of genetically modifying the VNTR sequence...
June 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29154277/potential-of-low-dose-leuco-methylthioninium-bis-hydromethanesulphonate-lmtm-monotherapy-for-treatment-of-mild-alzheimer-s-disease-cohort-analysis-as-modified-primary-outcome-in-a-phase-iii-clinical-trial
#14
Gordon K Wilcock, Serge Gauthier, Giovanni B Frisoni, Jianping Jia, Jiri H Hardlund, Hans J Moebius, Peter Bentham, Karin A Kook, Bjoern O Schelter, Damon J Wischik, Charles S Davis, Roger T Staff, Vesna Vuksanovic, Trevor Ahearn, Luc Bracoud, Kohkan Shamsi, Ken Marek, John Seibyl, Gernot Riedel, John M D Storey, Charles R Harrington, Claude M Wischik
BACKGROUND: LMTM is being developed as a treatment for AD based on inhibition of tau aggregation. OBJECTIVES: To examine the efficacy of LMTM as monotherapy in non-randomized cohort analyses as modified primary outcomes in an 18-month Phase III trial in mild AD. METHODS: Mild AD patients (n = 800) were randomly assigned to 100 mg twice a day or 4 mg twice a day. Prior to unblinding, the Statistical Analysis Plan was revised to compare the 100 mg twice a day as monotherapy subgroup (n = 79) versus 4 mg twice a day as randomized (n = 396), and 4 mg twice a day as monotherapy (n = 76) versus 4 mg twice a day as add-on therapy (n = 297), with strong control of family-wise type I error...
November 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29151619/improving-the-folding-of-supramolecular-copolymers-by-controlling-the-assembly-pathway-complexity
#15
Gijs M Ter Huurne, Lafayette N J de Windt, Yiliu Liu, E W Meijer, Ilja K Voets, Anja R A Palmans
A family of amphiphilic, heterograft copolymers containing hydrophilic, hydrophobic, and supramolecular units based on Jeffamine M-1000, dodecylamine, and benzene-1,3,5-tricarboxamide (BTA) motifs, respectively, was prepared via a postfunctionalization approach. The folding of the copolymers in water into nanometer-sized particles was analyzed by a combination of dynamic and static light scattering, circular dichroism spectroscopy, and small-angle neutron scattering. The sample preparation protocol was crucial for obtaining reproducible and consistent results, showing that only full control over the structure and pathway complexity will afford the desired folded structure, a phenomenon similar to protein folding...
November 14, 2017: Macromolecules
https://www.readbyqxmd.com/read/29147836/effects-of-saffron%C3%A2-and-its-constituents-%C3%A2-crocin-1-crocin-2-and-crocetin-on-%C3%AE-synuclein-fibrils
#16
Eiji Inoue, Yasuharu Shimizu, Ryo Masui, Tomomi Hayakawa, Tomoe Tsubonoya, Satoko Hori, Keiichi Sudoh
Saffron, the stigma of Crocus sativus Linné (Iridaceae family), has been known to inhibit aggregation of β-amyloid, a nerve tissue protein. α-Synuclein (αS) is a 140-amino acid protein found abundantly in various regions of the brain. Its abnormal aggregation and accumulation in nerve tissue are said to cause neurodegenerative diseases such as Parkinson's disease, Lewy body dementia, and multiple-system atrophy. This study (part of this study was presented at the 137th Annual Meeting of the Pharmaceutical Society of Japan) examined the effects of saffron, its constituents (crocin-1, crocin-2, crocetin, and safranal), and crocetin structural analogs (hexadecanedioic acid, norbixin, and trans, trans-muconic acid) on αS aggregation, and αS fibril dissociation...
November 17, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29146595/the-cartilage-specific-lectin-c-type-lectin-domain-family-3-member-a-clec3a-enhances-tissue-plasminogen-activator-mediated-plasminogen-activation
#17
Daniela Lau, Dzemal Elezagic, Gabriele Hermes, Matthias Mörgelin, Alexander P Wohl, Manuel Koch, Ursula Hartmann, Stefan Höllriegl, Raimund Wagener, Mats Paulsson, Thomas Streichert, Andreas R Klatt
C-type lectin domain family 3 member A (CLEC3A) is a poorly characterized protein belonging to the superfamily of C-type lectins. Its closest homologue tetranectin binds to the kringle 4 domain of plasminogen and enhances its association with tissue plasminogen activator (tPA) thereby enhancing plasmin production, but whether CLEC3A contributes to plasminogen activation is unknown. Here, we recombinantly expressed murine and human full-length CLEC3As as well as truncated forms of CLEC3A in HEK-293 EBNA cells...
November 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29146223/delivering-person-centered-care-important-preferences-for-recipients-of-long-term-services-and-supports
#18
Katherine M Abbott, Rachel Klumpp, Kendall A Leser, Jane K Straker, Gerald C Gannod, Kimberly Van Haitsma
OBJECTIVES: Although assessing individual consumer preferences are an important first step in providing person-centered care, the purpose of this study was to identify the top 10 shared preferences that are important to a majority of consumers receiving long-term services and supports. DESIGN: A cross-sectional survey design was used. SETTING AND PARTICIPANTS: Preference assessment interviews were conducted with 255 nursing home (NH) residents and 528 older adults receiving home and community-based services (HCBS)...
November 14, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/29145809/genome-wide-characterization-and-expression-profiling-of-pdi-family-gene-reveals-function-as-abiotic-and-biotic-stress-tolerance-in-chinese-cabbage-brassica-rapa-ssp-pekinensis
#19
Md Abdul Kayum, Jong-In Park, Ujjal Kumar Nath, Gopal Saha, Manosh Kumar Biswas, Hoy-Taek Kim, Ill-Sup Nou
BACKGROUND: Protein disulfide isomerase (PDI) and PDI-like proteins contain thioredoxin domains that catalyze protein disulfide bond, inhibit aggregation of misfolded proteins, and function in isomerization during protein folding in endoplasmic reticulum and responses during abiotic stresses.Chinese cabbage is widely recognized as an economically important, nutritious vegetable, but its yield is severely hampered by various biotic and abiotic stresses. Because of, it is prime need to identify those genes whose are responsible for biotic and abiotic stress tolerance...
November 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29143633/predicting-high-risk-births-with-contraceptive-prevalence-and-contraceptive-method-mix-in-an-ecologic-analysis
#20
Jamie Perin, Agbessi Amouzou, Neff Walker
BACKGROUND: Increased contraceptive use has been associated with a decrease in high parity births, births that occur close together in time, and births to very young or to older women. These types of births are also associated with high risk of under-five mortality. Previous studies have looked at the change in the level of contraception use and the average change in these types of high-risk births. We aim to predict the distribution of births in a specific country when there is a change in the level and method of modern contraception...
November 7, 2017: BMC Public Health
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