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https://www.readbyqxmd.com/read/28820253/bioinorganic-chemistry-of-parkinson-s-disease-affinity-and-structural-features-of-cu-i-binding-to-the-full-length-%C3%AE-synuclein-protein
#1
Marco C Miotto, Mayra D Pavese, Liliana Quintanar, Markus Zweckstetter, Christian Griesinger, Claudio O Fernández
Alterations in the levels of copper in brain tissue and formation of α-synuclein (αS)-copper complexes might play a key role in the amyloid aggregation of αS and the onset of Parkinson's disease (PD). Recently, we demonstrated that formation of the high-affinity Cu(I) complex with the N-terminally acetylated form of the protein αS substantially increases and stabilizes local conformations with α-helical secondary structure and restricted motility. In this work, we performed a detailed NMR-based structural characterization of the Cu(I) complexes with the full-length acetylated form of its homologue β-synuclein (βS), which is colocalized with αS in vivo and can bind copper ions...
August 18, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28820136/protective-effect-of-val129-prp-against-bovine-spongiform-encephalopathy-but-not-variant-creutzfeldt-jakob-disease
#2
Natalia Fernández-Borges, Juan Carlos Espinosa, Alba Marín-Moreno, Patricia Aguilar-Calvo, Emmanuel A Asante, Tetsuyuki Kitamoto, Shirou Mohri, Olivier Andréoletti, Juan María Torres
Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met129) or valine (Val129) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met129 Hu-PrP...
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28819924/dynamic-imaging-of-mitochondrial-membrane-proteins-in-specific-sub-organelle-membrane-locations
#3
REVIEW
Timo Appelhans, Karin B Busch
Mitochondria are cellular organelles with multifaceted tasks and thus composed of different sub-compartments. The inner mitochondrial membrane especially has a complex nano-architecture with cristae protruding into the matrix. Related to their function, the localization of mitochondrial membrane proteins is more or less restricted to specific sub-compartments. In contrast, it can be assumed that membrane proteins per se diffuse unimpeded through continuous membranes. Fluorescence recovery after photobleaching is a versatile technology used in mobility analyses to determine the mobile fraction of proteins, but it cannot provide data on subpopulations or on confined diffusion behavior...
August 17, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28819671/fullerenol-nanoparticles-suppress-rankl-induced-osteoclastogenesis-by-inhibiting-differentiation-and-maturation
#4
Huan Geng, Ya-Nan Chang, Xue Bai, Shuitao Liu, Qing Yuan, Weihong Gu, Juan Li, Kui Chen, Gengyan Xing, Gengmei Xing
Bone health requires regulation of homeostatic equilibrium between osteoblasts and osteoclasts. The over-activation of osteoclasts can disrupt bone metabolism, resulting in osteoporosis and other bone-loss diseases. Fullerenol, a polyhydroxy derivative of fullerene, exhibits excellent biocompatibility. Here we show that fullerenol nanoparticles exert two functions: inhibition of osteoclastic differentiation and blockage of pre-osteoclast fusion to restructure osteoclast maturation and function. Experimentally, the nanoparticles reduced pre-osteoclast migration and inhibited ruffled border formation to block their maturation...
August 18, 2017: Nanoscale
https://www.readbyqxmd.com/read/28818206/pharmacological-and-activated-fibroblast%C3%A2-targeting-of-g%C3%AE-%C3%AE-grk2-after%C3%A2-myocardial-ischemia-attenuates-heart-failure-progression
#5
Joshua G Travers, Fadia A Kamal, Iñigo Valiente-Alandi, Michelle L Nieman, Michelle A Sargent, John N Lorenz, Jeffery D Molkentin, Burns C Blaxall
BACKGROUND: Cardiac fibroblasts are a critical cell population responsible for myocardial extracellular matrix homeostasis. Upon injury or pathological stimulation, these cells transform to an activated myofibroblast state and play a fundamental role in myocardial fibrosis and remodeling. Chronic sympathetic overstimulation, a hallmark of heart failure (HF), induces pathological signaling through G protein βγ (Gβγ) subunits and their interaction with G protein-coupled receptor kinase 2 (GRK2)...
August 22, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28817800/tia1-mutations-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-promote-phase-separation-and-alter-stress-granule-dynamics
#6
Ian R Mackenzie, Alexandra M Nicholson, Mohona Sarkar, James Messing, Maria D Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B Perkerson, Aishe Kurti, Billie J Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R Hsiung, Charles Krieger, Melissa E Murray, Masato Kato, John D Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A Zivkovic, Veronica Hirsch-Reinshagen, Raymond P Roos, Stephan Züchner, Neill R Graff-Radford, Ronald C Petersen, Richard J Caselli, Zbigniew K Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B Boylan, J Paul Taylor, Rosa Rademakers
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10(-6)). Postmortem neuropathology of five TIA1 mutations carriers showed a consistent pathological signature with numerous round, hyaline, TAR DNA-binding protein 43 (TDP-43)-positive inclusions...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817690/resveratrol-and-caloric-restriction-prevent-hepatic-steatosis-by-regulating-sirt1-autophagy-pathway-and-alleviating-endoplasmic-reticulum-stress-in-high-fat-diet-fed-rats
#7
Shibin Ding, Jinjin Jiang, Guofu Zhang, Yongjun Bu, Guanghui Zhang, Xiangmei Zhao
BACKGROUND: Studies have demonstrated that resveratrol (a natural polyphenol) and caloric restriction activate Sirtuin-1 (SIRT1) and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD) development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy...
2017: PloS One
https://www.readbyqxmd.com/read/28817638/the-transcriptional-profiling-of-human-in-vivo-generated-plasma-cells-identifies-selective-imbalances-in-monoclonal-gammopathies
#8
Luis M Valor, Beatriz Rodríguez-Bayona, Ana B Ramos-Amaya, José A Brieva, Antonio Campos-Caro
Plasma cells (PC) represent the heterogeneous final stage of the B cells (BC) differentiation process. To characterize the transition of BC into PC, transcriptomes from human naïve BC were compared to those of three functionally-different subsets of human in vivo-generated PC: i) tonsil PC, mainly consisting of early PC; ii) PC released to the blood after a potent booster-immunization (mostly cycling plasmablasts); and, iii) bone marrow CD138+ PC that represent highly mature PC and include the long-lived PC compartment...
2017: PloS One
https://www.readbyqxmd.com/read/28817611/the-directed-migration-of-gonadal-distal-tip-cells-in-caenorhabditis-elegans-requires-ngat-1-a-%C3%A3-1-4-n-acetylgalactosaminyltransferase-enzyme
#9
Joseph Veyhl, Robert J Dunn, Wendy L Johnston, Alexa Bennett, Lijia W Zhang, James W Dennis, Harry Schachter, Joseph G Culotti
Glycoproteins such as growth factor receptors and extracellular matrix have well-known functions in development and cancer progression, however, the glycans at sites of modification are often heterogeneous molecular populations which makes their functional characterization challenging. Here we provide evidence for a specific, discrete, well-defined glycan modification and regulation of a stage-specific cell migration in Caenorhabditis elegans. We show that a chain-terminating, putative null mutation in the gene encoding a predicted β1,4-N-acetylgalactosaminyltransferase, named ngat-1, causes a maternally rescued temperature sensitive (ts) defect in the second phase of the three phase migration pattern of the posterior, but not the anterior, hermaphrodite Distal Tip Cell (DTC)...
2017: PloS One
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#10
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28816939/correlations-of-icam-1-gene-polymorphisms-with-susceptibility-and-multidrug-resistance-in-colorectal-cancer-in-a-chinese-population
#11
Lu-Bing Liu, Tong Liu, Fu-Ze Xin
BACKGROUND: Colorectal cancer (CRC) is a malignant gastrointestinal tumor with a high mortality rate, including both colon and rectal cancer. In order to provide clinical guidance for the treatment of CRC, this study is conducted to investigate the correlations of intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms with susceptibility and multidrug resistance (MDR) of colorectal cancer (CRC). METHODS: A total of 195 patients with CRC were selected as the observation group and 188 healthy people enrolled as the control group...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28816584/how-dellas-contribute-to-control-potassium-uptake-under-conditions-of-potassium-scarcity-hypotheses-and-uncertainties
#12
Sonia Oliferuk, Adriana Pérez, Vicente Martinez, Reyes Ródenas, Francisco Rubio, Guillermo E Santa María
Maintenance of the inward transport of potassium (K) by roots is a critical step to ensure K-nutrition for all plant tissues. When plants are grown at low external K concentrations a strong enhancement of the activity of the AtHAK5 transporter takes place. In a recent work, we observed that the gai-1 mutant of Arabidopsis thaliana, which bears an altered function version of a DELLA regulatory protein, displays reduced accumulation of AtHAK5 transcripts and reduced uptake of Rubidium, an analogue for K. In this Addendum we discuss some hypotheses and uncertainties regarding how DELLAs could contribute to the control of K uptake under those conditions...
August 17, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28816361/msel-1l-deficiency-affects-vasculogenesis-and-neural-stem-cell-lineage-commitment
#13
Cardano M, Diaferia G R, Conti L, Baronchelli S, Sessa A, Broccoli V, Barbieri A, De Blasio P, Biunno I
mSEL-1L is a highly conserved ER-resident type I protein, involved in the degradation of misfolded peptides through the ubiquitin-proteasome system (UPS), a pathway known to control the plasticity of the vascular smooth muscle cells (VSMC) phenotype and survival. In this article we demonstrate that mSEL-1L deficiency interferes with the murine embryonic vascular network, showing particular irregularities in the intracranic and intersomitic neurovascular units and in the cerebral capillary microcirculation. During murine embryogenesis, mSEL-1L is expressed in cerebral areas known to harbor progenitor neural cells, while in the adult brain the protein is specifically restricted to the stem cell niches, co-localizing with Sox2 and Nestin...
August 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28816268/-expression-and-localization-of-transmembrane-protein-cmtm2-in-human-testis-and-sperm
#14
X W Zhang, K Lan, W B Yang, Q Li, Y P Zhao, H Q Yin, B Kite, W J Bai, T Xu
OBJECTIVE: To study the expression of transmembrane protein CMTM2 in the testis and sperm of adult males and to approach the potential function of the protein in the male reproductive system. METHODS: The expression of CMTM2 in human testis and sperm was confirmed by Western blot. Immunohistochemical staining was used for detecting CMTM2 localization in the testis tissue, TRITC-CMTM2 and FITC-Hoechst double immunofluorescence staining was performed to examine the subcellular localization of CMTM2 in the human sperm before and after acrosome reaction, that is, immunofluorescent staining was used for detecting CMTM2 localization in both the testis and sperm before and after the acrosome reaction...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28815492/building-cre-knockin-rat-lines-using-crispr-cas9
#15
Yuanwu Ma, Lianfeng Zhang, Xingxu Huang
Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815215/structural-characterization-of-acidic-m17-leucine-aminopeptidases-from-the-tritryps-and-evaluation-of-their-role-in-nutrient-starvation-in-trypanosoma-brucei
#16
Jennifer Timm, Maria Valente, Daniel García-Caballero, Keith S Wilson, Dolores González-Pacanowska
Leucine aminopeptidase (LAP) is found in all kingdoms of life and catalyzes the metal-dependent hydrolysis of the N-terminal amino acid residue of peptide or amino acyl substrates. LAPs have been shown to participate in the N-terminal processing of certain proteins in mammalian cells and in homologous recombination and transcription regulation in bacteria, while in parasites, they are involved in host cell invasion and provision of essential amino acids for growth. The enzyme is essential for survival in Plasmodium falciparum, where its drug target potential has been suggested...
July 2017: MSphere
https://www.readbyqxmd.com/read/28814649/wnt-ligand-presentation-and-reception-from-the-stem-cell-niche-to-tissue-engineering
#17
REVIEW
Kate M Mills, James L A Szczerkowski, Shukry J Habib
Stem cells reside in niches where spatially restricted signals maintain a delicate balance between stem cell self-renewal and differentiation. Wnt family proteins are particularly suited for this role as they are modified by lipids, which constrain and spatially regulate their signalling range. In recent years, Wnt/β-catenin signalling has been shown to be essential for the self-renewal of a variety of mammalian stem cells. In this review, we discuss Wnt-responsive stem cells in their niche, and mechanisms by which Wnt ligands are presented to responsive cells...
August 2017: Open Biology
https://www.readbyqxmd.com/read/28814604/macrophage-restricted-shp2-tyrosine-phosphatase-acts-as-a-rheostat-for-mmp12-through-tgf-%C3%AE-activation-in-the-prevention-of-age-related-emphysema-in-mice
#18
Jiaqi Xu, Bo Tao, Xiaohong Guo, Shiyi Zhou, Yongda Li, Yuqin Zhang, Zanhua Zhou, Hongqiang Cheng, Xue Zhang, Yuehai Ke
Persistent activation of macrophages in lungs plays a critical role in the production of matrix metalloproteinases (MMPs) that contributes to the destruction of alveolar walls, a hallmark for pulmonary emphysema. Dysregulated TGF-β1 signaling has been an essential determinant in the elevation of MMPs during the development of emphysema. Nevertheless, the mechanism for this MMP-dependent pathogenesis has yet to be clearly investigated. Recently, we identified an important role for tyrosine phosphatase Src homology domain-containing protein tyrosine phosphatase 2 (Shp2) in regulating the activation of alveolar macrophages...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28814526/hiv-1-exploits-dynamic-multi-aminoacyl-trna-synthetase-complex-to-enhance-viral-replication
#19
Alice A Duchon, Corine St-Gelais, Nathan Titkemeier, Joshua Hatterschide, Li Wu, Karin Musier-Forsyth
A hallmark of retroviruses such as human immunodeficiency virus type 1 (HIV-1) is reverse transcription of genomic RNA to DNA, a process that is primed by cellular tRNAs. HIV-1 recruits human tRNA(Lys3) to serve as the reverse transcription primer via an interaction between lysyl-tRNA synthetase (LysRS) and the HIV-1 Gag polyprotein. LysRS is normally sequestered in a multi-aminoacyl-tRNA synthetase complex (MSC). Previous studies demonstrated that components of the MSC can be mobilized in response to certain cellular stimuli, but how LysRS is redirected from the MSC to viral particles for packaging is unknown...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28813663/a-crispr-activation-screen-identifies-a-pan-avian-influenza-virus-inhibitory-host-factor
#20
Brook E Heaton, Edward M Kennedy, Rebekah E Dumm, Alfred T Harding, Matthew T Sacco, David Sachs, Nicholas S Heaton
Influenza A virus (IAV) is a pathogen that poses significant risks to human health. It is therefore critical to develop strategies to prevent influenza disease. Many loss-of-function screens have been performed to identify the host proteins required for viral infection. However, there has been no systematic screen to identify the host factors that, when overexpressed, are sufficient to prevent infection. In this study, we used CRISPR/dCas9 activation technology to perform a genome-wide overexpression screen to identify IAV restriction factors...
August 15, 2017: Cell Reports
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