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https://www.readbyqxmd.com/read/28918091/opposed-effects-of-dityrosine-formation-in-soluble-and-aggregated-%C3%AE-synuclein-on-fibril-growth
#1
Michael M Wördehoff, Hamed Shaykhalishahi, Luca Groß, Lothar Gremer, Matthias Stoldt, Alexander K Buell, Dieter Willbold, Wolfgang Hoyer
Parkinson's disease (PD) is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY)-crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from PD patients. Here we report that α-syn is highly susceptible to UV-induced DiY formation...
September 13, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28917842/multi-scale-simulations-of-biological-systems-using-the-opep-coarse-grained-model
#2
Fabio Sterpone, Sébastien Doutreligne, Thanh Thuy Tran, Simone Melchionna, Marc Baaden, Phuong H Nguyen, Philippe Derreumaux
Biomolecules are complex machines that are optimized by evolution to properly fulfill or contribute to a variety of biochemical tasks in the cellular environment. Computer simulations based on quantum mechanics and atomistic force fields have been proven to be a powerful microscope for obtaining valuable insights into many biological, physical, and chemical processes. Many interesting phenomena involve, however, a time scale and a number of degrees of freedom, notably if crowding is considered, that cannot be explored at an atomistic resolution...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28917050/preparation-of-selenocysteine-containing-forms-of-human-selenok-and-selenos
#3
Zhengqi Zhang, Jun Liu, Sharon Rozovsky
Selenoprotein K (SELENOK) and Selenoprotein S (SELENOS) are the members of the endoplasmic-reticulum-associated degradation (ERAD) complex, which is responsible for translocating misfolded proteins from the endoplasmic reticulum (ER) to the cytosol for degradation. Besides its involvement in the ERAD, SELENOK was shown to bind and stabilize the palmitoyl transferase DHHC6, and thus contributes to palmitoylation. SELENOK and SELENOS reside in the ER membrane by the way of a single transmembrane helix. Both contain an intrinsically disordered region with a selenocysteine (Sec) located one or two residues away from the C-terminus...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28916499/-re-programming-of-subtype-specific-cardiomyocytes
#4
Frauke Hausburg, Julia Jeannine Jung, Matti Hoch, Markus Wolfien, Arash Yavari, Christian Rimmbach, Robert David
Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential -a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterised by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production...
September 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28915961/short-stem-total-hip-arthroplasty-potential-explanations-for-persistent-post-surgical-thigh-pain
#5
Isabel A C Baert, Enrique Lluch, Francis Van Glabbeek, Rudy Nuyts, Salim Rufai, Joanna Tuynman, Filip Struyf, Mira Meeus
Short stem uncemented femoral implants were developed with the aim of preserving proximal bone stock for future revisions, improving biomechanical reconstruction, aiding insertion through smaller incisions and potentially decreasing or limiting the incidence of thigh pain. Despite all the advantages of short stem designs, it remains unclear whether they are able to limit post-surgical thigh pain. In patients with short stem hip arthroplasty and persistent thigh pain, it is of the utmost importance to understand the potential etiologies of this chronic pain for selecting the appropriate treatment strategy...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28915322/hormonal-regulation-of-adipogenesis
#6
Mi-Jeong Lee
Adipose tissue includes multiple anatomical depots that serve as an energy reserve that can expand or contract to maintain metabolic homeostasis. During normal growth and in response to overnutrition, adipose tissue expands by increasing the volume of preexisting adipocytes (hypertrophy) and/or by generating new adipocytes (hyperplasia) via recruitment and differentiation of adipose progenitors. This so-called healthy expansion through hyperplasia is thought to be beneficial in that it protects against obesity associated metabolic disorders by allowing for the "safe" storage of excess energy...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28914483/the-thermodynamic-basis-of-the-fuzzy-interaction-of-an-intrinsically-disordered-protein
#7
San Hadži, Andrej Mernik, Črtomir Podlipnik, Remy Loris, Jurij Lah
Many intrinsically disordered proteins (IDP) that fold upon binding retain conformational heterogeneity in IDP-target complexes. The thermodynamics of such fuzzy interactions is poorly understood. Here we introduce a thermodynamic framework, based on analysis of ITC and CD spectroscopy data, that provides experimental description of IDP association in terms of folding and binding contributions which can be predicted using sequence folding propensities and molecular modeling. We show how IDP can modulate the entropy and enthalpy by adapting their bound-state structural ensemble to achieve optimal binding...
September 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28912698/altered-rich-club-and-frequency-dependent-subnetwork-organization-in-mild-traumatic-brain-injury-a-meg-resting-state-study
#8
Marios Antonakakis, Stavros I Dimitriadis, Michalis Zervakis, Andrew C Papanicolaou, George Zouridakis
Functional brain connectivity networks exhibit "small-world" characteristics and some of these networks follow a "rich-club" organization, whereby a few nodes of high connectivity (hubs) tend to connect more densely among themselves than to nodes of lower connectivity. The Current study followed an "attack strategy" to compare the rich-club and small-world network organization models using Magnetoencephalographic (MEG) recordings from mild traumatic brain injury (mTBI) patients and neurologically healthy controls to identify the topology that describes the underlying intrinsic brain network organization...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28912275/nmr-reveals-the-intrinsically-disordered-domain-2-of-ns5a-protein-as-an-allosteric-regulator-of-the-hepatitis-c-virus-rna-polymerase-ns5b
#9
Luiza M Bessa, Hélène Launay, Marie Dujardin, François-Xavier Cantrelle, Guy Lippens, Isabelle Landrieu, Robert Schneider, Xavier Hanoulle
Non-structural protein 5B (NS5B) is the RNAdependent RNA polymerase that catalyses replication of the hepatitis C virus (HCV) RNA genome, and so is central for its life cycle. NS5B interacts with the intrinsically disordered domain 2 of NS5A (NS5A-D2), another essential multifunctional HCV protein that is required for RNA replication. As a result, these two proteins represent important targets for anti-HCV chemotherapies. Despite this importance and the existence of NS5B crystal structures, our understanding of the conformational and dynamic behaviour of NS5B in solution and its relationship with NS5A-D2 remain incomplete...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912251/neuro-immune-interaction-and-the-regulation-of-intestinal-immune-homeostasis
#10
Simon Verheijden, Guy E Boeckxstaens
Many essential gastrointestinal functions, including motility, secretion and blood flow are regulated by the autonomic nervous system (ANS), both through intrinsic enteric neurons and extrinsic (sympathetic and parasympathetic) innervation. Recently identified neuro-immune mechanisms, in particular the interplay between enteric neurons and muscularis macrophages, are now considered to be essential for fine-tuning peristalsis. These findings shed new light on how intestinal immune cells can support enteric nervous function...
September 14, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28911049/aberrant-hyperconnectivity-in-the-motor-system-at-rest-is-linked-to-motor-abnormalities-in-schizophrenia-spectrum-disorders
#11
Sebastian Walther, Katharina Stegmayer, Andrea Federspiel, Stephan Bohlhalter, Roland Wiest, Petra V Viher
Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day...
September 1, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28905237/-1-h-13-c-and-15-n-assignments-of-the-c-terminal-intrinsically-disordered-cytosolic-fragment-of-the-receptor-tyrosine-kinase-erbb2
#12
YingHui Wang, Louise Pinet, Nadine Assrir, Latifa Elantak, Françoise Guerlesquin, Ali Badache, Ewen Lescop, Carine van Heijenoort
ErbB2 (or HER2) is a receptor tyrosine kinase that is involved in signaling pathways controlling cell division, motility and apoptosis. Though important in development and cell growth homeostasis, this protein, when overexpressed, participates in triggering aggressive HER2+ breast cancers. It is composed of an extracellular part and a transmembrane domain, both important for activation by dimerization, and a cytosolic tyrosine kinase, which activates its intrinsically disordered C-terminal end (CtErbB2). Little is known about this C-terminal part of 268 residues, despite its crucial role in interacting with adaptor proteins involved in signaling...
September 13, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28904001/kv3-channels-enablers-of-rapid-firing-neurotransmitter-release-and-neuronal-endurance
#13
REVIEW
Leonard K Kaczmarek, Yalan Zhang
The intrinsic electrical characteristics of different types of neurons are shaped by the K(+) channels they express. From among the more than 70 different K(+) channel genes expressed in neurons, Kv3 family voltage-dependent K(+) channels are uniquely associated with the ability of certain neurons to fire action potentials and to release neurotransmitter at high rates of up to 1,000 Hz. In general, the four Kv3 channels Kv3.1-Kv3.4 share the property of activating and deactivating rapidly at potentials more positive than other channels...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28903561/enhanced-sampling-of-intrinsic-structural-heterogeneity-of-the-bh3-only-protein-binding-interface-of-bcl-xl
#14
Xiaorong Liu, Zhiguang Jia, Jianhan Chen
Anti-apoptotic Bcl-xL plays central roles in regulating programed cell death. Partial unfolding of Bcl-xL has been observed at the interface upon specific binding to the pro-apoptotic BH3-only protein PUMA, which in turn disrupts the interaction of Bcl-xL with tumor suppressor p53 and promotes apoptosis. Previous analysis of existing Bcl-xL structures and atomistic molecular dynamics (MD) simulations have suggested that substantial intrinsic structure heterogeneity exists at the BH3-only protein binding interface of Bcl-xL to facilitate its conformational transitions upon binding...
September 13, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28902888/dendrimer-based-selective-autophagy-induction-rescues-%C3%AE-f508-cftr-and-inhibits-pseudomonas-aeruginosa-infection-in-cystic-fibrosis
#15
Scott Mackenzie Brockman, Manish Bodas, David Silverberg, Ajit Sharma, Neeraj Vij
BACKGROUND: Cystic Fibrosis (CF) is a genetic disorder caused by mutation(s) in the CF-transmembrane conductance regulator (Cftr) gene. The most common mutation, ΔF508, leads to accumulation of defective-CFTR protein in aggresome-bodies. Additionally, Pseudomonas aeruginosa (Pa), a common CF pathogen, exacerbates obstructive CF lung pathology. In the present study, we aimed to develop and test a novel strategy to improve the bioavailability and potentially achieve targeted drug delivery of cysteamine, a potent autophagy-inducing drug with anti-bacterial properties, by developing a dendrimer (PAMAM-DEN)-based cysteamine analogue...
2017: PloS One
https://www.readbyqxmd.com/read/28901557/intrinsically-disordered-proteins-and-desiccation-tolerance-elucidating-functional-and-mechanistic-underpinnings-of-anhydrobiosis
#16
Thomas C Boothby, Gary J Pielak
Over 300 years ago the father of microscopy, Antonie van Leeuwenhoek, observed dried rotifers (tiny animals) "coming back to life" upon rehydration. Since then, scientists have been fascinated by the enduring mystery of how certain organisms survive losing essentially drying out completely. Historically sugars, such as the disaccharide trehalose, have been viewed as major functional mediators of desiccation tolerance. However, some desiccation tolerant organisms do not produce this sugar, hinting that additional mediators, and potentially novel mechanisms exist...
September 13, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28900385/the-impact-of-stress-on-body-function-a-review
#17
REVIEW
Habib Yaribeygi, Yunes Panahi, Hedayat Sahraei, Thomas P Johnston, Amirhossein Sahebkar
Any intrinsic or extrinsic stimulus that evokes a biological response is known as stress. The compensatory responses to these stresses are known as stress responses. Based on the type, timing and severity of the applied stimulus, stress can exert various actions on the body ranging from alterations in homeostasis to life-threatening effects and death. In many cases, the pathophysiological complications of disease arise from stress and the subjects exposed to stress, e.g. those that work or live in stressful environments, have a higher likelihood of many disorders...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28900210/alterations-of-brain-functional-architecture-associated-with-psychopathic-traits-in-male-adolescents-with-conduct-disorder
#18
Weidan Pu, Qiang Luo, Yali Jiang, Yidian Gao, Qingsen Ming, Shuqiao Yao
Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900065/-establishment-and-maintenance-of-adult-neural-stem-cells
#19
Naoya Yuizumi, Yujin Harada
Neural stem cells (NSCs) in the adult mammalian brain produce new neurons throughout life. Defects in adult neurogenesis can influence neurodegenerative and psychiatric disorders. Hence, understanding long-term maintenance of adult NSCs is crucial. Cell-intrinsic and -extrinsic factors contribute to long-term maintenance of adult NSCs, and we have previously reported that NSCs produce their own niches that send a feedback signal for their own maintenance. In addition, we have identified a slowly dividing subpopulation of embryonic neural progenitor cells that is set aside during development, and later becomes a substantial fraction of NSCs in the adult subventricular zone...
September 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28899900/ret-receptor-tyrosine-kinase-sustains-proliferation-and-tissue-maturation-in-intestinal-epithelia
#20
Daniel Perea, Jordi Guiu, Bruno Hudry, Chrysoula Konstantinidou, Alexandra Milona, Dafni Hadjieconomou, Thomas Carroll, Nina Hoyer, Dipa Natarajan, Jukka Kallijärvi, James A Walker, Peter Soba, Nikhil Thapar, Alan J Burns, Kim B Jensen, Irene Miguel-Aliaga
Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation...
September 12, 2017: EMBO Journal
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