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https://www.readbyqxmd.com/read/28642368/the-influence-of-disulfide-bonds-on-the-mechanical-stability-of-proteins-is-context-dependent
#1
Aitor Manteca, Álvaro Alonso-Caballero, Marie Fertin, Simon Poly, David De Sancho, Raul Perez-Jimenez
Disulfide bonds play a crucial role in proteins, modulating their stability and constraining their conformational dynamics. A particularly important case is that of proteins that need to withstand forces arising from their normal biological function and that are often disulfide bonded. However, the influence of disulfides on the overall mechanical stability of proteins is poorly understood. Here, we used single-molecule force spectroscopy (smFS) to study the role of disulfide bonds in different mechanical proteins in terms of their unfolding forces...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28637916/model-based-analysis-of-an-outbreak-of-bubonic-plague-in-cairo-in-1801
#2
Xavier Didelot, Lilith K Whittles, Ian Hall
Bubonic plague has caused three deadly pandemics in human history: from the mid-sixth to mid-eighth century, from the mid-fourteenth to the mid-eighteenth century and from the end of the nineteenth until the mid-twentieth century. Between the second and the third pandemics, plague was causing sporadic outbreaks in only a few countries in the Middle East, including Egypt. Little is known about this historical phase of plague, even though it represents the temporal, geographical and phylogenetic transition between the second and third pandemics...
June 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28637678/regulation-of-the-unfolded-protein-response-by-non-coding-rna
#3
Mari McMahon, Afshin Samali, Eric Chevet
Cells are exposed to various intrinsic and extrinsic stresses in both physiological and pathological conditions. To adapt to those conditions, cells have evolved various mechanisms to cope with the disturbances in protein demand, largely through the Unfolded Protein Response (UPR) in the Endoplasmic Reticulum (ER), but also through the Integrated Stress Response (ISR). Both responses initiate downstream signaling to transcription factors that, in turn, trigger adaptive programs and/or in the case of prolonged stress, cell death mechanisms...
June 21, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28629619/slow-interconversion-in-a-heterogeneous-unfolded-state-ensemble-of-outer-membrane-phospholipase-a
#4
Georg Krainer, Pablo Gracia, Erik Frotscher, Andreas Hartmann, Philip Gröger, Sandro Keller, Michael Schlierf
Structural and dynamic investigations of unfolded proteins are important for understanding protein-folding mechanisms as well as the interactions of unfolded polypeptide chains with other cell components. In the case of outer-membrane proteins (OMPs), unfolded-state properties are of particular physiological relevance, because these proteins remain unfolded for extended periods of time during their biogenesis and rely on interactions with binding partners to support proper folding. Using a combination of ensemble and single-molecule spectroscopy, we have scrutinized the unfolded state of outer-membrane phospholipase A (OmpLA) to provide a detailed view of its structural dynamics on timescales from nanoseconds to milliseconds...
June 16, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28622138/cellular-and-plasma-nitrite-levels-in-myeloid-leukemia-a-pathogenetic-decrease
#5
Mili Jain, Ashutosh Kumar, Uma Shankar Singh, Rashmi Kushwaha, Abhishek Kumar Singh, Madhu Dikshit, Anil Kumar Tripathi
Nitric oxide (NO) has contributory role in hemopoietic cell growth and differentiation. The effects of NO on leukemic cell growth have been predominantly studied in in vitro settings. This study was done to assess the alterations in nitrite level in myeloid leukemias.Thirty six newly diagnosed cases of myeloid leukemia (16 AML and 20 CML) were enrolled in the study. Neutrophil precursors from the marrow aspirate and peripheral blood were separated into cell bands using Percoll density gradient method of Borregard and Cowland...
June 15, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28618518/random-walks-on-activity-driven-networks-with-attractiveness
#6
Laura Alessandretti, Kaiyuan Sun, Andrea Baronchelli, Nicola Perra
Virtually all real-world networks are dynamical entities. In social networks, the propensity of nodes to engage in social interactions (activity) and their chances to be selected by active nodes (attractiveness) are heterogeneously distributed. Here, we present a time-varying network model where each node and the dynamical formation of ties are characterized by these two features. We study how these properties affect random-walk processes unfolding on the network when the time scales describing the process and the network evolution are comparable...
May 2017: Physical Review. E
https://www.readbyqxmd.com/read/28617828/erad-defects-and-the-hfe-h63d-variant-are-associated-with-increased-risk-of-liver-damages-in-alpha-1-antitrypsin-deficiency
#7
Philippe Joly, Hélène Vignaud, Julie Di Martino, Mathias Ruiz, Roman Garin, Lioara Restier, Abdelouahed Belmalih, Christelle Marchal, Christophe Cullin, Benoit Arveiler, Patricia Fergelot, Aaron D Gitler, Alain Lachaux, Julien Couthouis, Marion Bouchecareilh
BACKGROUND: The most common and severe disease causing allele of Alpha 1-Antitrypsin Deficiency (1ATD) is Z-1AT. This protein aggregates in the endoplasmic reticulum, which is the main cause of liver disease in childhood. Based on recent evidences and on the frequency of liver disease occurrence in Z-1AT patients, it seems that liver disease progression is linked to still unknown genetic factors. METHODS: We used an innovative approach combining yeast genetic screens with next generation exome sequencing to identify and functionally characterize the genes involved in 1ATD associated liver disease...
2017: PloS One
https://www.readbyqxmd.com/read/28617612/effect-of-urea-on-g-quadruplex-stability
#8
Lusine Aslanyan, Jordan Ko, Byul G Kim, Ishkhan Vardanyan, Yeva B Dalyan, Tigran V Chalikian
G-quadruplexes represent a class of noncanonical nucleic acid structures implicated in transcriptional regulation, cellular function, and disease. An understanding of the forces involved in stabilization/destabilization of the G-quadruplex conformation relative to the duplex or single-stranded conformation is a key to elucidating the biological role of G-quadruplex-based genomic switches and the quest for therapeutic means for controlled induction or suppression of a G-quadruplex at selected genomic loci. Solute-solvent interactions provide a ubiquitous and, in many cases, the determining thermodynamic force in maintaining and modulating the stability of nucleic acids...
June 15, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28608264/the-small-heat-shock-protein-b8-hspb8-efficiently-removes-aggregating-species-of-dipeptides-produced-in-c9orf72-related-neurodegenerative-diseases
#9
Riccardo Cristofani, Valeria Crippa, Giulia Vezzoli, Paola Rusmini, Mariarita Galbiati, Maria Elena Cicardi, Marco Meroni, Veronica Ferrari, Barbara Tedesco, Margherita Piccolella, Elio Messi, Serena Carra, Angelo Poletti
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two neurodegenerative diseases in which similar pathogenic mechanisms are involved. Both diseases associate to the high propensity of specific misfolded proteins, like TDP-43 or FUS, to mislocalize and aggregate. This is partly due to their intrinsic biophysical properties and partly as a consequence of failure of the neuronal protein quality control (PQC) system. Several familial ALS/FTD cases are linked to an expansion of a repeated G4C2 hexanucleotide sequence present in the C9ORF72 gene...
June 12, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28589937/loss-of-parkinson-s-disease-associated-protein-chchd2-affects-mitochondrial-crista-structure-and-destabilizes-cytochrome-c
#10
Hongrui Meng, Chikara Yamashita, Kahori Shiba-Fukushima, Tsuyoshi Inoshita, Manabu Funayama, Shigeto Sato, Tomohisa Hatta, Tohru Natsume, Masataka Umitsu, Junichi Takagi, Yuzuru Imai, Nobutaka Hattori
Mutations in CHCHD2 have been identified in some Parkinson's disease (PD) cases. To understand the physiological and pathological roles of CHCHD2, we manipulated the expression of CHCHD2 in Drosophila and mammalian cells. The loss of CHCHD2 in Drosophila causes abnormal matrix structures and impaired oxygen respiration in mitochondria, leading to oxidative stress, dopaminergic neuron loss and motor dysfunction with age. These PD-associated phenotypes are rescued by the overexpression of the translation inhibitor 4E-BP and by the introduction of human CHCHD2 but not its PD-associated mutants...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28586577/pattern-and-profile-of-electric-burn-injury-cases-at-a-burn-centre
#11
Saeed Ashraf Cheema
BACKGROUND: Electrical burns are quite different from thermal and chemical burns. This study is from a centre which deals with job related electric burn injuries alone and thus can give a pure account of the electric burns and discuss the related peculiarities. Study aims to highlight the differences in the mechanism of electric burn injury, its mode of presentation, morbidity, complications and thus the treatment strategies as compared to rest of the burn injuries. METHODS: This is a descriptive case series study of first consecutive 61 electric burn victims treated at a Burn Unit and Plastic Surgery centre...
October 2016: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28585802/cu-zn-superoxide-dismutase-forms-amyloid-fibrils-under-near-physiological-quiescent-conditions-the-roles-of-disulfide-bonds-and-effects-of-denaturant
#12
M Ashhar I Khan, Michal Respondek, Sven Kjellstrom, Shashank Deep, Sara Linse, Mikael Akke
Cu/Zn superoxide dismutase (SOD1) forms intracellular aggregates that are pathological indicators of amyotrophic lateral sclerosis. A large body of research indicates that the entry point to aggregate formation is a monomeric, metal-ion free (apo), and disulfide-reduced species. Fibril formation by SOD1 in vitro has typically been reported only for harsh solvent conditions or mechanical agitation. Here we show that monomeric apo-SOD1 in the disulfide-reduced state forms fibrillar aggregates under near-physiological quiescent conditions...
June 6, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28585201/the-pathogenesis-of-obesity-associated-adipose-tissue-inflammation
#13
Atilla Engin
Obesity is characterized by a state of chronic, low-grade inflammation. However, excessive fatty acid release may worsen adipose tissue inflammation and contributes to insulin resistance. In this case, several novel and highly active molecules are released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines. Most likely cytokines that are released by inflammatory cells infiltrating obese adipose tissue are such as tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) (CCL-2) and IL-1...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28583356/theories-that-narrate-the-world-ronald-a-fisher-s-mass-selection-and-sewall-wright-s-shifting-balance
#14
Alirio Rosales
Theories are composed of multiple interacting components. I argue that some theories have narratives as essential components, and that narratives function as integrative devices of the mathematical components of theories. Narratives represent complex processes unfolding in time as a sequence of stages, and hold the mathematical elements together as pieces in the investigation of a given process. I present two case studies from population genetics: R. A. Fisher's "mas selection" theory, and Sewall Wright's shifting balance theory...
April 2017: Studies in History and Philosophy of Science
https://www.readbyqxmd.com/read/28560640/mers-cov-papain-like-protease-pl-pro-expression-purification-and-spectroscopic-thermodynamic-characterization
#15
Ajamaluddin Malik, Mohammad A Alsenaidy
Within a decade, MERS-CoV emerged with nearly four times higher case fatality rate than an earlier outbreak of SARS-CoV and spread out in 27 countries in short span of time. As an emerging virus, combating it requires an in-depth understanding of its molecular machinery. Therefore, conformational characterization studies of coronavirus proteins are necessary to advance our knowledge of the matter for the development of antiviral therapies. In this study, MERS-CoV papain-like protease (PL(pro)) was recombinantly expressed and purified...
June 2017: 3 Biotech
https://www.readbyqxmd.com/read/28557677/staying-the-course-using-hypnosis-to-help-cancer-patients-navigate-their-illness
#16
Carol Ginandes
Although sometimes maligned and often misunderstood, clinical hypnosis can be utilized as a powerful adjunct for the treatment of mind-body conditions, including cancer. Unlike customary medical regimens that treat diseases of the body and psychotherapies that address disorders of the psyche, hypnosis is a uniquely customizable multi-tool that can augment the treatment of both physical and emotional disorders as well as their complex interactions. This article presents a longitudinal, phase-oriented, clinical model that uses hypnosis in a series of sequential interventions that incorporate targeted suggestions to address the unfolding phases of the cancer continuum...
July 2017: American Journal of Clinical Hypnosis
https://www.readbyqxmd.com/read/28554471/when-is-the-unfolded-protein-response-not-the-unfolded-protein-response
#17
REVIEW
Stephen H Howell
As sessile organisms, plants are subjected to variety of stresses for which they have evolved different protection mechanisms. One mechanism involves endoplasmic reticulum (ER) stress in which the process of protein folding is disturbed and misfolded proteins accumulate in the ER. ER stress elicits the unfolded protein response (UPR) whereby the stress conditions in the ER are communicated to the nucleus to regulate stress response genes. Since the UPR is one of a number of different mechanisms by which plants respond to stress, it is often difficult to distinguish the UPR from other stress responses...
July 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28531308/challenges-of-research-recruitment-in-a-university-setting-in-england
#18
Claudia Vadeboncoeur, Charlie Foster, Nick Townsend
The recruitment is an integral part of most research projects in medical sciences involving human participants. In health promotion research, there is increasing work on the impact of environments. Settings represent environments such as schools where social, physical and psychological development unfolds. In this study, we investigated weight gain in students within a university setting. Barriers to access and recruitment of university students within a specific setting, in the context of health research are discussed...
May 20, 2017: Health Promotion International
https://www.readbyqxmd.com/read/28520725/reading-positional-codes-with-fmri-problems-and-solutions
#19
Kristjan Kalm, Dennis Norris
Neural mechanisms which bind items into sequences have been investigated in a large body of research in animal neurophysiology and human neuroimaging. However, a major problem in interpreting this data arises from a fact that several unrelated processes, such as memory load, sensory adaptation, and reward expectation, also change in a consistent manner as the sequence unfolds. In this paper we use computational simulations and data from two fMRI experiments to show that a host of unrelated neural processes can masquerade as sequence representations...
2017: PloS One
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#20
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
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