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https://www.readbyqxmd.com/read/28925976/shiga-toxin-therapeutics-beyond-neutralization
#1
REVIEW
Gregory Hall, Shinichiro Kurosawa, Deborah J Stearns-Kurosawa
Ribotoxic Shiga toxins are the primary cause of hemolytic uremic syndrome (HUS) in patients infected with Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), a pathogen class responsible for epidemic outbreaks of gastrointestinal disease around the globe. HUS is a leading cause of pediatric renal failure in otherwise healthy children, resulting in a mortality rate of 10% and a chronic morbidity rate near 25%. There are currently no available therapeutics to prevent or treat HUS in STEC patients despite decades of work elucidating the mechanisms of Shiga toxicity in sensitive cells...
September 19, 2017: Toxins
https://www.readbyqxmd.com/read/28916646/serac1-deficiency-causes-complicated-hsp-evidence-from-a-novel-splice-mutation-in-a-large-family
#2
Benjamin Roeben, Rebecca Schüle, Susanne Ruf, Benjamin Bender, Bader Alhaddad, Tanja Benkert, Thomas Meitinger, Selina Reich, Judith Böhringer, Claus-Dieter Langhans, Frédéric M Vaz, Saskia B Wortmann-Hagemann, Thorsten Marquardt, Tobias B Haack, Ingeborg Krägeloh-Mann, Ludger Schöls, Matthis Synofzik
OBJECTIVE: To demonstrate that mutations in the phosphatidylglycerol remodelling enzyme SERAC1 can cause juvenile-onset complicated hereditary spastic paraplegia (cHSP) clusters, thus adding SERAC1 to the increasing number of complex lipid cHSP genes. METHODS: Combined genomic and functional validation studies (whole-exome sequencing, mRNA, cDNA and protein), biomarker investigations (3-methyl-glutaconic acid, filipin staining and phosphatidylglycerols PG34:1/PG36:1), and clinical and imaging phenotyping were performed in six affected subjects from two different branches of a large consanguineous family...
September 15, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28915352/all-atom-simulations-reveal-protein-charge-decoration-in-the-folded-and-unfolded-ensemble-is-key-in-thermophilic-adaptation
#3
Lucas Sawle, Jonathan Huihui, Kingshuk Ghosh
Thermophilic proteins denature at much higher temperature compared to their mesophilic homologues, in spite of high structural and sequential similarity. Computational approaches to understand this puzzle faces three major challenges: i) unfolded ensembles are usually neglected, ii) simulation studies of the folded states are often too short and iii) majority of investigations focus on a few protein pairs, obscuring the prevalence of different strategies across multiple protein systems. We address these concerns by carrying out all-atom simulations to characterize physicochemical properties of both the folded and disordered ensemble in multiple (12) thermophilic-mesophilic homologous protein pairs...
September 15, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28904601/from-militant-voices-to-militant-irony-examining-identity-memory-and-conflict-in-the-basque-country
#4
Ignacio Brescó de Luna
Collective memory and identity so often go hand in hand with conflicts. Alongside the use of violence, conflicts unfold against the backdrop of different narratives about the past through which groups constantly remind themselves of the supposed origin of the conflict, and consequently, what position individuals are expected to take as members of the group. Narratives - as symbolic tools for interpreting the past and the present, as well as happenings that have yet to occur - simultaneously underpin, and are underpinned by, the position held by each warring faction...
August 2017: Europe's journal of psychology
https://www.readbyqxmd.com/read/28895137/bringing-radical-behaviorism-to-revolutionary-brazil-and-back-fred-keller-s-personalized-system-of-instruction-and-cold-war-engineering-education
#5
Atsushi Akera
This article traces the shifting epistemic commitments of Fred S. Keller and his behaviorist colleagues during their application of Skinnerian radical behaviorism to higher education pedagogy. Building on prior work by Alexandra Rutherford and her focus on the successive adaptation of Skinnerian behaviorism during its successive applications, this study utilizes sociologist of science Karin Knorr Cetina's concept of epistemic cultures to more precisely trace the changes in the epistemic commitments of a group of radical behaviorists as they shifted their focus to applied behavioral analysis...
September 12, 2017: Journal of the History of the Behavioral Sciences
https://www.readbyqxmd.com/read/28894122/onset-of-disorder-and-protein-aggregation-due-to-oxidation-induced-intermolecular-disulfide-bonds-case-study-of-rrm2-domain-from-tdp-43
#6
Sevastyan O Rabdano, Sergei A Izmailov, Dmitrii A Luzik, Adam Groves, Ivan S Podkorytov, Nikolai R Skrynnikov
We have investigated the behavior of second RNA-recognition motif (RRM2) of neuropathological protein TDP43 under the effect of oxidative stress as modeled in vitro. Toward this end we have used the specially adapted version of H/D exchange experiment, NMR relaxation and diffusion measurements, dynamic light scattering, controlled proteolysis, gel electrophoresis, site-directed mutagenesis and microsecond MD simulations. Under oxidizing conditions RRM2 forms disulfide-bonded dimers that experience unfolding and then assemble into aggregate particles (APs)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893942/kaposi-sarcoma-herpesvirus-pathogenesis
#7
REVIEW
Giuseppe Mariggiò, Sandra Koch, Thomas F Schulz
Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis...
October 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28846078/endoplasmic-reticulum-stress-signaling-and-chemotherapy-resistance-in-solid-cancers
#8
REVIEW
T Avril, E Vauléon, E Chevet
The unfolded protein response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress. During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply) challenges, with which they must cope to survive. Moreover, chemotherapy represents an additional extrinsic challenge that cancer cells are facing and to which they adapt in the case of resistance. As of today, resistance to chemotherapy and targeted therapies is one of the important issues that oncologists have to deal with for treating cancer patients...
August 28, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28836541/laser-assisted-multidisciplinary-approach-for-closure-and-prevention-of-relapse-of-midline-diastema
#9
Amol Kamble, Preetam Shah, Priyam Rajesh Velani, Ganesh Jadhav
Midline diastema, which occurs as spacing between the upper central incisors, is a common occurrence seen in the pediatric population. In the ugly duckling stage of development; no treatment is generally advocated as the diastema is a transient one. When diastemas occur due to other pathologies, they pose several problems in relation to esthetics and speech in a growing child. With the advent of time, patient's demand for esthetics has greatly increased. Along with this, a less time-consuming treatment option is a favorite...
July 2017: Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research
https://www.readbyqxmd.com/read/28834726/prospects-for-human-erythrocyte-skeleton-bilayer-dissociation-during-splenic-flow
#10
Qiang Zhu, Sara Salehyar, Pedro Cabrales, Robert J Asaro
Prospects of vesiculation occurring during splenic flow of erythrocytes are addressed via model simulations of RBC flow through the venous slits of the human spleen. Our model is multiscale and contains a thermally activated rate-dependent description of the entropic elasticity of the RBC spectrin cytoskeleton, including domain unfolding/refolding. Our model also includes detail of the skeleton attachment to the fluidlike lipid bilayer membrane, including a specific accounting for the expansion/contraction of the skeleton that may occur via anchor protein diffusive motion, that is, band 3 and glycophorin, through the membrane...
August 22, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28819293/effects-of-temporal-correlations-in-social-multiplex-networks
#11
Michele Starnini, Andrea Baronchelli, Romualdo Pastor-Satorras
Multi-layered networks represent a major advance in the description of natural complex systems, and their study has shed light on new physical phenomena. Despite its importance, however, the role of the temporal dimension in their structure and function has not been investigated in much detail so far. Here we study the temporal correlations between layers exhibited by real social multiplex networks. At a basic level, the presence of such correlations implies a certain degree of predictability in the contact pattern, as we quantify by an extension of the entropy and mutual information analyses proposed for the single-layer case...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817473/scaffolding-interprofessional-education-unfolding-case-studies-virtual-world-simulations-and-patient-centered-care
#12
Sharon Strang Zook, Linda J Hulton, Carol C Dudding, Anne L Stewart, Amy C Graham
Fragmentation of health care negatively impacts quality; one of the contributing factors may be ineffective collaboration among health care professionals. This article describes the implementation of an interprofessional education curriculum for graduate students enrolled in nursing, psychology, and speech-language pathology programs. Over 3 semesters, students engaged in interprofessional collaboration modules, unfolding case studies, virtual simulation, and shared case planning experiences. The curriculum's impact on students' attitudes and values toward interprofessional collaborative practice was measured...
August 16, 2017: Nurse Educator
https://www.readbyqxmd.com/read/28795614/shifting-borders-crossing-boundaries-the-case-of-combined-central-and-peripheral-demyelination
#13
Orhan Aktas
The case report by Puthenparampil et al. suggests that heterogeneity of demyelinating diseases may be more complex than expected. The authors describe a female patient starting with isolated but relapsing myelitis (in the absence of oligoclonal bands or anti-aquaporin 4 antibodies) and later experiencing the simultaneous occurrence of inflammatory demyelinating polyneuropathy and of a tumefactive hippocampal brain lesion responsive to immunotherapy. As testing for antibodies against established and novel auto-antigens including neurofascin-155 was negative, this case may be regarded as an example for the unfolding spectrum of combined central and peripheral demyelination (CCPD) syndromes with so far unknown immunological target(s)...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28781996/opinion-hazards-faced-by-macromolecules-when-confined-to-thin-aqueous-films
#14
REVIEW
Robert M Glaeser, Bong-Gyoon Han
Samples prepared for single-particle electron cryo-microscopy (cryo-EM) necessarily have a very high surface-to-volume ratio during the short period of time between thinning and vitrification. During this time, there is an obvious risk that macromolecules of interest may adsorb to the air-water interface with a preferred orientation, or that they may even become partially or fully unfolded at the interface. In addition, adsorption of macromolecules to an air-water interface may occur even before thinning. This paper addresses the question whether currently used methods of sample preparation might be improved if one could avoid such interfacial interactions...
2017: Biophysics Reports
https://www.readbyqxmd.com/read/28774748/investigation-on-different-chemical-stability-of-mitochondrial-hsp60-and-its-precursor
#15
Caterina Ricci, Rita Carrotta, Giacoma Cinzia Rappa, Maria Rosalia Mangione, Fabio Librizzi, Pier Luigi San Biagio, Heinz Amenitsch, Maria Grazia Ortore, Silvia Vilasi
In the large class of molecules that maintain protein homeostasis, called molecular chaperones, chaperonins constitute a subclass that specifically assist the correct folding of newly synthesized proteins. Among them, Hsp60 is composed of a double heptameric ring structure with a large central cavity where the unfolded protein binds via hydrophobic interactions and is supported, in this function, by the co-chaperonin Hsp10. Hsp60 is typically located in the mitochondria, but in some pathological situations, such as cancers and chronic inflammatory diseases, Hsp60 accumulates in the cytoplasm...
July 26, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28771092/advancing-nursing-scholarship-the-mozambique-model
#16
Judith C Bruce, Joan Dippenaar, Shelley Schmollgruber, David D Mphuthi, Agnes Huiskamp
BACKGROUND: Despite the importance of Human Resources for Health for the development and functioning of health systems worldwide, many countries continue to be plagued by poor health systems and a lack of adequate health care. Health systems failures may be attributed to both quantitative and qualitative nursing shortages including the lack of advanced skills to lead health initiatives, to conduct research and to educate other nurses. The response by development partners is usually framed around the production of skilled nurses through the processes of up-skilling and scaling-up...
2017: Global Health Action
https://www.readbyqxmd.com/read/28770577/sec-saxs-and-hdx-ms-a-powerful-combination-the-case-of-the-calcium-binding-domain-of-a-bacterial-toxin
#17
REVIEW
Darragh P O'Brien, Sébastien Brier, Daniel Ladant, Dominique Durand, Alexandre Chenal, Patrice Vachette
Small-angle X-ray Scattering (SAXS) is a relatively simple experimental technique that provides information on the global conformation of macromolecules in solution, be they fully structured, partially, or extensively unfolded. Size Exclusion chromatography in line with a SAXS measuring cell considerably improves the mono-dispersity and ideality of solutions, the two main requirements of a "good" SAXS sample. Hydrogen/Deuterium eXchange monitored by Mass Spectrometry (HDX-MS) offers a wealth of information regarding the solvent accessibility at the local (peptide) level...
August 2, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28759210/effective-conformational-sampling-in-explicit-solvent-with-gaussian-biased-accelerated-molecular-dynamics
#18
Qiang Shao, Weiliang Zhu
In this Article, a user-friendly Gaussian biased accelerated molecular dynamics (GbAMD) method is presented that uses a sum of Gaussians of potential energies as the biased force to accelerate the conformational sampling. The easy parameter setting of GbAMD is demonstrated in a variety of simulation tests for the conformational transitions of proteins with various complexity including the folding of Trpcage, GB1p, and HP35 peptides as well as the functional conformational changes of nCaM and HIV-1 PR proteins...
August 11, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28756158/bioluminescent-and-biochemical-properties-of-cys-free-ca-2-regulated-photoproteins-obelin-and-aequorin
#19
Elena V Eremeeva, Eugene S Vysotski
Bioluminescence of a variety of marine coelenterates is determined by Ca(2+)-regulated photoproteins. A strong interest in these proteins is for their wide analytical potential as intracellular calcium indicators and labels for in vitro binding assays. The presently known hydromedusan Ca(2+)-regulated photoproteins contain three (aequorin and clytin) or five (obelin and mitrocomin) cysteine residues with one of them strictly conserved. We have constructed Cys-free aequorin and obelin by substitution of all cysteines to serine residues...
July 23, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28755304/participation-of-dengue-virus-ns4b-protein-in-the-modulation-of-immune-effectors-dependent-on-er-stress-in-insect-cells
#20
Karla J Sepúlveda-Salinas, José Ramos-Castañeda
Organisms' reactions to adverse events result in the generation of immune effectors, which, in the case of insects, may be produced from the direct activation of pathways such as Toll, Jak-STAT, Imd, or RNAi or may be derived from the crosstalk of different intracellular pathways. One such pathway, the unfolded protein response (UPR), has the primary objective of restoring homeostasis in the endoplasmic reticulum. In addition, the UPR participates in signaling crosstalk with the immune pathways, generating protection against pathogenic organisms...
July 28, 2017: Cell Stress & Chaperones
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