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https://www.readbyqxmd.com/read/29141194/marginal-stability-drives-irreversible-unfolding-of-large-multi-domain-family-3-glycosylhydrolases-from-thermo-tolerant-yeast
#1
Mohammad Asif Shah, Saroj Mishra, Tapan Kumar Chaudhuri
Protein folding is an extremely complex and fast, yet perfectly defined process, involving interplay of many intra and inter-molecular forces. In vitro, these molecular interactions are reversible for many proteins e.g., smaller and monomeric, organized into single domains. However, refolding of larger multi-domain/multimeric proteins is much more complicated, proceeds in a hierarchal way and is often irreversible. In a comparative study on two large, multi-domain and multimeric isozymes, β -glucosidase I (BGLI) and β-glucosidase II (BGLII) from Pichia etchellsii, we studied spontaneous and assisted refolding under three denaturing conditions viz...
November 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29141152/tm-values-and-unfolded-fraction-can-predict-aggregation-rates-for-gcsf-variant-formulations-but-not-under-predominantly-native-conditions
#2
Mathew J Robinson, Paul Matejtschuk, Adrian F Bristow, Paul A Dalby
Protein engineering and formulation optimisation strategies can be taken to minimise protein aggregation in the biopharmaceutical industry. Short-term stability measures such as the mid-point transition temperature (Tm) for global unfolding provide convenient surrogates for longer-term (eg 2-year) degradation kinetics, with which to optimise formulations on practical time-scales. While successful in some cases, their limitations have not been fully evaluated or understood. Tm values are known to correlate with chemical degradation kinetics for wild-type granulocyte colony stimulating factor (GCSF) at pH 4-5...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29119952/fluorescence-lifetime-components-reveal-kinetic-intermediate-states-upon-equilibrium-denaturation-of-carbonic-anhydrase-ii
#3
Elena V Nemtseva, Olesya O Lashchuk, Marina A Gerasimova, Galina S Nagibina, Tatiana Melnik, Bogdan S Melnik
In most cases, intermediate states of multistage folding proteins are not "visible" under equilibrium conditions but are revealed in kinetic experiments. Time-resolved fluorescence spectroscopy was used in equilibrium denaturation studies. The technique allows detecting changes in the conformation and environment of tryptophan residues in different structural elements of carbonic anhydrase II which in its turn has made it possible to study intermediate states of carbonic anhydrase II under equilibrium conditions...
November 9, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/29114219/entanglement-of-upr-er-in-aging-driven-neurodegenerative-diseases
#4
REVIEW
Safikur Rahman, Arif Tasleem Jan, Archana Ayyagari, Jiwoo Kim, Jihoe Kim, Rinki Minakshi
The endoplasmic reticulum (ER) is an indispensable cellular organelle that remains highly active in neuronal cells. The ER bears the load of maintaining protein homeostasis in the cellular network by managing the folding of incoming nascent peptides; however, the stress imposed by physiological/environmental factors can cause ER dysfunctions that lead to the activation of ER unfolded protein response (UPR(ER)). Aging leads to deterioration of several cellular pathways and therefore weakening of the UPR(ER)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29097427/nlrp3-inflammasome-activation-in-aged-macrophages-is-diminished-during-streptococcus-pneumoniae-infection
#5
Soo Jung Cho, Kristen T Rooney, Augustine M K Choi, Heather W Stout-Delgado
Pneumococcal infections are the 8th leading cause of death in the United States and it is estimated that older patients (>65 years of age) account for the most serious cases. The goal of our current study is to understand the impact of biological aging on innate immune responses to Streptococcus pneumoniae, a causative agent of bacterial pneumonia. Using in vitro and in vivo aged murine models, our findings demonstrate that age-enhanced unfolded protein responses (UPR) contribute to diminished inflammasome assembly and activation during S...
November 2, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29096508/links-between-the-charge-model-and-bonded-parameter-force-constants-in-biomolecular-force-fields
#6
David S Cerutti, Karl T Debiec, David A Case, Lillian T Chong
The ff15ipq protein force field is a fixed charge model built by automated tools based on the two charge sets of the implicitly polarized charge method: one set (appropriate for vacuum) for deriving bonded parameters and the other (appropriate for aqueous solution) for running simulations. The duality is intended to treat water-induced electronic polarization with an understanding that fitting data for bonded parameters will come from quantum mechanical calculations in the gas phase. In this study, we compare ff15ipq to two alternatives produced with the same fitting software and a further expanded data set but following more conventional methods for tailoring bonded parameters (harmonic angle terms and torsion potentials) to the charge model...
October 28, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29091243/use-of-online-unfolding-case-studies-to-foster-critical-thinking
#7
Keeley Bowman
No abstract text is available yet for this article.
November 1, 2017: Journal of Nursing Education
https://www.readbyqxmd.com/read/29078392/exploitation-of-an-iron-transporter-for-bacterial-protein-antibiotic-import
#8
Paul White, Amar Joshi, Patrice Rassam, Nicholas G Housden, Renata Kaminska, Jonathan D Goult, Christina Redfield, Laura C McCaughey, Daniel Walker, Shabaz Mohammed, Colin Kleanthous
Unlike their descendants, mitochondria and plastids, bacteria do not have dedicated protein import systems. However, paradoxically, import of protein bacteriocins, the mechanisms of which are poorly understood, underpins competition among pathogenic and commensal bacteria alike. Here, using X-ray crystallography, isothermal titration calorimetry, confocal fluorescence microscopy, and in vivo photoactivatable cross-linking of stalled translocation intermediates, we demonstrate how the iron transporter FpvAI in the opportunistic pathogen Pseudomonas aeruginosa is hijacked to translocate the bacteriocin pyocin S2 (pyoS2) across the outer membrane (OM)...
October 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29077585/cardiovascular-complications-of-proteasome-inhibitors-used-in-multiple-myeloma
#9
Daniel C Cole, William H Frishman
The use of proteasome inhibitors (PI) as targeted chemotherapeutics have significantly improved survival in patients with multiple myeloma (MM). However, rare and serious cardiovascular complications have occurred as a result of their use, most commonly congestive heart failure, hypertension, and arrhythmias. MM occurs in an aged population with many concurrent cardiovascular risk factors. The primary disease process also contributes to cardiovascular complications. Furthermore, many MM patients have prior exposure to cardiotoxic chemotherapy such as anthracyclines...
October 25, 2017: Cardiology in Review
https://www.readbyqxmd.com/read/29068778/psychology-s-renaissance
#10
Leif D Nelson, Joseph Simmons, Uri Simonsohn
In 2010-2012, a few largely coincidental events led experimental psychologists to realize that their approach to collecting, analyzing, and reporting data made it too easy to publish false-positive findings. This sparked a period of methodological reflection that we review here and call Psychology's Renaissance. We begin by describing how psychologists' concerns with publication bias shifted from worrying about file-drawered studies to worrying about p-hacked analyses. We then review the methodological changes that psychologists have proposed and, in some cases, embraced...
October 25, 2017: Annual Review of Psychology
https://www.readbyqxmd.com/read/29064059/spiking-resonances-in-models-with-the-same-slow-resonant-and-fast-amplifying-currents-but-different-subthreshold-dynamic-properties
#11
Horacio G Rotstein
The generation of spiking resonances in neurons (preferred spiking responses to oscillatory inputs) requires the interplay of the intrinsic ionic currents that operate at the subthreshold voltage level and the spiking mechanisms. Combinations of the same types of ionic currents in different parameter regimes may give rise to different types of nonlinearities in the voltage equation (e.g., parabolic- and cubic-like), generating subthreshold (membrane potential) oscillations patterns with different properties...
October 24, 2017: Journal of Computational Neuroscience
https://www.readbyqxmd.com/read/29058444/combining-in-vitro-and-in-silico-single-molecule-force-spectroscopy-to-characterize-and-tune-cellulosomal-scaffoldin-mechanics
#12
Tobias Verdorfer, Rafael C Bernardi, Aylin Meinhold, Wolfgang Ott, Zaida Luthey-Schulten, Michael A Nash, Hermann E Gaub
Cellulosomes are polyprotein machineries that efficiently degrade cellulosic material. Crucial to their function are scaffolds consisting of highly homologous cohesin domains, which serve a dual role by coordinating a multiplicity of enzymes as well as anchoring the microbe to its substrate. Here we combined two approaches to elucidate the mechanical properties of the main scaffold ScaA of Acetivibrio cellulolyticus. A newly developed parallelized one-pot in vitro transcription-translation and protein pull-down protocol enabled high-throughput atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) measurements of all cohesins from ScaA with a single cantilever, thus promising improved relative force comparability...
November 3, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29056645/fertility-lost-fertility-found-narratives-from-the-leading-edge-of-oncofertility
#13
Teresa K Woodruff
A cancer diagnosis at a young age creates one of the most existential crises one can imagine. The good news is that for many of these young patients, they will survive their diagnosis. They will be told of the side effects of treatment including loss of hair but will not be told of the other losses associated with their reproductive function-loss of menstrual cycles, early menopause and the potential for pregnancy for women, loss of viable sperm for men, and loss of sexual libido in both cases. Not all cancer treatments result in the same series of fertility effects so one of the issues that physicians face is determining what the best course of fertility sparing options should be...
2017: Narrative Inquiry in Bioethics
https://www.readbyqxmd.com/read/29055527/multi-state-steric-mass-action-model-and-case-study-on-complex-high-loading-behavior-of-mab-on-ion-exchange-tentacle-resin
#14
Juliane Diedrich, William Heymann, Samuel Leweke, Stephen Hunt, Robert Todd, Christian Kunert, Will Johnson, Eric von Lieres
Tentacle resins for IEX are increasingly applied in preparative chromatography for their higher selectivity and higher capacities in comparison to IEX resins without tentacles. However, tentacle resins are often observed to cause unusual elution behavior of monoclonal antibodies under high loading conditions. Understanding this elution behavior is important for a quality by design approach, as it is now mandated by regulatory agencies. A model-based analysis of load, wash and gradient elution is performed for a monoclonal antibody (mAb) on Fractogel SO3(-)...
September 20, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29040746/characterization-of-an-in-house-developed-multi-cylindrical-moderator-neutron-spectrometer
#15
T Liamsuwan, J Channuie, S Wonglee, M Kowatari, S Nishino
This article describes the characterization of an in-house developed multi-cylindrical moderator neutron spectrometer, which consists of a cylindrical 3He proportional counter and cylindrical moderator shells of different sizes. The response matrix of the spectrometer was calculated by Monte Carlo simulations for neutron energies from 1 × 10-8 to 10 MeV and verified with measurements in 0.144 MeV, 1.2 MeV and 241AmBe neutron standard fields. Influence of scattered neutrons was properly eliminated from the measured response using the shadow cone technique...
October 13, 2017: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/29037593/untargeted-analysis-of-chromatographic-data-for-green-and-fermented-rooibos-problem-with-size-effect-removal
#16
Jade Tobin, Jan Walach, Dalene de Beer, Paul J Williams, Peter Filzmoser, Beata Walczak
While analyzing chromatographic data, it is necessary to preprocess it properly before exploration and/or supervised modeling. To make chromatographic signals comparable, it is crucial to remove the scaling effect, caused by differences in overall sample concentrations. One of the efficient methods of signal scaling is Probabilistic Quotient Normalization (PQN) [1]. However, it can be applied only to data for which the majority of features do not vary systematically among the studied classes of signals. When studying the influence of the traditional "fermentation" (oxidation) process on the concentration of 56 individual peaks detected in rooibos plant material, this assumption is not fulfilled...
October 9, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29029791/in-search-for-globally-disordered-apo-parvalbumins-case-of-parvalbumin-%C3%AE-1-from-coho-salmon
#17
Alisa A Vologzhannikova, Polina A Khorn, Alexei S Kazakov, Ramis G Ismailov, Andrei S Sokolov, Vladimir N Uversky, Eugene A Permyakov, Sergei E Permyakov
Parvalbumin (PA) is a classical EF-hand calcium-binding protein of muscle, neuronal, and other tissues, and a major fish allergen. Although certain apo-PAs lack tertiary structure, functional implications of that feature and its structural prerequisites remain unclear. In a search for unstable PAs, we probed conformational stability of parvalbumin β-1 from coho salmon (csPA), a cold water fish species, using circular dichroism, scanning calorimetry, hydrophobic probe fluorescence, limited proteolysis, chemical crosslinking and dynamic light scattering techniques...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29026978/enigma-of-scapular-foramen-and-tunnels-an-untold-story
#18
Nidhi Singh, Puja Chauhan, Hitendra Kumar Loh, Mangala Kohli, Rajesh Kumar Suri
PURPOSE: The study was undertaken to make a qualitative and quantitative assessment of unnamed foramen and tunnels in adult human scapulae with aid of plain and contrast radiographs. MATERIALS AND METHODS: A total of 120 dry bones, 60 each of the right and the left side were included in the study. Distribution of these foramina and tunnels was noted for their number, side, location, course and communication. Their morphometry was done using Vernier's caliper. RESULTS: Incidence of scapular foramina was 7...
October 12, 2017: Surgical and Radiologic Anatomy: SRA
https://www.readbyqxmd.com/read/28969278/expressional-analysis-of-msx1-human-revealed-its-role-in-sagittal-jaw-relationship
#19
Prateek Gupta, Thakur Prasad Chaturvedi, Vipul Sharma
INTRODUCTION: Abnormal skeletal jaw relationships is an important factor causing difficulty in speech, mastication, sleep and social interaction, thus affect the overall well being of an individual. AIM: The present study was an attempt to decipher the role of human MSX1 in terms of sagittal jaw relationship by employing Polymerase Chain Reaction (PCR) based analysis. MATERIALS AND METHODS: Ninety-eight case subjects belonging to North India with skeletal Class II and Class III jaw relationships were selected...
August 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28969125/unfolding-of-a-clinically-suspected-case-of-pulmonary-tuberculosis
#20
Savitha Thirouvengadame, Swapna Muthusamy, Vignesh Kanna Balaji, Joshy Maducolil Easow
Pulmonary nocardiosis caused by Nocardia mimics pulmonary tuberculosis in many aspects. Here, we report a case of suspected pulmonary tuberculosis turning into pulmonary nocardiosis following microbiological evaluation. Sputum sample of the patient grew Nocardia otitidiscaviarum. Identification was done by conventional methods and matrix assisted laser desorption ionization-time of flight. He was given co-trimoxazole based on susceptibility reports. Even though Nocardia is a rare entity, pulmonary nocardiosis should be ruled out before starting antitubercular treatment to avoid unnecessary burden to the patient and community...
August 2017: Journal of Clinical and Diagnostic Research: JCDR
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