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https://www.readbyqxmd.com/read/29329817/isothermal-chemical-denaturation-as-a-complimentary-tool-to-overcome-limitations-of-thermal-differential-scanning-fluorimetry-in-predicting-physical-stability-of-protein-formulations
#1
Hristo Svilenov, Uroš Markoja, Gerhard Winter
Various stability indicating techniques find application in the early stage development of novel therapeutic protein candidates. Some of these techniques are used to select formulation conditions that provide high protein physical stability. Such approach is highly dependent on the reliability of the stability indicating technique used. In this work, we present a formulation case study where we evaluate the ability of differential scanning fluorimetry (DSF) and isothermal chemical denaturation (ICD) to predict the physical stability of a model monoclonal antibody during accelerated stability studies...
January 9, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29328657/molecular-mechanism-of-protein-unfolding-under-shear-a-lattice-boltzmann-molecular-dynamics-study
#2
Fabio Sterpone, Philippe Derreumaux, Simone Melchionna
Proteins are marginally stable soft-matter entities that can be disrupted using a variety of perturbative stresses, including thermal, chemicals or mechanical ones. Fluid under extreme flow conditions is a possible route to probe the weakness of biomolecules and collect information on the molecular cohesive interactions that secure their stability. Moreover, in many cases, physiological flow triggers the functional response of specialised proteins as occurring in blood coagulation or cell adhesion. In this paper, we deploy the Lattice Boltzmann Molecular Dynamics technique based on the coarse grained model for protein OPEP, to study the mechanism of protein unfolding under Couette flow...
January 12, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29323889/transmetalation-for-flexible-pendant-armed-schiff-base-macrocyclic-complexes-influenced-by-halide-effects
#3
Fei-Fan Chang, Lei Zhang, Pei-Chen Zhao, Wei Huang
Three 46-membered [2 + 2] pendant-armed Schiff-base macrocyclic dinuclear CdII and CuII complexes (2a, 2b, and 3b) and one 23-membered [1 + 1] CuII macrocycle 4a were prepared from the template-directed condensation reactions between 1,2-bis(2-aminoethoxy)-ethane and extended Cl-dialdehyde in the presence of CdX2 and CuX2 (X = Cl and Br), in which halide effects play important roles in the organization of final macrocyclic complexes in addition to the dominant influence of metal cations. Transmetalation was intensively studied among these CdII and CuII complexes with large and flexible macrocyclic ligands, including two previously synthesized dinuclear ZnII macrocycles (1a and 1b)...
January 11, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29323786/pulmonary-endoplasmic-reticulum-stress-scars-smoke-and-suffocation
#4
REVIEW
Jennifer A Dickens, Elke Malzer, Joseph E Chambers, Stefan J Marciniak
Protein misfolding within the endoplasmic reticulum (ER stress) can be a cause or consequence of pulmonary disease. Mutation of proteins restricted to the alveolar type II pneumocyte can lead to inherited forms of pulmonary fibrosis, but even sporadic cases of pulmonary fibrosis appear to be strongly associated with activation of the unfolded protein response (UPR) and/or the integrated stress response (ISR). Inhalation of smoke can impair protein folding and may be an important cause of pulmonary ER stress...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29315494/isotype-dependent-on-column-non-reversible-aggregation-of-monoclonal-antibodies
#5
Monika Farys, Daniel Gibson, Alan Lewis, Will Lewis, Richard Kucia-Tran
Monoclonal antibodies of the IgG2 and IgG4 isotype were found to exhibit an increased propensity for displaying two-peak elution profiles during cation exchange chromatography. In some cases, this two-peak elution profile also resulted in the formation of non-reversible mAb aggregates. Comparison of IgG1, IgG2 and IgG4 molecules with the same variable region reveals that the two-peak behaviour is predominantly mediated by the constant region and most likely the lower CH1, hinge and upper CH2 regions of the mAb...
January 8, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29314060/dynamic-field-of-view-imaging-to-increase-temporal-resolution-in-the-early-phase-of-contrast-media-uptake-in-breast-dce-mri-a-feasibility-study
#6
Federico D Pineda, Ty O Easley, Gregory S Karczmar
PURPOSE: To increase diagnostic accuracy of breast MRI by increasing temporal resolution and more accurately sampling the early kinetics of contrast media uptake. We tested the feasibility of accelerating bilateral breast DCE-MRI by reducing the FOV, allowing aliasing, and unfolding the resulting images. METHODS: Previous experience with an 'ultrafast' protocol for bilateral breast DCE-MRI (6s-10s temporal resolution) showed that the number of significantly enhancing voxels is very low in the first 30 to 45 seconds after contrast media injection...
January 3, 2018: Medical Physics
https://www.readbyqxmd.com/read/29303072/generation-of-reactive-oxygen-species-by-photosensitizers-and-their-modes-of-action-on-proteins
#7
Itzhak Bilkis, Israel Silman, Lev Weiner
In this review, we first survey the mechanisms underlying the chemical modification of amino acid residues in proteins by singlet oxygen elicited by photosensitizers. Singlet oxygen has the capacity to cause widespread chemical damage to cellular proteins. Its use in photodynamic therapy of tumors thus requires the development of methodologies for specific addressing of the photosensitizer to malignant cells while sparing normal tissue. We describe three targeting paradigms for achieving this objective. The first involves the use of a photosensitizer with a high affinity for its target protein; in this case, the photosensitizer is methylene blue for acetylcholinesterase...
January 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29302164/doubling-syndemics-ethnographic-accounts-of-the-health-situation-of-homeless-romanian-roma-in-copenhagen
#8
Camilla Ida Ravnbøl
This study investigates health concerns and access to health services for Roma from Romania who live in homelessness in Copenhagen, Denmark. They collect refundable bottles and call themselves "badocari," which in Romanian refers to "people who work with bottles." Homeless Roma in Denmark have not previously been studied through ethnographic research. The study stresses the importance of a syndemic approach towards understanding badocari health concerns. Syndemics is understood as co-occurring diseases, which unfold within contexts of social injustice...
December 2017: Health and Human Rights
https://www.readbyqxmd.com/read/29300149/the-risks-and-rewards-of-speed-restorative-retelling-compressed-into-a-three-day-retreat
#9
Theresa Blakley, Nita Mehr, Donald Jordan
This article chronicles the process of reducing the 10 week restorative retelling (RR) group model (Rynearson & Correa, Accommodation to violent dying: A guide to restorative retelling and support, Violent Death Bereavement Society, 2006) into a 3 day retreat for families of homicide loss. Strategies used to address the intensity of the condensed version of the treatment model are described for both the participants and treatment team. The twists and turns of how the therapeutic retreat unfolded are presented through case examples...
January 4, 2018: Death Studies
https://www.readbyqxmd.com/read/29284171/post-tavi-follow-up-with-mdct-of-the-valve-prosthesis-technical-application-regular-findings-and-typical-local-post-interventional-complications
#10
Martin Soschynski, Fabio Capilli, Philipp Ruile, Franz-Josef Neumann, Mathias Langer, Tobias Krauss
BACKGROUND:  Transcatheter aortic valve implantation (TAVI) has evolved into an alternative procedure to surgical valve replacement for high-risk patients with aortic valve stenosis. Despite technical innovations, there is still a risk of complications during and after the intervention. After a TAVI procedure, ECG-gated multidetector computed tomography (MDCT) plays an important role in the early diagnosis of local complications. In this article, we explain for the first time how the technical acquisition of MDCT in the region of the aortic root is performed as post-interventional control of the TAVI prosthesis...
December 28, 2017: RöFo: Fortschritte Auf Dem Gebiete der Röntgenstrahlen und der Nuklearmedizin
https://www.readbyqxmd.com/read/29260073/endothelial-keratoplasty-for-posterior-polymorphous-corneal-dystrophy-in-a-4-month-old-infant
#11
M Hermina Strungaru, Asim Ali, David Rootman, Kamiar Mireskandari
Purpose: To report a case of endothelial keratoplasties (EKs) performed in a 4 month old with a posterior polymorphous corneal dystrophy. Observations: A 4 month old infant underwent Descemet membrane endothelial keratoplasty (DMEK) for posterior polymorphous corneal dystrophy. The graft was found to be dislocated on day 5 post-operatively and an attempt to unfold the DMEK scroll and re-bubble was not successful. The patient was then treated successfully with bilateral Descemet stripping automated endothelial keratoplasty (DSAEK)...
September 2017: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29258895/estimation-of-structure-and-stability-of-mure-ligase-from-salmonella-enterica-serovar-typhi
#12
Rohit Bansal, Md Anzarul Haque, Prakarsh Yadav, Deepali Gupta, Abdul S Ethayathulla, Md Imtaiyaz Hassan, Punit Kaur
MurE ligase catalyzes the assembly of peptide moiety, an essential component of bacterial cell wall. We have explored the conformational stability and unfolding equilibrium behaviour of the protein MurE ligase by determining the conformational free energy, entropy and enthalpy parameters under stress conditions. MurE from Salmonella enterica Serovar Typhi was cloned, expressed and purified. Conformational changes associated with increasing concentration of GdmCl- and urea-induced denaturation of MurE were monitored using Circular Dichroism (CD) and fluorescence spectroscopies...
December 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29223857/when-it-is-apt-to-adapt-flexible-reasoning-guides-children-s-use-of-talker-identity-and-disfluency-cues
#13
Justine M Thacker, Craig G Chambers, Susan A Graham
An eye-tracking methodology was used to examine whether children flexibly engage two voice-based cues, talker identity and disfluency, during language processing. Across two experiments, 5-year-olds (N = 58) were introduced to two characters with distinct color preferences. These characters then used fluent or disfluent instructions to refer to an object in a display containing items bearing either talker-preferred or talker-dispreferred colors. As the utterance began to unfold, the 5-year-olds anticipated that talkers would refer to talker-preferred objects...
December 7, 2017: Journal of Experimental Child Psychology
https://www.readbyqxmd.com/read/29222489/specific-binding-of-a-polymer-chain-to-a-sequence-of-surface-receptors
#14
Samuel Bell, Eugene M Terentjev
This paper considers a biologically relevant question of a Gaussian chain (such as an unfolded protein) binding to a sequence of receptors with matching multiple ligands distributed along the chain. Using the characteristic time for a tethered ligand to bind to a surface receptor, we study the case of multiple binding to a linear sequence of receptors on the surface. The tethered binding time is determined by the entropic barrier for the chain to be stretched sufficiently to reach the distant receptor target, and a restriction on chain conformations near the substrate...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29214060/interstitial-lung-disease-the-diagnostic-role-of-bronchoscopy
#15
REVIEW
Jad Kebbe, Tony Abdo
Interstitial lung diseases (ILDs) form one of the most fascinating fields in pulmonary medicine. They also pose one of the greatest challenges for accurate diagnosis and proper treatment. Even within the recommended and warranted multidisciplinary approach, differentiating between one disease and another may lead to frustration, especially when proper lung tissue is not available for adequate pathological review. A surgical lung biopsy (SLB) might render enough tissue for histopathology, but this could come at the expense of high morbidity and even mortality, as in the case of usual interstitial pneumonia (UIP)...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29194372/what-is-our-current-understanding-of-prpsc-associated-neurotoxicity-and-its-molecular-underpinnings
#16
REVIEW
Daniel Hughes, Mark Halliday
The prion diseases are a collection of fatal, transmissible neurodegenerative diseases that cause rapid onset dementia and ultimately death. Uniquely, the infectious agent is a misfolded form of the endogenous cellular prion protein, termed PrPSc. Despite the identity of the molecular agent remaining the same, PrPSc can cause a range of diseases with hereditary, spontaneous or iatrogenic aetiologies. However, the link between PrPSc and toxicity is complex, with subclinical cases of prion disease discovered, and prion neurodegeneration without obvious PrPSc deposition...
December 1, 2017: Pathogens
https://www.readbyqxmd.com/read/29188078/one-shot-synesthesia
#17
Alexandra Kirschner, Danko Nikolić
Synesthesia is commonly thought to be a phenomenon of fixed associations between an outside inducer and a vivid concurrent experience. Hence, it has been proposed that synesthesia occurs due to additional connections in the brain with which synesthetes are born. Here we show that synesthesia can be a much richer and more flexible phenomenon with a capability to creatively construct novel synesthetic experiences as events unfold in people's lives. We describe here cases of synesthetes who occasionally generate novel synesthetic experience, called one-shot synesthesias...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/29186961/relationship-between-ppp1r15a-gene-polymorphism-rs611251-and-epstein-barr-virus-associated-tumors
#18
Y Song, S Liu, Z Zhao, Y Zhang, Y Yang, B Luo
Protein phosphatase 1, regulatory subunit 15A (PPP1R15A), also known as growth arrest and DNA damage-inducible protein GADD34, plays a vital role in promoting cell death and the unfolded protein response (UPR). In order to explore whether the SNP (rs611251) of PPP1R15A gene has a role in different types of Epstein-Barr virus (EBV) - associated tumors, we detected the PPP1R15A gene rs611251 polymorphism in 195 cases of EBV positive tumors (93 lymphomas, 48 gastric carcinomas, 54 nasopharyngeal carcinomas), 208 cases of EBV-negative tumors (136 gastric carcinoma, 19 nasopharyngeal carcinomas, 53 lymphomas) and 113 peripheral blood samples from healthy individuals...
2017: Acta Virologica
https://www.readbyqxmd.com/read/29165709/structural-basis-for-the-gtp-specificity-of-the-rna-kinase-domain-of-fungal-trna-ligase
#19
Barbara S Remus, Yehuda Goldgur, Stewart Shuman
Fungal tRNA ligase (Trl1) is an essential enzyme that repairs RNA breaks with 2',3'-cyclic-PO4 and 5'-OH ends inflicted during tRNA splicing and non-canonical mRNA splicing in the fungal unfolded protein response. Trl1 is composed of C-terminal cyclic phosphodiesterase and central polynucleotide kinase domains that heal the broken ends to generate the 3'-OH,2'-PO4 and 5'-PO4 termini required for sealing by an N-terminal ligase domain. Trl1 enzymes are found in all human fungal pathogens and are promising targets for antifungal drug discovery because their domain compositions and biochemical mechanisms are unique compared to the mammalian RtcB-type tRNA splicing enzyme...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29161089/protein-folding-and-the-challenges-of-maintaining-endoplasmic-reticulum-proteostasis-in-idiopathic-pulmonary-fibrosis
#20
Freddy Romero, Ross Summer
Alveolar epithelial type II (AEII) cells are "professional" secretory cells that synthesize and secrete massive quantities of proteins to produce pulmonary surfactant and maintain airway immune defenses. To facilitate this high level of protein synthesis, AEII cells are equipped with an elaborate endoplasmic reticulum (ER) structure and possess an abundance of the machinery needed to fold, assemble, and secrete proteins. However, conditions that suddenly increase the quantity of new proteins entering the ER or that impede the capacity of the ER to fold proteins can cause misfolded or unfolded proteins to accumulate in the ER lumen, also called ER stress...
November 2017: Annals of the American Thoracic Society
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