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https://www.readbyqxmd.com/read/27915153/room-temperature-structure-of-human-igg4-fc-from-crystals-analysed-in-situ
#1
Anna M Davies, Theo Rispens, Pleuni Ooijevaar-de Heer, Rob C Aalberse, Brian J Sutton
The Fc region of IgG antibodies (Cγ2 and Cγ3 domains) is responsible for effector functions such as antibody-dependent cell-mediated cytotoxicity and phagocytosis, through engagement with Fcγ receptors, although the ability to elicit these functions differs between the four human IgG subclasses. A key determinant of Fcγ receptor interactions is the FG loop in the Cγ2 domain. High resolution cryogenic IgG4-Fc crystal structures have revealed a unique conformation for this loop, which could contribute to the particular biological properties of this subclass...
December 1, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27915030/the-effect-of-anionic-dicephalic-surfactants-on-fabrication-of-varied-core-nanocarriers-for-sustained-release-of-porphyrin-photosensitizers
#2
Urszula Bazylińska, Renata Frąckowiak, Zbigniew Brzózka, Kazimiera A Wilk
Double-headed anionic surfactants could provide a profound group of efficient stabilizers of new template-mediated nanocarriers for effective encapsulation and sustained release of highly hydrophobic photosensitizers, and therefore their improved therapeutic activity in photodynamic therapy (PDT) protocols. We have thus encapsulated porphyrin-origin dyes, i.e., verteporfin (VP) and meso-tetraphenylporphyrin (TPP) in different types of sodium alkyliminobisacetates, Cn(COONa)2-stabilized nanosystems including biocompatible poly(l-glutamic acid)/poly(l-lysine) - PGA/PLL, multilayer nanocapsules (NCs)...
November 19, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27915009/exploring-gastrointestinal-variables-affecting-drug-and-formulation-behavior-methodologies-challenges-and-opportunities
#3
REVIEW
Bart Hens, Maura Corsetti, Robin Spiller, Luca Marciani, Tim Vanuytsel, Jan Tack, Arjang Talattof, Gordon L Amidon, Mirko Koziolek, Werner Weitschies, Clive G Wilson, Roelof J Bennink, Joachim Brouwers, Patrick Augustijns
Various gastrointestinal (GI) factors affect drug and formulation behavior after oral administration, including GI transfer, motility, pH and GI fluid volume and composition. An in-depth understanding of these physiological and anatomical variables is critical for a continued progress in oral drug development. In this review, different methodologies (invasive versus non-invasive) to explore the impact of physiological variables on formulation behavior in the human GI tract are presented, revealing their strengths and limitations...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27914762/distribution-of-the-neuro-regulatory-peptide-galanin-in-the-human-eye
#4
Alexandra Kaser-Eichberger, Andrea Trost, Clemens Strohmaier, Barbara Bogner, Christian Runge, Daniela Bruckner, Bettina Hohberger, Anselm Jünemann, Barbara Kofler, Herbert A Reitsamer, Falk Schrödl
Galanin (GAL) is a neuro-regulatory peptide involved in many physiological and pathophysiological processes. While data of GAL origin/distribution in the human eye are rather fragmentary and since recently the presence of GAL-receptors in the normal human eye has been reported, we here systematically search for sources of ocular GAL in the human eye. Human eyes (n=14) were prepared for single- and double-immunohistochemistry of GAL and neurofilaments (NF). Cross- and flat-mount sections were achieved; confocal laser-scanning microscopy was used for documentation...
November 25, 2016: Neuropeptides
https://www.readbyqxmd.com/read/27914702/renal-xenotransplantation-experimental-progress-and-clinical-prospects
#5
Martin Wijkstrom, Hayato Iwase, Wayne Paris, Hidetaka Hara, Mohamed Ezzelarab, David K C Cooper
There are >100,000 patients waiting for kidney transplants in the United States and a vast need worldwide. Xenotransplantation, in the form of the transplantation of kidneys from genetically engineered pigs, offers the possibility of overcoming the chronic shortage of deceased and living human donors. These genetic manipulations can take the form of (i) knockout of pig genes that are responsible for the expression of antigens against which the primate (human or nonhuman primate) has natural "preformed" antibodies that bind and initiate complement-mediated destruction or (ii) the insertion of human transgenes that provide protection against the human complement, coagulation, or inflammatory responses...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27914400/a-comparative-study-of-seven-human-cochlear-filter-models
#6
Amin Saremi, Rainer Beutelmann, Mathias Dietz, Go Ashida, Jutta Kretzberg, Sarah Verhulst
Auditory models have been developed for decades to simulate characteristics of the human auditory system, but it is often unknown how well auditory models compare to each other or perform in tasks they were not primarily designed for. This study systematically analyzes predictions of seven publicly-available cochlear filter models in response to a fixed set of stimuli to assess their capabilities of reproducing key aspects of human cochlear mechanics. The following features were assessed at frequencies of 0...
September 2016: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/27914377/evaluating-multipulse-integration-as-a-neural-health-correlate-in-human-cochlear-implant-users-relationship-to-spatial-selectivity
#7
Ning Zhou, Bryan E Pfingst
The decrease of psychophysical detection thresholds as a function of pulse rate for a fixed-duration electrical pulse train is referred to as multipulse integration (MPI). The MPI slopes correlate with anatomical and physiological indices of cochlear health in guinea pigs with cochlear implants. The aim of the current study was to assess whether the MPI slopes were related to the spatial spread of activation by electrical stimulation. The hypothesis was that MPI is dependent on the total number of excitable neurons at the stimulation site, with broader neural excitation producing a steeper threshold decrease as a function of stimulation rate...
September 2016: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/27914253/protein-conjugation-with-pamam-nanoparticles-microscopic-and-thermodynamic-analysis
#8
P Chanphai, E Froehlich, J S Mandeville, H A Tajmir-Riahi
PAMAM dendrimers form strong protein conjugates that are used in drug delivery systems. We report the thermodynamic and binding analysis of polyamidoamine (PAMAM-G4) conjugation with human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (b-LG) in aqueous solution at physiological pH. Hydrophobicity played a major role in PAMAM-protein interactions with more hydrophobic b-LG forming stronger polymer-protein conjugates. Thermodynamic parameters showed PAMAM-protein bindings occur via hydrophobic and H-bonding contacts for b-LG, while van der waals and H-bonding interactions prevail in HSA and BSA-polymer conjugates...
November 27, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27913853/the-role-of-intestinal-oxalate-transport-in-hyperoxaluria-and-the-formation-of-kidney-stones-in-animals-and-man
#9
REVIEW
Jonathan M Whittamore, Marguerite Hatch
The intestine exerts a considerable influence over urinary oxalate in two ways, through the absorption of dietary oxalate and by serving as an adaptive extra-renal pathway for elimination of this waste metabolite. Knowledge of the mechanisms responsible for oxalate absorption and secretion by the intestine therefore have significant implications for understanding the etiology of hyperoxaluria, as well as offering potential targets for future treatment strategies for calcium oxalate kidney stone disease. In this review, we present the recent developments and advances in this area over the past 10 years, and put to the test some of the new ideas that have emerged during this time, using human and mouse models...
December 2, 2016: Urolithiasis
https://www.readbyqxmd.com/read/27913593/higher-heart-rate-variability-is-associated-with-vmpfc-activity-and-increased-resistance-to-temptation-in-dietary-self-control-challenges
#10
Silvia U Maier, Todd A Hare
: Higher levels of self-control in decision making have been linked to better psychosocial and physical health. A similar link to health outcomes has been reported for heart rate variability (HRV), a marker of physiological flexibility. Here, we sought to link these two, largely separate, research domains by testing the hypothesis that greater HRV would be associated with better dietary self-control in humans. Specifically, we examined whether total HRV at sedentary rest (measured as the standard deviation of normal-to-normal intervals, SDNN) can serve as a biomarker for the neurophysiological adaptability that putatively underlies self-controlled behavior...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27913322/automatic-detection-and-classification-of-high-frequency-oscillations-in-depth-eeg-signals
#11
Nisrine Jrad, Amar Kachenoura, Isabelle Merlet, Fabrice Bartolomei, Anca Nica, Arnaud Biraben, Fabrice Wendling
GOAL: Interictal High Frequency Oscillations (HFOs [30-600 Hz]) have proven to be relevant biomarkers in epilepsy. In this paper, four categories of HFOs are considered: Gamma ([30- 80 Hz]), High-Gamma ([80-120 Hz]), Ripples ([120-250 Hz]) and Fast-Ripples ([250-600 Hz]). A universal detector of the four types of HFOs is proposed. It has the advantages of i) classifying HFOs, and thus being robust to inter- and intra-subject variability; ii) rejecting artefacts, thus being specific. METHODS: Gabor atoms are tuned to cover the physiological bands...
November 29, 2016: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/27913291/a-saposin-deficiency-model-in-drosophila-lysosomal-storage-progressive-neurodegeneration-and-sensory-physiological-decline
#12
Samantha J Hindle, Sarita Hebbar, Dominik Schwudke, Christopher J Elliott, Sean T Sweeney
Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids...
November 29, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27912785/transmission-of-viruses-via-our-microbiomes
#13
Melissa Ly, Marcus B Jones, Shira R Abeles, Tasha M Santiago-Rodriguez, Jonathan Gao, Ivan C Chan, Chandrabali Ghose, David T Pride
BACKGROUND: Bacteria inhabiting the human body have important roles in a number of physiological processes and are known to be shared amongst genetically-related individuals. Far less is known about viruses inhabiting the human body, but their ecology suggests they may be shared between close contacts. RESULTS: Here, we report the ecology of viruses in the guts and mouths of a cohort and demonstrate that substantial numbers of gut and oral viruses were shared amongst genetically unrelated, cohabitating individuals...
December 2, 2016: Microbiome
https://www.readbyqxmd.com/read/27912678/the-physiology-and-molecular-underpinnings-of-the-effects-of-bariatric-surgery-on-obesity-and-diabetes
#14
Simon S Evers, Darleen A Sandoval, Randy J Seeley
Bariatric surgeries, such as Roux-en-Y gastric bypass and vertical sleeve gastrectomy, produce significant and durable weight loss in both humans and rodents. Recently, these surgical interventions have also been termed metabolic surgery because they result in profound metabolic improvements that often surpass the expected improvement due to body weight loss alone. In this review we focus on the weight-loss independent effects of bariatric surgery, which encompass energy expenditure and macronutrient preference, the luminal composition of the gut (i...
November 28, 2016: Annual Review of Physiology
https://www.readbyqxmd.com/read/27912098/characterization-of-hippo-pathway-components-by-gene-inactivation
#15
Steven W Plouffe, Zhipeng Meng, Kimberly C Lin, Brian Lin, Audrey W Hong, Justin V Chun, Kun-Liang Guan
The Hippo pathway is important for regulating tissue homeostasis, and its dysregulation has been implicated in human cancer. However, it is not well understood how the Hippo pathway becomes dysregulated because few mutations in core Hippo pathway components have been identified. Therefore, much work in the Hippo field has focused on identifying upstream regulators, and a complex Hippo interactome has been identified. Nevertheless, it is not always clear which components are the most physiologically relevant in regulating YAP/TAZ...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27911941/copper-oxide-nanoparticles-impact-several-toxicological-endpoints-and-cause-neurodegeneration-in-caenorhabditis-elegans
#16
Michael J Mashock, Tyler Zanon, Anthony D Kappell, Lisa N Petrella, Erik C Andersen, Krassimira R Hristova
Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C...
2016: PloS One
https://www.readbyqxmd.com/read/27911860/id4-regulates-transcriptional-activity-of-wild-type-and-mutant-p53-via-k373-acetylation
#17
Derrick J Morton, Divya Patel, Jugal Joshi, Aisha Hunt, Ashley E Knowell, Jaideep Chaudhary
Given that mutated p53 (50% of all human cancers) is over-expressed in many cancers, restoration of mutant p53 to its wild type biological function has been sought after as cancer therapy. The conformational flexibility has allowed to restore the normal biological function of mutant p53 by short peptides and small molecule compounds. Recently, studies have focused on physiological mechanisms such as acetylation of lysine residues to rescue the wild type activity of mutant p53. Using p53 null prostate cancer cell line we show that ID4 dependent acetylation promotes mutant p53 DNA-binding capabilities to its wild type consensus sequence, thus regulating p53-dependent target genes leading to subsequent cell cycle arrest and apoptosis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911858/the-antidepressant-fluoxetine-induces-necrosis-by-energy-depletion-and-mitochondrial-calcium-overload
#18
Emilie Charles, Mehdi Hammadi, Philippe Kischel, Vanessa Delcroix, Nicolas Demaurex, Cyril Castelbout, Anne-Marie Vacher, Anne Devin, Thomas Ducret, Paula Nunes, Pierre Vacher
Selective Serotonin Reuptake Inhibitor antidepressants, such as fluoxetine (Prozac), have been shown to induce cell death in cancer cells, paving the way for their potential use as cancer therapy. These compounds are able to increase cytosolic calcium concentration ([Ca2+]cyt), but the involved mechanisms and their physiological consequences are still not well understood. Here, we show that fluoxetine induces an increase in [Ca2+]cyt by emptying the endoplasmic reticulum (ER) through the translocon, an ER Ca2+ leakage structure...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911394/confirmation-of-myocardial-ischemia-and-reperfusion-injury-in-mice-using-surface-pad-electrocardiography
#19
Stephanie L C Scofield, Krishna Singh
Many animal models have been established for the study of myocardial remodeling and heart failure due to its status as the number one cause of mortality worldwide. In humans, a pathologic occlusion forms in a coronary artery and reperfusion of that occluded artery is considered essential to maintain viability of the myocardium at risk. Although essential for myocardial recovery, reperfusion of the ischemic myocardium creates its own tissue injury. The physiologic response and healing of an ischemia/reperfusion injury is different from a chronic occlusion injury...
November 24, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911383/parallel-measurement-of-circadian-clock-gene-expression-and-hormone-secretion-in-human-primary-cell-cultures
#20
Volodymyr Petrenko, Camille Saini, Laurent Perrin, Charna Dibner
Circadian clocks are functional in all light-sensitive organisms, allowing for an adaptation to the external world by anticipating daily environmental changes. Considerable progress in our understanding of the tight connection between the circadian clock and most aspects of physiology has been made in the field over the last decade. However, unraveling the molecular basis that underlies the function of the circadian oscillator in humans stays of highest technical challenge. Here, we provide a detailed description of an experimental approach for long-term (2-5 days) bioluminescence recording and outflow medium collection in cultured human primary cells...
November 11, 2016: Journal of Visualized Experiments: JoVE
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