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https://www.readbyqxmd.com/read/28723554/hypoxia-sensitive-commd1-integrates-signaling-and-cellular-metabolism-in-human-macrophages-and-suppresses-osteoclastogenesis
#1
Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723415/pharmacology-of-human-trace-amine-associated-receptors-therapeutic-opportunities-and-challenges
#2
REVIEW
Mark D Berry, Raul R Gainetdinov, Marius C Hoener, Mohammed Shahid
The discovery in 2001 of a G protein-coupled receptor family, subsequently termed trace amine-associated receptors (TAAR), triggered a resurgence of interest in so-called trace amines. Initial optimism quickly faded, however, as the TAAR family presented a series of challenges preventing the use of standard medicinal chemistry and pharmacology technologies. Consequently the development of basic tools for probing TAAR and translating findings from model systems to humans has been problematic. Despite these challenges the last 5 years have seen considerable advances, in particular with respect to TAAR1, which appears to function as an endogenous rheostat, maintaining central neurotransmission within defined physiological limits, in part through receptor heterodimerization yielding biased signaling outputs...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28723063/using-cooperatively-folded-peptides-to-measure-interaction-energies-and-conformational-propensities
#3
Maziar S Ardejani, Evan T Powers, Jeffery W Kelly
The rates and equilibria of the folding of biopolymers are determined by the conformational preferences of the subunits that make up the sequence of the biopolymer and by the interactions that are formed in the folded state in aqueous solution. Because of the centrality of these processes to life, quantifying conformational propensities and interaction strengths is vitally important to understanding biology. In this Account, we describe our use of peptide model systems that fold cooperatively yet are small enough to be chemically synthesized to measure such quantities...
July 19, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28722310/capitalizing-on-scientific-advances-to-improve-access-to-and-quality-of-children-s-mental-health-care
#4
Ann F Garland, Florencia Lebensohn-Chialvo, Kristopher G Hall, Erika R N Cameron
The majority of mental health problems begin in childhood or adolescence. The potential benefits of early identification and treatment of such problems are well established, and models of effective mental health interventions for children have proliferated in recent decades. However, barriers in access to care and challenges in assuring delivery of high-quality care significantly limit the public health impact of services for children and families. Specifically, the majority of children who need mental health care do not receive it, and when children are in care, many do not receive interventions that are most likely to have the greatest positive impact...
July 19, 2017: Behavioral Sciences & the Law
https://www.readbyqxmd.com/read/28721949/rising-to-the-challenge-applying-biofabrication-approaches-for-better-drug-and-chemical-product-development
#5
Anthony M Holmes, Alex Charlton, Brian Derby, Lorna Ewart, Andrew Scott, Wenmiao Shu
Many industrial sectors, from pharmaceuticals to consumer products, are required to provide data on their products to demonstrate their efficacy and that they are safe for patients, consumers and the environment. This period of testing typically requires the use of animal models, the validity of which has been called into question due to the high rates of attrition across many industries. There is increasing recognition of the limitations of animal models and demands for safety and efficacy testing paradigms which embrace the latest technological advances and knowledge of human biology...
July 19, 2017: Biofabrication
https://www.readbyqxmd.com/read/28721857/stress-adaptation
#6
Alistair J P Brown, Leah E Cowen, Antonio di Pietro, Janet Quinn
Fungal species display an extraordinarily diverse range of lifestyles. Nevertheless, the survival of each species depends on its ability to sense and respond to changes in its natural environment. Environmental changes such as fluctuations in temperature, water balance or pH, or exposure to chemical insults such as reactive oxygen and nitrogen species exert stresses that perturb cellular homeostasis and cause molecular damage to the fungal cell. Consequently, fungi have evolved mechanisms to repair this damage, detoxify chemical insults, and restore cellular homeostasis...
July 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28721669/mimicking-parkinson-s-disease-in-a-dish-merits-and-pitfalls-of-the-most-commonly-used-dopaminergic-in-vitro-models
#7
REVIEW
Fernanda Martins Lopes, Ivi Juliana Bristot, Leonardo Lisbôa da Motta, Richard B Parsons, Fabio Klamt
Parkinson's disease (PD) is the second most common neurodegenerative disorder and has both unknown etiology and non-curative therapeutic options. Patients begin to present the classic motor symptoms of PD-tremor at rest, bradykinesia and rigidity-once 50-70% of the dopaminergic neurons of the nigrostriatal pathway have degenerated. As a consequence of this, it is difficult to investigate the early-stage events of disease pathogenesis. In vitro experimental models are used extensively in PD research because they present a controlled environment that enables the direct investigation of the early molecular mechanisms that are potentially involved with dopaminergic degeneration, as well as for the screening of potential therapeutic drugs...
July 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28720427/the-challenges-and-promise-of-targeting-the-liver-x-receptors-for-treatment-of-inflammatory-disease
#8
REVIEW
Michael B Fessler
The Liver X Receptors (LXRs) are oxysterol-activated transcription factors that upregulate a suite of genes that together promote coordinated mobilization of excess cholesterol from cells and from the body. The LXRs, like other nuclear receptors, are anti-inflammatory, inhibiting signal-dependent induction of pro-inflammatory genes by nuclear factor-κB, activating protein-1, and other transcription factors. Synthetic LXR agonists have been shown to ameliorate atherosclerosis and a wide range of inflammatory disorders in preclinical animal models...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28720318/immunogenicity-and-protective-efficacy-of-a-newly-developed-tri-component-diphtheria-tetanus-and-acellular-pertussis-vaccine-in-a-murine-model
#9
Dong Ho Huh, Seung Beom Han, Hye Jo Shin, Dong Ho Ahn, Gi Sub Choi, Kyu Ri Kang, Bo Ram Kim, Jin Han Kang
BACKGROUND/PURPOSE: Although assessing the immunogenicity and protective efficacy of acellular pertussis (aP) vaccines via murine model studies faces limitations, preliminary assessments have been achieved by evaluating respiratory challenge and humoral and cellular immunity. METHODS: We performed a long-term intranasal respiratory challenge with reference and clinically isolated strains of Bordetella pertussis. Simultaneously, we assessed humoral and cellular immunity for evaluating the immunogenicity of a newly developed tri-component diphtheria-tetanus-aP (DTaP) vaccine...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28719601/clic-a-tool-for-expanding-biological-pathways-based-on-co-expression-across-thousands-of-datasets
#10
Yang Li, Alexis A Jourdain, Sarah E Calvo, Jun S Liu, Vamsi K Mootha
In recent years, there has been a huge rise in the number of publicly available transcriptional profiling datasets. These massive compendia comprise billions of measurements and provide a special opportunity to predict the function of unstudied genes based on co-expression to well-studied pathways. Such analyses can be very challenging, however, since biological pathways are modular and may exhibit co-expression only in specific contexts. To overcome these challenges we introduce CLIC, CLustering by Inferred Co-expression...
July 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28718445/mouse-versus-human-neutrophils-in-cancer-a-major-knowledge-gap
#11
REVIEW
Evgeniy B Eruslanov, Sunil Singhal, Steven M Albelda
Many types of cancer recruit neutrophils that could have protumor or antitumor effects on tumor development. Numerous findings in murine models suggest a predominantly protumoral role for neutrophils in cancer development. However, there are fundamental differences between mouse and human tumors in the evolution of tumors, genetic diversity, immune response, and also in the intrinsic biology of neutrophils that might have a profound impact on tumor development and the function of these cells. A crucial difference is that the majority of mouse tumor models lack the prolonged initial phases of multistage tumor evolution present in humans when antitumoral mechanisms are activated...
February 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718049/good-things-in-small-packages-an-innovative-delivery-approach-for-inhaled-insulin
#12
James B Fink, Lisa Molloy, John S Patton, Valdecir Castor Galindo-Filho, Jacqueline de Melo Barcelar, Luciana Alcoforado, Simone Cristina Soares Brandão, Armèle Dornelas de Andrade
PURPOSE: The design development of a small, hand held, battery operated, breath actuated inhaler as a drug/device platform for inhaled insulin posed a number of technical challenges. Our goal was to optimize lung deposition and distribution with aerosol generators producing 3-6 μm particle size distribution. METHODS: In silico modeling with computational fluid dynamics (CFD) and in vitro testing of device components were assessed using an Alberta idealized adult airway (Copley, UK) to optimize mouthpiece and aerosol path design for dose delivered distal to the trachea...
July 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28717029/the-metabolite-transporter-peg344-is-required-for-the-full-virulence-of-the-hypervirulent-klebsiella-pneumoniae-strain-hvkp1-after-pulmonary-but-not-subcutaneous-challenge
#13
Jeffrey Bulger, Ulrike MacDonald, Ruth Olson, Janet Beanan, Thomas A Russo
Hypervirulent Klebsiella pneumoniae (hvKP) is an emerging pathotype that is capable of causing tissue-invasive, organ and life threatening infections in healthy individuals from the community. Knowledge on the virulence factors specific to hvKP is limited. In this report we describe a new factor (PEG344) that increases the virulence of the hvKP strain hvKP1. peg344 is present on the hvKP1 virulence plasmid, is broadly prevalent among hvKP strains, and has increased RNA abundance when grown in human ascites...
July 17, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28716961/the-structural-basis-of-large-scale-functional-connectivity-in-the-mouse
#14
Joanes Grandjean, Valerio Zerbi, Joshua Balsters, Nicole Wenderoth, Markus Rudina
Translational neuroimaging requires approaches and techniques that can bridge between multiple different species and disease states. One candidate method, which offers insights into the brain's functional connectivity (FC), is resting state fMRI (rs-fMRI). In both humans and non-human primates, patterns of functional connectivity (often referred to as the functional connectome) have been related to the underlying structural connectivity (structural connectome). Given the recent rise in pre-clinical neuroimaging of mouse models it is an important question whether the mouse functional connectome conforms to the underlying structural connectivity...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28716928/support-for-redistribution-is-shaped-by-compassion-envy-and-self-interest-but-not-a-taste-for-fairness
#15
Daniel Sznycer, Maria Florencia Lopez Seal, Aaron Sell, Julian Lim, Roni Porat, Shaul Shalvi, Eran Halperin, Leda Cosmides, John Tooby
Why do people support economic redistribution? Hypotheses include inequity aversion, a moral sense that inequality is intrinsically unfair, and cultural explanations such as exposure to and assimilation of culturally transmitted ideologies. However, humans have been interacting with worse-off and better-off individuals over evolutionary time, and our motivational systems may have been naturally selected to navigate the opportunities and challenges posed by such recurrent interactions. We hypothesize that modern redistribution is perceived as an ancestral scene involving three notional players: the needy other, the better-off other, and the actor herself...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716816/sphingosine-1-phosphate-receptor-1-promotes-environment-induced-and-acquired-chemoresistance
#16
Veronica Lifshitz, Saul J Priceman, Wenzhao Li, Gregory Cherryholmes, Heehyoung Lee, Adar Makovski-Silverstein, Lucia Borriello, Yves A DeClerck, Hua Yu
Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1) leading to their resistance to chemotherapy...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716627/membrane-proteins-structures-a-review-on-computational-modeling-tools
#17
REVIEW
Jose G Almeida, Antonio J Preto, Panagiotis I Koukos, Alexandre M J J Bonvin, Irina S Moreira
BACKGROUND: Membrane proteins (MPs) play diverse and important functions in living organisms. They constitute 20% to 30% of the known bacterial, archaean and eukaryotic organisms' genomes. In humans, their importance is emphasized as they represent 50% of all known drug targets. Nevertheless, experimental determination of their three-dimensional (3D) structure has proven to be both time consuming and rather expensive, which has led to the development of computational algorithms to complement the available experimental methods and provide valuable insights...
July 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28716582/a-probabilistic-poisson-based-model-accounts-for-an-extensive-set-of-absolute-auditory-threshold-measurements
#18
Peter Heil, Artur Matysiak, Heinrich Neubauer
Thresholds for detecting sounds in quiet decrease with increasing sound duration in every species studied. The neural mechanisms underlying this trade-off, often referred to as temporal integration, are not fully understood. Here, we probe the human auditory system with a large set of tone stimuli differing in duration, shape of the temporal amplitude envelope, duration of silent gaps between bursts, and frequency. Duration was varied by varying the plateau duration of plateau-burst (PB) stimuli, the duration of the onsets and offsets of onset-offset (OO) stimuli, and the number of identical bursts of multiple-burst (MB) stimuli...
June 27, 2017: Hearing Research
https://www.readbyqxmd.com/read/28716551/application-of-human-induced-pluripotent-stem-cells-to-model-fibrodysplasia-ossificans-progressiva
#19
Emilie Barruet, Edward C Hsiao
Fibrodysplasia ossificans progressiva (FOP) is a genetic condition characterized by massive heterotopic ossification. FOP patients with mutations in the Activin A type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. FOP is a progressive and debilitating disease characterized by bone formation flares that often occur after trauma. Since it is often difficult or impossible to obtain large amounts of tissue from human donors due to the risks of inciting more heterotopic bone formation, human induced pluripotent stem cells (hiPSCs) provide an attractive source for establishing in vitro disease models and for applications in drug screening...
July 14, 2017: Bone
https://www.readbyqxmd.com/read/28715976/astrovirus-biology-and-pathogenesis
#20
Valerie Cortez, Victoria A Meliopoulos, Erik A Karlsson, Virginia Hargest, Cydney Johnson, Stacey Schultz-Cherry
Astroviruses are nonenveloped, positive-sense single-stranded RNA viruses that cause gastrointestinal illness. Although a leading cause of pediatric diarrhea, human astroviruses are among the least characterized enteric RNA viruses. However, by using in vitro methods and animal models to characterize virus-host interactions, researchers have discovered several important properties of astroviruses, including the ability of astrovirus capsid to act as an enterotoxin, disrupting the gut epithelial barrier. Improved animal models are needed to study this phenomenon, along with the pathogenesis of astroviruses, particularly in those strains that can cause extraintestinal disease...
July 17, 2017: Annual Review of Virology
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