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https://www.readbyqxmd.com/read/29151218/structures-of-dynamic-protein-complexes-hybrid-techniques-to-study-map-kinase-complexes-and-the-escrt-system
#1
Wolfgang Peti, Rebecca Page, Evzen Boura, Bartosz Różycki
The integration of complementary molecular methods (including X-ray crystallography, NMR spectroscopy, small angle X-ray/neutron scattering, and computational techniques) is frequently required to obtain a comprehensive understanding of dynamic macromolecular complexes. In particular, these techniques are critical for studying intrinsically disordered protein regions (IDRs) or intrinsically disordered proteins (IDPs) that are part of large protein:protein complexes. Here, we explain how to prepare IDP samples suitable for study using NMR spectroscopy, and describe a novel SAXS modeling method (ensemble refinement of SAXS; EROS) that integrates the results from complementary methods, including crystal structures and NMR chemical shift perturbations, among others, to accurately model SAXS data and describe ensemble structures of dynamic macromolecular complexes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29151163/strengthening-the-healthy-start-workforce-a-mixed-methods-study-to-understand-the-roles-of-community-health-workers-in-healthy-start-and-inform-the-development-of-a-standardized-training-program
#2
Katherine Rachel DeAngelis, Katelyn Flaherty Doré, Deborah Dean, Paul Osterman
Introduction Healthy Start (HS) is dedicated to preventing infant mortality, improving birth outcomes, and reducing disparities in maternal and infant health. In 2014, the HS program was reenvisioned and standardization of services and workforce development were prioritized. This study examined how HS community health workers (CHW), as critical members of the workforce, serve families and communities in order to inform the development of a CHW training program to advance program goals. Methods In 2015, an online organizational survey of all 100 HS programs was conducted...
November 18, 2017: Maternal and Child Health Journal
https://www.readbyqxmd.com/read/29151002/management-of-arrhythmia-in-sepsis-and-septic-shock
#3
Martin Balik, Vojtech Matousek, Michal Maly, Tomas Brozek
The occurrence of supraventricular arrhythmias is associated with an unfavourable prognosis in septic shock. Available trials are difficult to apply in sepsis and septic shock patients due to included cohorts, control groups and because "one size does not fit all". The priorities in the critically ill are maintenance of a sinus rhythm and diastolic ventricular filling. The rate control modality should be reserved for chronic AF and in situations when a sinus rhythm is difficult to maintain due to extreme stress conditions resulting from a high dosage of vasoactive agents...
November 18, 2017: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/29150999/focus-on-focus-lack-of-coherence-between-systemic-and-microvascular-indices-of-edema-formation
#4
Birkitt Ten Tusscher, Corien Gudden, Suus van Vliet, Bob Smit, Can Ince, E Christiaan Boerma, Harm-Jan S de Grooth, Paul W G Elbers
BACKGROUND: Fluid therapy remains a cornerstone of therapy in shock states. However, fluid overloading ultimately results in edema formation which is related to excess morbidity and mortality. Handheld microscopes are now frequently used to study the sublingual microcirculation. As a corollary, these devices measure focal distance, or surface to capillary distance. Physiologically, this could represent a microvascular index of edema formation and could have the potential to guide fluid therapy...
November 18, 2017: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/29150976/salt-bridge-interactions-within-the-%C3%AE-2-integrin-%C3%AE-7-helix-mediate-force-induced-binding-and-shear-resistance-ability
#5
Xiao Zhang, Linda Li, Ning Li, Xinyu Shu, Lüwen Zhou, Shouqin Lü, Shenbao Chen, Debin Mao, Mian Long
The functional performance of αI domain α7 helix in β2 integrin activation depends on the allostery of the α7 helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the α7 helix. Molecular Dynamics (MD) simulations for three β2 integrin members of LFA-1 (αL β2 ), Mac-1 (αM β2 ) and αx β2 indicated that the magnitude of the salt bridge interaction is related to the stability of the αI domain and the strength of the corresponding force-induced allostery...
November 18, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29150961/modulation-of-igg1-immunoeffector-function-by-glycoengineering-of-the-gdp-fucose-biosynthesis-pathway
#6
Ronan M Kelly, Ronald L Kowle, Zhirui Lian, Beth A Strifler, Derrick R Witcher, Bhavin S Parekh, Tongtong Wang, Christopher C Frye
Cross-linking of the Fcγ receptors expressed on the surface of hematopoietic cells by IgG immune complexes triggers the activation of key immune effector mechanisms, including antibody-dependent cell mediated cytotoxicity (ADCC). A conserved N-glycan positioned at the N-terminal region of the IgG CH 2 domain is critical in maintaining the quaternary structure of the molecule for Fcγ receptor engagement. The removal of a single core fucose residue from the N-glycan results in a considerable increase in affinity for FcγRIIIa leading to an enhanced receptor-mediated immunoeffector function...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150954/physiological-role-of-urothelial-cancer-associated-1-long-noncoding-rna-in-human-skeletogenic-cell-differentiation
#7
Takanori Ishikawa, Takashi Nishida, Mitsuaki Ono, Takeshi Takarada, Nguyen Ha, Shinnosuke Kurihara, Takayuki Furumatsu, Yurika Murase, Masaharu Takigawa, Toshitaka Oohashi, Hiroshi Kamioka, Satoshi Kubota
A vast number of long-noncoding RNAs (lncRNA) are found expressed in human cells, which RNAs have been developed along with human evolution. However, the physiological functions of these lncRNAs remain mostly unknown. In the present study, we for the first time uncovered the fact that one of such lncRNAs plays a significant role in the differentiation of chondrocytes and, possibly, of osteoblasts differentiated from mesenchymal stem cells, which cells eventually construct the human skeleton. The urothelial cancer-associated 1 (UCA1) lncRNA is known to be associated with several human malignancies...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150946/lncrna-tcons_00034812-in-cell-proliferation-and-apoptosis-of-pulmonary-artery-smooth-muscle-cells-and-its-mechanism
#8
Yun Liu, Zengxian Sun, Jinquan Zhu, Bingxin Xiao, Jie Dong, Xiaomin Li
Long noncoding RNAs (lncRNAs) have been discovered to be playing important role in various biological processes. However, the contribution of lncRNAs to pulmonary artery hypertension (PAH) remains largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Here, we investigated the biological role of lncRNAs in PAH. Differences in the lncRNAs and mRNAs between hypoxia PAH rats and normoxia rats were screened using microarray analysis...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150944/toll-like-receptor-signaling-pathway-as-a-potential-therapeutic-target-in-colorectal-cancer
#9
REVIEW
Reyhaneh Moradi-Marjaneh, Seyed Mahdi Hassanian, Hamid Fiuji, Saman Soleimanpour, Gordon A Ferns, Amir Avan, Majid Khazaei
Toll like receptor (TLR) signaling is involved in activating innate and adaptive immune responses and plays a critical role in inflammation-induced diseases such as colorectal cancer (CRC). Dysregulation of this signaling pathway can result in disturbance of epithelial layer hemostasis, chronic inflammatory, excessive repair responses and development of CRC. There is now substantial evidence for the benefit of targeting of this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150876/toxicological-characterization-of-zno-nanoparticles-in-malignant-and-non-malignant-cells
#10
Helena Moratin, Agmal Scherzad, Thomas Gehrke, Pascal Ickrath, Katrin Radeloff, Norbert Kleinsasser, Stephan Hackenberg
The increasing usage of zinc oxide nanoparticles (ZnO-NPs) in industrial applications as well as in consumer products raises concern regarding their potential adverse effects to a greater extend. Numerous studies have demonstrated toxic properties of NPs, however there is still a lack of knowledge concerning the underlying mechanisms. This study was designed to systematically investigate cytotoxicity, apoptosis, cell cycle alterations, and genotoxicity induced by ZnO-NP. Moreover, it was an aim of the investigations to specify the diverse effects of nanoparticle exposure in malignant in comparison with non-malignant cells...
November 18, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29150872/predicting-the-onset-of-freezing-of-gait-a-longitudinal-study
#11
Kaylena A Ehgoetz Martens, Emily L Lukasik, Matthew J Georgiades, Moran Gilat, Julie M Hall, Courtney C Walton, Simon J G Lewis
BACKGROUND: Freezing of gait is a disabling symptom of Parkinson's disease that ultimately affects approximately 80% of patients, yet very little research has focused on predicting the onset of freezing of gait and tracking the longitudinal progression of symptoms prior to its onset. The objective of the current study was to examine longitudinal data spanning the transition period when patients with PD developed freezing of gait to identify symptoms that may precede freezing and create a prediction model that identifies those "at risk" for developing freezing of gait in the year to follow...
November 18, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29150847/chronic-sun-exposure-is-associated-with-distinct-histone-acetylation-changes-in-human-skin
#12
S Ding, J Chen, Q Zeng, J Lu, L Tan, A Guo, J Kang, S Yang, Y Xiang, C Zuo, J Huang
BACKGROUND: Photoaging is attributed to continuous sunlight or artificial UV exposure and manifests the clinical and histological changes of skin. Epigenetic changes have been found to be involved in the pathogenesis of photoaging. However, the underlying mechanisms are unclear. OBJECTIVES: To analyse histone modification patterns in sun-exposed and non-exposed skins, and identify the abnormally histone modified-genes related to photoaging. METHODS: Skin biopsies were collected both from the outer forearm (sun-exposed area) and the buttock (sun-protected area) in 20 healthy middle-aged female volunteers...
November 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29150838/gi-530159-a-novel-selective-mechano-sensitive-k2p-channel-opener-reduces-rat-dorsal-root-ganglion-drg-neuron-excitability
#13
Alexandre J C Loucif, Pierre-Philippe Saintot, Jia Liu, Brett M Antonio, Shannon G Zellmer, Katrina Yoger, Emma L Veale, Anna Wilbrey, Kiyoyuki Omoto, Lishuang Cao, Alex Gutteridge, Neil A Castle, Edward B Stevens, Alistair Mathie
BACKGROUND AND PURPOSE: TREK two pore domain potassium channels play a critical role in regulating the excitability of somatosensory nociceptive neurons and are important mediators of pain perception. An understanding of the roles of TREK channels in pain perception and, indeed, in other pathophysiological conditions, has been severely hampered by the lack of potent and/or selective activators and inhibitors. In this study we describe a new, selective opener of TREK channels, GI-530159 (4,4'-(Hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline)...
November 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29150676/severe-pollution-in-china-amplified-by-atmospheric-moisture
#14
Xuexi Tie, Ru-Jin Huang, Junji Cao, Qiang Zhang, Yafang Cheng, Hang Su, Di Chang, Ulrich Pöschl, Thorsten Hoffmann, Uli Dusek, Guohui Li, Douglas R Worsnop, Colin D O'Dowd
In recent years, severe haze events often occurred in China, causing serious environmental problems. The mechanisms responsible for the haze formation, however, are still not well understood, hindering the forecast and mitigation of haze pollution. Our study of the 2012-13 winter haze events in Beijing shows that atmospheric water vapour plays a critical role in enhancing the heavy haze events. Under weak solar radiation and stagnant moist meteorological conditions in winter, air pollutants and water vapour accumulate in a shallow planetary boundary layer (PBL)...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150632/mucoadhesive-functionality-of-cell-wall-structures-from-fruits-and-grains-electrostatic-and-polymer-network-interactions-mediated-by-soluble-dietary-polysaccharides
#15
Oliver W Meldrum, Gleb E Yakubov, Ghanendra Gartaula, Michael A McGuckin, Michael J Gidley
We demonstrate the enhancement of intestinal mucin (Muc2) binding to plant cell wall structures from fruit (parenchymal apple tissue) and grain (wheat endosperm) mediated by soluble dietary fibers embedded within cellulose networks. Mucin binding occurs through two distinct mechanisms; for pectin polysaccharides characteristic of fruits and vegetables, it is governed by molecular mucoadhesive interactions, while for neutral polysaccharides, arabinoxylan and β-glucan characteristic of cereal grains, the interaction stems from the properties of their polymer network...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150628/artificial-topography-changes-the-growth-strategy-of-spartina-alterniflora-case-study-with-wave-exposure-as-a-comparison
#16
Hualong Hong, Minyue Dai, Haoliang Lu, Jingchun Liu, Jie Zhang, Chaoqi Chen, Kang Xia, Chongling Yan
This paper reports findings about the growth of Spartina alterniflora (Loisel.) near an engineered coastal protection defences to discover the potential influences on vegetation growth from the artificial topography. Impacts of the artificial topography on the sediment element composition were detected by comparing the fixed effects caused by artificial topography and wave exposure using linear mixed models. Surficial sediments under the impacts of artificial topography contain elevated levels of biogenic elements and heavy metals, including C (and organic carbon), N, S, Al, Fe, Mn, Cu, Zn, As, Cd, Cr, Ni, and Pb...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150622/evidence-of-quantum-phase-transition-in-real-space-vacuum-entanglement-of-higher-derivative-scalar-quantum-field-theories
#17
S Santhosh Kumar, S Shankaranarayanan
In a bipartite set-up, the vacuum state of a free Bosonic scalar field is entangled in real space and satisfies the area-law- entanglement entropy scales linearly with area of the boundary between the two partitions. In this work, we show that the area law is violated in two spatial dimensional model Hamiltonian having dynamical critical exponent z = 3. The model physically corresponds to next-to-next-to-next nearest neighbour coupling terms on a lattice. The result reported here is the first of its kind of violation of area law in Bosonic systems in higher dimensions and signals the evidence of a quantum phase transition...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150601/decoding-critical-long-non-coding-rna-in-ovarian-cancer-epithelial-to-mesenchymal-transition
#18
Ramkrishna Mitra, Xi Chen, Evan J Greenawalt, Ujjwal Maulik, Wei Jiang, Zhongming Zhao, Christine M Eischen
Long non-coding RNA (lncRNA) are emerging as contributors to malignancies. Little is understood about the contribution of lncRNA to epithelial-to-mesenchymal transition (EMT), which correlates with metastasis. Ovarian cancer is usually diagnosed after metastasis. Here we report an integrated analysis of >700 ovarian cancer molecular profiles, including genomic data sets, from four patient cohorts identifying lncRNA DNM3OS, MEG3, and MIAT overexpression and their reproducible gene regulation in ovarian cancer EMT...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150590/subtype-specific-effects-of-dopaminergic-d2-receptor-activation-on-synaptic-trains-in-layer-v-pyramidal-neurons-in-the-mouse-prefrontal-cortex
#19
Jonna M Leyrer-Jackson, Mark P Thomas
In humans, prefrontal cortical areas are known to support executive functions. In mice, these functions are mediated by homologous regions in the medial prefrontal cortex (mPFC). Executive processes are critically dependent on optimal levels of dopamine (DA), but the cellular mechanisms of DA modulation are incompletely understood. Stable patterns of neuronal activity may be sensitive to frequency-dependent changes in synaptic transmission. We characterized the effects of D2 receptor (D2R) activation on short-term excitatory postsynaptic potential (EPSP) dynamics evoked at varying frequencies in the two subtypes of layer V pyramidal neurons in mouse mPFC We isolated NMDA receptor and non-NMDA receptor-mediated components of EPSP trains evoked by stimulating fibers within layer V or layer I...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29150487/dynamin-inhibitors-block-mtorc1-activation-by-amino-acids-independently-of-dynamin
#20
Persaud Avinash, Cormerais Yann, Pouyssegur Jacques, Rotin Daniela
mTORC1 plays a critical role in protein synthesis and cell proliferation and growth. It is activated by growth factors and amino acids, including essential amino acid (EAA), such as Leu; Leu enters cells via the Leu transporter LAT1-4F2hc and potentially via endocytosis. Here we investigated the contribution of the different routes of Leu entry into cells to mTORC1 activation using pharmacological inhibitors and cells that lack LAT1 or dynamin1/2/3. Our results show that LAT1 is the major route of Leu entry into cells and mTORC1 activation (∼70%), while dynamin-dependent endocytosis and macropinocytosis contribute minimally to both (5-15%)...
November 17, 2017: Journal of Cell Science
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