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https://www.readbyqxmd.com/read/27927007/ginsenoside-re-inhibits-osteoclast-differentiation-in-mouse-bone-marrow-derived-macrophages-and-zebrafish-scale-model
#1
Chan-Mi Park, Hye-Min Kim, Dong Hyun Kim, Ho-Jin Han, Haneul Noh, Jae-Hyuk Jang, Soo-Hyun Park, Han-Jung Chae, Soo-Wan Chae, Eun Kyoung Ryu, Sangku Lee, Kangdong Liu, Haidan Liu, Jong-Seog Ahn, Young Ock Kim, Bo-Yeon Kim, Nak-Kyun Soung
Ginsenosides, which are the active materials of ginseng, have biological functions that include anti-osteoporotic effects. Aqueous ginseng extract inhibits osteoclast differentiation induced by receptor activator of NF-kappaB ligand (RANKL). Aqueous ginseng extract produces chromatography peaks characteristic of ginsenosides. Among these peaks, ginsenoside Re is a major component. However, the preventive effects of ginsenoside Re against osteoclast differentiation are not known. We studied the effect of ginsenoside Re on osteoclast differentiation, RANKL induced tartrate-resistant acid phosphatase (TRAP) activity, and formation of multinucleated osteoclasts in vitro...
December 6, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27926996/small-molecule-modulator-of-sigma-2-receptor-is-neuroprotective-and-reduces-cognitive-deficits-and-neuro-inflammation-in-experimental-models-of-alzheimer-s-disease
#2
Bitna Yi, James J Sahn, Pooneh Memar Ardestani, Andrew K Evans, Luisa Scott, Jessica Z Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan Pierce-Shimomura, Stephen F Martin, Mehrdad Shamloo
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R binding ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease (AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca(2+) levels in human SK-N-SH neuroblastoma cells. The Sig2R antagonists SAS-0132 and JVW-1009 are neuroprotective in a C...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926944/targeting-neutrophils-to-prevent-malaria-associated-acute-lung-injury-acute-respiratory-distress-syndrome-in-mice
#3
Michelle K Sercundes, Luana S Ortolan, Daniela Debone, Paulo V Soeiro-Pereira, Eliane Gomes, Elizabeth H Aitken, Antonio Condino Neto, Momtchilo Russo, Maria R D' Império Lima, José M Alvarez, Silvia Portugal, Claudio R F Marinho, Sabrina Epiphanio
Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926943/the-mouse-cytomegalovirus-gene-m42-targets-surface-expression-of-the-protein-tyrosine-phosphatase-cd45-in-infected-macrophages
#4
Nadine Thiel, Kirsten A Keyser, Niels A W Lemmermann, Jennifer D Oduro, Karen Wagner, Carina Elsner, Anne Halenius, Tihana Lenac Roviš, Melanie M Brinkmann, Stipan Jonjić, Luka Cicin-Sain, Martin Messerle
The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926940/inflammasome-independent-nlrp3-restriction-of-a-protective-early-neutrophil-response-to-pulmonary-tularemia
#5
Sivakumar Periasamy, Hongnga T Le, Ellen B Duffy, Heather Chin, Jonathan A Harton
Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft challenge, more mature myeloid cells are elicited and are protective. In addition, inflammasome-dependent IL-1β and IL-18 are important for protection. As Nlrp3 appears dispensable for resistance to infection with Francisella novicida, we considered its role during infection with the virulent Type A strain SchuS4 and the attenuated Type B live vaccine strain LVS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926936/scaling-properties-of-dimensionality-reduction-for-neural-populations-and-network-models
#6
Ryan C Williamson, Benjamin R Cowley, Ashok Litwin-Kumar, Brent Doiron, Adam Kohn, Matthew A Smith, Byron M Yu
Recent studies have applied dimensionality reduction methods to understand how the multi-dimensional structure of neural population activity gives rise to brain function. It is unclear, however, how the results obtained from dimensionality reduction generalize to recordings with larger numbers of neurons and trials or how these results relate to the underlying network structure. We address these questions by applying factor analysis to recordings in the visual cortex of non-human primates and to spiking network models that self-generate irregular activity through a balance of excitation and inhibition...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27926891/type-2-diabetes-the-pathologic-basis-of-reversible-%C3%AE-cell-dysfunction
#7
REVIEW
Michael G White, James A M Shaw, Roy Taylor
The reversible nature of early type 2 diabetes has been demonstrated in in vivo human studies. Recent in vivo and in vitro studies of β-cell biology have established that the β-cell loses differentiated characteristics, including glucose-mediated insulin secretion, under metabolic stress. Critically, the β-cell dedifferentiation produced by long-term excess nutrient supply is reversible. Weight loss in humans permits restoration of first-phase insulin secretion associated with the return to normal of the elevated intrapancreatic triglyceride content...
November 2016: Diabetes Care
https://www.readbyqxmd.com/read/27926880/luminal-iron-levels-govern-intestinal-tumorigenesis-after-apc-loss-in%C3%A2-vivo
#8
Sorina Radulescu, Matthew J Brookes, Pedro Salgueiro, Rachel A Ridgway, Ewan McGhee, Kurt Anderson, Samuel J Ford, Daniel H Stones, Tariq H Iqbal, Chris Tselepis, Owen J Sansom
No abstract text is available yet for this article.
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926871/in%C3%A2-vivo-visualization-of-cardiomyocyte-apicobasal-polarity-reveals-epithelial-to-mesenchymal-like-transition-during-cardiac-trabeculation
#9
Vanesa Jiménez-Amilburu, S Javad Rasouli, David W Staudt, Hiroyuki Nakajima, Ayano Chiba, Naoki Mochizuki, Didier Y R Stainier
Despite great strides in understanding cardiac trabeculation, many mechanistic aspects remain unclear. To elucidate how cardiomyocyte shape changes are regulated during this process, we engineered transgenes to label their apical and basolateral membranes. Using these tools, we observed that compact-layer cardiomyocytes are clearly polarized while delaminating cardiomyocytes have lost their polarity. The apical transgene also enabled the imaging of cardiomyocyte apical constriction in real time. Furthermore, we found that Neuregulin signaling and blood flow/cardiac contractility are required for cardiomyocyte apical constriction and depolarization...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926869/robust-asymmetric-localization-of-planar-polarity-proteins-is-associated-with-organization-into-signalosome-like-domains-of-variable-stoichiometry
#10
Helen Strutt, Jessica Gamage, David Strutt
In developing epithelia, the core planar polarity proteins physically interact with each other and localize asymmetrically at opposite cell ends, forming intercellular complexes that link the polarity of neighboring cells. Using quantitative imaging to examine the composition of the core protein complex in vivo, we find that complex composition is unexpectedly plastic. The transmembrane proteins Frizzled and Flamingo form a stoichiometric nucleus in the complex, while the relative levels of the other four core proteins can vary independently...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926868/cmyc-regulates-the-size-of-the-premigratory-neural-crest-stem-cell-pool
#11
Laura Kerosuo, Marianne E Bronner
The neural crest is a transient embryonic population that originates within the central nervous system (CNS) and then migrates into the periphery and differentiates into multiple cell types. The mechanisms that govern neural crest stem-like characteristics and self-renewal ability are poorly understood. Here, we show that the proto-oncogene cMyc is a critical factor in the chick dorsal neural tube, where it regulates the size of the premigratory neural crest stem cell pool. Loss of cMyc dramatically decreases the number of emigrating neural crest cells due to reduced self-renewal capacity, increased cell death, and shorter duration of the emigration process...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926864/low-cd38-identifies-progenitor-like-inflammation-associated-luminal-cells-that-can-initiate-human-prostate-cancer-and-predict-poor-outcome
#12
Xian Liu, Tristan R Grogan, Haley Hieronymus, Takao Hashimoto, Jack Mottahedeh, Donghui Cheng, Lijun Zhang, Kevin Huang, Tanya Stoyanova, Jung Wook Park, Ruzanna O Shkhyan, Behdokht Nowroozizadeh, Matthew B Rettig, Charles L Sawyers, David Elashoff, Steve Horvath, Jiaoti Huang, Owen N Witte, Andrew S Goldstein
Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38(lo) luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38(lo) luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926856/insulin-dependent-activation-of-mch-neurons-impairs-locomotor-activity-and-insulin-sensitivity-in-obesity
#13
A Christine Hausen, Johan Ruud, Hong Jiang, Simon Hess, Hristo Varbanov, Peter Kloppenburg, Jens C Brüning
Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926851/energy-output-from-a-single-outer-hair-cell
#14
Kuni H Iwasa
Electromotility of outer hair cells (OHCs) has been extensively studied with in vitro experiments because of its physiological significance to the cochlear amplifier, which provides the exquisite sensitivity and frequency selectivity of the mammalian ear. However, these studies have been performed largely under load-free conditions or with static load, while these cells function in vivo in a dynamic environment, receiving electrical energy to enhance mechanical oscillation in the inner ear. This gap leaves uncertainties in addressing a key issue, how much mechanical energy an OHC provides...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926845/membrane-bound-alpha-synuclein-clusters-induce-impaired-lipid-diffusion-and-increased-lipid-packing
#15
Aditya Iyer, Nathalie Schilderink, Mireille M A E Claessens, Vinod Subramaniam
The aggregation of membrane-bound α-synuclein (αS) into oligomers and/or amyloid fibrils has been suggested to cause membrane damage in in vitro model phospholipid membrane systems and in vivo. In this study, we investigate how αS interactions that precede the formation of well-defined aggregates influence physical membrane properties. Using three truncated variants of αS with different aggregation propensities and comparable phospholipid membrane binding affinities we show, using fluorescence recovery after photobleaching (FRAP) and fluorescence anisotropy measurements, that formation of αS clusters on supported lipid bilayers (SLBs) impairs lateral lipid diffusion and increases lipid packing beneath the αS clusters...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926843/membrane-anchoring-and-ion-entry-dynamics-in-p-type-atpase-copper-transport
#16
Christina Grønberg, Oleg Sitsel, Erik Lindahl, Pontus Gourdon, Magnus Andersson
Cu(+)-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu(+)-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu(+) entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu(+) delivery...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926839/circular-dichroism-spectroscopy-of-collagen-fibrillogenesis-a-new-use-for-an-old-technique
#17
Kathryn E Drzewiecki, Daniel R Grisham, Avanish S Parmar, Vikas Nanda, David I Shreiber
Type-I collagen assembles in a stepwise, hierarchic fashion from the folding of the triple helix to the assembly of fibrils into fibers. The mature assembled fibers are crucial for tissue structure and mechanics, cell interactions, and other functions in vivo. Although triple helix folding can be followed with the use of optical methods such as circular dichroism (CD) spectroscopy, fibrillogenesis is typically measured by alternative methods such as turbidity, rheology, and microscopy. Together, these approaches allow for investigation of the mechanical properties and architectures of collagen-based scaffolds and excised tissues...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926753/in-vivo-observation-of-lens-regeneration-in-rat-using-ultra-long-scan-depth-optical-coherence-tomography
#18
Kai-Jing Zhou, Yi-Ni Li, Fu-Rong Huang, Qin-Mei Wang, A-Yong Yu
Purpose: To evaluate morphologic changes of lens regeneration in rats in vivo after extracapsular lens extraction (ECLE) by ultra-long scan depth optical coherence tomography (UL-OCT). Methods: A total of 42 Sprague-Dawley rats were used in this study. We performed ECLE on the right eyes of animals in the surgery group (n = 34). Biomicroscopy and UL-OCT scans were carried out for the surgery group immediately (within 1 hour postoperatively) and at days 1 and 3, weeks 1 and 2, and months 1, 2, and 3 postoperatively...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27926752/corneal-resistance-to-keratolysis-after-collagen-crosslinking-with-rose-bengal-and-green-light
#19
Ali Fadlallah, Hong Zhu, Samer Arafat, Irene Kochevar, Samir Melki, Joseph B Ciolino
Purpose: The purpose of this study was to evaluate the resistance to degradation by collagenase A of corneas that have been crosslinked with Rose Bengal and green light (RGX). Methods: The ex vivo crosslinking procedure was performed on enucleated rabbit corneas. Corneas were deepithelialized after applying 30% alcohol. Corneas were stained with Rose Bengal (RB, 0.1%) for 2 minutes and then exposed to green light (532 nm) at 0.25 W/cm2 for times to deliver doses of 50, 100, 150, or 200 J/cm2 (n = 5 per group)...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27926730/integrin-yap-taz-jnk-cascade-mediates-atheroprotective-effect-of-unidirectional-shear-flow
#20
Li Wang, Jiang-Yun Luo, Bochuan Li, Xiao Yu Tian, Li-Jing Chen, Yuhong Huang, Jian Liu, Dan Deng, Chi Wai Lau, Song Wan, Ding Ai, King-Lun Kingston Mak, Ka Kui Tong, Kin Ming Kwan, Nanping Wang, Jeng-Jiann Chiu, Yi Zhu, Yu Huang
The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), effectors of the Hippo pathway, have been identified as mediators for mechanical stimuli. However, the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow, and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis...
December 7, 2016: Nature
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