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https://www.readbyqxmd.com/read/28231307/differential-regulation-of-c5a-receptor-1-in-innate-immune-cells-during-the-allergic-asthma-effector-phase
#1
Fanny Ender, Anna V Wiese, Inken Schmudde, Jing Sun, Tillman Vollbrandt, Peter König, Yves Laumonnier, Jörg Köhl
C5a drives airway constriction and inflammation during the effector phase of allergic asthma, mainly through the activation of C5a receptor 1 (C5aR1). Yet, C5aR1 expression on myeloid and lymphoid cells during the allergic effector phase is ill-defined. Recently, we generated and characterized a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we used this reporter strain to monitor C5aR1 expression in airway, pulmonary and lymph node cells during the effector phase of OVA-driven allergic asthma...
2017: PloS One
https://www.readbyqxmd.com/read/28230313/crosstalk-between-smad2-3-and-specific-isoforms-of-erk-in-tgf-%C3%AE-1-induced-timp-3-expression-in-rat-chondrocytes
#2
Yanhui Zhu, Jianhua Gu, Tong Zhu, Chen Jin, Xiaopeng Hu, Xiang Wang
This study investigated the roles of ERK1 and ERK2 in transforming growth factor-β1 (TGF-β1)-induced tissue inhibitor of metalloproteinases-3 (TIMP-3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF-β1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF-β1...
February 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28230247/digest-less-than-the-sum-of-its-parts-negative-epistasis-in-bacterial-swarming
#3
Sonia Singhal, Katrina van Raay
Understanding how mutations change phenotypes is vital to evolutionary biology. However, predicting evolutionary outcomes is complicated by the fact that a mutation's effect may depend on the individual's genetic background. Epistasis occurs when interactions among different genes or mutations result in phenotypes that differ from the sum of their parts. Uncovering epistasis usually involves genetic engineering of point mutations and then comparing the phenotypic effect of each mutation individually against its effect in combination with others (e...
February 23, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28230213/knock-in-human-fgfr3-achondroplasia-mutation-as-a-mouse-model-for-human-skeletal-dysplasia
#4
Yi-Ching Lee, I-Wen Song, Ya-Ju Pai, Sheng-De Chen, Yuan-Tsong Chen
Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3(G380R) (FGFR3(ACH)) cDNA, the most common mutation in human ACH...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229933/nuclear-lamins-and-progerin-are-dispensable-for-antioxidant-nrf2-response-to-arsenic-and-cadmium
#5
Kazunori Hashimoto, Rima Majumdar, Yoshiaki Tsuji
Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Here we examined whether nuclear lamins are important for a cellular antioxidant mechanism, and whether progerin compromises it. We investigated the activation of nuclear factor-E2-related factor 2 (Nrf2) which regulates various antioxidant genes including heme oxygenase-1 (HMOX1), following exposure to sodium arsenite or cadmium chloride in lamin knockdown human cell lines and primary HGPS human fibroblasts...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28229450/endogenous-nitric-oxide-formation-in-cardiac-myocytes-does-not-control-respiration-during-%C3%AE-adrenergic-stimulation
#6
Michael Kohlhaas, Alexander G Nickel, Stefanie Bergem, Barbara Casadei, Ulrich Laufs, Christoph Maack
Endothelial nitric oxide (NO) controls cardiac oxygen (O2 ) consumption in a paracrine way by slowing respiration at the mitochondrial electron transport chain. While NO synthases (NOS) are also expressed in cardiac myocytes, it is unclear whether they control respiration in an intracrine way. Furthermore, the existence of a mitochondrial NOS is controversial. Here, by combining fluorescence imaging with electrical field stimulation, the patch-clamp method and knock-out technology, we determined the sources and consequences of intracellular NO formation during workload transitions in isolated murine and guinea pig cardiac myocytes and mitochondria...
February 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28228763/cardiolipin-supports-respiratory-enzymes-in-plants-in-different-ways
#7
Jakob Petereit, Kenta Katayama, Christin Lorenz, Linda Ewert, Peter Schertl, Andreas Kitsche, Hajime Wada, Margrit Frentzen, Hans-Peter Braun, Holger Eubel
In eukaryotes the presence of the dimeric phospholipid cardiolipin (CL) is limited to the mitochondrial membranes. It resides predominantly in the inner membrane where it interacts with components of the mitochondrial electron transfer chain. CL deficiency has previously been shown to affect abundances of the plant NADH-dehydrogenase complex and its association with dimeric cyctochrome c reductase. Using an Arabidopsis thaliana knock-out mutant for the final enzyme of CL biosynthesis we here extend current knowledge on the dependence of plant respiration on CL...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28228588/investigation-of-the-role-of-protein-kinase-d-in-human-rhinovirus-replication
#8
Anabel Guedán, Dawid Swieboda, Mark Charles, Marie Toussaint, Sebastian L Johnston, Amin Asfor, Anusha Panjwani, Tobias J Tuthill, Henry Danahay, Tony Raynham, Aurelie Mousnier, Roberto Solari
Picornavirus replication is known to cause extensive remodelling of Golgi and endoplasmic reticulum membranes and a number of the host proteins involved in the viral replication complex have been identified, including oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP and PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi vesicular and lipid transport, we hypothesised that PKD played a role in viral replication...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28228480/a-stable-but-reversible-integrated-surrogate-reporter-for-assaying-crispr-cas9-stimulated-homology-directed-repair
#9
Yahong Wen, Grace Liao, Thomas Pritchard, Ting-Ting Zhao, Jon P Connelly, Shondra M Pruett-Miller, Valerie Blanc, Nicholas O Davidson, Blair B Madison
The discovery and application of CRISPR/Cas9 technology for genome editing has greatly accelerated targeted mutagenesis in a variety of organisms. CRISPR/Cas9-mediated site-specific cleavage is typically exploited for the generation of insertions or deletions (indels) following aberrant dsDNA repair via the endogenous non-homology end-joining (NHEJ) pathway, or alternatively, for enhancing homology directed repair (HDR) to facilitate the generation of a specific mutation (or knock-in). However, there is a need for efficient cellular assays that can measure Cas9/guide RNA (gRNA) activity...
February 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28228125/rna-seq-of-life-stages-of-the-oomycete-phytophthora-infestans-reveals-dynamic-changes-in-metabolic-signal-transduction-and-pathogenesis-genes-and-a-major-role-for-calcium-signaling-in-development
#10
Audrey M V Ah-Fong, Kyoung Su Kim, Howard S Judelson
BACKGROUND: The oomycete Phytophthora infestans causes the devastating late blight diseases of potato and tomato. P. infestans uses spores for dissemination and infection, like many other filamentous eukaryotic plant pathogens. The expression of a subset of its genes during spore formation and germination were studied previously, but comprehensive genome-wide data have not been available. RESULTS: RNA-seq was used to profile hyphae, sporangia, sporangia undergoing zoosporogenesis, motile zoospores, and germinated cysts of P...
February 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28225294/role-of-rock-isoforms-in-regulation-of-stiffness-induced-myofibroblast-differentiation-in-lung-fibrosis
#11
Su S Htwe, Byung H Cha, Kan Yue, Ali Khademhosseini, Alan J Knox, Amir M Ghaemmaghami
Fibrosis is a major cause of progressive organ dysfunction in several chronic pulmonary diseases. Rho associated coiled-coil forming kinase (ROCK) has shown to be involved in myofibroblast differentiation driven by altered matrix stiffness in fibrotic state. There are two known ROCK isoforms in human, ROCK1 (ROKβ) and ROCK2 (ROKα), but specific role of each isoform in myofibroblast differentiation in lung fibrosis remains unknown. To study this, we developed a Gelatin methacryloyl (GelMA) hydrogel based culture system with different stiffness levels relevant to healthy and fibrotic lungs...
February 22, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28225068/relish2-mediates-bursicon-homodimer-induced-prophylactic-immunity-in-the-mosquito-aedes-aegypti
#12
Hongwei Zhang, Shengzhang Dong, Xi Chen, David Stanley, Brenda Beerntsen, Qili Feng, Qisheng Song
Bursicon is a neuropeptide hormone consisting of two cystine-knot proteins (burs α and burs β), responsible for cuticle tanning and other developmental processes in insects. Recent studies show that each bursicon subunit forms homodimers that induce prophylactic immunity in Drosophila melanogaster. Here, we investigated the hypothesis that bursicon homodimers act in prophylactic immunity in insects, and possibly arthropods, generally, using the mosquito, Aedes aegypti. We found that burs α and burs β are expressed in larvae, pupae and newly emerged adults...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224663/loss-of-mlh1-sensitizes-colon-cancer-cells-to-dna-pkcs-inhibitor-ku60648
#13
Inga Hinrichsen, Anne Ackermann, Tonja Düding, Annika Graband, Natalie Filmann, Guido Plotz, Stefan Zeuzem, Angela Brieger
Germline mutations of MLH1 are responsible for tumor generation in nearly 50% of patients with Lynch Syndrome, and around 15% of sporadic colorectal cancers show MLH1-deficiency due to promotor hypermethylation. Although these tumors are of lower aggressiveness the benefit for these patients from standard chemotherapy is still under discussion. Recently, it was shown that the sensitivity to the DNA-PKcs inhibitor KU60648 is linked to loss of the MMR protein MSH3. However, loss of MSH3 is rather secondary, as a consequence of MMR-deficiency, and frequently detectable in MLH1-deficient tumors...
February 22, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28223918/rpph1-upregulates-cdc42-expression-and-promotes-hippocampal-neuron-dendritic-spine-formation-by-competing-with-mir-330-5p
#14
Yifei Cai, Ziling Sun, Huizhen Jia, Hongxue Luo, Xiaoyang Ye, Qi Wu, Yi Xiong, Wei Zhang, Jun Wan
Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease. Recent studies employing microRNA-seq and genome-wide sequencing have identified some non-coding RNAs that are influentially involved in AD pathogenesis. Non-coding RNAs can compete with other endogenous RNAs by microRNA response elements (MREs) and manipulate biological processes, such as tumorigenesis. However, only a few non-coding RNAs have been reported in the pathogenesis of AD. In this study, we constructed the first competing endogenous RNA (ceRNA) network leveraging whole transcriptome sequencing and a previously studied microRNA-seq of APPswe/PS1ΔE9 transgenic mice...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28223821/asparaginyl-endopeptidase-improves-the-resistance-of-microtubule-targeting-drugs-in-gastric-cancer-through-iqgap1-modulating-the-egfr-jnk-erk-signaling-pathway
#15
Yuehong Cui, Qian Li, Hong Li, Yan Wang, Hongshan Wang, Weidong Chen, Shangmin Zhang, Jian Cao, Tianshu Liu
PURPOSE: In recent years, understanding of the role of asparaginyl endopeptidase (AEP) in tumorigenesis has steadily increased. In this study, we investigated whether AEP expression correlates with sensitivity to chemotherapeutic drugs in gastric cancer and explored the mechanism. PATIENTS AND METHODS: AEP expression in the serum of patients' peripheral blood was measured by enzyme-linked immunosorbent assay. Patient survival time was evaluated using univariate and multivariate analyses...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223541/targeting-growth-hormone-receptor-in-human-melanoma-cells-attenuates-tumor-progression-and-epithelial-mesenchymal-transition-via-suppression-of-multiple-oncogenic-pathways
#16
Reetobrata Basu, Shiyong Wu, John J Kopchick
Recent reports have confirmed highest levels of growth hormone (GH) receptor (GHR) transcripts in melanoma, one of the most aggressive forms of human cancer. Yet the mechanism of GH action in melanoma remains mostly unknown. Here, using human malignant melanoma cells, we examined the effects of GH excess or siRNA mediated GHR knock-down (GHRKD) on tumor proliferation, migration and invasion. GH promoted melanoma progression while GHRKD attenuated the same. Western blot analysis revealed drastic modulation of multiple oncogenic signaling pathways (JAK2, STAT1, STAT3, STAT5, AKT, mTOR, SRC and ERK1/2) following addition of GH or GHRKD...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223441/rima-dependent-nuclear-accumulation-of-iyo-triggers-auxin-irreversible-cell-differentiation-in-arabidopsis
#17
Alfonso Muñoz, Silvina Mangano, Mary Paz González-García, Ramón Contreras, Michael B Sauer, Bert De Rybel, Dolf Weijers, José J Sánchez-Serrano, Maite Sanmartín, Enrique Rojo
The transcriptional regulator MINIYO (IYO) is essential and rate-limiting for initiating cell differentiation in Arabidopsis thaliana. Moreover, IYO moves from the cytosol into the nucleus in cells at the meristem periphery, possibly triggering their differentiation. However, the genetic mechanisms controlling IYO nuclear accumulation were unknown and the evidence that increased nuclear IYO levels trigger differentiation remained correlative. Searching for IYO interactors, we have identified RPAP2 IYO Mate (RIMA), a homologue of yeast and human proteins linked to nuclear import of selective cargo...
February 21, 2017: Plant Cell
https://www.readbyqxmd.com/read/28223178/direct-experimental-manipulation-of-intestinal-cells-in-ascaris-suum-with-minor-influences-on-the-global-transcriptome
#18
Bruce A Rosa, Samantha N McNulty, Makedonka Mitreva, Douglas P Jasmer
Ascaris suum provides a powerful model for studying parasitic nematodes, including individual tissues such as the intestine, an established target for anthelmintic treatments. Here, we add a valuable experimental component to our existing functional, proteomic, transcriptomic and phylogenomic studies of the Ascaris suum intestine, by developing a method to manipulate intestinal cell functions via direct delivery of experimental treatments (in this case, double-stranded (ds)RNA) to the apical intestinal membrane...
February 18, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28223099/transient-knock-down-of-kcna2-reduces-sleep-in-larval-zebrafish
#19
S Srdanovic, H Þorsteinsson, Þ FriÐriksson, S Ó Pétursson, V H Maier, K Æ Karlsson
In the current study we set out to determine the effects of morpholino oligonucleotide (MO) knock-down of kcna2 on sleep-wake cycles in zebrafish. The results were compared to a non-overlapping MO injection, Dec2, whós mutant is also linked with a short sleep phenotype. Four groups of fish were used in the experiment: naïve fish, and fish injected with either control, kcna2, or Dec2 MO. All groups underwent 24-hour behavioral monitoring of sleep-wake cycles at four and seven days-post-fertilization (dpf)...
February 18, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28222767/knockdown-of-slc41a1-magnesium-transporter-promotes-mineralization-and-attenuates-magnesium-inhibition-during-osteogenesis-of-mesenchymal-stromal-cells
#20
Yu-Tzu Tsao, Ya-Yi Shih, Yu-An Liu, Yi-Shiuan Liu, Oscar K Lee
BACKGROUND: Magnesium is essential for numerous physiological functions. Magnesium exists mostly in bone and the amount is dynamically regulated by skeletal remodeling. Accelerating bone mass loss occurs when magnesium intake is insufficient; whereas high magnesium could lead to mineralization defects. However, the underlying magnesium regulatory mechanisms remain elusive. In the present study, we investigated the effects of high extracellular magnesium concentration on osteogenic differentiation of mesenchymal stromal/stem cells (MSCs) and the role of magnesium transporter SLC41A1 in the mineralization process...
February 21, 2017: Stem Cell Research & Therapy
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