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https://www.readbyqxmd.com/read/28229450/endogenous-nitric-oxide-formation-in-cardiac-myocytes-does-not-control-respiration-during-%C3%AE-adrenergic-stimulation
#1
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/28222737/dynamic-genome-scale-metabolic-modeling-of-the-yeast-pichia-pastoris
#2
Francisco Saitua, Paulina Torres, José Ricardo Pérez-Correa, Eduardo Agosin
BACKGROUND: Pichia pastoris shows physiological advantages in producing recombinant proteins, compared to other commonly used cell factories. This yeast is mostly grown in dynamic cultivation systems, where the cell's environment is continuously changing and many variables influence process productivity. In this context, a model capable of explaining and predicting cell behavior for the rational design of bioprocesses is highly desirable. Currently, there are five genome-scale metabolic reconstructions of P...
February 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28216876/wheatgrass-extract-ameliorates-hypoxia-induced-mucin-gene-expression-in-a549-cells
#3
Ju Hwan Sim, Moon-Hee Choi, Hyun-Jae Shin, Ji-Eun Lee
BACKGROUND: Wheatgrass is known to have antioxidant, antiaging, and anti-inflammatory effect. However, its protective effect against hypoxia is not yet evaluated. OBJECTIVE: In this study, we evaluated the protective and anti-inflammatory effect of wheatgrass against the hypoxia in airway epithelial cells. MATERIALS AND METHODS: A549 human lung adenocarcinoma cells were incubated in a hypoxic condition (CO2 5%/O2 1%) for 24 hr in the presence of different concentration of wheatgrass 50, 75, 100, and 150 μg/mL, and the magnitude of each immunologic response produced by the A549 cells was compared...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28213441/secreted-metalloproteinase-adamts-3-inactivates-reelin
#4
Himari Ogino, Arisa Hisanaga, Takao Kohno, Yuta Kondo, Kyoko Okumura, Takana Kamei, Tempei Sato, Hiroshi Asahara, Hitomi Tsuiji, Masaki Fukata, Mitsuharu Hattori
The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, non-invasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro, but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28210784/novel-aids-therapies-based-on-gene-editing
#5
REVIEW
Kamel Khalili, Martyn K White, Jeffrey M Jacobson
HIV/AIDS remains a major public health issue. In 2014, it was estimated that 36.9 million people are living with HIV worldwide, including 2.6 million children. Since the advent of combination antiretroviral therapy (cART), in the 1990s, treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS has become increasingly rare. However, while people with HIV can expect to live a normal life span with cART, lifelong medication is required and cardiovascular, renal, liver, and neurologic diseases are still possible, which continues to prompt research for a cure for HIV...
February 16, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28199486/gsg1-trnp1-and-tmem215-mark-subpopulations-of-bipolar-interneurons-in-the-mouse-retina
#6
Ko Uoon Park, Grace Randazzo, Kenneth L Jones, Joseph A Brzezinski
Purpose: How retinal bipolar cell interneurons are specified and assigned to specialized subtypes is only partially understood. In part, this is due to a lack of early pan- and subtype-specific bipolar cell markers. To discover these factors, we identified genes that were upregulated in Blimp1 (Prdm1) mutant retinas, which exhibit precocious bipolar cell development. Methods: Postnatal day (P)2 retinas from Blimp1 conditional knock-out (CKO) mice and controls were processed for RNA sequencing...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28196404/a-p57-conditional-mutant-allele-that-allows-tracking-of-p57-expressing-cells
#7
Despoina Mademtzoglou, Sonia Alonso-Martin, Ted Hung-Tse Chang, Keren Bismuth, Bernadette Drayton-Libotte, Frédéric Aurade, Frédéric Relaix
p57(Kip2) (p57) is a maternally expressed imprinted gene regulating growth arrest which belongs to the CIP/KIP family of Cyclin-Dependent Kinase Inhibitors. While initially identified as a cell cycle arrest protein through inhibition of cyclin and cyclin-dependent kinase complexes, p57 activity has also been linked to differentiation, apoptosis, and senescence. In addition, p57 has recently been shown to be involved in tumorigenesis and cell fate decisions in stem cells. Yet, p57 function in adult tissues remains poorly characterized due to the perinatal lethality of p57 knock-out mice...
February 14, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28188272/aldehyde-oxidase-4-plays-a-critical-role-in-delaying-silique-senescence-by-catalyzing-aldehyde-detoxification
#8
Sudhakar Srivastava, Galina Brychkova, Dmitry Yarmolinsky, Aigerim Soltabayeva, Talya Samani, Moshe Sagi
The Arabidopsis aldehyde oxidases are a multigene family of four AAOs (1-4) that oxidize a variety of aldehydes, amongst them abscisic aldehyde, which is oxidized to the phytohormone abscisic acid.Toxic aldehydes are generated in plants both under normal conditions and in response to stress.The detoxification of such aldehydes by oxidation is attributed to aldehyde dehydrogenases but never to aldehyde oxidases. The feasibility of detoxification of aldehydes in siliques via oxidation by AAO4 was demonstrated, first, by its ability to efficiently oxidize an array of aromatic and aliphatic aldehydes, including the reactive carbonyl species (RCS) acrolein, hydroxyl-2-nonenal, and malondialdehyde (MDA)...
February 10, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28130367/characterization-of-the-regulatory-function-of-the-h-ns-protein-in-the-benthic-bacterium-shewanella-piezotolerans-wp3-under-cold-conditions
#9
Huahua Jian, Guanpeng Xu, Fengping Wang, Xiang Xiao
The histone-like nucleoid structuring (H-NS) protein is conserved in gram-negative bacteria and plays important roles as a multifunctional bacterial modulator. However, its roles in deep-sea microorganisms warrant investigation. In this study, the relationship between temperature and the regulatory function of H-NS was characterized in the benthic bacterium Shewanella piezotolerans WP3. Comparative microarray analysis of the hns knock-out mutant and wild-type strain identified a total of 264 differentially expressed genes at 4°C, which is significantly less than that at 20°C...
January 26, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28129943/beta-site-amyloid-precursor-protein-cleaving-enzyme-1-inhibition-impairs-synaptic-plasticity-via-seizure-protein-6
#10
Kaichuan Zhu, Xianyuan Xiang, Severin Filser, Petar Marinković, Mario M Dorostkar, Sophie Crux, Ulf Neumann, Derya R Shimshek, Gerhard Rammes, Christian Haass, Stefan F Lichtenthaler, Jenny M Gunnersen, Jochen Herms
BACKGROUND: Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a promising drug target for the treatment of Alzheimer's disease. Prolonged BACE1 inhibition interferes with structural and functional synaptic plasticity in mice, most likely by altering the metabolism of BACE1 substrates. Seizure protein 6 (SEZ6) is predominantly cleaved by BACE1, and Sez6 knockout mice share some phenotypes with BACE1 inhibitor-treated mice. We investigated whether SEZ6 is involved in BACE1 inhibition-induced structural and functional synaptic alterations...
December 26, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28122715/primary-cilia-regulate-the-osmotic-stress-response-of-renal-epithelial-cells-through-trpm3
#11
Brian J Siroky, Nancy K Kleene, Steven J Kleene, Charles D Varnell, Raven G Comer, Jialiu Liu, Lu Lu, Nolan W Pachciarz, John J Bissler, Bradley P Dixon
Primary cilia sense environmental conditions including osmolality, but whether cilia participate in osmotic response in renal epithelial cells is not known. Transient receptor potential (TRP) channels TRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia in certain cell types, while renal subcellular localization of TRPM3 is not known. We hypothesized that primary cilia are required for maximal activation of the osmotic response of renal epithelial cells, and that ciliary TRPM3 and TRPV4 mediate that response...
January 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28119452/microrna-375-is-induced-in-cisplatin-nephrotoxicity-to-repress-hepatocyte-nuclear-factor-1-beta
#12
Jielu Hao, Qiang Lou, Qingqing Wei, Shuqin Mei, Lin Li, Qing-Sheng Mi, Changlin Mei, Zheng Dong
Nephrotoxicity is a major adverse effect of cisplatin-mediated chemotherapy in cancer patients. The pathogenesis of cisplatin-induced nephrotoxicity remains largely unclear, making it difficult to design effective renoprotective approaches. Here, we have examined the role of microRNAs (miRNAs) in cisplatin-induced nephrotoxicity. We show that cisplatin nephrotoxicity was not affected by overall depletion of both beneficial and detrimental miRNAs from kidney proximal tubular cells in mice in which the miRNA-generating enzyme Dicer had been conditionally knocked out...
January 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28119050/targeted-basic-research-to-highlight-the-role-of-estrogen-and-estrogen-receptors-in-the-cardiovascular-system
#13
REVIEW
Elke Dworatzek, Shokoufeh Mahmoodzadeh
Epidemiological, clinical and animal studies revealed that sex differences exist in the manifestation and outcome of cardiovascular disease (CVD). The underlying molecular mechanisms implicated in these sex differences are not fully understood. The reasons for sex differences in CVD are definitely multifactorial, but major evidence points to the contribution of sex steroid hormone, 17β-estradiol (E2), and its receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). In this review, we summarize past and present studies that implicate E2 and ER as important determinants of sexual dimorphism in the physiology and pathophysiology of the heart...
January 21, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28117678/mechanism-governing-human-kappa-opioid-receptor-expression-under-desferrioxamine-induced-hypoxic-mimic-condition-in-neuronal-nmb-cells
#14
Jennifer Babcock, Alberto Herrera, George Coricor, Christopher Karch, Alexander H Liu, Aida Rivera-Gines, Jane L Ko
Cellular adaptation to hypoxia is a protective mechanism for neurons and relevant to cancer. Treatment with desferrioxamine (DFO) to induce hypoxia reduced the viability of human neuronal NMB cells. Surviving/attached cells exhibited profound increases of expression of the human kappa-opioid receptor (hKOR) and hypoxia inducible factor-1α (HIF-1α). The functional relationship between hKOR and HIF-1α was investigated using RT-PCR, Western blot, luciferase reporter, mutagenesis, siRNA and receptor-ligand binding assays...
January 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28117598/cr6-interacting-factor-1-deficiency-impairs-vascular-function-by-inhibiting-the-sirt1-enos-pathway
#15
Harsha Nagar, Saetbyel Jung, Min Jeong Ryu, Su Jung Choi, Shuyu Piao, Hee Jung Song, Shin Kwang Kang, Nara Shin, Dong Woon Kim, Seon-Ah Jin, Jin-Ok Jeong, Kaikobad Irani, Byeong Hwa Jeon, Minho Shong, Gi Ryang Kweon, Cuk Seong Kim
AIMS: Mitochondrial dysfunction has emerged as a major contributing factor to endothelial dysfunction and vascular disease, but the key mechanisms underlying mitochondrial dysfunction-induced endothelial dysfunction remain to be elucidated. In this study, we aim to determine whether mitochondrial dysfunction in endothelial cells plays a key role in vascular disease, by examining the phenotype of endothelial-specific CR6-interacting factor 1 (CRIF1) knockout mice. We also used siRNA mediated downregulation of CRIF1 gene in the endothelial cells to study about the in vitro pathophysiological underlying mechanisms...
January 24, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28107345/syk-regulates-neutrophilic-airway-hyper-responsiveness-in-a-chronic-mouse-model-of-allergic-airways-inflammation
#16
Sepehr Salehi, Xiaomin Wang, Stephen Juvet, Jeremy A Scott, Chung-Wai Chow
BACKGROUND: Asthma is a chronic inflammatory disease characterized by airways hyper-responsiveness (AHR), reversible airway obstruction, and airway inflammation and remodeling. We previously showed that Syk modulates methacholine-induced airways contractility in naïve mice and in mice with allergic airways inflammation. We hypothesize that Syk plays a role in the pathogenesis of AHR; this was evaluated in a chronic 8-week mouse model of house dust mite (HDM)-induced allergic airways inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28100775/cool-associated-tyrosine-phosphorylated-protein-1-is-required-for-the-anchorage-independent-growth-of-cervical-carcinoma-cells-by-binding-paxillin-and-promoting-akt-activation
#17
Sungsoo M Yoo, Arash Latifkar, Richard A Cerione, Marc A Antonyak
Cool-associated tyrosine phosphorylated protein-1 (Cat-1) is a signaling scaffold, as well as an ADP-ribosylation factor-GTPase-activating protein (ARF-GAP). Although best known for its role in cell migration, we recently showed that the ability of Cat-1 to bind paxillin, a major constituent of focal complexes, was also essential for the anchorage-independent growth of HeLa cervical carcinoma cells. Here, we set out to learn more about the underlying mechanism by which Cat-paxillin interactions mediate this effect...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100752/differential-vulnerability-of-ca1-versus-ca3-pyramidal-neurons-after-ischemia-possible-relationship-to-sources-of-zn2-accumulation-and-its-entry-into-and-prolonged-effects-on-mitochondria
#18
Yuliya V Medvedeva, Sung G Ji, Hong Z Yin, John H Weiss
: Excitotoxic mechanisms contribute to the degeneration of hippocampal pyramidal neurons after recurrent seizures and brain ischemia. However, susceptibility differs, with CA1 neurons degenerating preferentially after global ischemia and CA3 neurons after limbic seizures. Whereas most studies address contributions of excitotoxic Ca(2+) entry, it is apparent that Zn(2+) also contributes, reflecting accumulation in neurons either after synaptic release and entry through postsynaptic channels or upon mobilization from intracellular Zn(2+)-binding proteins such as metallothionein-III (MT-III)...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100747/selective-deletion-of-sodium-salt-taste-during-development-leads-to-expanded-terminal-fields-of-gustatory-nerves-in-the-adult-mouse-nucleus-of-the-solitary-tract
#19
Chengsan Sun, Edith Hummler, David L Hill
: Neuronal activity plays a key role in the development of sensory circuits in the mammalian brain. In the gustatory system, experimental manipulations now exist, through genetic manipulations of specific taste transduction processes, to examine how specific taste qualities (i.e., basic tastes) impact the functional and structural development of gustatory circuits. Here, we used a mouse knock-out model in which the transduction component used to discriminate sodium salts from other taste stimuli was deleted in taste bud cells throughout development...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100740/epilepsy-associated-kcnq2-channels-regulate-multiple-intrinsic-properties-of-layer-2-3-pyramidal-neurons
#20
Zachary Niday, Virginia E Hawkins, Heun Soh, Daniel K Mulkey, Anastasios V Tzingounis
: KCNQ2 potassium channels are critical for normal brain function, as both loss-of-function and gain-of-function KCNQ2 variants can lead to various forms of neonatal epilepsy. Despite recent progress, the full spectrum of consequences as a result of KCNQ2 dysfunction in neocortical pyramidal neurons is still unknown. Here, we report that conditional ablation of Kcnq2 from mouse neocortex leads to hyperexcitability of layer 2/3 (L2/3) pyramidal neurons, exhibiting an increased input resistance and action potential frequency, as well as a reduced medium afterhyperpolarization (mAHP), a conductance partly mediated by KCNQ2 channels...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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