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https://www.readbyqxmd.com/read/28212178/the-long-journey-through-renal-filtration-new-pieces-in-the-puzzle-of-slit-diaphragm-architecture
#1
Sara Conti, Luca Perico, Florian Grahammer, Tobias B Huber
PURPOSE OF REVIEW: The podocyte slit diaphragm is probably the least understood component of the kidney filtration barrier. In this review, we aim to integrate the most recent findings on the molecular make-up and structural architecture of this specialized cell-cell junction into a current concept of glomerular filtration. RECENT FINDINGS: Analysis of cryopreserved mammalian tissue revealed a bipartite composition of the slit diaphragm. Single NEPH1 molecules span the lower part of the slit close to the glomerular basement membrane whereas NEPHRIN molecules are positioned in the apical part toward Bowman's space...
February 16, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28209987/targeting-phospholipase-d-in-cancer-infection-and-neurodegenerative-disorders
#2
REVIEW
H Alex Brown, Paul G Thomas, Craig W Lindsley
Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209730/role-of-stard4-in-sterol-transport-between-the-endocytic-recycling-compartment-and-the-plasma-membrane
#3
David B Iaea, Shu Mao, Frederik W Lund, Frederick R Maxfield
Cholesterol is an essential constituent of membranes in mammalian cells. The plasma membrane and the endocytic recycling compartment (ERC) are both highly enriched in cholesterol. The abundance and distribution of cholesterol among organelles are tightly controlled by a combination of mechanisms involving vesicular and non-vesicular sterol transport processes. Using the fluorescent cholesterol analog, dehydroergosterol, we examined sterol transport between the plasma membrane and the ERC using fluorescence recovery after photobleaching and a novel sterol efflux assay...
February 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#4
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#5
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28203140/tamoxifen-activation-of-cre-recombinase-has-no-persisting-effects-on-adult-neurogenesis-or-learning-and-anxiety
#6
Peter Rotheneichner, Pasquale Romanelli, Lara Bieler, Sebastian Pagitsch, Pia Zaunmair, Christina Kreutzer, Richard König, Julia Marschallinger, Ludwig Aigner, Sébastien Couillard-Després
Adult neurogenesis is a tightly regulated process continuously taking place in the central nervous system of most mammalian species. In neuroscience research, transgenic animals bearing the tamoxifen-inducible CreER(T2)-Lox system are widely used. In this study, we made use of a Nestin-CreER(T2)/R26R-YFP transgenic mouse model in which the CreER(T2) activates the expression of YFP in multipotent neural stem cells upon tamoxifen application. Humoral factors, such as the levels of estrogens, have been reported to affect the hippocampal neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28202675/the-molecular-basis-of-mtorc1-regulated-translation
#7
REVIEW
Carson C Thoreen
The mammalian target of rapamycin (mTOR) signaling pathway is a master regulator of cell growth throughout eukaryotes. The pathway senses nutrient and other growth signals, and then orchestrates the complex systems of anabolic and catabolic metabolism that underpin the growth process. A central target of mTOR signaling is the translation machinery. mTOR uses a multitude of translation factors to drive the bulk production of protein that growth requires, but also to direct a post-transcriptional program of growth-specific gene expression...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202334/synthesis-of-specifically-deuterated-ceramide-ap-c18-and-its-biophysical-characterization-using-neutron-diffraction
#8
Stefan Sonnenberger, Adina Eichner, Thomas Hauß, Annett Schroeter, Reinhard H H Neubert, Bodo Dobner
The very heterogeneous group of ceramides is known to be mandatory for proper barrier functions of the outermost layer of mammalian skin, referred to as stratum corneum (SC). The synthesis of a specifically deuterated ceramide [AP]-C18 variant is described. The synthesized ceramide contains the racemic forms of the α hydroxy fatty acid. For the biophysical implementation, the received diastereomeric ceramide was applied in a neutron diffraction experiment. Therefore, a SC lipid model membrane was prepared containing the described ceramide (CER), cholesterol (CHOL), stearic acid (SA), and cholesterol sulfate (ChS) in a ratio of 55/25/15/5wt%...
February 12, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28199303/mechanical-stretch-triggers-rapid-epithelial-cell-division-through-piezo1
#9
S A Gudipaty, J Lindblom, P D Loftus, M J Redd, K Edes, C F Davey, V Krishnegowda, J Rosenblatt
Despite acting as a barrier for the organs they encase, epithelial cells turn over at some of the fastest rates in the body. However, epithelial cell division must be tightly linked to cell death to preserve barrier function and prevent tumour formation. How does the number of dying cells match those dividing to maintain constant numbers? When epithelial cells become too crowded, they activate the stretch-activated channel Piezo1 to trigger extrusion of cells that later die. However, it is unclear how epithelial cell division is controlled to balance cell death at the steady state...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28197999/parallel-experimental-design-and-multivariate-analysis-provides-efficient-screening-of-cell-culture-media-supplements-to-improve-biosimilar-product-quality
#10
David Brühlmann, Michael Sokolov, Alessandro Butté, Markus Sauer, Jürgen Hemberger, Jonathan Souquet, Hervé Broly, Martin Jordan
Rational and high-throughput optimization of mammalian cell culture media has a great potential to modulate recombinant protein product quality. We present a process design method based on parallel design-of-experiment (DoE) of CHO fed-batch cultures in 96-deepwell plates to modulate monoclonal antibody (mAb) glycosylation using medium supplements. To reduce risk of losing valuable information in an intricate joint screening, 17 compounds were separated into five different groups, considering their mode of biological action...
February 15, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28197335/caspase-8-not-so-silently-deadly
#11
REVIEW
Rebecca Feltham, James E Vince, Kate E Lawlor
Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28196862/mtorc1-activity-is-required-to-maintain-canonical-endocytic-recycling-pathway-against-lysosomal-delivery
#12
Kristin Dauner, Walaa Eid, Riya Raghupathy, John Presley, Xiaohui Zha
The plasma membrane of mammalian cells undergoes constitutive endocytosis, endocytic sorting and recycling, which delivers nutrients to the lysosomes. The receptors, along with membrane lipids, are normally returned to the plasma membrane to sustain this action. It is not known, however, whether this process is influenced by metabolic conditions. Here we report that endocytic recycling requires active mTORC1, a master metabolic sensor. Upon mTORC1 inactivation, either by starvation or by inhibitors, plasma membrane lipids and recycling receptors, such as sphingomyelin and transferrin receptors, are delivered to the lysosomes...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28196538/functional-studies-of-drosophila-zinc-transporters-reveal-the-mechanism-for-zinc-excretion-in-malpighian-tubules
#13
Sai Yin, Qiuhong Qin, Bing Zhou
BACKGROUND: Zinc is an essential metal involved in many physiological processes. Previous work has identified a set of zinc transporters involved in Drosophila dietary zinc absorption. However, zinc excretion and reabsorption, the other two important processes to maintain zinc homeostasis, are not as well understood. In this work, we screened all the potential zinc transporter Zip (SLC39) and ZnT (SLC30) members for their likely roles in zinc excretion in Malpighian tubules, an insect organ functionally analogous to mammalian kidneys...
February 14, 2017: BMC Biology
https://www.readbyqxmd.com/read/28195124/pervasive-translational-regulation-of-the-cell-signalling-circuitry-underlies-mammalian-development
#14
Kotaro Fujii, Zhen Shi, Olena Zhulyn, Nicolas Denans, Maria Barna
The degree and dynamics of translational control during mammalian development remain poorly understood. Here we monitored translation of the mammalian genome as cells become specified and organize into tissues in vivo. This identified unexpected and pervasive translational regulation of most of the core signalling circuitry including Shh, Wnt, Hippo, PI3K and MAPK pathways. We further identify and functionally characterize a complex landscape of upstream open reading frames (uORFs) across 5'-untranslated regions (UTRs) of key signalling components...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193818/processing-of-single-photon-responses-in-the-mammalian-on-and-off-retinal-pathways-at-the-sensitivity-limit-of-vision
#15
Daisuke Takeshita, Lina Smeds, Petri Ala-Laurila
Visually guided behaviour at its sensitivity limit relies on single-photon responses originating in a small number of rod photoreceptors. For decades, researchers have debated the neural mechanisms and noise sources that underlie this striking sensitivity. To address this question, we need to understand the constraints arising from the retinal output signals provided by distinct retinal ganglion cell types. It has recently been shown in the primate retina that On and Off parasol ganglion cells, the cell types likely to underlie light detection at the absolute visual threshold, differ fundamentally not only in response polarity, but also in the way they handle single-photon responses originating in rods...
April 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28193136/ccctc-binding-factor-ctcf-transcriptionally-targets-wdr5-to-mediate-somatic-cell-reprogramming
#16
Feng Wang, Jinghua Han, Li Wang, Ying Jing, Zhu Zhu, Dawei Hui, Zhaohui Wang, Yangzi Wang, Yang Dong, Tao Tan
It was previously reported that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax complex, is a key regulator for the maintenance of ES cell pluripotency and somatic cell reprogramming. However, it remains unclear whether other factors also involve in this process. Here, we show that CTCF is an upstream regulator of Wdr5, it physically associates with Wdr5 and further transcriptionally controls its expression by directly targeting on Wdr5 gene promoter. As a downstream effector, overexpression of Wdr5 can rescue ES cells growth defect and decreased formation of induced pluripotent stem (iPS) cells caused by CTCF knockdown...
February 14, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28192112/multiple-blood-brain-barrier-transport-mechanisms-limit-bumetanide-accumulation-and-therapeutic-potential-in-the-mammalian-brain
#17
Kerstin Römermann, Maren Fedrowitz, Philip Hampel, Edith Kaczmarek, Kathrin Töllner, Thomas Erker, Douglas H Sweet, Wolfgang Löscher
There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders...
February 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28191879/visualizing-the-early-stages-of-phagocytosis
#18
Ali Rashidfarrokhi, Veronica Richina, Fikadu G Tafesse
The mammalian body is equipped with various layers of mechanisms that help to defend itself from pathogen invasions. Professional phagocytes of the immune system - such as neutrophils, dendritic cells, and macrophages - retain the innate ability to detect and clear such invading pathogens through phagocytosis(1). Phagocytosis involves choreographed events of membrane reorganization and actin remodeling at the cell surface(2)(,)(3). Phagocytes successfully internalize and eradicate foreign molecules only when all stages of phagocytosis are fulfilled...
February 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28190810/visualization-of-the-spatial-arrangement-of-nuclear-organization-using-three-dimensional-fluorescence-in-situ-hybridization-in-early-mouse-embryos-a-new-easi-fish-chamber-glass-for-mammalian-embryos
#19
Masataka Nakaya, Hideyuki Tanabe, Shingo Takamatsu, Misaki Hosokawa, Tasuku Mitani
The fertilized oocyte begins cleavage, leading to zygotic gene activation (ZGA), which re-activates the resting genome to acquire totipotency. In this process, genomic function is regulated by the dynamic structural conversion in the nucleus. Indeed, a considerable number of genes that are essential for embryonic development are located near the pericentromeric regions, wherein the heterochromatin is formed. These genes are repressed transcriptionally in somatic cells. Three-dimensional fluorescence in situ hybridization (3D-FISH) enables the visualization of the intranuclear spatial arrangement, such as gene loci, chromosomal domains, and chromosome territories (CTs)...
February 11, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28188528/lumier-a-discovery-tool-for-mammalian-protein-interaction-networks
#20
Miriam Barrios-Rodiles, Jonathan D Ellis, Benjamin J Blencowe, Jeffrey L Wrana
Protein-protein interactions (PPIs) play an essential role in all biological processes. In vivo, PPIs occur dynamically and depend on extracellular cues. To discover novel protein-protein interactions in mammalian cells, we developed a high-throughput automated technology called LUMIER (LUminescence-based Mammalian IntERactome). In this approach, we co-express a Luciferase (LUC)-tagged fusion protein along with a Flag-tagged protein in an efficiently transfectable cell line such as HEK-293T cells. The interaction between the two proteins is determined by co-immunoprecipitation using an anti-Flag antibody, and the presence of the LUC-tagged interactor in the complex is subsequently detected via its luciferase activity...
2017: Methods in Molecular Biology
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