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https://www.readbyqxmd.com/read/28646406/podocytes-and-the-quest-for-precision-medicines-for-kidney-diseases
#1
REVIEW
Peter Mundel
In this review, I describe a 30-year journey in the quest for precision medicines for patients with kidney diseases. In 1987, when I started my reseach career, most scientists studying glomerular disease biology were focused on mesangial cells. The crucial role of the podocyte in many kidney diseases characterized by proteinuria, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, had not yet been recognized. We were not aware of genetic causes or drivers of kidney diseases nor of molecular markers and cell culture systems for mechanistic studies of podocyte biology...
June 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28646090/cellular-functions-of-wasp-family-proteins-at-a-glance
#2
REVIEW
Olga Alekhina, Ezra Burstein, Daniel D Billadeau
Proteins of the Wiskott-Aldrich syndrome protein (WASP) family function as nucleation-promoting factors for the ubiquitously expressed Arp2/3 complex, which drives the generation of branched actin filaments. Arp2/3-generated actin regulates diverse cellular processes, including the formation of lamellipodia and filopodia, endocytosis and/or phagocytosis at the plasma membrane, and the generation of cargo-laden vesicles from organelles including the Golgi, endoplasmic reticulum (ER) and the endo-lysosomal network...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28645851/nanotubes-connecting-b-lymphocytes-high-impact-of-differentiation-dependent-lipid-composition-on-their-growth-and-mechanics
#3
Eszter A Tóth, Ádám Oszvald, Mária Péter, Gábor Balogh, Anikó Osteikoetxea-Molnár, Tamás Bozó, Edina Szabó-Meleg, Miklós Nyitrai, Imre Derényi, Miklós Kellermayer, Toshiyuki Yamaji, Kentaro Hanada, László Vígh, János Matkó
Nanotubes (NTs) are thin, long membranous structures forming novel, yet poorly known communication pathways between various cell types. Key mechanisms controlling their growth still remained poorly understood. Since NT-forming capacity of immature and mature B cells was found largely different, we investigated how lipid composition and molecular order of the membrane affect NT-formation. Screening B cell lines with various differentiation stages revealed that NT-growth linearly correlates with membrane ganglioside levels, while it shows maximum as a function of cholesterol level...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28645333/sac-1004-a-vascular-leakage-blocker-reduces-cerebral-ischemia-reperfusion-injury-by-suppressing-blood-brain-barrier-disruption-and-inflammation
#4
Haiying Zhang, Joon Ha Park, Sony Maharjan, Jeong Ae Park, Kyu-Sung Choi, Hyojin Park, Yoonjeong Jeong, Ji Hyeon Ahn, In Hye Kim, Jae-Chul Lee, Jeong Hwi Cho, In-Kyu Lee, Choong Hyun Lee, In Koo Hwang, Young-Myeong Kim, Young-Ger Suh, Moo-Ho Won, Young-Guen Kwon
BACKGROUND: Blood-brain barrier (BBB) breakdown and inflammation are critical events in ischemic stroke, contributing to aggravated brain damage. The BBB mainly consists of microvascular endothelial cells sealed by tight junctions to protect the brain from blood-borne substances. Thus, the maintenance of BBB integrity may be a potential target for neuroprotection. Sac-1004, a pseudo-sugar derivative of cholesterol, enhances the endothelial barrier by the stabilization of the cortical actin ring...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28645189/the-potential-role-of-retinoic-acid-receptor-%C3%AE-on-glomerulosclerosis-in-rats-and-podocytes-injury-is-associated-with-the-induction-of-mmp2-and-mmp9
#5
Xiuping Chen, Yuanhan Qin, Tianbiao Zhou, Ling Jiang, Fengying Lei, He Qin, Lei Zhang, Zhiqiang Zhou
Retinoic acid receptor α (RARα) plays a crucial role in kidney disease. However, the underlying mechanisms in glomerulosclerosis (GS) is still not clear. The roles of RARα in an adriamycin (ADR)-induced GS rat model and in ADR-induced podocyte injury in vitro were investigated. RARα was over-expressed in GS rats, and serum, urine and kidney samples were collected to detect the induction of the expression of the receptor. RARα expression was inhibited and/or over-expressed in cultured podocytes following injury, as demonstrated by morphometric assays, cell toxicity, and matrix metalloproteinase (MMP) enzymatic activity...
June 22, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28645175/perturbation-to-cholesterol-at-the-neuromuscular-junction-confers-botulinum-neurotoxin-a-sensitivity-to-neonatal-mice
#6
Baskaran Thyagarajan, Joseph G Potian, Joseph J McArdle, Padmamalini Baskaran
Botulinum neurotoxin A (BoNT/A) cleaves SNAP25 at the motor nerve terminals (MNT) and inhibits stimulus evoked acetylcholine release (SEAR). This causes skeletal muscle paralysis. However, younger neonatal mice (<P7; less than 7 days old) are resistant to the neuroparalytic effects of BoNT/A. That is, in vivo injection of BoNT/A at the innervations of Extensor digitorum longus (EDL) muscle in the hindlimbs inhibited the toe spread reflex within 24 hours following BoNT/A injection in adult mouse and in older (> P7) neonatal mice younger than 7 days-age remained unaffected by BoNT/A injection...
June 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28644898/spatio-temporal-orientation-of-microtubules-controls-conical-cell-shape-in-arabidopsis-thaliana-petals
#7
Huibo Ren, Xie Dang, Xianzhi Cai, Peihang Yu, Yajun Li, Shanshan Zhang, Menghong Liu, Binqing Chen, Deshu Lin
The physiological functions of epidermal cells are largely determined by their diverse morphologies. Most flowering plants have special conical-shaped petal epidermal cells that are thought to influence light capture and reflectance, and provide pollinator grips, but the molecular mechanisms controlling conical cell shape remain largely unknown. Here, we developed a live-confocal imaging approach to quantify geometric parameters of conical cells in Arabidopsis thaliana (A.thaliana). Through genetic screens, we identified katanin (KTN1) mutants showing a phenotype of decreased tip sharpening of conical cells...
June 23, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28644884/ligand-induced-rapid-skeletal-muscle-atrophy-in-hsa-fv2e-perk-transgenic-mice
#8
Masato Miyake, Masashi Kuroda, Hiroshi Kiyonari, Kenji Takehana, Satoshi Hisanaga, Masatoshi Morimoto, Jun Zhang, Miho Oyadomari, Hiroshi Sakaue, Seiichi Oyadomari
BACKGROUND: Formation of 43S and 48S preinitiation complexes plays an important role in muscle protein synthesis. There is no muscle-wasting mouse model caused by a repressed 43S preinitiation complex assembly. OBJECTIVE: The aim of the present study was to develop a convenient mouse model of skeletal muscle wasting with repressed 43S preinitiation complex assembly. MATERIAL AND METHODS: A ligand-activatable PERK derivative Fv2E-PERK causes the phosphorylation of eukaryotic initiation factor 2α (eIF2α), which inhibits 43S preinitiation complex assembly...
2017: PloS One
https://www.readbyqxmd.com/read/28644870/effects-of-nicotine-on-corneal-wound-healing-following-acute-alkali-burn
#9
Jong Won Kim, Chae Woong Lim, Bumseok Kim
Epidemiological studies have indicated that smoking is a pivotal risk factor for the progression of several chronic diseases. Nicotine, the addictive component of cigarettes, has powerful pathophysiological properties in the body. Although the effects of cigarette smoking on corneal re-epithelialization have been studied, the effects of nicotine on corneal wound healing-related neovascularization and fibrosis have not been fully demonstrated. The aim of this study was to evaluate the effects of chronic administration of nicotine on corneal wound healing following acute insult induced by an alkali burn...
2017: PloS One
https://www.readbyqxmd.com/read/28644569/gastrointestinal-stromal-tumors-of-the-esophagus-a-clinicopathologic-and-molecular-analysis-of-27-cases
#10
Guhyun Kang, Yuna Kang, Kyung-Hee Kim, Sang Yun Ha, Jung Yeon Kim, Young Mog Shim, Michael C Heinrich, Kyoung-Mee Kim, Christopher L Corless
AIMS: Gastrointestinal stromal tumors (GISTs) may arise anywhere in the gastrointestinal tract, but are rare in the esophagus. We describe the clinical, pathologic, and molecular characteristics of 27 primary esophageal GISTs, the largest series to date. METHODS AND RESULTS: DNA was extracted and exons 9, 11, 13 and 17 of KIT, exons 12, 14 and 18 of PDGFRA and exon 15 of BRAF were amplified and sequenced. Esophageal GISTs occurred in 14 men and 13 women between 22 and 80 years of age (mean, 56 years)...
June 23, 2017: Histopathology
https://www.readbyqxmd.com/read/28643776/ezrin-enhances-line-tension-along-transcellular-tunnel-edges-via-nmiia-driven-actomyosin-cable-formation
#11
Caroline Stefani, David Gonzalez-Rodriguez, Yosuke Senju, Anne Doye, Nadia Efimova, Sébastien Janel, Justine Lipuma, Meng Chen Tsai, Daniel Hamaoui, Madhavi P Maddugoda, Olivier Cochet-Escartin, Coline Prévost, Frank Lafont, Tatyana Svitkina, Pekka Lappalainen, Patricia Bassereau, Emmanuel Lemichez
Transendothelial cell macroaperture (TEM) tunnels control endothelium barrier function and are triggered by several toxins from pathogenic bacteria that provoke vascular leakage. Cellular dewetting theory predicted that a line tension of uncharacterized origin works at TEM boundaries to limit their widening. Here, by conducting high-resolution microscopy approaches we unveil the presence of an actomyosin cable encircling TEMs. We develop a theoretical cellular dewetting framework to interpret TEM physical parameters that are quantitatively determined by laser ablation experiments...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28643557/pooled-sample-testing-for-bonamia-ostreae-a-tale-of-two-sybr-green-real-time-pcr-assays
#12
Henry S Lane, J Brian Jones, Wendy L McDonald
Pooled testing of samples is a common laboratory practice to increase efficiency and reduce expenses. We investigated the efficacy of 2 published SYBR Green real-time PCR assays when used to detect the haplosporidian parasite Bonamia ostreae in pooled samples of infected oyster tissue. Each PCR targets a different gene within the B. ostreae genome: the actin 1 gene or the 18S rRNA gene. Tissue homogenates (150 mg) of the New Zealand flat oyster Ostrea chilensis were spiked with ~1.5 × 10(3) purified B. ostreae cells to create experimental pools of 3, 5, and 10...
June 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28643432/the-penetration-and-phenotype-modulation-of-smooth-muscle-cells-on-surface-heparin-modified-poly-%C3%AE%C2%B5-caprolactone-vascular-scaffold
#13
Jie Cao, Xue Geng, Juan Wen, Qingxuan Li, Lin Ye, Aiying Zhang, Zengguo Feng, Lianrui Guo, Yongquan Gu
The tubular porous poly(ε-caprolactone)(PCL) scaffold was fabricated by electrospinning. After then, the scaffold's surface was firstly eroded by hexyldiamine to endow amine group, and heparin was covalently grafted to the surface to get surface heparin modified scaffold(ShPCL scaffold). It was found that ShPCL scaffold can induce smooth muscle cells (SMCs) to penetrate the scaffold surface, while the SMCs can't penetrate the surface of PCL scaffold. Subsequently, the rabbit SMCs were seeded on the ShPCL scaffold and cultured for 14 days...
June 23, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28642683/object-phobia-and-altered-rhoa-signaling-in-amygdala-of-mice-lacking-rich2
#14
Tasnuva Sarowar, Stefanie Grabrucker, Tobias M Boeckers, Andreas M Grabrucker
RICH2 knockout (RICH2 KO) mice exhibit neophobia in the novel object test. To gain further insight into their anxiety-related phenotype, we subjected these mice to additional behavioral tests to elucidate whether the behavioral abnormality in these mice is a consequence of reduced exploratory motivation, and whether the neophobia is linked specifically to objects or also present for other modalities. RICH2 KO mice engage in normal exploration in a novel environment, suggesting that the anxiety-related phenotype is not due to reduced exploratory drive...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28642549/focal-adhesion-kinase-regulates-hepatic-stellate-cell-activation-and-liver-fibrosis
#15
Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642487/hypoxia-is-a-key-driver-of-alternative-splicing-in-human-breast-cancer-cells
#16
Jian Han, Jia Li, Jolene Caifeng Ho, Grace Sushin Chia, Hiroyuki Kato, Sudhakar Jha, Henry Yang, Lorenz Poellinger, Kian Leong Lee
Adaptation to hypoxia, a hallmark feature of many tumors, is an important driver of cancer cell survival, proliferation and the development of resistance to chemotherapy. Hypoxia-induced stabilization of hypoxia-inducible factors (HIFs) leads to transcriptional activation of a network of hypoxia target genes involved in angiogenesis, cell growth, glycolysis, DNA damage repair and apoptosis. Although the transcriptional targets of hypoxia have been characterized, the alternative splicing of transcripts that occurs during hypoxia and the roles they play in oncogenesis are much less understood...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642367/the-activities-of-the-c-terminal-regions-of-the-formin-protein-disheveled-associated-activator-of-morphogenesis-daam-in-actin-dynamics
#17
Andrea Teréz Vig, István Földi, Szilárd Szikora, Ede Migh, Rita Gombos, Mónika Ágnes Tóth, Tamás Huber, Réka Pintér, Gábor Csaba Talián, József Mihály, Beáta Bugyi
Disheveled-associated activator of morphogenesis (DAAM) is a diaphanous-related formin protein essential for the regulation of actin cytoskeleton dynamics in diverse biological processes. The conserved formin homology 1 and 2 (FH1-FH2) domains of DAAM catalyze actin nucleation and processively mediate filament elongation. These activities are indirectly regulated by the N-, and C-terminal regions flanking the FH1-FH2 domains. Recently, the C-terminal diaphanous-autoregulatory domain (DAD) and the C-terminus (CT) of formins have also been shown to regulate actin assembly by directly interacting with actin...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28642276/dedifferentiation-proliferation-and-redifferentiation-of-adult-mammalian-cardiomyocytes-after-ischemic-injury
#18
Wei Eric Wang, Liangpeng Li, Xuewei Xia, Wenbin Fu, Qiao Liao, Cong Lan, Dezhong Yang, Hongmei Chen, Rongchuan Yue, Cindy S Zeng, Lin Zhou, Bin Zhou, Dayue D Duan, Xiongwen Chen, Steven R Houser, Chunyu Zeng
Background -Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACM) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. Methods -β-actin-GFP transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs...
June 22, 2017: Circulation
https://www.readbyqxmd.com/read/28642260/cigarette-smoke-disrupts-monolayer-integrity-by-altering-epithelial-cell-cell-adhesion-and-cortical-tension
#19
Kristine Nishida, Kieran A Brune, Nirupama Putcha, Pooja Mandke, Wanda K O'Neal, Danny Shade, Vasudha Srivastava, Menghen Wang, Hong Lam, Steven S An, M Bradley Drummond, Nadia N Hansel, Douglas N Robinson, Venkataramana K Sidhaye
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Cigarette smoke (CS) drives disease development and progression. The epithelial barrier is damaged by CS with increased monolayer permeability. However, the molecular changes that cause this barrier disruption and the interaction between adhesion proteins and the cytoskeleton are not well defined. We hypothesized that CS alters monolayer integrity by increasing cell contractility and decreasing cell adhesion in epithelia...
June 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28642137/overexpression-cdc42-attenuates-isoflurane-induced-neurotoxicity-in-developmental-brain-of-rats
#20
Xi Fang, Shiyong Li, Qiang Han, Yilin Zhao, Jie Gao, Jing Yan, Ailin Luo
Nowadays many children receive operations with general anesthesia. Isoflurane is a commonly-used general anesthetic. Numbers of studies demonstrated that isoflurane induced neurotoxicity and neurobehavioral deficiency in young rats, however, the underlying mechanism remained unknown. Cell division cycle 42 (cdc42) played an important role in regulating synaptic vesicle trafficking and actin dynamics in neuron, which closely linked to synaptic plasticity and dendritic spine formation. Meanwhile, cdc42 also involved in many neurodegenerative diseases...
June 19, 2017: Biochemical and Biophysical Research Communications
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