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https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#1
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#2
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28214012/the-endothelium-solves-problems-that-endothelial-cells-do-not-know-exist
#3
REVIEW
John G McCarron, Matthew D Lee, Calum Wilson
The endothelium is the single layer of cells that lines the entire cardiovascular system and regulates vascular tone and blood-tissue exchange, recruits blood cells, modulates blood clotting, and determines the formation of new blood vessels. To control each function, the endothelium uses a remarkable sensory capability to continuously monitor vanishingly small changes in the concentrations of many simultaneously arriving extracellular activators that each provides cues to the physiological state. Here we suggest that the extraordinary sensory capabilities of the endothelium do not come from single cells but from the combined activity of a large number of endothelial cells...
February 14, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28213976/enhancement-of-%C3%AE-globin-gene-expression-in-thalassemic-ivs2-654-induced-pluripotent-stem-cell-derived-erythroid-cells-by-modified-u7-snrna
#4
Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng
The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of β-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat β-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 β-thalassemia...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213922/expression-of-kv3-1b-potassium-channel-is-widespread-in-macaque-motor-cortex-pyramidal-cells-a-histological-comparison-between-rat-and-macaque
#5
David Soares, Isabelle Goldrick, Roger N Lemon, Alexander Kraskov, Linda Greensmith, Bernadett Kalmar
There are substantial differences across species in the organisation and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration 'thin' spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids...
February 18, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28213886/dysregulation-of-metabolic-pathways-in-a-mouse-model-of-allergic-asthma
#6
Kevin D Quinn, Michaela Schedel, Yasmeen Nkrumah-Elie, Anthony Joetham, Michael Armstrong, Charmion Cruickshank-Quinn, Richard Reisdorph, Erwin W Gelfand, Nichole Reisdorph
BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function...
February 18, 2017: Allergy
https://www.readbyqxmd.com/read/28213824/an-approach-to-the-research-on-ion-and-water-properties-in-the-interphase-between-the-plasma-membrane-and-bulk-extracellular-solution
#7
REVIEW
Hiroshi Hibino, Madoka Takai, Hidenori Noguchi, Seishiro Sawamura, Yasufumi Takahashi, Hideki Sakai, Hitoshi Shiku
In vivo, cells are immersed in an extracellular solution that contains a variety of bioactive substances including ions and water. Classical electrophysiological analyses of epithelial cells in the stomach and small intestine have revealed that within a distance of several hundred micrometers above their apical plasma membrane, lies an extracellular layer that shows ion concentration gradients undetectable in the bulk phase. This "unstirred layer", which contains stagnant solutes, may also exist between the bulk extracellular solution and membranes of other cells in an organism and may show different properties...
February 17, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28213771/a-novel-spiroindoline-targets-cell-cycle-and-migration-via-modulation-of-microtubule-cytoskeleton
#8
Naveen Kumar, Santanu Hati, Parthapratim Munshi, Subhabrata Sen, Seema Sehrawat, Shailja Singh
Natural product-inspired libraries of molecules with diverse architectures have evolved as one of the most useful tools for discovering lead molecules for drug discovery. In comparison to conventional combinatorial libraries, these molecules have been inferred to perform better in phenotypic screening against complicated targets. Diversity-oriented synthesis (DOS) is a forward directional strategy to access such multifaceted library of molecules. From a successful DOS campaign of a natural product-inspired library, recently a small molecule with spiroindoline motif was identified as a potent anti-breast cancer compound...
February 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28213718/reprogramming-cell-fates-by-small-molecules
#9
REVIEW
Xiaojie Ma, Linghao Kong, Saiyong Zhu
Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our understanding of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on reprogramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for various applications, such as disease modeling and cell-based transplantation, but also hold great promise to be further developed as drugs to stimulate patients' endogenous cells to repair and regenerate in vivo...
February 17, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28213644/circulating-micrornas-and-diabetes-mellitus-a-novel-tool-for-disease-prediction-diagnosis-and-staging
#10
REVIEW
G Sebastiani, L Nigi, G E Grieco, F Mancarella, G Ventriglia, F Dotta
Diabetes is a complex, multifactorial group of metabolic diseases characterized by chronic hyperglycaemia due to pancreatic beta-cell dysfunction and/or loss. It is characterized by an asymptomatic and highly variable prodromic phase, which renders diabetes mellitus difficult to be predicted with sufficient accuracy. Despite several efforts in the identification and standardization of newly trustable. Biomarkers able to predict and follow-up diabetes and to specifically subtype its different forms, few of them have proven of clinical utility...
February 17, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28213525/conformational-profiling-of-the-at1-angiotensin-ii-receptor-reflects-biased-agonism-g-protein-coupling-and-cellular-context
#11
Dominic Devost, Rory Sleno, Darlaine Petrin, Alice Zhang, Yuji Shinjo, Rakan Okde, Junken Aoki, Asuka Inoue, Terence E Hebert
Here, we report the design and use of GPCR-based biosensors to monitor ligand-mediated conformational changes in receptors in intact cells. These biosensors use Bioluminescence Resonance Energy Transfer (BRET) with Renilla luciferase (RlucII) as an energy donor, placed at the distal end of the receptor C-tail and the small fluorescent molecule FlAsH, as an energy acceptor, its binding site inserted at different positions throughout the intracellular loops and carboxy-terminal tail of the angiotensin II type I receptor (AT1R)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213494/plc%C3%AE%C2%B51-regulates-sdf-1%C3%AE-induced-lymphocyte-adhesion-and-migration-to-sites-of-inflammation
#12
Marianne Strazza, Inbar Azoulay-Alfaguter, Michael Peled, Alan V Smrcka, Edward Y Skolnik, Shekhar Srivastava, Adam Mor
Regulation of integrins is critical for lymphocyte adhesion to endothelium and migration throughout the body. Inside-out signaling to integrins is mediated by the small GTPase Ras-proximate-1 (Rap1). Using an RNA-mediated interference screen, we identified phospholipase Cε 1 (PLCε1) as a crucial regulator of stromal cell-derived factor 1 alpha (SDF-1α)-induced Rap1 activation. We have shown that SDF-1α-induced activation of Rap1 is transient in comparison with the sustained level following cross-linking of the antigen receptor...
February 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28213469/insulin-signaling-via-the-pi3k-akt-pathway-regulates-airway-glucose-uptake-and-barrier-function-in-a-cftr-dependent-manner
#13
Samuel A Molina, Hannah K Moriarty, Danny T Infield, Barry R Imhoff, Rachel J Vance, Agnes H Kim, Jason M Hansen, William R Hunt, Michael Koval, Nael A McCarty
Cystic fibrosis-related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF) and correlates with increased rates of lung function decline. Since glucose is a nutrient present in the airways of patients with bacterial airway infections and since insulin controls glucose metabolism, the effect of insulin on CF airway epithelia was investigated to determine the role of insulin receptors and glucose transport in regulating glucose availability in the airway. The response to insulin by human airway epithelial cells was characterized by qPCR, immunoblot, immunofluorescence, and glucose uptake assays...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213432/targeting-cancer-cells-with-bet-bromodomain-inhibitors
#14
Yali Xu, Christopher R Vakoc
Cancer cells are often hypersensitive to the targeting of transcriptional regulators, which may reflect the deregulated gene expression programs that underlie malignant transformation. One of the most prominent transcriptional vulnerabilities in human cancer to emerge in recent years is the bromodomain and extraterminal (BET) family of proteins, which are coactivators that link acetylated transcription factors and histones to the activation of RNA polymerase II. Despite unclear mechanisms underlying the gene specificity of BET protein function, small molecules targeting these regulators preferentially suppress the transcription of cancer-promoting genes...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28213379/slowed-decay-of-mrnas-enhances-platelet-specific-translation
#15
Eric W Mills, Rachel Green, Nicholas T Ingolia
Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of mRNAs, ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA-Seq and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro derived MK cells and these platelet-enriched transcripts are broadly occupied by ribosomes...
February 17, 2017: Blood
https://www.readbyqxmd.com/read/28213378/prognostic-role-of-circulating-exosomal-mirnas-in-multiple-myeloma
#16
Salomon Manier, Chia-Jen Liu, Hervé Avet-Loiseau, Jihye Park, Jiantao Shi, Federico Campigotto, Karma Z Salem, Daisy Huynh, Siobhan V Glavey, Bradley Rivotto, Antonio Sacco, Aldo M Roccaro, Juliette Bouyssou, Stéphane Minvielle, Philippe Moreau, Thierry Facon, Xavier Leleu, Edie Weller, Lorenzo Trippa, Irene M Ghobrial
Exosomes, secreted by several cell types, including cancer cells, can be isolated from the peripheral blood and have been shown to be powerful markers of disease progression in cancer. In this study, we examined the prognostic significance of circulating exosomal microRNAs (miRNAs) in multiple myeloma (MM). A cohort of 156 patients with newly diagnosed MM, uniformly treated and followed, was studied. Circulating exosomal miRNAs were isolated and used to perform small RNA sequencing analysis on 10 samples and a qRT-PCR array on 156 samples...
February 17, 2017: Blood
https://www.readbyqxmd.com/read/28213182/microbial-nickel-cellular-uptake-and-delivery-to-enzyme-centers
#17
REVIEW
Conor J Zeer-Wanklyn, Deborah B Zamble
Nickel enzymes allow microorganisms to access chemistry that can be vital for survival and virulence. In this review we highlight recent work on several systems that import nickel ions and deliver them to the active sites of these enzymes. Small molecules, in particular l-His and derivatives, may chelate nickel ions before import at TonB-dependent outer-membrane and ABC-type inner-membrane transporters. Inside the cell, nickel ions are used by maturation factors required to produce nickel enzymes such as [NiFe]-hydrogenase, urease and lactate racemase...
February 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28213059/multidisciplinary-team-learning-in-the-management-of-the-morbidly-adherent-placenta-outcome-improvements-over-time
#18
Alireza A Shamshirsaz, Karin A Fox, Hadi Erfani, Steven L Clark, Bahram Salmanian, B Wycke Baker, Michael Coburn, Amir A Shamshirsaz, Zhoobin H Bateni, Jimmy Espinoza, Ahmed A Nassr, Edwina J Popek, Shiu-Ki Hui, Jun Teruya, Celestine Shauching Tung, Jeffery A Jones, Martha Rac, Gary A Dildy, Michael A Belfort
BACKGROUND: Morbidly adherent placenta (MAP) is a serious obstetric complication causing mortality and morbidity. OBJECTIVE: To evaluate whether outcomes of patients with morbidly adherent placenta improve with increasing experience within a well-established multidisciplinary team at a single referral center. STUDY DESIGN: All singleton pregnancies with pathology-confirmed MAP (including placenta accreta, increta or percreta) managed by a multidisciplinary team between January 2011 and August 2016 were included in this retrospective study...
February 14, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28213057/utilization-of-sentinel-lymph-node-biopsy-for-uterine-cancer
#19
Jason D Wright, Stephanie Cham, Ling Chen, William M Burke, June Y Hou, Ana I Tergas, Vrunda Desai, Jim C Hu, Cande V Ananth, Alfred I Neugut, Dawn L Hershman
BACKGROUND: To limit the potential short and long-term morbidity of lymphadenectomy, sentinel lymph node (SLN) biopsy has been proposed for endometrial cancer. The principle of SLN biopsy relies on removal of a small number of lymph nodes that are the first drainage basins from a tumor and thus the most likely to harbor tumor cells. While the procedure may reduce morbidity, efficacy data is limited and little is known about how commonly the procedure is performed. OBJECTIVE: We examined the patterns and predictors of use of SLN biopsy and outcomes of the procedure in women with endometrial cancer who underwent hysterectomy...
February 14, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28213008/the-prognostic-impact-of-tumor-volume-on-stage-i-non-small-cell-lung-cancer
#20
Xiao-Dong Su, Hao-Jun Xie, Qian-Wen Liu, Yun-Xian Mo, Hao Long, Tie-Hua Rong
OBJECTIVES: The purpose of this study was to investigate the prognostic impact of tumor volume (TV) on patients with stage I non-small cell lung cancer (NSCLC) after complete resection. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological characteristics of 274 patients with stage I NSCLC who had received preoperative chest computed tomography (CT) scans and complete resection. TV was semi-automatically measured from chest CT scans by using an imaging software program...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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