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https://www.readbyqxmd.com/read/27912756/mechanisms-of-inflammatory-responses-and-development-of-insulin-resistance-how-are-they-interlinked
#1
Kanwal Rehman, Muhammad Sajid Hamid Akash
BACKGROUND: Insulin resistance (IR) is one of the major hallmark for pathogenesis and etiology of type 2 diabetes mellitus (T2DM). IR is directly interlinked with various inflammatory responses which play crucial role in the development of IR. Inflammatory responses play a crucial role in the pathogenesis and development of IR which is one of the main causative factor for the etiology of T2DM. METHODS: A comprehensive online English literature was searched using various electronic search databases...
December 3, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27908935/posttranslational-regulation-of-smads
#2
REVIEW
Pinglong Xu, Xia Lin, Xin-Hua Feng
Transforming growth factor β (TGF-β) family signaling dictates highly complex programs of gene expression responses, which are extensively regulated at multiple levels and vary depending on the physiological context. The formation, activation, and destruction of two major functional complexes in the TGF-β signaling pathway (i.e., the TGF-β receptor complexes and the Smad complexes that act as central mediators of TGF-β signaling) are direct targets for posttranslational regulation. Dysfunction of these complexes often leads or contributes to pathogenesis in cancer and fibrosis and in cardiovascular, and autoimmune diseases...
December 1, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27906189/distinct-outcomes-of-crl-nedd8-pathway-inhibition-reveal-cancer-cell-plasticity
#3
Anastasia V Rulina, Frédérique Mittler, Patricia Obeid, Sophie Gerbaud, Laurent Guyon, Eric Sulpice, Frédérique Kermarrec, Nicole Assard, Monika E Dolega, Xavier Gidrol, Maxim Y Balakirev
Inhibition of protein degradation by blocking Cullin-RING E3 ligases (CRLs) is a new approach in cancer therapy though of unknown risk because CRL inhibition may stabilize both oncoproteins and tumor suppressors. Probing CRLs in prostate cancer cells revealed a remarkable plasticity of cells with TMPRSS2-ERG translocation. CRL suppression by chemical inhibition or knockdown of RING component RBX1 led to reversible G0/G1 cell cycle arrest that prevented cell apoptosis. Conversely, complete blocking of CRLs at a higher inhibitor dose-induced cytotoxicity that was amplified by knockdown of CRL regulator Cand1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27904738/recent-developments-in-the-management-of-invasive-fungal-infections-in-patients-with-oncohematological-diseases
#4
REVIEW
Markus Ruhnke, Stefan Schwartz
Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904234/allocation-of-rehabilitation-services-for-older-adults-in-the-ontario-home-care-system
#5
Joshua J Armstrong, Joanie Sims-Gould, Paul Stolee
Background: Physiotherapy and occupational therapy services can play a critical role in maintaining or improving the physical functioning, quality of life, and overall independence of older home care clients. Despite their importance, however, there is limited understanding of the factors that influence how rehabilitation services are allocated to older home care clients. The aim of this pilot study was to develop a preliminary understanding of the factors that influence decisions to allocate rehabilitation therapy services to older clients in the Ontario home care system, as perceived by three stakeholder groups...
2016: Physiotherapy Canada. Physiothérapie Canada
https://www.readbyqxmd.com/read/27903651/t-cells-encountering-myeloid-cells-programmed-for-amino-acid-dependent-immunosuppression-use-rictor-mtorc2-for-proliferative-checkpoint-decisions
#6
Lee-Ann Van de Velde, Chitra Subramanian, Amber M Smith, Luke Barron, Joseph E Qualls, Geoffrey Neale, Adolfo Alfonso-Pecchio, Suzanne Jackowski, Charles O Rock, Thomas A Wynn, Peter J Murray
Modulation of T cell proliferation and function by immunoregulatory myeloid cells is an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage: T cell co-culture system, we show that macrophage Arginase-1 (Arg1) is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by L-arginine elimination rather than metabolite generation...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903120/molecular-pathology-of-adamantinomatous-craniopharyngioma-review-and-opportunities-for-practice
#7
John Richard Apps, Juan Pedro Martinez-Barbera
Since the first identification of CTNNB1 mutations in adamantinomatous craniopharyngioma (ACP), much has been learned about the molecular pathways and processes that are disrupted in ACP pathogenesis. To date this understanding has not translated into tangible patient benefit. The recent development of novel techniques and a range of preclinical models now provides an opportunity to begin to support treatment decisions and develop new therapeutics based on molecular pathology. In this review the authors summarize many of the key findings and pathways implicated in ACP pathogenesis and discuss the challenges that need to be tackled to translate these basic science findings for the benefit of patients...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27902699/modeling-cellular-noise-underlying-heterogeneous-cell-responses-in-the-epidermal-growth-factor-signaling-pathway
#8
Kazunari Iwamoto, Yuki Shindo, Koichi Takahashi
Cellular heterogeneity, which plays an essential role in biological phenomena, such as drug resistance and migration, is considered to arise from intrinsic (i.e., reaction kinetics) and extrinsic (i.e., protein variability) noise in the cell. However, the mechanistic effects of these types of noise to determine the heterogeneity of signal responses have not been elucidated. Here, we report that the output of epidermal growth factor (EGF) signaling activity is modulated by cellular noise, particularly by extrinsic noise of particular signaling components in the pathway...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27902487/identification-of-laryngeal-cancer-prognostic-biomarkers-using-an-inflammatory-gene-related-competitive-endogenous-rna-network
#9
Qun He, Linli Tian, Hao Jiang, Jiarui Zhang, Qiang Li, Yanan Sun, Jiannan Zhao, Huijun Li, Ming Liu
Competitive endogenous RNAs (ceRNAs) act as molecular sponges for microRNAs (miRNAs), and are associated with tumorigenesis in various cancers, including laryngeal cancer (LC). In this work, we constructed an LC-specific inflammatory gene-related ceRNA network (IceNet). In IceNet, ceRNAs targeting inflammation-related genes tended to be network hubs. Additionally, the betweenness centralities of these hub ceRNAs were higher than those of the inflammation-related genes themselves, indicating that the hub ceRNAs in this study played critical roles in communication between IceNet molecules...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901111/optogenetic-clustering-of-cnk1-reveals-mechanistic-insights-in-raf-and-akt-signalling-controlling-cell-fate-decisions
#10
Adrian Fischer, Bettina Warscheid, Wilfried Weber, Gerald Radziwill
Scaffold proteins such as the multidomain protein CNK1 orchestrate the signalling network by integrating and controlling the underlying pathways. Using an optogenetic approach to stimulate CNK1 uncoupled from upstream effectors, we identified selective clusters of CNK1 that either stimulate RAF-MEK-ERK or AKT signalling depending on the light intensity applied. OptoCNK1 implemented in MCF7 cells induces differentiation at low light intensity stimulating ERK activity whereas stimulation of AKT signalling by higher light intensity promotes cell proliferation...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899996/quantitative-label-free-mass-spectrometry-analysis-of-formalin-fixed-paraffin-embedded-tissue-representing-the-invasive-cutaneous-malignant-melanoma-proteome
#11
Paul Dowling, Benvon Moran, Edel McAuley, Paula Meleady, Michael Henry, Martin Clynes, Mairin McMenamin, Niamh Leonard, Mary Monks, Bairbre Wynne, Patrick Ormond, Annemarie Larkin
Understanding the events at a protein level that govern the progression from melanoma in situ to invasive melanoma are important areas of current research to be developed. Recent advances in the analysis of formalin-fixed, paraffin-embedded tissue by proteomics, particularly using the filter-aided sample preparation protocol, has opened up the possibility of studying vast archives of clinical material and associated medical records. In the present study, quantitative protein profiling was performed using tandem mass spectrometry, and the proteome differences between melanoma in situ and invasive melanoma were compared...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899803/novel-targets-in-the-treatment-of-chronic-graft-versus-host-disease
#12
REVIEW
A Im, F T Hakim, S Z Pavletic
Despite advances that have improved survival after allogeneic hematopoietic stem cell transplantation (HCT), chronic graft-versus-host disease (GVHD) remains a leading cause of late morbidity and mortality after transplant. Current treatment options show limited efficacy in steroid-refractory disease, and there exists a paucity of robust data to guide management decisions. Lack of United States Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved agents in GVHD underscore the importance of developing novel therapies...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899776/-new-classification-for-advanced-colorectal-cancer-using-cancerplex%C3%A2-genomic-tests
#13
Hitoshi Kameyama, Yoshifumi Shimada, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Shujiro Okuda, Yiwei Ling, Hiroshi Izutsu, Keisuke Kodama, Mitsutaka Nakada, Toshifumi Wakai
Recently, targeted drugs have been developed for the treatment of colorectal cancer(CRC). Among targets, it is well known that KRAS mutations are associated with resistance to epidermal growth factor receptor(EGFR)monoclonal antibodies. However, response rates using anti-EGFR monotherapy for CRC were less than 20-30% in previous clinical studies. Thus, because the RAS/MAP2K/MAPK and PI3K/AKT pathways are associated with CRC resistance to chemotherapy, we analyzed gene mutations in Stage IV CRC patients using a genomic test(CancerPlex®)...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27895661/the-genome-conformation-as-an-integrator-of-multi-omic-data-the-example-of-damage-spreading-in-cancer
#14
Fabio Tordini, Marco Aldinucci, Luciano Milanesi, Pietro Liò, Ivan Merelli
Publicly available multi-omic databases, in particular if associated with medical annotations, are rich resources with the potential to lead a rapid transition from high-throughput molecular biology experiments to better clinical outcomes for patients. In this work, we propose a model for multi-omic data integration (i.e., genetic variations, gene expression, genome conformation, and epigenetic patterns), which exploits a multi-layer network approach to analyse, visualize, and obtain insights from such biological information, in order to use achieved results at a macroscopic level...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27894418/discovery-of-methylfarnesoate-as-the-annelid-brain-hormone-reveals-an-ancient-role-of-sesquiterpenoids-in-reproduction
#15
Sven Schenk, Christian Krauditsch, Peter Frühauf, Christopher Gerner, Florian Raible
Animals require molecular signals to determine when to divert resources from somatic functions to reproduction. This decision is vital in animals that reproduce in an all-or-nothing mode, such as bristle worms: females committed to reproduction spend roughly half their body mass for yolk and egg production; following mass spawning, the parents die. An enigmatic brain hormone activity suppresses reproduction. We now identify this hormone as the sesquiterpenoid methylfarnesoate. Methylfarnesoate suppresses transcript levels of the yolk precursor Vitellogenin both in cell culture and in vivo, directly inhibiting a central energy-costly step of reproductive maturation...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27894303/integrated-agriculture-programs-to-address-malnutrition-in-northern-malawi
#16
Rachel Bezner Kerr, Emmanuel Chilanga, Hanson Nyantakyi-Frimpong, Isaac Luginaah, Esther Lupafya
BACKGROUND: In countries where the majority of undernourished people are smallholder farmers, there has been interest in agricultural interventions to improve nutritional outcomes. Addressing gender inequality, however, is a key mechanism by which agriculture can improve nutrition, since women often play a crucial role in farming, food processing and child care, but have limited decision-making and control over agricultural resources. This study examines the approaches by which gender equity in agrarian, resource-poor settings can be improved using a case study in Malawi...
November 28, 2016: BMC Public Health
https://www.readbyqxmd.com/read/27885092/nuclear-and-radiological-preparedness-the-achievements-of-the-european-research-project-prepare
#17
Thierry Schneider, Florian Gering, Sylvie Charron, Mark Zhelezniak, Spyros Andronopoulos, Gilles Heriard-Dubreuil, Johan Camps, Wolfgang Raskob
The PREPARE project aimed closing gaps identified in nuclear and radiological preparedness in Europe following the first evaluation of the Fukushima disaster. With 46 partners from Europe and Japan, it collected the key players in the area of emergency management and rehabilitation preparedness. Starting from February 2013, the project ended in January 2016. Among others, the project reviewed existing operational procedures for long-lasting releases, cross-border problems in radiation monitoring and food safety and further developed missing functionalities in decision support systems ranging from improved source term estimation and dispersion modelling to the inclusion of hydrological pathways for European water bodies...
November 24, 2016: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/27884478/vaccine-provision-delivering-sustained-widespread-use
#18
Scott Preiss, Nathalie Garçon, Anthony L Cunningham, Richard Strugnell, Leonard R Friedland
The administration of a vaccine to a recipient is the final step in a development and production process that may have begun several decades earlier. Here we describe the scale and complexity of the processes that brings a candidate vaccine through clinical development to the recipient. These challenges include ensuring vaccine quality (between 100 and 500 different Quality Control tests are performed during production to continually assess safety, potency and purity); making decisions about optimal vaccine presentation (pre-filled syringes versus multi-dose vials) that affect capacity and supply; and the importance of maintaining the vaccine cold chain (most vaccines have stringent storage temperature requirements necessary to maintain activity and potency)...
November 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27881890/co-management-as-a-catalyst-pathways-to-post-colonial-forestry-in-the-klamath-basin-california
#19
Sibyl Diver
Co-management frameworks are intended to facilitate sustainable resource management and more equitable power sharing between state agencies and Indigenous communities. However, there is significant debate about who benefits from co-management in practice. This article addresses two competing perspectives in the literature, which alternately portrays co-management as an instrument for co-optation or for transformation. Through a case study of co-management negotiations involving the Karuk Tribe and the U.S. Forest Service in the Klamath Basin of Northern California, this study examines how Indigenous communities use co-management to build greater equity in environmental decision-making, despite its limitations...
2016: Human Ecology: An Interdisciplinary Journal
https://www.readbyqxmd.com/read/27879568/effect-of-immunotherapy-status-on-outcomes-in-patients-with-metastatic-melanoma-to-the-spine
#20
Ganesh M Shankar, Bryan D Choi, Benjamin L Grannan, Kevin Oh, John H Shin
STUDY DESIGN: Retrospective cohort study OBJECTIVE.: We performed a retrospective study of patients treated at our institution over the last 3 years to assess predictive value of immunotherapy exposure on overall survival of patients with metastatic melanoma to the spine in an effort to better inform surgical decision making. SUMMARY OF BACKGROUND DATA: Modern management of metastatic melanoma includes adjuvant targeted therapies and immunomodulators that have shown to significantly improve overall survival...
November 22, 2016: Spine
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