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https://www.readbyqxmd.com/read/28724009/the-dialog-between-health-and-foreign-policy-in-brazilian-cooperation-in-human-milk-banks
#1
Tiago Mocellin Pittas, Clarissa Franzoi Dri
Mother's milk is the primary source of nourishment in early infancy. When this source is unavailable, secondary sources may be used, such as human milk banks. The first milk bank in Brazil was created in 1943, and they have been used ever since. A national model was developed through a number of phases, culminating in the Brazilian Network of Human Milk Banks. This gave rise to a number of international cooperation projects, with the Brazilian model particularly relevant for developing nations. The main objective of this analysis is to understand what drives Brazil to promote milk banks internationally...
July 2017: Ciência & Saúde Coletiva
https://www.readbyqxmd.com/read/28723935/responses-of-molluscan-communities-to-centuries-of-human-impact-in-the-northern-adriatic-sea
#2
Ivo Gallmetzer, Alexandra Haselmair, Adam Tomašových, Michael Stachowitsch, Martin Zuschin
In sediment cores spanning ~500 years of history in the Gulf of Trieste, down-core changes in molluscan community structure are characterized by marked shifts in species and functional composition. Between the 16th and 19th century, a strong heavy metal contamination of the sediments, most notably by Hg, together with the effects of natural climatic oscillations (increased sedimentation and organic enrichment) drive community changes. Since the early 20th century up to 2013, the combined impacts of cultural eutrophication, frequent hypoxic events and intensifying bottom trawling replace heavy metal contamination and climatic factors as the main drivers...
2017: PloS One
https://www.readbyqxmd.com/read/28723647/set-contributes-to-the-epithelial-mesenchymal-transition-of-pancreatic-cancer
#3
Hardik R Mody, Sau Wai Hung, Kineta Naidu, Haesung Lee, Caitlin A Gilbert, Toan Thanh Hoang, Rakesh K Pathak, Radhika Manoharan, Shanmugam Muruganandan, Rajgopal Govindarajan
Pancreatic cancer has a devastating prognosis due to 80-90% of diagnostic cases occurring when metastasis has already presented. Activation of the epithelial-mesenchymal transition (EMT) is a prerequisite for metastasis because it allows for the dissemination of tumor cells to blood stream and secondary organs. Here, we sought to determine the role of SET oncoprotein, an endogenous inhibitor of PP2A, in EMT and pancreatic tumor progression. Among the two major isoforms of SET (isoform 1 and isoform 2), higher protein levels of SET isoform 2 were identified in aggressive pancreatic cancer cell lines...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723569/xiap-loss-triggers-ripk3-and-caspase-8-driven-il-1%C3%AE-activation-and-cell-death-as-a-consequence-of-tlr-myd88-induced-ciap1-traf2-degradation
#4
Kate E Lawlor, Rebecca Feltham, Monica Yabal, Stephanie A Conos, Kaiwen W Chen, Stephanie Ziehe, Carina Graß, Yifan Zhan, Tan A Nguyen, Cathrine Hall, Angelina J Vince, Simon M Chatfield, Damian B D'Silva, Kenneth C Pang, Kate Schroder, John Silke, David L Vaux, Philipp J Jost, James E Vince
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723562/integrative-genomics-identifies-the-molecular-basis-of-resistance-to-azacitidine-therapy-in-myelodysplastic-syndromes
#5
Ashwin Unnikrishnan, Elli Papaemmanuil, Dominik Beck, Nandan P Deshpande, Arjun Verma, Ashu Kumari, Petter S Woll, Laura A Richards, Kathy Knezevic, Vashe Chandrakanthan, Julie A I Thoms, Melinda L Tursky, Yizhou Huang, Zara Ali, Jake Olivier, Sally Galbraith, Austin G Kulasekararaj, Magnus Tobiasson, Mohsen Karimi, Andrea Pellagatti, Susan R Wilson, Robert Lindeman, Boris Young, Raj Ramakrishna, Christopher Arthur, Richard Stark, Philip Crispin, Jennifer Curnow, Pauline Warburton, Fernando Roncolato, Jacqueline Boultwood, Kevin Lynch, Sten Eirik W Jacobsen, Ghulam J Mufti, Eva Hellstrom-Lindberg, Marc R Wilkins, Karen L MacKenzie, Jason W H Wong, Peter J Campbell, John E Pimanda
Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723515/understanding-mechanisms-of-resistance-in-metastatic-castration-resistant-prostate-cancer-the-role-of-the-androgen-receptor
#6
REVIEW
Derya Tilki, Edward M Schaeffer, Christopher P Evans
CONTEXT: After initiation of androgen deprivation therapy (ADT), most patients progress to castration-resistant prostate cancer (CRPC) within 2 or 3 yr. In the USA, approximately 67000 men are estimated to have metastatic CRPC. OBJECTIVE: To provide an overview of different mechanisms driving resistance to therapy in metastatic CRPC, with a focus on androgen receptor (AR)-dependent pathways. EVIDENCE ACQUISITION: A Medline search via PubMed was performed using the keywords metastatic castration resistant prostate cancer (mCRPC), castration-resistant, CRPC, prostate cancer, androgen resistance, hormone-refractory, hormone-independent, androgen receptor, and androgen receptor axis...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723478/low-t-cell-receptor-diversity-high-somatic-mutation-burden-and-high-neoantigen-load-as-predictors-of-clinical-outcome-in-muscle-invasive-bladder-cancer
#7
Noura J Choudhury, Kazuma Kiyotani, Kai Lee Yap, Alexa Campanile, Tatjana Antic, Poh Yin Yew, Gary Steinberg, Jae Hyun Park, Yusuke Nakamura, Peter H O'Donnell
BACKGROUND: The success of cancer immunotherapies has highlighted the potent ability of local adaptive immune responses to eradicate cancer cells by targeting neoantigens generated by somatic alterations. However, how these factors interact to drive the natural history of muscle-invasive bladder cancer (MIBC) is not well understood. OBJECTIVE: To investigate the role of immune regulation in MIBC disease progression, we performed massively parallel T-cell receptor (TCR) sequencing of tumor-infiltrating T cells (TILs), in silico neoantigen prediction from exome sequences, and expression analysis of immune-related genes...
October 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723273/the-repair-project-examining-the-biological-impacts-of-sub-background-radiation-exposure-within-snolab-a-deep-underground-laboratory
#8
Christopher Thome, Sujeenthar Tharmalingam, Jake Pirkkanen, Andrew Zarnke, Taylor Laframboise, Douglas R Boreham
Considerable attention has been given to understanding the biological effects of low-dose ionizing radiation exposure at levels slightly above background. However, relatively few studies have been performed to examine the inverse, where natural background radiation is removed. The limited available data suggest that organisms exposed to sub-background radiation environments undergo reduced growth and an impaired capacity to repair genetic damage. Shielding from background radiation is inherently difficult due to high-energy cosmic radiation...
July 19, 2017: Radiation Research
https://www.readbyqxmd.com/read/28723210/bipolar-electrodes-with-100-current-efficiency-for-sensors
#9
Xiaowei Zhang, Qingfeng Zhai, Huanhuan Xing, Jing Li, Erkang Wang
A bipolar electrode (BPE) is an electron conductor that is embedded in the electrolyte solution without the direct connection with the external power source (driving electrode). When the sufficient voltage was provided, the two poles of BPE promote different oxidation and reduction reactions. During the past few years, BPEs with wireless feature and easy integration showed great promise in the various fields including asymmetric modification/synthesis, motion control, targets enrichment/separation, and chemical sensing/biosensing combined with the quantitative relationship between two poles of BPE...
March 24, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28723067/structural-and-spectroscopic-properties-of-assemblies-of-self-replicating-peptide-macrocycles
#10
Pim W J M Frederix, Julien Idé, Yigit Altay, Gaël Schaeffer, Mathieu Surin, David Beljonne, Anna S Bondarenko, Thomas L C Jansen, Sijbren Otto, Siewert J Marrink
Self-replication at the molecular level is often seen as essential to the early origins of life. Recently a mechanism of self-replication has been discovered in which replicator self-assembly drives the process. We have studied one of the examples of such self-assembling self-replicating molecules to a high level of structural detail using a combination of computational and spectroscopic techniques. Molecular Dynamics simulations of self-assembled stacks of peptide-derived replicators provide insights into the structural characteristics of the system and serve as the basis for semi-empirical calculations of the UV/Vis, circular dichroism (CD) and infrared (IR) absorption spectra that reflect the chiral organization and peptide secondary structure of the stacks...
July 19, 2017: ACS Nano
https://www.readbyqxmd.com/read/28723063/using-cooperatively-folded-peptides-to-measure-interaction-energies-and-conformational-propensities
#11
Maziar S Ardejani, Evan T Powers, Jeffery W Kelly
The rates and equilibria of the folding of biopolymers are determined by the conformational preferences of the subunits that make up the sequence of the biopolymer and by the interactions that are formed in the folded state in aqueous solution. Because of the centrality of these processes to life, quantifying conformational propensities and interaction strengths is vitally important to understanding biology. In this Account, we describe our use of peptide model systems that fold cooperatively yet are small enough to be chemically synthesized to measure such quantities...
July 19, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28722765/multivariate-association-analysis-with-somatic-mutation-data
#12
Qianchuan He, Yang Liu, Ulrike Peters, Li Hsu
Somatic mutations are the driving forces for tumor development, and recent advances in cancer genome sequencing have made it feasible to evaluate the association between somatic mutations and cancer-related traits in large sample sizes. However, despite increasingly large sample sizes, it remains challenging to conduct statistical analysis for somatic mutations, because the vast majority of somatic mutations occur at very low frequencies. Furthermore, cancer is a complex disease and it is often accompanied by multiple traits that reflect various aspects of cancer; how to combine the information of these traits to identify important somatic mutations poses additional challenges...
July 19, 2017: Biometrics
https://www.readbyqxmd.com/read/28722658/the-golgi-localized-gamma-ear-containing-arf-binding-gga-protein-family-alters-alpha-synuclein-%C3%AE-syn-oligomerization-and-secretion
#13
Bjoern von Einem, Judith Eschbach, Martin Kiechle, Anke Wahler, Dietmar R Thal, Pamela J McLean, Jochen H Weishaupt, Albert C Ludolph, Christine A F von Arnim, Karin M Danzer
Several age-related neurodegenerative disorders are associated with protein misfolding and aggregation of toxic peptides. α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinson's disease (PD) as well as dementia with Lewy bodies. Rising evidence points to oligomeric and pre-fibrillar forms as the pathogenic species, and oligomer secretion seems to be crucial for the spreading and progression of PD pathology. Recent studies implicate that dysfunctions in endolysosomal/autophagosomal pathways increase α-syn secretion...
July 15, 2017: Aging
https://www.readbyqxmd.com/read/28722655/key-steps-in-unconventional-secretion-of-fibroblast-growth-factor-2-reconstituted-with-purified-components
#14
Julia P Steringer, Sascha Lange, Sabína Čujová, Radek Šachl, Chetan Poojari, Fabio Lolicato, Oliver Beutel, Hans-Michael Müller, Sebastian Unger, Ünal Coskun, Alf Honigmann, Ilpo Vattulainen, Martin Hof, Christian Freund, Walter Nickel
FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membrane translocation is thermodynamically driven by PI(4,5)P2-induced membrane insertion of FGF2 oligomers. The latter serve as dynamic translocation intermediates of FGF2 with a subunit number in the range of 8-12 FGF2 molecules...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28722652/the-packing-density-of-a-supramolecular-membrane-protein-cluster-is-controlled-by-cytoplasmic-interactions
#15
Elisa Merklinger, Jan-Gero Schloetel, Pascal Weber, Helena Batoulis, Sarah Holz, Nora Karnowski, Jérôme Finke, Thorsten Lang
Molecule clustering is an important mechanism underlying cellular self-organization. In the cell membrane, a variety of fundamentally different mechanisms drive membrane protein clustering into nanometre-sized assemblies. To date, it is unknown whether this clustering process can be dissected into steps differentially regulated by independent mechanisms. Using clustered syntaxin molecules as an example, we study the influence of a cytoplasmic protein domain on the clustering behaviour. Analysing protein mobility, cluster size and accessibility to myc-epitopes we show that forces acting on the transmembrane segment produce loose-clusters, while cytoplasmic protein interactions mediate a tightly packed state...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28722554/improving-maternal-and-child-health-policymaking-processes-in-nigeria-an-assessment-of-policymakers-needs-barriers-and-facilitators-of-evidence-informed-policymaking
#16
Chigozie J Uneke, Issiaka Sombie, Namoudou Keita, Virgil Lokossou, Ermel Johnson, Pierre Ongolo-Zogo
BACKGROUND: In Nigeria, interest in the evidence-to-policy process is gaining momentum among policymakers involved in maternal, newborn and child health (MNCH). However, numerous gaps exist among policymakers on use of research evidence in policymaking. The objective of this study was to assess the perception of MNCH policymakers regarding their needs and the barriers and facilitators to use of research evidence in policymaking in Nigeria. METHODS: The study design was a cross-sectional assessment of perceptions undertaken during a national MNCH stakeholders' engagement event convened in Abuja, Nigeria...
July 12, 2017: Health Research Policy and Systems
https://www.readbyqxmd.com/read/28722548/the-change-makers-of-west-africa
#17
EDITORIAL
Sue Godt, Sharmila Mhatre, Anne-Marie Schryer-Roy
West Africa was the focus of global attention during the Ebola virus disease outbreak, when systemic health system weaknesses compounded a serious emergency and complicated response efforts. Following the crisis, calls were made to strengthen health systems, but investments to date have fallen short of delivering the support needed to build strong health systems able to prevent and manage future outbreaks.In part, this reality serves to highlight the shortcomings of the solutions being repeatedly prioritised by external funders and experts, solutions that often fail to consider the wealth of West African evidence and actors actively working to strengthen the leadership and health systems needed to drive and sustainably improve national health outcomes...
July 12, 2017: Health Research Policy and Systems
https://www.readbyqxmd.com/read/28722539/an-autophagy-driven-pathway-of-atp-secretion-supports-the-aggressive-phenotype-of-braf-v600e-inhibitor-resistant-metastatic-melanoma-cells
#18
Shaun Martin, Aleksandra M Dudek-Peric, Abhishek D Garg, Heleen Roose, Seyma Demirsoy, Sofie Van Eygen, Freya Mertens, Peter Vangheluwe, Hugo Vankelecom, Patrizia Agostinis
The ingrained capacity of melanoma cells to rapidly evolve towards an aggressive phenotype is manifested by their increased ability to develop drug-resistance, evident in the case of vemurafenib, a therapeutic-agent targeting BRAF(V600E). Previous studies indicated a tight correlation between heightened melanoma-associated macroautophagy/autophagy and acquired Vemurafenib resistance. However, how this vesicular trafficking pathway supports Vemurafenib resistance remains unclear. Here, using isogenic human and murine melanoma cell lines of Vemurafenib-resistant and patient-derived melanoma cells with primary resistance to the BRAF(V600E) inhibitor, we found that the enhanced migration and invasion of the resistant melanoma cells correlated with an enhanced autophagic capacity and autophagosome-mediated secretion of ATP...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28722536/travel-burden-associated-with-granulocyte-colony-stimulating-factor-administration-in-a-medicare-aged-population-a-geospatial-analysis
#19
J Mark Stephens, Mark Bensink, Charles Bowers, Christopher S Hollenbeak
OBJECTIVE: Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is recommended for patients receiving myelosuppressive chemotherapy regimens with a high risk of febrile neutropenia (FN). G-CSFs should be administered starting the day after chemotherapy, necessitating return trips to the oncology clinic at the end of each cycle. We examined the travel burden related to prophylactic G-CSF injections after chemotherapy in the United States (US). METHODS: We used 2012-2014 Medicare claims data to identify a national cohort of beneficiaries age 65+ with non-myeloid cancers who received both chemotherapy and prophylactic G-CSFs...
July 19, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28722214/impairment-due-to-combined-sleep-restriction-and-alcohol-is-not-mitigated-by-decaying-breath-alcohol-concentration-or-rest-breaks
#20
Jessica E Manousakis, Clare Anderson
OBJECTIVE: Epidemiological and laboratory-based driving simulator studies have shown the detrimental impact of moderate, legal levels of alcohol consumption on driving performance in sleepy drivers. As less is known about the time course of decaying alcohol alongside performance impairment, our study examined impairment and recovery of performance alongside decaying levels of alcohol, with and without sleep restriction. METHODS: Sixteen healthy young males (18-27 years) underwent 4 counterbalanced conditions: Baseline, Alcohol (breath alcohol concentration [BrAC] < 0...
July 18, 2017: Human Psychopharmacology
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