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https://www.readbyqxmd.com/read/28441061/precisely-where-are-we-going-charting-the-new-terrain-of-precision-prevention
#1
Karen M Meagher, Michelle L McGowan, Richard A Settersten, Jennifer R Fishman, Eric T Juengst
In addition to genetic data, precision medicine research gathers information about three factors that modulate gene expression: lifestyles, environments, and communities. The relevant research tools-epidemiology, environmental assessment, and socioeconomic analysis-are those of public health sciences rather than molecular biology. Because these methods are designed to support inferences and interventions addressing population health, the aspirations of this research are expanding from individualized treatment toward precision prevention in public health...
April 24, 2017: Annual Review of Genomics and Human Genetics
https://www.readbyqxmd.com/read/28440301/the-environmental-yeast-cryptococcus-liquefaciens-produces-capsular-and-secreted-polysaccharides-with-similar-pathogenic-properties-to-those-of-c-neoformans
#2
Glauber R de S Araújo, Gustavo J C Freitas, Fernanda L Fonseca, Paulo Emilio C Leite, Gustavo Miranda Rocha, Wanderley de Souza, Daniel A Santos, Susana Frases
Invasive fungal infections, including cryptococcosis, are a growing threat to immunocompromised patients. Although Cryptococcus neoformans and Cryptococcus gattii are the main agents of human cryptococcosis, opportunistic infections by environmental species, such as C. liquefaciens, have been observed recently. The main Cryptococcus virulence factor is the production and secretion of polysaccharides (PS). Previously, we showed that both species produce PS of similar composition. Here, we examined the ultrastructure and biological activity of capsular and secreted PS from C...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439531/genome-and-cd4-t-cell-methylome-wide-association-study-of-circulating-trimethylamine-n-oxide-in-the-genetics-of-lipid-lowering-drugs-and-diet-network-goldn
#3
Stella Aslibekyan, Marguerite R Irvin, Bertha A Hidalgo, Rodney T Perry, Elias J Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N Hopkins, Michael A Province, Hemant K Tiwari, Jose M Ordovas, Devin M Absher, Donna K Arnett
BACKGROUND: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels. METHODS AND RESULTS: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans...
June 2017: Journal of Nutrition & Intermediary Metabolism
https://www.readbyqxmd.com/read/28439007/ocean-warming-since-1982-has-expanded-the-niche-of-toxic-algal-blooms-in-the-north-atlantic-and-north-pacific-oceans
#4
Christopher J Gobler, Owen M Doherty, Theresa K Hattenrath-Lehmann, Andrew W Griffith, Yoonja Kang, R Wayne Litaker
Global ocean temperatures are rising, yet the impacts of such changes on harmful algal blooms (HABs) are not fully understood. Here we used high-resolution sea-surface temperature records (1982 to 2016) and temperature-dependent growth rates of two algae that produce potent biotoxins, Alexandrium fundyense and Dinophysis acuminata, to evaluate recent changes in these HABs. For both species, potential mean annual growth rates and duration of bloom seasons significantly increased within many coastal Atlantic regions between 40°N and 60°N, where incidents of these HABs have emerged and expanded in recent decades...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438975/galectin-3-is-a-target-for-proteases-involved-in-the-virulence-of-staphylococcus-aureus
#5
Jonas Elmwall, Jakub Kwiecinski, Manli Na, Abukar Ahmed Ali, Veronica Osla, Lindsey Shaw, Wanzhong Wang, Karin Sävman, Elisabet Josefsson, Johan Bylund, Tao Jin, Amanda Welin, Anna Karlsson
Staphylococcus aureus is a major cause of skin and soft-tissue infection. The bacterium expresses four major proteases emerging as virulence factors; aureolysin (Aur), V8 protease (SspA), staphopain A (ScpA), and staphopain B (SspB). We hypothesized that human galectin-3, a β-galactoside-binding lectin involved in immune regulation and antimicrobial defense, is a target for these proteases, and that proteolysis of galectin-3 is a novel immune evasion mechanism. Indeed, supernatants from laboratory strains and clinical isolates of S...
April 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28438915/conservation-development-and-the-management-of-infectious-disease-avian-influenza-in-china-2004-2012
#6
Tong Wu, Charles Perrings
There is growing evidence that wildlife conservation measures have mixed effects on the emergence and spread of zoonotic disease. Wildlife conservation has been found to have both positive (dilution) and negative (contagion) effects. In the case of avian influenza H5N1 in China, the focus has been on negative effects. Lakes and wetlands attracting migrating waterfowl have been argued to be disease hotspots. We consider the implications of waterfowl conservation for H5N1 infections in both poultry and humans between 2004 and 2012...
June 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28437394/selective-degradation-of-splicing-factor-caper%C3%AE-by-anticancer-sulfonamides
#7
Taisuke Uehara, Yukinori Minoshima, Koji Sagane, Naoko Hata Sugi, Kaoru Ogawa Mitsuhashi, Noboru Yamamoto, Hiroshi Kamiyama, Kentaro Takahashi, Yoshihiko Kotake, Mai Uesugi, Akira Yokoi, Atsushi Inoue, Taku Yoshida, Miyuki Mabuchi, Akito Tanaka, Takashi Owa
Target-protein degradation is an emerging field in drug discovery and development. In particular, the substrate-receptor proteins of the cullin-ubiquitin ligase system play a key role in selective protein degradation, which is an essential component of the anti-myeloma activity of immunomodulatory drugs (IMiDs), such as lenalidomide. Here, we demonstrate that a series of anticancer sulfonamides NSC 719239 (E7820), indisulam, and NSC 339004 (chloroquinoxaline sulfonamide, CQS) induce proteasomal degradation of the U2AF-related splicing factor coactivator of activating protein-1 and estrogen receptors (CAPERα) via CRL4(DCAF15) mediated ubiquitination in human cancer cell lines...
April 24, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28437184/control-of-mosquito-borne-diseases-in-northwestern-italy-preparedness-from-one-season-to-the-next
#8
Federica Verna, Paola Modesto, Maria Cristina Radaelli, Danila Raffaella Francese, Enrico Monaci, Rosanna Desiato, Carla Grattarola, Simone Peletto, Andrea Mosca, Giovanni Savini, Rosa Chianese, Vittorio Demicheli, Marino Prearo, Laura Chiavacci, Alessandra Pautasso, Cristina Casalone
INTRODUCTION: Mosquito-borne diseases (MBDs) are spreading worldwide due to globalization and climate change, representing a threat for both humans and animals. Of great concern are the infections caused by viruses belonging to the Flavivirus genus as West Nile virus (WNV) and Usutu virus (USUV) transmitted by Culex sp. or Dengue virus and Zika virus (ZIKV), transmitted by Aedes sp. This work describes the surveillance protocol enforced in Piedmont (Northwestern Italy) to control MBDs spread, focusing on the activities performed on mosquitoes during the 2015 vector season...
February 23, 2017: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28436242/current-status-of-ramucirumab-in-gastroesophageal-adenocarcinoma
#9
Elena Elimova, Quan Lin, Shumei Song, Jaffer A Ajani
Outcomes of patients with advanced gastric or gastroesophageal junction adenocarcinoma (GEAC) remain poor despite recent advances. The standard of care in the management of this disease had not changed much over the past decade. In the first line, a platinum containing doublet/triplet is used, while in <20% of patients with human epithelial growth factor receptor type 2 overexpressing GEACs, trasuzumab can provide a modest advantage. Until recently, no standard second-line regimens existed; however, the results of the REGARD and RAINBOW trials led to the approval of ramucirumab in the second-line setting...
April 24, 2017: Future Oncology
https://www.readbyqxmd.com/read/28435892/dramatic-improvement-of-crispr-cas9-editing-in-candida-albicans-by-increased-single-guide-rna-expression
#10
Henry Ng, Neta Dean
The clustered regularly interspaced short palindromic repeat system with CRISPR-associated protein 9 nuclease (CRISPR/Cas9) has emerged as a versatile tool for genome editing in Candida albicans. Mounting evidence from other model systems suggests that the intracellular levels of single guide RNA (sgRNA) limit the efficiency of Cas9-dependent DNA cleavage. Here, we tested this idea and describe a new means of sgRNA delivery that improves previously described methods by ~10-fold. The efficiency of Cas9/sgRNA-dependent cleavage and repair of a single-copy yeast enhanced monomeric red fluorescent protein (RFP) gene was measured as a function of various parameters that are hypothesized to affect sgRNA accumulation, including transcriptional and posttranscriptional processing...
March 2017: MSphere
https://www.readbyqxmd.com/read/28435888/continental-drift-and-speciation-of-the-cryptococcus-neoformans-and-cryptococcus-gattii-species-complexes
#11
Arturo Casadevall, Joudeh B Freij, Christopher Hann-Soden, John Taylor
Genomic analysis has placed the origins of two human-pathogenic fungi, the Cryptococcus gattii species complex and the Cryptococcus neoformans species complex, in South America and Africa, respectively. Molecular clock calculations suggest that the two species separated ~80 to 100 million years ago. This time closely approximates the breakup of the supercontinent Pangea, which gave rise to South America and Africa. On the basis of the geographic distribution of these two species complexes and the coincidence of the evolutionary divergence and Pangea breakup times, we propose that a spatial separation caused by continental drift resulted in the emergence of the C...
March 2017: MSphere
https://www.readbyqxmd.com/read/28435679/targeting-the-pro-inflammatory-factor-ccl2-mcp-1-with-bindarit-for-influenza-a-h7n9-treatment
#12
Stefan Wolf, Scott Johnson, Olivia Perwitasari, Suresh Mahalingam, Ralph A Tripp
Influenza A viruses are important human and animal pathogens. Seasonal influenza viruses cause infections every year, and occasionally zoonotic viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. Three cases of laboratory confirmed human infection with avian influenza A (H7N9) virus were reported in 2013, and there have been several cases reported across South East Asia, and recently in North America. Most patients experience severe respiratory illness, with mortality rates approaching 40%...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435007/stem-cells-and-their-potential-clinical-applications-in-psychiatric-disorders
#13
REVIEW
Mariusz Z Ratajczak, Andrzej K Ciechanowicz, Jolanta Kucharska-Mazur, Jerzy Samochowiec
The robustness of stem cells is one of the major factors that directly impacts life quality and life span. Evidence has accumulated that changes in the stem cell compartment affect human mental health and serve as an indicator of psychiatric problems. It is well known that stem cells continuously replace differentiated cells and tissues that are used up during life, although this replacement occurs at a different pace in the various organs. However, the participation of local neural stem cells in regeneration of the central nervous system is controversial...
April 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28434038/emerging-potential-of-gene-silencing-approaches-targeting-anti-chondrogenic-factors-for-cell-based-cartilage-repair
#14
REVIEW
Andrea Lolli, Letizia Penolazzi, Roberto Narcisi, Gerjo J V M van Osch, Roberta Piva
The field of cartilage repair has exponentially been growing over the past decade. Here, we discuss the possibility to achieve satisfactory regeneration of articular cartilage by means of human mesenchymal stem cells (hMSCs) depleted of anti-chondrogenic factors and implanted in the site of injury. Different types of molecules including transcription factors, transcriptional co-regulators, secreted proteins, and microRNAs have recently been identified as negative modulators of chondroprogenitor differentiation and chondrocyte function...
April 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28433050/zoonotic-potential-of-emerging-paramyxoviruses-knowns-and-unknowns
#15
Patricia A Thibault, Ruth E Watkinson, Andres Moreira-Soto, Jan F Drexler, Benhur Lee
The risk of spillover of enzootic paramyxoviruses and the susceptibility of recipient human and domestic animal populations are defined by a broad collection of ecological and molecular factors that interact in ways that are not yet fully understood. Nipah and Hendra viruses were the first highly lethal zoonotic paramyxoviruses discovered in modern times, but other paramyxoviruses from multiple genera are present in bats and other reservoirs that have unknown potential to spillover into humans. We outline our current understanding of paramyxovirus reservoir hosts and the ecological factors that may drive spillover, and we explore the molecular barriers to spillover that emergent paramyxoviruses may encounter...
2017: Advances in Virus Research
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#16
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
April 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28428643/-misscare-survey-italian-version-findings-from-an-italian-validation-study
#17
Luisa Sist, Carla Contini, Anna Bandini, Stefania Bandini, Licia Massa, Roberta Zanin, Rita Maricchio, Gloria Gianesini, Erika Bassi, Daniela Tartaglini, Alvisa Palese, Annamaria Ferraresi
BACKGROUND: The Missed Nursing Care (MNC) refers to nursing interventions that are not completed, partially completed, or postponed. Despite the relevance of MNC, no assessment tools are available in the Italian context, and no data regarding the occurrence of this phenomenon has been documented on a large scale to date. OBJECTIVES: The study aims were: (1) to validate the Italian version of the MISSCARE Survey tool; (2) to measure the prevalence of missed interventions and reasons for missed care as perceived by clinical nurses working in Italian health care settings...
January 2017: Igiene e Sanità Pubblica
https://www.readbyqxmd.com/read/28427061/emerging-insights-into-pathogenesis
#18
Edoardo Midena, Elisabetta Pilotto
Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus (DM). Persistent hyperglycemia leads to the activation of multiple cellular pathways involved in the pathogenesis of DR, resulting in increased inflammation, oxidative stress, and vascular dysfunction. DR has been considered a "chronic, low-grade inflammatory disease of the retina". However, an increasing body of evidence suggests that inflammation and neurodegeneration both occur in human diabetes even before the development of clinical signs of DR...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28423601/a-novel-lncrna-gasl1-inhibits-cell-proliferation-and-restricts-e2f1-activity
#19
Lital Gasri-Plotnitsky, Aviv Ovadia, Katerina Shamalov, Tali Nizri-Megnaji, Shimrit Meir, Irit Zurer, Cyrille J Cohen, Doron Ginsberg
The human genome encodes thousands of unique long non-coding RNAs (lncRNAs), many of which are emerging as critical regulators of cell fate. However, their functions as well as their transcriptional regulation are only partially understood. The E2F1 transcription factor induces both proliferation and apoptosis, and is a critical downstream target of the tumor suppressor, RB. Here, we provide evidence that a novel lncRNA named GASL1 is transcriptionally regulated by E2F1; GASL1 levels are elevated upon activation of exogenous E2F1 or endogenous E2Fs...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423511/atm-kinase-sustains-breast-cancer-stem-like-cells-by-promoting-atg4c-expression-and-autophagy
#20
Martina Antonelli, Flavie Strappazzon, Ivan Arisi, Rossella Brandi, Mara D'Onofrio, Manolo Sambucci, Gwenola Manic, Ilio Vitale, Daniela Barilà, Venturina Stagni
The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels...
March 28, 2017: Oncotarget
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