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Marie Todd
A venous leg ulcer (VLU) is defined as the loss of skin below the knee on the leg or foot in the presence of venous disease, which takes more than two weeks to heal. The prevalence of VLUs is increasing, especially in older people, which will increase the demand for nursing care. Development of a lower leg ulcer should trigger immediate assessment of risk factors for chronic venous disease followed by action to identify the cause and initiate treatment, which should prevent progression to more complex and chronic problems...
June 19, 2018: Nursing Older People
Mohua Das, Yang Tianming, Dong Jinghua, Fransisca Prasetya, Xie Yiming, Kendra Wong, Adeline Cheong, Esther C Y Woon
Dynamic combinatorial chemistry (DCC) is a powerful supramolecular approach for discovering ligands for biomolecules. To date, most, if not all, biologically-templated DCC employ only a single biomolecule in directing the self-assembly process. To expand the scope and potential of DCC, herein, we developed a novel multi-protein DCC strategy which combines the discriminatory power of zwitterionic 'thermal-tag' with the sensitivity of differential scanning fluorimetry. This strategy enables the discovery of ligands against several proteins of interest concurrently...
June 19, 2018: Chemistry, An Asian Journal
Christian Lieven, Markus J Herrgård, Nikolaus Sonnenschein
Developing methylotrophic bacteria into cell factories that meet the chemical demand of the future could be both economical and environmentally friendly. Methane is not only an abundant, low-cost resource but also a potent greenhouse gas, the capture of which could help to reduce greenhouse gas emissions. Rational strain design workflows rely on the availability of carefully combined knowledge often in the form of genome-scale metabolic models to construct high-producer organisms. In this review, we present the most recent genome-scale metabolic models in aerobic methylotrophy and their applications...
June 19, 2018: Biotechnology Journal
Raymond Barnhill, Peter Vermeulen, Sofie Daelemans, Pieter-Jan van Dam, Sergio Roman-Roman, Vincent Servois, Ilse Hurbain, Sophie Gardrat, Graça Raposa, Nicolas André, Rémi Dendale, Gaëlle Pierron, Laurence Desjardins, Nathalie Cassoux, Sophie Piperno-Neumann, Pascale Mariani, Claire Lugassy
Up to 50% of uveal melanomas (UM) metastasize to the liver within 10 years of diagnosis, and these almost always prove rapidly fatal. Since histopathological growth patterns (HGP) of liver metastases of the replacement and desmoplastic type, particularly from colon and breast carcinoma, may import valuable biological and prognostic information, we have studied HGP in a series of 41 UM liver metastases originating from 41 patients from the period 2006-2017. Twenty patients underwent enucleation while 21 had radiation therapy...
June 19, 2018: Journal of Pathology. Clinical Research
Mingfeng Cao, Meirong Gao, Deon Ploessl, Cunjiang Song, Zengyi Shao
Scheffersomyces stipitis, renowned for its native xylose-utilizing capacity, has recently demonstrated its potential in producing health-promoting shikimate pathway derivatives. However, its broader application is hampered by the low transformation efficiency and the lack of genetic engineering tools to enable sophisticated genomic manipulations. S. stipitis employees the predominant non-homologous end joining (NHEJ) mechanism for repairing DNA double-strand breaks (DSB), which is less desired due to its incompetence in achieving precise genome editing...
June 19, 2018: Biotechnology Journal
Katia Tarasava, Eun Joong Oh, Carrie A Eckert, Ryan T Gill
In recent years CRISPR-Cas technologies have revolutionized microbial engineering approaches. Genome editing and non-editing applications of various CRISPR-Cas systems have expanded the throughput and scale of engineering efforts, as well as opened up new avenues for manipulating genomes of non-model organisms. As we expand the range of organisms used for biotechnological applications, we need to develop better, more versatile tools for manipulation of these systems. Here we summarize the current advances in microbial gene editing using CRISPR-Cas based tools, and highlight state-of-the-art methods for high-throughput, efficient genome-scale engineering in model organisms Escherichia coli and Saccharomyces cerevisiae...
June 19, 2018: Biotechnology Journal
Radhe Shyam, Nicolas Charbonnel, Aurélie Job, Christelle Blavignac, Christiane Forestier, Claude Taillefumier, Sophie Faure
Amphipathic cationic peptoids (N-substituted glycine oligomers) represent a promising class of antimicrobial peptide mimics. The aim of this study is to explore the potential of the triazolium group as a cationic moiety and helix inducer to develop potent antimicrobial helical peptoids. We report here the first solid-phase synthesis of peptoid oligomers incorporating 1,2,3-triazolium-type side chains, and their evaluation against Escherichia coli, Enterococcus faecalis and Staphylococcus aureus. Several triazolium-based oligomers, even of short length, selectively kill bacteria over mammalian cells...
June 19, 2018: ChemMedChem
Jing Hou, Heping Zheng, Wen-Shyong Tzou, David R Cooper, Maksymilian Chruszcz, Mahendra D Chordia, Keehwan Kwon, Marek Grabowski, Wladek Minor
Vibrio cholerae, the causative pathogen of the life-threatening infection cholera, encodes two copies of β-ketoacyl-ACP synthase III (vcFabH1 and vcFabH2). vcFabH1 and vcFabH2 are pathogenic proteins associated with fatty acid synthesis, lipid metabolism, and potential applications in biofuel production. Our biochemical assays characterize vcFabH1 as exhibiting specificity for acetyl-CoA and CoA thioesters with short acyl chains, similar to that observed for FabH homologs found in most Gram-negative bacteria...
June 19, 2018: FEBS Journal
William Greggs, Thomas Burns, Peter Egeghy, Michelle R Embry, Peter Fantke, Bonnie Gaborek, Lauren Heine, Olivier Jolliet, Carolyn Lee, Derek Muir, Kathy Plotzke, Joseph Rinkevich, Neha Sunger, Jennifer Y Tanir, Margaret Whittaker
Most alternatives assessments (AAs) published to date are largely hazard-based rankings, thereby ignoring potential differences in human and/or ecosystem exposures; as such, they may not represent a fully informed consideration of the advantages and disadvantages of possible alternatives. Building on the 2014 US National Academy of Sciences recommendations to improve AA decisions by including comparative exposure assessment into AAs, the ILSI Health and Environmental Sciences Institute's Sustainable Chemical Alternatives Technical Committee, which comprises scientists from academia, industry, government, and nonprofit organizations, developed a qualitative comparative exposure approach...
June 19, 2018: Integrated Environmental Assessment and Management
Ievgen Strielkov, Nicole Catherine Krause, Natasha Sommer, Ralph Theo Schermuly, Hossein Ardeschir Ghofrani, Friedrich Grimminger, Thomas Gudermann, Alexander Dietrich, Norbert Weissmann
NEW FINDINGS: What is the central question of this study? Hypoxic pulmonary vasoconstriction has never been characterized in isolated mouse pulmonary arteries of different generations in detail. What is the main finding and its importance? We found that only small intrapulmonary arteries (80 - 200 μm in diameter) exhibit hypoxic pulmonary vasoconstriction. The observed response was sustained, significantly potentiated by depolarization-induced preconstriction, and not dependent on endothelium and TRPC6 channels...
June 19, 2018: Experimental Physiology
Michael John Kerins, John Milligan, James Akira Wohlschlegel, Aikseng Ooi
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome characterized by inactivation of the Krebs cycle enzyme fumarate hydratase (FH). HLRCC patients are at a high risk of developing kidney cancer of type 2 papillary morphology that is refractory to current radio-, immuno-, and chemo- therapies. Hence, an effective therapy for this deadly form of cancer is urgently needed. Here we show that FH inactivation (FH-/- ) proves synthetic lethal with inducers of ferroptosis, an iron-dependent and nonapoptotic form of cell death...
June 19, 2018: Cancer Science
Christian Lis, Stefan Rubner, Corinna Gröst, Ralf Hoffmann, Daniel Knappe, Thorsten Berg
Strain-promoted azide-alkyne cycloadditions (SPAAC) have proven extremely useful for labeling of biomolecules, but typically produce isomeric mixtures. This is not appropriate for the formation of bioactive molecules in living cells. Here, we report the first use of SPAAC for the isomer-free synthesis of a bioactive molecule, both in vitro and inside cultured cells. We developed the symmetrical cyclooctyne SYPCO and used it for the generation of a chemically uniform triazole inhibitor of protein-protein interactions mediated by Bcl-xL via isomer-free SPAAC (iSPAAC)...
June 19, 2018: Chemistry: a European Journal
Joaquín García-Álvarez, Eva Hevia, Vito Capriati
There is a strong imperative to reduce the release of volatile organic compounds (VOCs) into the environment, and many efforts are currently being made to replace conventional hazardous VOCs in favour of safe, green and bio-renewable reaction media that are not based on crude petroleum. Recent ground-breaking studies from a few laboratories worldwide have shown that both Grignard and (functionalised) organolithium reagents, traditionally handled under strict exclusion of air and humidity and in anhydrous VOCs, can smoothly promote both nucleophilic additions to unsaturated substrates and nucleophilic substitutions in water and other bio-based solvents (glycerol, deep eutectic solvents), competitively with protonolysis, at room temperature and under air...
June 19, 2018: Chemistry: a European Journal
Jie Gao, Zhao Wang, Gao-Ju Wang, Na Gao, Jing Li, Yun-Fei Zhang, Jun Zhou, Hong-Xin Zhang, Qiang Wen, Han Jin, Hai-Ling Qiao
Hepatofibrosis is an important susceptibility factor for hepatocarcinogenesis. However, only a handful of cases of hepatofibrosis will develop into hepatocellular carcinoma (HCC). As cytochrome P450 2E1 (CYP2E1) is involved in the metabolism and activation of many known environmental toxicants and procarcinogens, this enzyme may play a role in the development of hepatocarcinogenesis subsequent to hepatofibrosis. Herein, we evaluated whether higher CYP2E1 activity is a risk factor for the development of hepatocarcinogenesis from hepatofibrosis...
June 19, 2018: Molecular Carcinogenesis
Guo-Jin Wu, Jun Pen, Ying Huang, Su An, Ying Liu, Yang Yang, Qian Hao, Xiao-Xi Guo, Tian-Rui Xu
Aberrant activation of the Raf-MEK-ERK pathway has frequently been associated with various cancers, especially lung cancer. However, the key regulators of this pathway are largely unknown. Using functional proteomics screening, we found that KAP1 interacts with c-Raf. Knocking out KAP1 decreased c-Raf phosphorylation at serine 259 and increased its phosphorylation at serine 338, which activated MEK and ERK. We detected higher KAP1 expression in lung cancer tissues than in normal peri-tumoral tissues. KAP1 knockdown arrested A549 lung cancer cells in the G0/G1 phase of the cell cycle and attenuated cell growth, metastasis, the epithelial-mesenchymal transition, angiogenesis, stemness, and colony formation...
June 19, 2018: Molecular Carcinogenesis
Irene Sintini, William S Burton, Paul Sade, Jason M Chavarria, Peter J Laz
Morphological variability in the shoulder influences the joint biomechanics and is an important consideration in arthroplasty and implant design. The objectives of this study were to quantify cortical and cancellous proximal humeral morphology and to assess whether shape variation was influenced by gender and ethnicity, with the overarching goal of informing implant design and treatment. A statistical shape model of the proximal humeral cortical and cancellous regions was developed for a training set of 84 subjects of both genders and different ethnicities...
June 19, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Masahiro Miura, Tatsuaki Takata, Daiki Nishikawa, Koji Hirano
A copper-catalyzed net hydroamination of vinylphosphine boranes with hydrosilanes and O-benzoylhydroxylamines has been developed. The reaction proceeds regioselectively to form the corresponding alpha-aminophosphine boranes of potent interest in medicinal and pharmaceutical chemistry. This copper catalysis is based on an umpolung, electrophilic amination strategy and provides a new electrophilic amination approach to alpha-aminophosphine derivatives. Additionally, while still preliminary, asymmetric synthesis is also achieved by judicious choice of chiral bisphosphine-ligated copper complex...
June 19, 2018: Chemistry: a European Journal
Naglaa A Mostafa, Magda Assaf, Sami Elhakim, Mona R E Abdel-Halim, Eman El-Nabarawy, Khaled Ghareeb
BACKGROUND: The distinction of trichoepithelioma from basal cell carcinoma in small superficial biopsies is important but often challenging. This has inspired many scientists to test the validity of immunohistochemical markers in the differential diagnosis. OBJECTIVES: to develop an immunohistochemical protocol that helps in differentiation between both TE and BCC with higher sensitivity and specificity. METHODS: Using standard immunohistochemical techniques, we examined 10 TEs and 19 BCCs for the expression of CK19, Ki67, Androgen receptors (AR), CD10, and PHLDA1...
June 19, 2018: Journal of Cutaneous Pathology
Rupak Desai, Sandeep Singh, Maryam Baikpour, Hemant Goyal, Abhijeet Dhoble, Abhishek Deshmukh, Gautam Kumar, Rajesh Sachdeva
BACKGROUND: It is well known that obesity can lead to increased oxidative stress, which is one of the proposed mechanisms in the etiopathogenesis of Takotsubo Cardiomyopathy (TCM). However, it is unknown if the presence of obesity affects the outcomes in patients with TCM. METHODS: We queried the National Inpatient Sample database from 2010-2014 to identify adult patients who admitted with a principal diagnosis of TCM with and without obesity. We compared the categorical and continuous variables by Pearson's chi-square and Student's t-test respectively in propensity-score matched cohorts...
June 19, 2018: Clinical Cardiology
Youngmi Kang, Kwisoon Choe, Jinna Yu
AIM: This study identified the moderating role of the amount of caregiving tasks on relationships between dementia family caregivers' characteristics (age, education, etc.) and outcomes (burden, etc.). DESIGN: A cross-sectional analysis of surveyed data. METHOD: A convenience sample of 369 family caregivers (151 males, 218 females) aged 20 years or older was recruited from 10 cities in the southern area of South Korea. Data were collected from November - December 2011...
June 19, 2018: Journal of Advanced Nursing
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