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James R Whiting, Isabel S Magalhaes, Abdul R Singkam, Shaun Robertson, Daniele D'Agostino, Janette E Bradley, Andrew D C MacColl
Understanding how wild immune variation covaries with other traits can reveal how costs and trade-offs shape immune evolution in the wild. Divergent life history strategies may increase or alleviate immune costs, helping shape immune variation in a consistent, testable way. Contrasting hypotheses suggest that shorter life histories may alleviate costs by offsetting them against increased mortality; or increase the effect of costs if immune responses are traded off against development or reproduction. We investigated the evolutionary relationship between life history and immune responses within an island radiation of three-spined stickleback, with discrete populations of varying life histories and parasitism...
June 20, 2018: Molecular Ecology
Isaac B Rhea, Guilherme H Oliveira
PURPOSE OF REVIEW: With the continuing development of newer targeted therapies in oncology, it is necessary to understand their potential cardiovascular side effects. In this review, we discuss the association of novel targeted agents and left ventricular systolic dysfunction. RECENT FINDINGS: Within the last 5 years, multiple new agents have been developed to target specific cancer pathways and found to have off-targeted cardiotoxicity. The most recent example is the recognition of myocarditis caused by immune checkpoint inhibitors...
June 19, 2018: Current Treatment Options in Cardiovascular Medicine
Rebecca Fish, Andrew G Renehan, Grant Punnett, Omer Aziz, Paul Fulford, Chelliah Selvasekar, Malcolm Wilson, Rebecca Halstead, Sarah T O'Dwyer
AIM: Pseudomyxoma peritonei (PMP) is a rare neoplasm of the appendix, which if untreated disseminates throughout the abdominal cavity and generates considerable morbidity. Since 2002 in the UK, patients with PMP have been managed via two nationally commissioned centres. We evaluated referrals and treatment pathways over time at the Manchester centre. METHOD: Data from all patients referred with suspected PMP were prospectively collected (2002-2015). Definitive treatment was cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC)...
June 19, 2018: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
Bing Chen, Martin E Feder, Le Kang
Heat-shock proteins (Hsps) and their cognates are primary mitigators of cell stress. With increasingly severe impacts of climate change and other human modifications of the biosphere, the ability of the heat-shock system to affect evolutionary fitness in environments outside the laboratory and to evolve in response are topics of growing importance. Since the last major reviews, several advances have occurred. First, demonstrations of the heat-shock response outside the laboratory now include many additional taxa and environments...
June 19, 2018: Molecular Ecology
Michael W Mullowney, Ryan A McClure, Matthew T Robey, Neil L Kelleher, Regan J Thomson
Covering: up to 2018Thioester reductase domains catalyze two- and four-electron reductions to release natural products following assembly on nonribosomal peptide synthetases, polyketide synthases, and their hybrid biosynthetic complexes. This reductive off-loading of a natural product yields an aldehyde or alcohol, can initiate the formation of a macrocyclic imine, and contributes to important intermediates in a variety of biosyntheses, including those for polyketide alkaloids and pyrrolobenzodiazepines. Compounds that arise from reductase-terminated biosynthetic gene clusters are often reactive and exhibit biological activity...
June 19, 2018: Natural Product Reports
Samuel Heuts, Jean H T Daemen, Sebastian A F Streukens, Jules R Olsthoorn, Jindrich Vainer, Emile C Cheriex, Jos G Maessen, Peyman Sardari Nia
OBJECTIVE: Transapical off-pump minimally invasive mitral valve repair (TOP-MINI) is a new technique for the surgical repair of degenerative mitral regurgitation based on mitral valve prolapse. The aim of this study is to demonstrate the preoperative planning tools available for starting this new procedure in a safe manner. METHODS: The first patients undergoing TOP-MINI by a single surgeon in 2016 were prospectively included. All patients underwent identical clinical pathways and underwent extensive preoperative planning for a safe start of the program...
June 14, 2018: Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery
Datong Wu, Yin Yu, Jie Zhang, Lili Guo, Yong Kong
Here a novel fluorescent chiral poly(ionic liquid) (S)-PCIL-4 with non-conjugated backbone is designed and synthesized in the control of micelle through free radical polymerization, whose fluorescence emission maximum is at λem,max = 430 nm. It is observed that polymers with spatially proximate units (phenyl group and pyridinium cation) have photoluminescence through spatial π-π and ion-π interaction. Then (S)-PCIL-4 can be served as a fluorescent turn-off/on sensor for chiral recognition of phenylalaninol and tryptophan in the presence of Cu(II)...
June 18, 2018: ACS Applied Materials & Interfaces
Jennifer Sarah Maria Loose, Magnus Øverlie Arntzen, Bastien Bissaro, Roland Ludwig, Vincent G H Eijsink, Gustav Vaaje-Kolstad
Lytic polysaccharide monooxygenases (LPMOs) play a crucial role in the degradation of polysaccharides in biomass by catalyzing powerful oxidative chemistry using only a single copper ion as co-factor. Despite the natural abundance and importance of these powerful mono-copper enzymes, the structural determinants of their functionality have remained largely unknown. We have used site-directed mutagenesis to probe the roles of 13 conserved amino acids located on the flat substrate-binding surface of CBP21, a chitin-active family AA10 LPMO from Serratia marcescens, also known as SmLPMO10A...
June 14, 2018: Biochemistry
Alex Toft, Rachel Taylor, Lee Claridge, Charlotte Clowes, James Ferguson, Jonathon Hind, Rebecca Jones, Patricia McClean, Patrick McKiernan, Marianne Samyn, Jane Coad
BACKGROUND: The period of transition from pediatric to adult services represents a time when young people need support, information, and appropriate care in order to successfully move. It is a period that is associated with nonadherence and disengagement with care. OBJECTIVE: To explore the experiences of young liver transplant recipients transitioning to adult services and determine what they require in order to achieve a successful move. The research also explored the possibility of using a mobile phone application (app) as a tool to support transition...
January 1, 2018: Progress in Transplantation
Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo
Purpose: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). Materials and Methods: This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration: 50 mg to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 mg to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints...
June 13, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Graeme A King, Maryam Hashemi Shabestari, Kees-Karel H Taris, Ashutosh K Pandey, Sundararajan Venkatesh, Jayapalraja Thilagavathi, Kamalendra Singh, Rama Krishna Koppisetti, Dmitry Temiakov, Wouter H Roos, Carolyn K Suzuki, Gijs J L Wuite
Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression and transmission of mitochondrial DNA (mtDNA). However, mechanisms for the post-translational regulation of TFAM are poorly understood. Here, we show that TFAM is lysine acetylated within its high-mobility-group box 1, a domain that can also be serine phosphorylated. Using bulk and single-molecule methods, we demonstrate that site-specific phosphoserine and acetyl-lysine mimics of human TFAM regulate its interaction with non-specific DNA through distinct kinetic pathways...
April 20, 2018: Nucleic Acids Research
Xiaoxu Wang, Menno Van Lookeren Campagne, Kenneth J Katschke, Damodar Gullipalli, Takashi Miwa, Yoshiyasu Ueda, Yuan Wang, Matthew Palmer, Guolan Xing, Wen-Chao Song
Background C3 glomerulopathy (C3G) is a life-threatening kidney disease caused by dysregulation of the alternative pathway of complement (AP) activation. No approved specific therapy is available for C3G, although an anti-C5 mAb has been used off-label in some patients with C3G, with mixed results. Thus, there is an unmet medical need to develop other inhibitors of complement for C3G. Methods We used a murine model of lethal C3G to test the potential efficacy of an Fc fusion protein of complement receptor of the Ig superfamily (CRIg-Fc) in the treatment of C3G...
June 12, 2018: Journal of the American Society of Nephrology: JASN
Xiaomin Zhao, Wu-Seng Lung
Surface runoff following rainfall events can transport estrogens from agricultural land to water systems, causing potential risks to aquatic biota. This study adopted two simple models, the wash-off and empirical models, to quantify the pathway of three prevalent manure-borne estrogens, estrone (E1), 17β-estradiol (E2β) and 17α-estradiol (E2α), from agricultural land to the receiving water following rainfall events. The complex interconversion of the three estrogens during attenuation was considered in the models...
June 2018: Water Science and Technology: a Journal of the International Association on Water Pollution Research
Antonio C Bianco, Rodrigo R da Conceição
Thyroid hormone signaling is customized in a time and cell-specific manner by the deiodinases, homodimeric thioredoxin fold containing selenoproteins. This ensures adequate T3 action in developing tissues, healthy adults and many disease states. D2 activates thyroid hormone by converting the pro-hormone T4 to T3, the biologically active thyroid hormone. D2 expression is tightly regulated by transcriptional mechanisms triggered by endogenous as well as environmental cues. There is also an on/off switch mechanism that controls D2 activity that is triggered by catalysis and functions via D2 ubiquitination/deubiquitination...
2018: Methods in Molecular Biology
Pricila Pfluger, Vanessa Rodrigues Coelho, Gabriela Gregory Regner, Lucas Lima da Silva, Karina Martinez, Alan Fonseca, Cassiana Macagnan Viau, Patricia Pereira
BACKGROUND: Gamma-decanolactone (GD) is a monoterpene compound that presents anticonvulsant effect in acute and chronic models of epilepsy and it acts as a noncompetitive glutamate antagonist. OBJECTIVE: This study evaluated the anticonvulsant profile and the possible mechanism of action of GD in seizures induced by isoniazid (INH; 250 mg/kg), picrotoxin (PCT; 5 mg/kg) and 4-aminopyridine (4-AP; 13 mg/kg) in male mice. METHOD: Thirty minutes before the convulsants administration, animals received a single administration of saline, GD (100 or 300 mg/kg) or the positive control diazepam (DZP; 2 mg/kg)...
June 10, 2018: Central Nervous System Agents in Medicinal Chemistry
Julita Pietrzak, Corinne M Spickett, Tomasz Płoszaj, László Virág, Agnieszka Robaszkiewicz
Although electrophiles are considered as detrimental to cells, accumulating recent evidence indicates that proliferating non-cancerous and particularly cancerous cells utilize these agents for pro-survival and cell cycle promoting signaling. Hence, the redox shift to mild oxidant release must be balanced by multiple defense mechanisms. Our latest findings demonstrate that cell cycle progression, which dictates oxidant level in stress-free conditions, determines PARP1 transcription. Growth modulating factors regulate CDK4/6-RBs-E2Fs axis...
June 2, 2018: Redox Biology
Lars Morso, Berit Schiøttz-Christensen, Jens Søndergaard, Nils-Bo de Vos Andersen, Flemming Pedersen, Kim Rose Olsen, Morten Sall Jensen, Jonathan Hill, David Høyrup Christiansen
BACKGROUND: Prior studies indicate that stratified care for low back pain results in better clinical outcome and reduced costs in healthcare compared to current practice. Stratified care may be associated with clinical benefits for patients with low back pain at a lower cost, but evidence is sparse. Hence this study aims to evaluate the clinical effects and cost-effectiveness of stratified care in patients with non-specific low back pain compared to current practice. METHODS/DESIGN: The study is a two-armed randomised controlled trial in primary care in the Regions of Southern and Central Denmark (2...
June 8, 2018: Trials
Wenli Pan, Binli Xue, Chulei Yang, Linlin Miao, Lingli Zhou, Queyue Chen, Qing Cai, Yi Liu, Dongchun Liu, Haibing He, Yu Zhang, Tian Yin, Xing Tang
Deglycosylation is the most important gastrointestinal metabolism which ginsenosides are split off from glycosyl moieties by the enzymes secreted from intestinal microflora, and two possible metabolic pathways of protopanaxdiol-type and protopanaxtriol-type ginsenosides have been concluded. The former is deglycosylated at C-3 and/or C-20, and transformed to protopanaxdiol (PPD). By comparison, the latter is deglycosylated at C-6 and/or C-20, and eventually transformed to protopanaxtriol (PPT) instead. The pharmacokinetic behavior of protopanaxdiol-type ginsenosides (PPD-type ginsenosides) and protopanaxtriol-type ginsenosides (PPT-type ginsenosides) is different, mainly in a faster absorption and elimination rate of PPD-type ginsenosides, but almost all of ginsenosides have a low oral bioavailability, which is relevant to the properties, the stability in the gastrointestinal tract, membrane permeability and the intestinal and hepatic first-pass effect of ginsenosides...
June 5, 2018: Fitoterapia
Yafeng Liang, Yu Han, Chenfang Wang, Cong Jiang, Jin-Rong Xu
Ustilaginoidea virens is the causal agent of rice false smut, one of the major fungal diseases of rice. However, there are only limited molecular studies with this important pathogen due to the lack of efficient approaches for generating targeted gene disruption mutants. In this study, we used the CRISPR-Cas9 system to efficiently generate mutants deleted of the USTA ustiloxin and UvSLT2 MAP kinase genes. Three gRNA spacers of USTA , UA01, UA13, and UA21, were expressed with the RNAP III promoter of Gln-tRNA...
2018: Frontiers in Plant Science
Eric J Chow, Zoltan Antal, Louis S Constine, Rebecca Gardner, W Hamish Wallace, Brent R Weil, Jennifer M Yeh, Elizabeth Fox
Incremental improvements in the treatment of children and adolescents with cancer have led to 5-year survival rates reaching nearly 85%. In the past decade, impressive progress has been made in understanding the biology of many pediatric cancers. With that understanding, multiple new agents have become available that offer the promise of more-effective and less-toxic treatment. These include agents that target various cell surface antigens and engage the adaptive immune system, as well as those that interfere with key signaling pathways involved in tumor development and growth...
June 6, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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