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Joseph D Turner, Nicolas Pionnier, Julio Furlong-Silva, Hanna Sjoberg, Stephen Cross, Alice Halliday, Ana F Guimaraes, Darren A N Cook, Andrew Steven, Nico Van Rooijen, Judith E Allen, Stephen J Jenkins, Mark J Taylor
Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection...
March 16, 2018: PLoS Pathogens
David Williams, Joanne L Fothergill, Benjamin Evans, Jessica Caples, Sam Haldenby, Martin J Walshaw, Michael A Brockhurst, Craig Winstanley, Steve Paterson
Pseudomonas aeruginosa chronic infections of cystic fibrosis (CF) airways are a paradigm for within-host evolution with abundant evidence for rapid evolutionary adaptation and diversification. Recently emerged transmissible strains have spread globally, with the Liverpool Epidemic Strain (LES) the most common strain infecting the UK CF population. Previously we have shown that highly divergent lineages of LES can be found within a single infection, consistent with super-infection among a cross-sectional cohort of patients...
March 16, 2018: Microbial Genomics
María José Garcés Hernández, Miguel Klünder, Nayely Garibay Nieto, Juan Carlos López Alvarenga, Jenny Vilchis Gil, Samuel Flores Huerta, Rosa Quispe Siccha, Joselin Hernandez
OBJECTIVE: Visceral adiposity index (VAI) is a mathematical model associated with cardiometabolic risk in adults, but studies on children failed to support this association. Our group has proposed a pediatric VAI model using pediatric ranges, but it has not yet been evaluated and needs further adjustments. The objective of this study was to further adjust the proposed pediatric VAI by age, creating a new pediatric metabolic index (PMI), and assess the correlation of the PMI with insulin resistance indexes and hepatic enzymes...
March 2018: Endocrine Practice
Godwin U Ebiloma, Teresa Díaz Ayuga, Emmanuel O Balogun, Lucía Abad Gil, Anne Donachie, Marcel Kaiser, Tomás Herraiz, Daniel K Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs...
February 26, 2018: European Journal of Medicinal Chemistry
Mariana Avalos, Gilles P van Wezel, Jos M Raaijmakers, Paolina Garbeva
Microorganisms represent a large and still resourceful pool for the discovery of novel compounds to combat antibiotic resistance in human and animal pathogens. The ability of microorganisms to produce structurally diverse volatile compounds has been known for decades, yet their biological functions and antimicrobial activities have only recently attracted attention. Various studies revealed that microbial volatiles can act as infochemicals in long-distance cross-kingdom communication as well as antimicrobials in competition and predation...
March 12, 2018: Current Opinion in Microbiology
Carol Kelly, James D Chalmers, Iain Crossingham, Nicola Relph, Lambert M Felix, David J Evans, Stephen J Milan, Sally Spencer
BACKGROUND: Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation and distortion of the smaller airways. Bacterial colonisation of the damaged airways leads to chronic cough and sputum production, often with breathlessness and further structural damage to the airways. Long-term macrolide antibiotic therapy may suppress bacterial infection and reduce inflammation, leading to fewer exacerbations, fewer symptoms, improved lung function, and improved quality of life...
March 15, 2018: Cochrane Database of Systematic Reviews
Nan Shwe Nwe Htun, Peter Odermatt, Ivan Müller, Peiling Yap, Peter Steinmann, Christian Schindler, Markus Gerber, Rosa Du Randt, Cheryl Walter, Uwe Pühse, Jürg Utzinger, Nicole Probst-Hensch
BACKGROUND: Low- and middle-income countries are facing a dual disease burden with infectious diseases (e.g., gastrointestinal tract infections) and non-communicable diseases (e.g., diabetes) being common. For instance, chronic parasite infections lead to altered immune regulatory networks, anemia, malnutrition, and diarrhea with an associated shift in the gut microbiome. These can all be pathways of potential relevance for insulin resistance and diabetes. The aim of this study was to investigate the association between common gastrointestinal tract infections and glycemia in children from non-fee paying schools in South Africa...
March 15, 2018: PLoS Neglected Tropical Diseases
Michael W Deem, Melia Elizabeth Bonomo
Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) constitute a multi-functional, constantly evolving immune system in bacteria and archaea cells. A heritable, molecular memory is generated of phage, plasmids, or other mobile genetic elements that attempt to attack the cell. This memory is used to recognize and interfere with subsequent invasions from the same genetic elements. This versatile prokaryotic tool has also been used to advance applications in biotechnology...
March 15, 2018: Physical Biology
Jared M Dickinson, Andrew C D'Lugos, Marcus A Naymik, Ashley L Siniard, Amanda J Wolfe, Donald P Curtis, Matthew J Huentelman, Chad C Carroll
Aerobic (AE) and resistance exercise (RE) elicit unique adaptations in skeletal muscle that have distinct implications for health and performance. The purpose of this study was to identify the unique transcriptome response of skeletal muscle to acute AE and RE. In a counter-balanced, cross-over design, six healthy, recreationally active young men (27{plus minus}3y) completed acute AE (40 min cycling, ~70% maximal HR) and RE (8 sets, 10 reps, ~65% 1RM), separated by ~1wk. Muscle biopsies ( vastus lateralis) were obtained before and at 1 and 4h post exercise...
March 15, 2018: Journal of Applied Physiology
Albert Boada, Mariona Pons-Vigués, Jordi Real, Elisabet Grezner, Bonventura Bolíbar, Carl Llor
INTRODUCTION: Commensal flora of healthy people is becoming an important reservoir of resistant bacteria. OBJECTIVES: To evaluate the relationship of previous antibiotic-dispensed and resistance pattern of strains of Staphylococcus aureus in primary care patients. METHODS: A cross-sectional study was carried out in seven primary care centres in Catalonia, Spain, from October 2010 to May 2011, as part of the APRES (The appropriateness of prescribing antibiotics in primary care in Europe concerning antibiotic resistance) study...
December 2018: European Journal of General Practice
Omar Ramos-Lopez, Mirian Samblas, Fermin I Milagro, M Angeles Zulet, Maria L Mansego, Jose I Riezu-Boj, J Alfredo Martinez
Folate deficiency has been putatively implicated in the onset of diverse metabolic abnormalities, including insulin resistance, by altering epigenetic processes on key regulatory genes. The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is involved in the regulation of critical metabolic processes such as adiposity and glucose homeostasis. This study hypothesized associations between low folate intakes and lower methylation levels of the CAMKK2 gene, with the presence of metabolic alterations in subjects with obesity...
February 2018: Nutrition Research
Xin Li, Shengfu Zhong, Wanquan Chen, Syeda Akash Fatima, Qianglan Huang, Qing Li, Feiquan Tan, Peigao Luo
Fusarium head blight (FHB), mainly caused by Fusarium graminearum , is one of the most destructive fungal diseases of wheat ( Triticum aestivum L.). Because of the quantitative nature of FHB resistance, its mechanism is poorly understood. We conducted a comparative transcriptome analysis to identify genes that are differentially expressed in FHB-resistant and FHB-susceptible wheat lines grown under field conditions for various periods after F. graminearum infection and determined the chromosomal distribution of the differentially expressed genes (DEGs)...
March 14, 2018: International Journal of Molecular Sciences
Satyendra Kumar Singh, Ajit Kumar, Gopal Nath, Tej Bali Singh, Mukti Nath Mishra
BACKGROUND: WHO MDT is the main drug regimen for treating leprosy and has been used for more than three decades. Many cases of relapse of leprosy have been reported, which points towards the emergence of drug resistance with the antileprotic drugs. OBJECTIVES: To find the resistance with the antileprotic drugs by detecting the mutations in drug resistance determining region of the rpoB, folP1 and gyrA genes of Mycobacterium leprae. METHODS: Leprosy patients with bacterial index ≥2 were included in the study...
March 14, 2018: Indian Journal of Dermatology, Venereology and Leprology
Angela M Ramos-Lobo, Isadora C Furigo, Pryscila D S Teixeira, Thais T Zampieri, Frederick Wasinski, Daniella C Buonfiglio, Jose Donato
Several metabolic adaptations emerge during pregnancy and continue through lactation, including increases in food intake and body weight, as well as insulin and leptin resistance. These maternal adaptations are thought to play a role in offspring viability and success. Using a model of attenuated maternal metabolic adaptations induced by ablation of the Socs3 gene in leptin receptor expressing cells (SOCS3 KO mice), our study aimed to investigate whether maternal metabolic changes are required for normal offspring development, and if their absence causes metabolic imbalances in adulthood...
March 2018: Physiological Reports
Vasyl Kovalishyn, Julie Grouleff, Ivan Semenyuta, Vitaliy O Sinenko, Sergiy R Slivchuk, Diana Hodyna, Volodymyr Brovarets, Volodymyr Blagodatny, Gennady Poda, Igor V Tetko, Larysa Metelytsia
The problem of designing new anti-tubercular drugs against multiple-drug-resistant tuberculosis (MDR-TB) was addressed using advanced machine learning methods. Since there are only few published measurements against MDR-TB, we collected a large literature dataset and developed models against the non-resistant H37Rv strain. The predictive accuracy of these models had a coefficient of determination q2 = 0.7-0.8 (regression models), and balanced accuracies of about 80% (classification models) with cross-validation and independent test sets...
March 14, 2018: Chemical Biology & Drug Design
Emma L Cross, Elizabeth M Harper, Lloyd S Peck
The inability of organisms to cope in changing environments poses a major threat to their survival. Rising carbon dioxide concentrations, recently exceeding 400 μatm, are rapidly warming and acidifying our oceans. Current understanding of organism responses to this environmental phenomenon is based mainly on relatively short- to medium-term laboratory and field experiments, which cannot evaluate the potential for long-term acclimation and adaptation, the processes identified as most important to confer resistance...
March 14, 2018: Global Change Biology
Mohamed E M Saeed, Nuha Mahmoud, Yoshikazu Sugimoto, Thomas Efferth, Heba Abdel-Aziz
For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance...
2018: Frontiers in Pharmacology
Tadasu Horai, Akitoyo Hishimoto, Ikuo Otsuka, Tatsuhiro So, Kentaro Mouri, Naofumi Shimmyo, Shuken Boku, Noriaki Okishio, Ichiro Sora
Background: Alcohol dependence induces low bone mineral density (BMD), predicting osteoporosis, while low and moderate alcohol consumption may even increase BMD. In recent years, undercarboxylated osteocalcin (ucOC) and tartrate-resistant acid phosphatase-5b (TRACP-5b), bone turnover markers, have gained special interest as useful indicators of low BMD. However, it remains unclear whether other alcohol-related variables (eg, duration of abstinence and continuous drinking) are linked to aberrant BMD...
2018: Neuropsychiatric Disease and Treatment
Emilie Clement, Hiroyuki Inuzuka, Naoe T Nihira, Wenyi Wei, Alex Toker
The PI3K-AKT kinase signaling pathway is frequently deregulated in human cancers, particularly breast cancer, where amplification and somatic mutations of PIK3CA occur with high frequency in patients. Numerous small-molecule inhibitors targeting both PI3K and AKT are under clinical evaluation, but dose-limiting toxicities and the emergence of resistance limit therapeutic efficacy. Various resistance mechanisms to PI3K inhibitors have been identified, including de novo mutations, feedback activation of AKT, or cross-talk pathways...
March 13, 2018: Science Signaling
Adam J Pelzek, Bo Shopsin, Emily E Radke, Kayan Tam, Beatrix M Ueberheide, David Fenyö, Stuart M Brown, Qianhao Li, Ada Rubin, Yi Fulmer, William K Chiang, David N Hernandez, Hanane El Bannoudi, William E Sause, Alexis Sommerfield, Isaac P Thomsen, Andy O Miller, Victor J Torres, Gregg J Silverman
Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S...
March 13, 2018: MBio
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