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https://www.readbyqxmd.com/read/28812723/the-unconstrained-evolution-of-fast-and-efficient-antibiotic-resistant-bacterial-genomes
#1
Carlos Reding-Roman, Mark Hewlett, Sarah Duxbury, Fabio Gori, Ivana Gudelj, Robert Beardmore
Evolutionary trajectories are constrained by trade-offs when mutations that benefit one life history trait incur fitness costs in other traits. As resistance to tetracycline antibiotics by increased efflux can be associated with an increase in length of the Escherichia coli chromosome of 10% or more, we sought costs of resistance associated with doxycycline. However, it was difficult to identify any because the growth rate (r), carrying capacity (K) and drug efflux rate of E. coli increased during evolutionary experiments where the species was exposed to doxycycline...
January 30, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812552/competition-along-trajectories-governs-adaptation-rates-towards-antimicrobial-resistance
#2
C Brandon Ogbunugafor, Margaret J Eppstein
The increasing availability of genotype-phenotype maps for different combinations of mutations has empowered evolutionary biologists with the tools to interrogate the predictability of adaptive evolution, especially in the context of the evolution of antimicrobial resistance. Large microbial populations are known to generate competing beneficial mutations, but determining how these mutations contribute to the adaptive trajectories that are most likely to be followed remains a challenge. Despite a recognition that there may also be competition between successive alleles on the same trajectory, prior studies have not fully considered how this impacts adaptation rates along, or likelihood of following, individual trajectories...
November 21, 2016: Nature ecology & evolution
https://www.readbyqxmd.com/read/28812437/autophagy-induced-kdr-vegfr-2-activation-promotes-the-formation-of-vasculogenic-mimicry-by-glioma-stem-cells
#3
Hai-Bo Wu, Shuai Yang, Hai-Yan Weng, Qian Chen, Xi-Long Zhao, Wen-Juan Fu, Qin Niu, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Xiao-Hong Yao, Xiu-Wu Bian
Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma. However, the benefits are transient due to elusive mechanisms underlying resistance to the antiangiogenic therapy. Glioma stem cells (GSCs) are capable of forming vasculogenic mimicry (VM), an alternative microvascular circulation independent of VEGF-driven angiogenesis. Herein, we report that the formation of VM was promoted by bevacizumab-induced macroautophagy/autophagy in GSCs, which was associated with tumor resistance to antiangiogenic therapy...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#4
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
https://www.readbyqxmd.com/read/28812358/bioinspired-active-stealth-magneto-nanomicelles-for-theranostics-combining-efficient-mri-and-enhanced-drug-delivery
#5
Kai-Long Zhang, Jie Zhou, Hong Zhou, Ying Wu, Rui Liu, Li-Li Wang, Wei-Wen Lin, Guoming Huang, Huang-Hao Yang
The mononuclear phagocyte system (MPS), with key roles in recognition and clearance of foreign particles, is a major constraint to nanoparticle-based delivery systems. The desire to improve the delivery efficiency has prompted the search for stealthy long-circulating nanoplatforms. Herein, we design an antiphagocytic delivery system with "active" stealth behavior for cancer theranostics combining efficient MRI and enhanced drug delivery. We modify self-peptide, a synthetic peptide for active immunomodulation, to biodegradable poly (lactide-glycolide)-poly (ethylene glycol) (PLGA-PEG), then utilize the self-assembly properties of PLGA-PEG to form nanomicelles that encapsulating iron oxide (IO) nanoparticles and anticancer drug paclitaxel (PTX)...
August 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28812327/design-and-synthesis-of-terephthalic-acid-based-histone-deacetylase-inhibitors-with-dual-stage-anti-plasmodium-activity
#6
Katharina Stenzel, Ming Jang Chua, Sandra Duffy, Yevgeniya Antonova-Koch, Stephan Meister, Alexandra Hamacher, Matthias U Kassack, Elizabeth A Winzeler, Vicky M Avery, Thomas Kurz, Katherine T Andrews, Finn Kristian Hansen
In this work we aimed to develop parasite-selective HDAC inhibitors with activity against the disease-causing asexual blood stages of Plasmodium as well as causal prophylactic and/or transmission blocking properties. We report the design, synthesis and biological testing of a series of 13 terephthalic acid-based histone deacetylase inhibitors. All compounds showed low cytotoxicity against human embryonic kidney (HEK293) cells (IC50 8 - >51 µM), with 11 also having sub-micromolar in vitro activity against drug-sensitive (3D7) and multi-drug resistant (Dd2) asexual blood stage Plasmodium falciparum parasites (IC50 ~ 0...
August 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28812009/the-bacteriological-quality-safety-and-antibiogram-of-salmonella-isolates-from-fresh-meat-in-retail-shops-of-bahir-dar-city-ethiopia
#7
Melkamnesh Azage, Mulugeta Kibret
The habit of raw meat consumption in addition to the poor hygienic standards and lack of knowledge contribute to food-borne diseases outbreaks. The objective of this research was to assess the bacterial quality and safety of fresh meat from retail Bahir Dar City, Ethiopia. A total of 30 fresh meat samples were collected from butcher shops. Standard bacteriological methods were used to isolate and enumerate bacteria. Kirby-Bauer disk diffusion method was used for antimicrobial susceptibility testing of Salmonella isolates...
2017: International journal of food science
https://www.readbyqxmd.com/read/28811917/drug-information-update-lithium-and-chronic-kidney-disease-debates-and-dilemmas
#8
Sumeet Gupta, Udayan Khastgir
Lithium is an established treatment for bipolar disorder and an augmenting agent for treatment-resistant depression. Despite awareness of renal adverse effects, including chronic kidney disease, for the past five decades, there has been a lack of research evidence. This has led to debates around the existence and magnitude of the risk. This article discusses the current evidence base regarding the link between lithium and chronic kidney disease, monitoring of renal functions and its clinical implications.
August 2017: BJPsych Bulletin
https://www.readbyqxmd.com/read/28811792/antimicrobial-susceptibility-patterns-of-clinical-isolates-of-pseudomonas-aeruginosa-isolated-from-patients-of-respiratory-tract-infections-in-a-tertiary-care-hospital-peshawar
#9
Abdul Samad, Tanveer Ahmed, Afaq Rahim, Abdul Khalil, Iftikhar Ali
OBJECTIVE: This study aims to determine the prevalence and susceptibility pattern of Pseudomonas aeruginosa and multidrug-resistant (MDR) isolates in patients suffering from respiratory tract infection. METHODS: A cross sectional study was conducted from January to December 2014 in Northwest General Hospital and Research Centre, Peshawar. A total of 615 sputum samples were collected from both in and out-patients. Sputum samples were collected as per standard procedure and were inoculated on Blood, MacConkey and Chocolate agar...
May 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28811659/identification-synthesis-and-biological-activity-of-alkyl-guanidine-oligomers-as-potent-antibacterial-agents
#10
C Zamperini, G Maccari, D Deodato, C Pasero, I D'Agostino, F Orofino, F De Luca, E Dreassi, J D Docquier, M Botta
In the last two decades, the repertoire of clinically effective antibacterials is shrinking due to the rapidly increasing of multi-drug-resistant pathogenic bacteria. New chemical classes with innovative mode of action are required to prevent a return to the pre-antibiotic era. We have recently reported the identification of a series of linear guanidine derivatives and their antibacterial properties. A batch of a promising candidate for optimization studies (compound 1) turned out to be a mixture containing two unknown species with a better biological activity than the pure compound...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811642/octahedron-iron-oxide-nanocrystals-prohibited-clostridium-difficile-spore-germination-and-attenuated-local-and-systemic-inflammation
#11
Wei-Ting Lee, Ya-Na Wu, Yi-Hsuan Chen, Shang-Rung Wu, Tsai-Miao Shih, Tsung-Ju Li, Li-Xing Yang, Chen-Sheng Yeh, Pei-Jane Tsai, Dar-Bin Shieh
Clinical management of Clostridium difficile infection is still far from satisfactory as bacterial spores are resistant to many chemical agents and physical treatments. Certain types of nanoparticles have been demonstrated to exhibit anti-microbial efficacy even in multi-drug resistance bacteria. However, most of these studies failed to show biocompatibility to the mammalian host cells and no study has revealed in vivo efficacy in C. difficile infection animal models. The spores treated with 500 µg/mL Fe3-δO4 nanoparticles for 20 minutes, 64% of the spores were inhibited from transforming into vegetative cells, which was close to the results of the sodium hypochlorite-treated positive control...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811600/exploring-leishmania-secretory-proteins-to-design-b-and-t-cell-multi-epitope-subunit-vaccine-using-immunoinformatics-approach
#12
Nazia Khatoon, Rajan Kumar Pandey, Vijay Kumar Prajapati
Visceral leishmaniasis (VL) is a fatal form of leishmaniasis which affects 70 countries, worldwide. Increasing drug resistance, HIV co-infection, and poor health system require operative vaccination strategy to control the VL transmission dynamics. Therefore, a holistic approach is needed to generate T and B memory cells to mediate long-term immunity against VL infection. Consequently, immunoinformatics approach was applied to design Leishmania secretory protein based multi-epitope subunit vaccine construct consisting of B and T cell epitopes...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811545/sealing-the-pores-of-peo-coating-with-mg-al-layered-double-hydroxide-enhanced-corrosion-resistance-cytocompatibility-and-drug-delivery-ability
#13
Feng Peng, Donghui Wang, Yaxin Tian, Huiliang Cao, Yuqin Qiao, Xuanyong Liu
In recent years, magnesium (Mg) alloys show a promising application in clinic as degradable biomaterials. Nevertheless, the poor corrosion resistance of Mg alloys is the main obstacle to their clinical application. Here we successfully seal the pores of plasma electrolytic oxidation (PEO) coating on AZ31 with Mg-Al layered double hydroxide (LDH) via hydrothermal treatment. PEO/LDH composite coating possess a two layer structure, an inner layer made up of PEO coating (~5 μm) and an outer layer of Mg-Al LDH (~2 μm)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811524/synthesis-of-sulfo-sialic-acid-analogues-potent-neuraminidase-inhibitors-in-regards-to-anomeric-functionality
#14
Christopher J Vavricka, Chiaki Muto, Tomohisa Hasunuma, Yoshinobu Kimura, Michihiro Araki, Yan Wu, George F Gao, Hiroshi Ohrui, Minoru Izumi, Hiromasa Kiyota
The design, synthesis and application of N-acetylneuraminic acid-derived compounds bearing anomeric sulfo functional groups are described. These novel compounds, which we refer to as sulfo-sialic acid analogues, include 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid and its 4-deoxy-3,4-dehydrogenated pseudoglycal. While 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid contains no further modifications of the 2-deoxy-pyranose ring, it is still a more potent inhibitor of avian-origin H5N1 neuraminidase (NA) and drug-resistant His275Tyr NA as compared to the oxocarbenium ion transition state analogue 2,3-dehydro-2-deoxy-N-acetylneuraminic acid...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811343/comparative-genomics-of-escherichia-coli-isolated-from-skin-and-soft-tissue-and-other-extraintestinal-infections
#15
Amit Ranjan, Sabiha Shaik, Nishant Nandanwar, Arif Hussain, Sumeet K Tiwari, Torsten Semmler, Savita Jadhav, Lothar H Wieler, Munirul Alam, Rita R Colwell, Niyaz Ahmed
Escherichia coli, an intestinal Gram-negative bacterium, has been shown to be associated with a variety of diseases in addition to intestinal infections, such as urinary tract infections (UTIs), meningitis in neonates, septicemia, skin and soft tissue infections (SSTIs), and colisepticemia. Thus, for nonintestinal infections, it is categorized as extraintestinal pathogenic E. coli (ExPEC). It is also an opportunistic pathogen, causing cross infections, notably as an agent of zoonotic diseases. However, comparative genomic data providing functional and genetic coordinates for ExPEC strains associated with these different types of infections have not proven conclusive...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811330/epithelial-to-mesenchymal-and-mesenchymal-to-epithelial-transition-in-mesenchymal-tumors-a-paradox-in-sarcomas
#16
REVIEW
Giuseppina Sannino, Aruna Marchetto, Thomas Kirchner, Thomas G P Grünewald
The epithelial-to-mesenchymal transition (EMT) is a reversible process comprised of various subprograms via which epithelial cells reduce their intercellular adhesions and proliferative capacity while gaining a mesenchymal phenotype with increased migratory and invasive properties. This process has been well described in several carcinomas, which are cancers of epithelial origin, and is crucial to metastatic tumor cell dissemination and drug resistance. In contrast, the precise role of EMT-related processes in tumors originating from mesenchymal tissues, such as bone and soft-tissues sarcomas, is still largely unclear...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28811304/selectin-catch-bonds-mechanotransduce-integrin-activation-and-neutrophil-arrest-on-inflamed-endothelium-under-shear-flow
#17
Vasilios A Morikis, Shannon Chase, Ted Wun, Elliot L Chaikof, John L Magnani, Scott I Simon
E-selectin extends from the plasma membrane of inflamed endothelium and serves to capture leukocytes from flowing blood via long-lived catch-bonds that support slow leukocyte rolling under shear stress. Its ligands are glycosylated with the tetrasaccharide sialyl Lewis(x) (sLe(x)), which contributes to bond affinity and specificity. E-selectin mediated rolling transmits signals into neutrophils that triggers activation of high-affinity β2-integrins necessary for transition to shear resistant adhesion and transendothelial migration...
August 15, 2017: Blood
https://www.readbyqxmd.com/read/28811241/utility-of-prior-cultures-in-predicting-antibiotic-resistance-of-bloodstream-infections-due-to-gram-negative-pathogens-a-multicenter-observational-cohort-study
#18
Derek R MacFadden, Bryan Coburn, Nirav Shah, Ari Robicsek, Rachel Savage, Marion Elligsen, Nick Daneman
OBJECTIVES: Appropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections. METHODS: We conducted a multi-center observational cohort study, in two large health systems in Canada and the United States, including 1,832 hospitalized patients with Gram-negative bloodstream infection (community, hospital, and ICU acquired) from April 2010 to March 2015...
August 12, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28811200/globular-adiponectin-reverses-osteo-sarcopenia-and-altered-body-composition-in-ovariectomized-rats
#19
Shyamsundar Pal China, Subhashis Pal, Sourav Chattopadhyay, Konica Porwal, Sapana Kushwaha, Sharmishtha Bhattacharyya, Monika Mittal, Anagha A Gurjar, Tarun Barbhuyan, Abhishek K Singh, Arun K Trivedi, Jiaur R Gayen, Sabyasachi Sanyal, Naibedya Chattopadhyay
Adiponectin regulates various metabolic processes including glucose flux, lipid breakdown and insulin response. We recently reported that adiponectin receptor1 (adipoR1) activation by a small molecule reverses osteopenia in leptin receptor deficient db/db (diabetic) mice. However, the role of adiponectin in bone metabolism under the setting of post-menopausal (estrogen-deficiency) osteopenia and associated metabolic derangements has not been studied. Here, we studied the therapeutic effect of the globular form of adiponectin (gAd), which is predominantly an adipoR1 agonist, in aged ovariectomized (OVX) rats and compared it with standard-of-care anti-osteoporosis drugs...
August 12, 2017: Bone
https://www.readbyqxmd.com/read/28811193/a-novel-detection-procedure-for-mutations-in-the-23s-rrna-gene-of-mycoplasma-pneumoniae-with-peptide-nucleic-acid-mediated-loop-mediated-isothermal-amplification-assay
#20
Jun Sakai, Takuya Maeda, Norihito Tarumoto, Kazuhisa Misawa, Shinsuke Tamura, Kazuo Imai, Toshiyuki Yamaguchi, Satoshi Iwata, Takashi Murakami, Shigefumi Maesaki
Rapid and easy detection of a single nucleotide point mutation of bacterial genes, which is directly linked to drug susceptibility, is essential for the proper use of antimicrobial agents. Here, we established a detection method using a peptide nucleic acid mediated loop-mediated amplification (LAMP) assay for macrolide (ML)-susceptible Mycoplasma pneumoniae. This assay specifically detected the absence of missense mutations encoding the central loop of domain V in the gene encoding 23S rRNA, which can reduce the affinity for MLs and subsequently generate ML-resistant strains of M...
August 12, 2017: Journal of Microbiological Methods
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