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Human Challenge Model

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https://www.readbyqxmd.com/read/29150398/glycyrrhiza-glabra-extract-and-quercetin-reverses-cisplatin-resistance-in-triple-negative-mda-mb-468-breast-cancer-cells-via-inhibition-of-cytochrome-p450-1b1-enzyme
#1
Rajni Sharma, Linda Gatchie, Ibidapo S Williams, Shreyans K Jain, Ram A Vishwakarma, Bhabatosh Chaudhuri, Sandip B Bharate
The development of multi-drug resistance to existing anticancer drugs is one of the major challenges in cancer treatment. The over-expression of cytochrome P450 1B1 enzyme has been reported to cause resistance to cisplatin. With an objective to discover cisplatin-resistance reversal agents, herein, we report the evaluation of Glycyrrhiza glabra (licorice) extracts and its twelve chemical constituents for inhibition of CYP1B1 (and CYP1A1) enzyme in Sacchrosomes and live human cells. The hydroalcoholic extract showed potent inhibition of CYP1B1 in both Sacchrosomes as well as in live cells with IC50 values of 21 and 16 µg/mL, respectively...
November 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29150005/crispr-libraries-and-screening
#2
John T Poirier
CRISPR-Cas9 technology has revolutionized large-scale functional genomic screening in mammalian cell-culture systems. Due in part to optimized lentiviral delivery vectors; it is now possible to perform CRISPR-Cas9 screens in animals in order to study biological processes in the context of a whole organism and within more physiologically relevant environment. This chapter focuses primarily on mouse models of human cancers; viral vectors used for simultaneous tumor initiation and genome editing and sgRNA library design considerations...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29150003/crispr-cas9-technology-applications-and-human-disease-modeling
#3
Marta Martinez-Lage, Raúl Torres-Ruiz, Sandra Rodriguez-Perales
The CRISPR/Cas9 system development has revolutionized the field of genome engineering through the efficient creation of targeted breaks in the DNA of almost any organism and cell type, opening an avenue for a wide range of applications in biomedical research and medicine. Apart from gene edition through knock-in or knock-out approaches, CRISPR/Cas9 technology has been used for many other purposes, including regulation of endogenous gene expression, epigenome editing, live-cell imaging of chromosomal loci, edition of RNA and high-throughput screening...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29150000/towards-a-unitary-approach-to-human-action-control
#4
REVIEW
Bernhard Hommel, Reinout W Wiers
From its academic beginnings the theory of human action control has distinguished between endogenously driven, intentional action and exogenously driven, habitual, or automatic action. We challenge this dual-route model and argue that attempts to provide clear-cut and straightforward criteria to distinguish between intentional and automatic action have systematically failed. Specifically, we show that there is no evidence for intention-independent action, and that attempts to use the criterion of reward sensitivity and rationality to differentiate between intentional and automatic action are conceptually unsound...
December 2017: Trends in Cognitive Sciences
https://www.readbyqxmd.com/read/29149869/characterisation-of-sucking-dynamics-of-breastfeeding-preterm-infants-a-cross-sectional-study
#5
Donna T Geddes, Kok Chooi, Kathryn Nancarrow, Anna R Hepworth, Hazel Gardner, Karen Simmer
BACKGROUND: Full breastfeeding is the ultimate aim for preterm infants to ensure they receive the full benefits of human milk however, preterm infants face a number of challenges associated with their immaturity and associated morbidities. In order to facilitate oral feeding, it is essential to have a sound knowledge of the sucking dynamics of the breastfed infant. The aim of this study was to measure and describe the sucking dynamics of the preterm breastfeeding infant. METHODS: A prospective cross sectional observational study was carried out at King Edward Memorial Hospital, Perth...
November 17, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/29149679/innovative-urban-forestry-governance-in-melbourne-investigating-green-placemaking-as-a-nature-based-solution
#6
Natalie Marie Gulsrud, Kelly Hertzog, Ian Shears
A nature-based approach to climate resilience aims to challenge and re-frame conventional environmental management methods by refocusing solutions from technological strategies to socio-ecological principles such as human well-being and community-based governance models, thereby improving and legitimizing the delivery of ecosystem services (ES). There are, however, many challenges to applying a socio-ecological agenda to urban climate resilience and thereby re-framing ES delivery as community and people focused, a knowledge gap extensively outlined in the environmental governance literature...
November 14, 2017: Environmental Research
https://www.readbyqxmd.com/read/29149077/rna-virus-evolution-via-a-quasispecies-based-model-reveals-a-drug-target-with-a-high-barrier-to-resistance
#7
Richard J Bingham, Eric C Dykeman, Reidun Twarock
The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly...
November 17, 2017: Viruses
https://www.readbyqxmd.com/read/29148104/neuregulin-1-promotes-remyelination-and-fosters-a-pro-regenerative-inflammatory-response-in-focal-demyelinating-lesions-of-the-spinal-cord
#8
Hardeep Kataria, Arsalan Alizadeh, Ghazaleh M Shahriary, Shekoofeh Saboktakin Rizi, Ryan Henrie, Kallivalappil T Santhosh, James A Thliveris, Soheila Karimi-Abdolrezaee
Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination...
November 17, 2017: Glia
https://www.readbyqxmd.com/read/29147980/a-long-term-comparative-assessment-of-human-health-risk-to-leachate-contaminated-groundwater-from-heavy-metal-with-different-liner-systems
#9
Harshit Mishra, Subhankar Karmakar, Rakesh Kumar, Praneeth Kadambala
The handling and management of municipal solid waste (MSW) are major challenges for solid waste management in developing countries. Open dumping is still the most common waste disposal method in India. However, landfilling also causes various environmental, social, and human health impacts. The generation of heavily polluted leachate is a major concern to public health. Engineered barrier systems (EBSs) are commonly used to restrict potentially harmful wastes by preventing the leachate percolation to groundwater and overflow to surface water bodies...
November 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29146488/kinetics-of-parasite-distribution-after-reinfection-with-genetically-distinct-strains-of-toxoplasma-gondii
#10
Julia Gatti Ladeia Costa, Alice Thomáz Tavares, Daliane Regis Correa Silva, Lorena Velozo Pinto, Ramon Castro Araújo Baraviera, Maria Lourdes Meirelles Noviello, Rosa Maria Esteves Arantes, Ricardo Wagner Almeida Vitor
Recent data shows that prior infection by Toxoplasma gondii does not protect the host from subsequent reinfection even after the development of immunological memory. Although animal models for T. gondii reinfection were proposed after cases of natural human reinfection were described, little is known about the events that occur immediately after challenge. To further understand these events, BALB/c mice were chronically infected with D8 non-virulent strain (genotype ToxoDB#8 BrIII) and challenged with two different virulent strains: EGS (genotype ToxoDB #229) or CH3 strain (genotype ToxoDB #19)...
November 13, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/29145728/understanding-how-emergency-medicine-physicians-survive-and-thrive-in-rural-practice-a-theoretical-model
#11
Ashra Kolhatkar, Andrea Keesey, Bob Bluman, Brenna Lynn, Tandi Wilkinson
INTRODUCTION: The challenges facing emergency medicine (EM) services in Canada reflect the limitations of the entire healthcare system. The emergency department (ED) is uniquely situated in the healthcare system such that shortcomings in hospital- and community-based services are often first revealed there. This is especially true in rural settings, where there are additional site-specific barriers to the provision of EM care. Existing studies look at the factors that influence rural EM physicians in isolation...
November 2017: Rural and Remote Health
https://www.readbyqxmd.com/read/29145631/rifaximin-fails-to-prevent-campylobacteriosis-in-the-human-challenge-model-a-randomized-double-blind-placebo-controlled-trial
#12
Joanna E Rimmer, Clayton Harro, David A Sack, Kawsar R Talaat, Ramiro L Gutierrez, Barbara DeNearing, Jessica Brubaker, Renee M Laird, Frédéric Poly, Alexander C Maue, Kayla Jaep, Ashley Alcala, Yelizaveta Mochalova, Christina L Gariepy, Subhra Chakraborty, Patricia Guerry, David R Tribble, Chad K Porter, Mark S Riddle
Background: Campylobacter species are a leading cause of diarrheal disease globally with significant morbidity. Primary prevention efforts have yielded limited results. Rifaximin chemoprophylaxis decreases travelers' diarrhea rates and may be suitable for high risk persons. We assessed the efficacy of rifaximin in the controlled human infection model (CHIM) for Campylobacter jejuni. Methods: Twenty-eight subjects were admitted to an inpatient facility and randomized to a twice daily dose of 550 mg rifaximin or placebo...
November 14, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29145614/methionine-and-choline-deficient-mcd-model-in-predicting-adverse-drug-reactions-in-human-nash
#13
Hui Li, Erica Toth, Nathan J Cherrington
In the past few decades, great conceptual and technological advances have been made in the field of toxicology, but animal model-based research still remains one of the most widely-used and readily available tools for furthering our current knowledge. However, animal models are not perfect in predicting all systemic toxicity in humans. Extrapolating animal data to accurately predict human toxicities remains a challenge, and researchers are obligated to question the appropriateness of their chosen animal model...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29145463/the-chicken-or-the-egg-exploring-bi-directional-associations-between-newcastle-disease-vaccination-and-village-chicken-flock-size-in-rural-tanzania
#14
Julia de Bruyn, Peter C Thomson, Brigitte Bagnol, Wende Maulaga, Elpidius Rukambile, Robyn G Alders
Newcastle disease (ND) is a viral disease of poultry with global importance, responsible for the loss of a potential source of household nutrition and economic livelihood in many low-income food-deficit countries. Periodic outbreaks of this endemic disease result in high mortality amongst free-ranging chicken flocks and may serve as a disincentive for rural households to invest time or resources in poultry-keeping. Sustainable ND control can be achieved through vaccination using a thermotolerant vaccine administered via eyedrop by trained "community vaccinators"...
2017: PloS One
https://www.readbyqxmd.com/read/29145016/thermal-effect-on-the-degradation-of-hiapp20-29-fibrils
#15
H X Zhang, Lei Liu, Jie Wang, Christian Bortolini, Mingdong Dong
Uncontrolled misfolding of proteins resulting in the formation of amyloid deposits is associated with over 40 types of diseases, for instance, type-2 diabetes. The human Islet amyloid polypeptide (hIAPP) amyloid formation is thought to be the cause of type-2 diabetes occurrence. A possible strategy to the current challenge of reducing the toxicity of its aggregates to pancreatic β-cell is the discovery of an efficient way to degrading amyloid deposits. In this work, hIAPP20-29, a core fibrillating fragment of hIAPP, was selected as model system to explore the thermal effect at different temperature on the degradation of hIAPP20-29 mature fibrils...
October 31, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29143777/margination-of-fluorescent-polylactic-acid-polyaspartamide-based-nanoparticles-in-microcapillaries-in-vitro-the-effect-of-hematocrit-and-pressure
#16
Emanuela Fabiola Craparo, Rosa D'Apolito, Gaetano Giammona, Gennara Cavallaro, Giovanna Tomaiuolo
The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier-wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop...
October 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29143667/validation-of-whole-blood-transcriptome-signature-during-microdose-recombinant-human-erythropoietin-rhuepo-administration
#17
Guan Wang, Jérôme Durussel, Jonathan Shurlock, Martin Mooses, Noriyuki Fuku, Georgie Bruinvels, Charles Pedlar, Richard Burden, Andrew Murray, Brendan Yee, Anne Keenan, John D McClure, Pierre-Edouard Sottas, Yannis P Pitsiladis
BACKGROUND: Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo. METHODS: Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively)...
November 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29142334/approaches-to-macroevolution-2-sorting-of-variation-some-overarching-issues-and-general-conclusions
#18
David Jablonski
Approaches to macroevolution require integration of its two fundamental components, within a hierarchical framework. Following a companion paper on the origin of variation, I here discuss sorting within an evolutionary hierarchy. Species sorting-sometimes termed species selection in the broad sense, meaning differential origination and extinction owing to intrinsic biological properties-can be split into strict-sense species selection, in which rate differentials are governed by emergent, species-level traits such as geographic range size, and effect macroevolution, in which rates are governed by organism-level traits such as body size; both processes can create hitchhiking effects, indirectly causing the proliferation or decline of other traits...
2017: Evolutionary Biology
https://www.readbyqxmd.com/read/29142286/discovery-of-bladder-cancer-related-genes-using-integrative-heterogeneous-network-modeling-of-multi-omics-data
#19
Chen Peng, Ao Li, Minghui Wang
In human health, a fundamental challenge is the identification of disease-related genes. Bladder cancer (BC) is a worldwide malignant tumor, which has resulted in 170,000 deaths in 2010 up from 114,000 in 1990. Moreover, with the emergence of multi-omics data, more comprehensive analysis of human diseases become possible. In this study, we propose a multi-step approach for the identification of BC-related genes by using integrative Heterogeneous Network Modeling of Multi-Omics data (iHNMMO). The heterogeneous network model properly and comprehensively reflects the multiple kinds of relationships between genes in the multi-omics data of BC, including general relationships, unique relationships under BC condition, correlational relationships within each omics and regulatory relationships between different omics...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142256/quantitative-analysis-of-protein-protein-interactions-and-post-translational-modifications-in-rare-immune-populations
#20
Ayelet Avin, Maayan Levy, Ziv Porat, Jakub Abramson
In spite of recent advances in proteomics, quantitative analyses of protein-protein interactions (PPIs) or post-translational modifications (PTMs) in rare cell populations remain challenging. This is in particular true for analyses of rare immune and/or stem cell populations that are directly isolated from humans or animal models, and which are often characterized by multiple surface markers. To overcome these limitations, here we have developed proximity ligation imaging cytometry (PLIC), a protocol for proteomic analysis of rare cells...
November 15, 2017: Nature Communications
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