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https://www.readbyqxmd.com/read/28535276/live-attenuated-pertussis-vaccine-bpze1-protects-baboons-against-b-pertussis-disease-and-infection
#1
Camille Locht, James F Papin, Sophie Lecher, Anne-Sophie Debrie, Marcel Thalen, Ken Solovay, Keith Rubin, Nathalie Mielcarek
Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of IgG and IgA to all antigens tested, while causing no adverse symptoms or leukocytosis...
May 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28535263/gene-expression-variability-and-the-analysis-of-large-scale-rna-seq-studies-with-the-mdseq
#2
Di Ran, Z John Daye
Rapidly decreasing cost of next-generation sequencing has led to the recent availability of large-scale RNA-seq data, that empowers the analysis of gene expression variability, in addition to gene expression means. In this paper, we present the MDSeq, based on the coefficient of dispersion, to provide robust and computationally efficient analysis of both gene expression means and variability on RNA-seq counts. The MDSeq utilizes a novel reparametrization of the negative binomial to provide flexible generalized linear models (GLMs) on both the mean and dispersion...
May 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28534661/characterization-of-human-fetal-brain-endothelial-cells-reveals-barrier-properties-suitable-for-in%C3%A2-vitro-modeling-of-the-bbb-with-syngenic-co-cultures
#3
Allison M Andrews, Evan M Lutton, Lee A Cannella, Nancy Reichenbach, Roshanak Razmpour, Matthew J Seasock, Steven J Kaspin, Steven F Merkel, Dianne Langford, Yuri Persidsky, Servio H Ramirez
Endothelial cells (ECs) form the basis of the blood-brain barrier (BBB), a physical barrier that selectively restricts transport into the brain. In vitro models can provide significant insight into BBB physiology, mechanisms of human disease pathology, toxicology, and drug delivery. Given the limited availability of primary human adult brain microvascular ECs ( aBMVECs), human fetal tissue offers a plausible alternative source for multiple donors and the opportunity to build syngenic tri-cultures from the same host...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28534432/gastrointestinal-microphysiological-systems
#4
Sarah E Blutt, James R Broughman, Winnie Zou, Xi-Lei Zeng, Umesh C Karandikar, Julie In, Nicholas C Zachos, Olga Kovbasnjuk, Mark Donowitz, Mary K Estes
Gastrointestinal diseases are a significant health care and economic burden. Prevention and treatment of these diseases have been limited by the available human biologic models. Microphysiological systems comprise organ-specific human cultures that recapitulate many structural, biological, and functional properties of the organ in smaller scale including aspects of flow, shear stress and chemical gradients. The development of intestinal microphysiological system platforms represents a critical component in improving our understanding, prevention, and treatment of gastrointestinal diseases...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28533743/neonatal-hypoxia-ischaemia-mechanisms-models-and-therapeutic-challenges
#5
REVIEW
Lancelot J Millar, Lei Shi, Anna Hoerder-Suabedissen, Zoltán Molnár
Neonatal hypoxia-ischaemia (HI) is the most common cause of death and disability in human neonates, and is often associated with persistent motor, sensory, and cognitive impairment. Improved intensive care technology has increased survival without preventing neurological disorder, increasing morbidity throughout the adult population. Early preventative or neuroprotective interventions have the potential to rescue brain development in neonates, yet only one therapeutic intervention is currently licensed for use in developed countries...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28533484/insights-from-animal-models-of-bladder-cancer-recent-advances-challenges-and-opportunities
#6
REVIEW
Bincy Anu John, Neveen Said
Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533363/collective-action-and-the-evolution-of-social-norm-internalization
#7
Sergey Gavrilets, Peter J Richerson
Human behavior is strongly affected by culturally transmitted norms and values. Certain norms are internalized (i.e., acting according to a norm becomes an end in itself rather than merely a tool in achieving certain goals or avoiding social sanctions). Humans' capacity to internalize norms likely evolved in our ancestors to simplify solving certain challenges-including social ones. Here we study theoretically the evolutionary origins of the capacity to internalize norms. In our models, individuals can choose to participate in collective actions as well as punish free riders...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533339/structure-based-prediction-of-wnt-binding-affinities-for-frizzled-type-cysteine-rich-domain
#8
Mark Agostino, Sebastian Öther-Gee Pohl, Arunasalam Dharmarajan
Wnt signaling pathways are of significant interest in development and oncogenesis. The first step in these pathways typically involves the binding of a Wnt protein to the cysteine-rich domain (CRD) of a Frizzled receptor; Wnt-Frizzled interactions can be antagonized by secreted Frizzled-related proteins (sFRPs), which also contain a Frizzled-like CRD. The large number of Wnts, Frizzleds and sFRPs, as well as the hydrophobic nature of Wnt, pose challenges to laboratory-based investigations of interactions involving Wnt...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533121/recent-progress-in-hepatocyte-culture-models-and-their-application-to-the-assessment-of-drug-metabolism-transport-and-toxicity-in-drug-discovery-the-value-of-tissue-engineering-for-the-successful-development-of-a-microphysiological-system
#9
REVIEW
Kazuhiro Tetsuka, Masato Ohbuchi, Kenji Tabata
Tissue engineering technology has provided many useful culture models. This article reviews the merits of this technology in a hepatocyte culture system, and describes the applications of the sandwich-cultured hepatocyte model in drug discovery. In addition, we also review recent investigations of the utility of the three-dimensional bioprinted human liver tissue model and spheroid model. Finally, we present the future direction and developmental challenges of a hepatocyte culture model for the successful establishment of a microphysiological system, represented as an organ-on-a-chip and even as a human-on-a-chip...
May 19, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28532500/extending-access-to-essential-services-against-constraints-the-three-tier-health-service-delivery-system-in-rural-china-1949-1980
#10
Xing Lin Feng, Melisa Martinez-Alvarez, Jun Zhong, Jin Xu, Beibei Yuan, Qingyue Meng, Dina Balabanova
BACKGROUND: China has made remarkable progress in scaling up essential services during the last six decades, making health care increasingly available in rural areas. This was partly achieved through the building of a three-tier health system in the 1950s, established as a linked network with health service facilities at county, township and village level, to extend services to the whole population. METHODS: We developed a Theory of Change to chart the policy context, contents and mechanisms that may have facilitated the establishment of the three-tier health service delivery system in rural China...
May 23, 2017: International Journal for Equity in Health
https://www.readbyqxmd.com/read/28532305/production-and-use-of-estimates-for-monitoring-progress-in-the-health-sector-the-case-of-bangladesh
#11
Karar Zunaid Ahsan, Tazeen Tahsina, Afrin Iqbal, Nazia Binte Ali, Suman Kanti Chowdhury, Tanvir M Huda, Shams El Arifeen
BACKGROUND:  In order to support the progress towards the post-2015 development agenda for the health sector, the importance of high-quality and timely estimates has become evident both globally and at the country level. OBJECTIVE AND METHODS: Based on desk review, key informant interviews and expert panel discussions, the paper critically reviews health estimates from both the local (i.e. nationally generated information by the government and other agencies) and the global sources (which are mostly modeled or interpolated estimates developed by international organizations based on different sources of information), and assesses the country capacity and monitoring strategies to meet the increasing data demand in the coming years...
January 2017: Global Health Action
https://www.readbyqxmd.com/read/28532218/flow-chamber-and-microfluidic-approaches-for-measuring-thrombus-formation-in-genetic-bleeding-disorders
#12
Rogier M Schoeman, Marcus Lehmann, Keith B Neeves
Platelet adhesion and aggregation, coagulation, fibrin formation, and fibrinolysis are regulated by the forces and flows imposed by blood at the site of a vascular injury. Flow chambers designed to observe these events are an indispensable part of doing hemostasis and thrombosis research, especially with human blood. Microfluidic methods have provided the flexibility to design flow chambers with complex geometries and features that more closely mimic the anatomy and physiology of blood vessels. Additionally, microfluidic systems with integrated optics and/or pressure sensors and on-board signal processing could transform what have been primarily research tools into clinical assays...
May 22, 2017: Platelets
https://www.readbyqxmd.com/read/28531310/nascent-rna-sequencing-reveals-mechanisms-of-gene-regulation-in-the-human-malaria-parasite-plasmodium-falciparum
#13
Xueqing Maggie Lu, Gayani Batugedara, Michael Lee, Jacques Prudhomme, Evelien M Bunnik, Karine G Le Roch
Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28531291/a-novel-virus-vectored-respiratory-mucosal-vaccine-enhances-anti-tuberculosis-immunity-in-a-humanized-model-system
#14
Yushi Yao, Rocky Lai, Sam Afkhami, Siamak Haddadi, Anna Zganiacz, Fatemeh Vahedi, Ali A Ashkar, Charu Kaushic, Mangalakumari Jeyanathan, Zhou Xing
Background: The translation of pre-clinically promising novel tuberculosis (TB) vaccines to ultimate human applications has met with the challenge of lacking markedly improved animal models for vaccine testing with an immune system of human equivalent in its genetic diversity and level of susceptibility to TB. Methods: We have developed a humanized mice (Hu-mice) TB model system to investigate the clinical relevance of a novel virus-vectored (VV) TB vaccine administered via respiratory mucosal (RM) or parenteral route...
May 20, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28530654/allele-specific-expression-reveals-interactions-between-genetic-variation-and-environment
#15
David A Knowles, Joe R Davis, Hilary Edgington, Anil Raj, Marie-Julie Favé, Xiaowei Zhu, James B Potash, Myrna M Weissman, Jianxin Shi, Douglas F Levinson, Philip Awadalla, Sara Mostafavi, Stephen B Montgomery, Alexis Battle
Identifying interactions between genetics and the environment (GxE) remains challenging. We have developed EAGLE, a hierarchical Bayesian model for identifying GxE interactions based on associations between environmental variables and allele-specific expression. Combining whole-blood RNA-seq with extensive environmental annotations collected from 922 human individuals, we identified 35 GxE interactions, compared with only four using standard GxE interaction testing. EAGLE provides new opportunities for researchers to identify GxE interactions using functional genomic data...
May 22, 2017: Nature Methods
https://www.readbyqxmd.com/read/28530164/biocompatibility-of-intensified-decellularized-equine-carotid-arteries-in-a-rat-subcutaneous-implantation-model-and-in-a-human-in-vitro-model
#16
Niklas Jeinsen, Lavinia Maegel, Danny Jonigk, Melanie Klingenberg, Axel Haverich, Mathias Wilhelmi, Ulrike Böer
Limited biocompatibility of decellularized scaffolds is an ongoing challenge in tissue engineering. We recently demonstrated that intensified detergent-based decellularization of equine carotid artery (dEACintens) removed residual cellular molecules from the scaffold more efficiently than a conventional decellularization (dEACcon) though this approach did not eliminate its immunogenicity entirely. CCN1 has been shown to improve biocompatibility of dEACcon in a sheep model. Here, we tested the biocompatibility of dEACintens and dEACcon with or without CCN1-coating after subcutaneous implantation in rats for up to 12 weeks...
May 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28530039/transition-from-paediatric-to-adult-care-of-adolescents-living-with-hiv-in-sub-saharan-africa-challenges-youth-friendly-models-and-outcomes
#17
Désiré Lucien Dahourou, Chloé Gautier-Lafaye, Chloe A Teasdale, Lorna Renner, Marcel Yotebieng, Sophie Desmonde, Samuel Ayaya, Mary-Ann Davies, Valériane Leroy
INTRODUCTION: The number of adolescents with perinatally or behaviourally acquired HIV is increasing in low-income countries, and especially in sub-Saharan Africa where HIV prevalence and incidence are the highest. As they survive into adulthood in the era of antiretroviral therapy, there is a pressing need to transfer them from paediatric to adult care, known as the transition of care. We conducted a narrative review of recent evidence on their transition outcomes in Africa, highlighting the specific needs and challenges in these populations and settings, and the different models of care for transition...
May 16, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28529938/senescence-inflammatory-regulation-of-reparative-cellular-reprogramming-in-aging-and-cancer
#18
Javier A Menendez, Tomás Alarcón
The inability of adult tissues to transitorily generate cells with functional stem cell-like properties is a major obstacle to tissue self-repair. Nuclear reprogramming-like phenomena that induce a transient acquisition of epigenetic plasticity and phenotype malleability may constitute a reparative route through which human tissues respond to injury, stress, and disease. However, tissue rejuvenation should involve not only the transient epigenetic reprogramming of differentiated cells, but also the committed re-acquisition of the original or alternative committed cell fate...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28529840/adoptive-cell-therapy-with-tregs-to-improve-transplant-outcomes-the-promise-and-the-stumbling-blocks
#19
Mohamed B Ezzelarab, Angus W Thomson
The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28529704/towards-a-systems-approach-for-chronic-diseases-based-on-health-state-modeling
#20
Michael Rebhan
Rising pressure from chronic diseases means that we need to learn how to deal with challenges at a different level, including the use of systems approaches that better connect across fragments, such as disciplines, stakeholders, institutions, and technologies. By learning from progress in leading areas of health innovation (including oncology and AIDS), as well as complementary indications (Alzheimer's disease), I try to extract the most enabling innovation paradigms, and discuss their extension to additional areas of application within a systems approach...
2017: F1000Research
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