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Priming agents

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https://www.readbyqxmd.com/read/28710492/nek1-kinase-domain-structure-and-its-dynamic-protein-interactome-after-exposure-to-cisplatin
#1
Talita D Melo-Hanchuk, Priscila Ferreira Slepicka, Gabriela Vaz Meirelles, Fernanda Luisa Basei, Diogo Ventura Lovato, Daniela Campos Granato, Bianca Alves Pauletti, Romenia Ramos Domingues, Adriana Franco Paes Leme, Alessandra Luiza Pelegrini, Guido Lenz, Stefan Knapp, Jonathan M Elkins, Jörg Kobarg
NEK family kinases are serine/threonine kinases that have been functionally implicated in the regulation of the disjunction of the centrosome, the assembly of the mitotic spindle, the function of the primary cilium and the DNA damage response. NEK1 shows pleiotropic functions and has been found to be mutated in cancer cells, ciliopathies such as the polycystic kidney disease, as well as in the genetic diseases short-rib thoracic dysplasia, Mohr-syndrome and amyotrophic lateral sclerosis. NEK1 is essential for the ionizing radiation DNA damage response and priming of the ATR kinase and of Rad54 through phosphorylation...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28680744/intratumoral-delivery-of-tumor-antigen-loaded-dc-and-tumor-primed-cd4-t-cells-combined-with-agonist-%C3%AE-gitr-mab-promotes-durable-cd8-t-cell-dependent-antitumor-immunity
#2
Zuqiang Liu, Xingxing Hao, Yi Zhang, Jiying Zhang, Cara D Carey, Louis D Falo, Walter J Storkus, Zhaoyang You
The progressive tumor microenvironment (TME) coordinately supports tumor cell expansion and metastasis, while it antagonizes the survival and (poly-)functionality of antitumor T effector cells. There remains a clear need to develop novel therapeutic strategies that can transform the TME into a pro-inflammatory niche that recruits and sustains protective immune cell populations. While intravenous treatment with tumor-primed CD4(+) T cells combined with intraperitoneal delivery of agonist anti-glucocorticoid-induced TNF receptor (α-GITR) mAb results in objective antitumor responses in murine early stage disease models, this approach is ineffective against more advanced tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28678031/immunotherapy-based-combinations-current-status-and-perspectives
#3
María J de Miguel-Luken, André Mansinho, Valentina Boni, Emiliano Calvo
PURPOSE OF REVIEW: Since the approval of ipilimumab, different immune checkpoint inhibitors, vaccines and costimulatory agonists have been developed with success, improving patient's survival in a number of different tumour types. However, immunotherapy results in durable responses but only in a fraction of patients. In order to improve this, combination of different immune agents is currently being attempted in the clinic with the potential of becoming one day the next wave of immune treatments available for our cancer patients...
July 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28676386/prodrugs-in-medicinal-chemistry-and-enzyme-prodrug-therapies
#4
Raoul Walther, Jarkko Rautio, Alexander N Zelikin
Prodrugs are cunning derivatives of therapeutic agents designed to improve the pharmacokinetics profile of the drug. Within a prodrug, pharmacological activity of the drug is masked and is recovered within the human body upon bioconversion of the prodrug, a process that is typically mediated by enzymes. This concept is highly successful and a significant fraction of marketed therapeutic formulations is based on prodrugs. An advanced subset of prodrugs can be engineered such as to achieve site-specific bioconversion of the prodrug - to comprise the highly advantageous "enzyme prodrug therapy", EPT...
July 1, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28675654/bioinformatory-assisted-analysis-of-next-generation-sequencing-data-for-precision-medicine-in-pancreatic-cancer
#5
Linnéa Malgerud, Johan Lindberg, Valtteri Wirta, Maria Gustafsson-Liljefors, Masoud Karimi, Carlos Fernández Moro, Katrin Stecker, Alexander Picker, Carolin Huelsewig, Martin Stein, Regina Bohnert, Marco Del Chiaro, Stephan L Haas, Rainer L Heuchel, Johan Permert, Markus J Maeurer, Stephan Brock, Caroline S Verbeke, Lars Engstrand, David B Jackson, Henrik Grönberg, J-Matthias Löhr
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly due to chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes Next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity...
July 4, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28667661/recovery-and-immune-priming-modulate-the-evolutionary-trajectory-of-infection-induced-reproductive-strategies
#6
Hoang Luu, Ann T Tate
In response to parasite exposure, organisms from a variety of taxa undergo a shift in reproductive investment that may trade off with other life history traits including survival and immunity. By suppressing reproduction in favor of somatic and immunological maintenance, hosts can enhance the probability of survival and recovery from infection. By plastically enhancing reproduction through terminal investment, on the other hand, hosts under the threat of disease-induced mortality could enhance their lifetime reproductive fitness through reproduction rather than survival...
July 1, 2017: Journal of Evolutionary Biology
https://www.readbyqxmd.com/read/28665980/the-effects-of-name-and-religious-priming-on-ratings-of-a-well-known-political-figure-president-barack-obama
#7
Gary A Williams, AnaMarie C Guichard, JungHa An
Priming with race-typed names and religious concepts have been shown to activate stereotypes and increase prejudice towards out-groups. We examined the effects of name and religious word priming on views of a specific and well-known person, President Barack Obama. We predicted that politically conservative participants primed with President Obama's middle name (Hussein) would rate him more negatively and be more likely to view him as a Muslim than those not shown his middle name. We also examined whether conservatives primed with concrete religious words would rate President Obama more negatively and be more likely to view him as Muslim than those primed with other word types...
2017: PloS One
https://www.readbyqxmd.com/read/28662952/vaccination-against-histomonosis-limits-pronounced-changes-of-b-cells-and-t-cell-subsets-in-turkeys-and-chickens
#8
Taniya Mitra, Wilhelm Gerner, Fana Alem Kidane, Patricia Wernsdorf, Michael Hess, Armin Saalmüller, Dieter Liebhart
The protozoan parasite Histomonas meleagridis is the causative agent of histomonosis in gallinaceous birds. In turkeys, the disease can result in high mortality due to severe inflammation and necrosis in caecum and liver, whereas in chickens the disease is less severe. Recently, experimental vaccination was shown to protect chickens and turkeys against histomonosis but dynamics in the cellular immune response are not yet demonstrated. In the present work, different groups of birds of both species were vaccinated with attenuated, and/or infected with virulent histomonads...
June 26, 2017: Vaccine
https://www.readbyqxmd.com/read/28659882/dendritic-cells-primed-with-paracoccidioides-brasiliensis-peptide-p10-are-therapeutic-in-immunosuppressed-mice-with-paracoccidioidomycosis
#9
Leandro B R Silva, Lucas S Dias, Glauce M G Rittner, Julián E Muñoz, Ana C O Souza, Joshua D Nosanchuk, Luiz R Travassos, Carlos P Taborda
Paracoccidioidomycosis (PCM) is an endemic systemic mycosis in Latin America, with the highest prevalence in Brazil, Colombia, and Venezuela. Fungi of the Paracoccidioides genus are etiologic agents of the disease. The 15 amino acid peptide P10 is derived from gp43, the main diagnostic antigen of Paracoccidioides brasiliensis. We previously reported that P10-pulsed dendritic cells (DCs) induce a protective response against P. brasiliensis. Presently, dexamethasone-treated BALB/c mice were intratracheally infected with P...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28642013/identifying-mechanisms-driving-formation-of-granuloma-associated-fibrosis-during-mycobacterium-tuberculosis-infection
#10
Hayley C Warsinske, Robert M DiFazio, Jennifer J Linderman, JoAnne L Flynn, Denise E Kirschner
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a pulmonary pathogen of major global concern. A key feature of Mtb infection in primates is the formation of granulomas, dense cellular structures surrounding infected lung tissue. These structures serve as the main site of host-pathogen interaction in TB, and thus to effectively treat TB we must clarify mechanisms of granuloma formation and their function in disease. Fibrotic granulomas are associated with both good and bad disease outcomes...
June 20, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28638979/endocytosis-is-required-for-exocytosis-and-priming-of-respiratory-burst-activity-in-human-neutrophils
#11
T Michael Creed, Shweta Tandon, Richard A Ward, Kenneth R McLeish
OBJECTIVE AND DESIGN: Neutrophil generation of reactive oxygen species (ROS) is enhanced by exposure to pro-inflammatory agents in a process termed priming. Priming is depending on exocytosis of neutrophil granules and p47(phox) phosphorylation-dependent translocation of cytosolic NADPH oxidase components. Clathrin-mediated endocytosis was recently reported to be necessary for priming, but the mechanism linking endocytosis to priming was not identified. The present study examined the hypothesis that endocytosis regulates neutrophil priming by controlling granule exocytosis...
June 21, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28636769/is-cannabis-treatment-for-anxiety-mood-and-related-disorders-ready-for-prime-time
#12
REVIEW
Jasmine Turna, Beth Patterson, Michael Van Ameringen
Anxiety and related disorders are the most common mental conditions affecting the North American population. Despite their established efficacy, first-line antidepressant treatments are associated with significant side effects, leading many afflicted individuals to seek alternative treatments. Cannabis is commonly viewed as a natural alternative for a variety of medical and mental health conditions. Currently, anxiety ranks among the top five medical symptoms for which North Americans report using medical marijuana...
June 21, 2017: Depression and Anxiety
https://www.readbyqxmd.com/read/28629321/the-biocontrol-agent-pseudomonas-chlororaphis-pa23-primes-brassica-napus-defenses-through-distinct-gene-networks
#13
Kelly A Duke, Michael G Becker, Ian J Girard, Jenna L Millar, W G Dilantha Fernando, Mark F Belmonte, Teresa R de Kievit
BACKGROUND: The biological control agent Pseudomonas chlororaphis PA23 is capable of protecting Brassica napus (canola) from the necrotrophic fungus Sclerotinia sclerotiorum via direct antagonism. While we have elucidated bacterial genes and gene products responsible biocontrol, little is known about how the host plant responds to bacterial priming on the leaf surface, including global changes in gene activity in the presence and absence of S. sclerotiorum. RESULTS: Application of PA23 to the aerial surfaces of canola plants reduced the number of S...
June 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28628715/overcoming-the-resistance-of-pancreatic-cancer-to-immune-checkpoint-inhibitors
#14
REVIEW
Richard A Skelton, Ammar Javed, Lei Zheng, Jin He
Immunotherapy has become a new modality of cancer treatment, but has had a limited success in treating PDAC. A combination approach to immunotherapy, using both immune checkpoint inhibitors and immune activating agonists, is needed, as PDAC does not respond to single-agent checkpoint inhibitors. Studies have also supported using vaccine-based therapies to prime the tumor microenvironment of PDAC with effector T-cells. Other therapeutic strategies including epigenetic agents, stroma modulators, radiotherapy, and T-cell transfer therapies may also prime the tumor microenvironment to overcome resistance to immune checkpoint inhibitors...
July 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28621364/single-molecule-probing-of-amyloid-nano-ensembles-using-the-polymer-nanoarray-approach
#15
Sibaprasad Maity, Ekaterina Viazovkina, Alexander Gall, Yuri L Lyubchenko
Soluble amyloid-beta (Aβ) oligomers are the prime causative agents of cognitive deficits during early stages of Alzheimer's disease (AD). The transient nature of the oligomers makes them difficult to characterize by traditional techniques, suggesting that advanced approaches are necessary. Previously developed fluorescence-based tethered approach for probing intermolecular interactions (TAPIN) and AFM-based single-molecule force spectroscopy are capable of probing dimers of Aβ peptides. In this paper, a novel polymer nanoarray approach to probe trimers and tetramers formed by the Aβ(14-23) segment of Aβ protein at the single-molecule level is applied...
June 28, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28620681/cardiac-t1-mapping-in-congenital-heart-disease-bolus-vs-infusion-protocols-for-measurements-of-myocardial-extracellular-volume-fraction
#16
Nadya Al-Wakeel-Marquard, Sanaz Rastin, Frédéric Muench, Darach O H-Ici, Sevim Yilmaz, Felix Berger, Titus Kuehne, Daniel R Messroghli
Myocardial extracellular volume fraction (ECV) reflecting diffuse myocardial fibrosis can be measured with T1 mapping cardiovascular magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be obtained with a primed contrast infusion (equilibrium contrast-CMR). We hypothesized that equilibrium can also be achieved with a single contrast bolus to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD)...
June 15, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28620583/engineering-of-genetically-arrested-parasites-gaps-for-a-precision-malaria-vaccine
#17
REVIEW
Oriana Kreutzfeld, Katja Müller, Kai Matuschewski
Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including Plasmodium species, the causative agents of malaria. Efficient elimination of Plasmodium liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in Plasmodium berghei, P. yoelii and P. falciparum and compare their vaccine potential...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28615944/the-interactions-of-single-wall-carbon-nanohorns-with-polar-epithelium
#18
Yujie Shi, Zujin Shi, Suxin Li, Yuan Zhang, Bing He, Dong Peng, Jie Tian, Ming Zhao, Xueqing Wang, Qiang Zhang
Single-wall carbon nanohorns (SWCNHs), which have multitudes of horn interstices, an extensive surface area, and a spherical aggregate structure, offer many advantages over other carbon nanomaterials being used as a drug nanovector. The previous studies on the interaction between SWCNHs and cells have mostly emphasized on cellular uptake and intracellular trafficking, but seldom on epithelial cells. Polar epithelium as a typical biological barrier constitutes the prime obstacle for the transport of therapeutic agents to target site...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28611802/involvement-of-trichoderma-harzianum-epl-1-protein-in-the-regulation-of-botrytis-virulence-and-tomato-defense-related-genes
#19
Eriston V Gomes, Cirano J Ulhoa, Rosa E Cardoza, Roberto N Silva, Santiago Gutiérrez
Several Trichoderma spp. are well known for their ability to: (i) act as important biocontrol agents against phytopathogenic fungi; (ii) function as biofertilizers; (iii) increase the tolerance of plants to biotic and abiotic stresses; and (iv) induce plant defense responses via the production and secretion of elicitor molecules. In this study, we analyzed the gene-regulation effects of Trichoderma harzianum Epl-1 protein during the interactions of mutant Δepl-1 or wild-type T. harzianum strains with: (a) the phytopathogen Botrytis cinerea and (b) with tomato plants, on short (24 h hydroponic cultures) and long periods (4-weeks old plants) after Trichoderma inoculation...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28598048/hepatotoxicity-in-hiv-patients-an-observational-study-in-patients-from-tertiary-care-centre-of-western-india
#20
Smrati Bajpai, Kavita Joshi
OBJECTIVE: HIV AIDS has currently become a chronic manageable condition with HAART, but with its chronicity and lifelong therapy currently the adverse drug reactions to these drugs are the main concern for any treating physician. Hepatotoxicity is one of the prime concerns of any physician managing HIV patients. We observe a number of patients reporting hepatotoxicity in our cohort and this had great impact on the efficacy and intake of the HAART drugs, this led us to explore this area and to find out the prevalence and etiologies in our cohort...
May 2017: Journal of the Association of Physicians of India
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