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https://www.readbyqxmd.com/read/27933316/systemic-therapy-with-oncolytic-myxoma-virus-cures-established-residual-multiple-myeloma-in-mice
#1
Eric Bartee, Mee Y Bartee, Bjarne Bogen, Xue-Zhong Yu
Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. It has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells during autologous transplant...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933310/dynamics-of-antigen-presentation-to-transgene-product-specific-cd4-t-cells-and-of-treg-induction-upon-hepatic-aav-gene-transfer
#2
George Q Perrin, Irene Zolotukhin, Alexandra Sherman, Moanaro Biswas, Ype P de Jong, Cox Terhorst, Andrew M Davidoff, Roland W Herzog
The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4(+) T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933039/the-contribution-of-mathematical-modeling-to-understanding-dynamic-aspects-of-rumen-metabolism
#3
André Bannink, Henk J van Lingen, Jennifer L Ellis, James France, Jan Dijkstra
All mechanistic rumen models cover the main drivers of variation in rumen function, which are feed intake, the differences between feedstuffs and feeds in their intrinsic rumen degradation characteristics, and fractional outflow rate of fluid and particulate matter. Dynamic modeling approaches are best suited to the prediction of more nuanced responses in rumen metabolism, and represent the dynamics of the interactions between substrates and micro-organisms and inter-microbial interactions. The concepts of dynamics are discussed for the case of rumen starch digestion as influenced by starch intake rate and frequency of feed intake, and for the case of fermentation of fiber in the large intestine...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932950/amyloid-precursor-proteins-are-dynamically-trafficked-and-processed-during-neuronal-development
#4
Jenna M Ramaker, Robert S Cargill, Tracy L Swanson, Hanil Quirindongo, Marlène Cassar, Doris Kretzschmar, Philip F Copenhaver
Proteolytic processing of the Amyloid Precursor Protein (APP) produces beta-amyloid (Aβ) peptide fragments that accumulate in Alzheimer's Disease (AD), but APP may also regulate multiple aspects of neuronal development, albeit via mechanisms that are not well understood. APP is a member of a family of transmembrane glycoproteins expressed by all higher organisms, including two mammalian orthologs (APLP1 and APLP2) that have complicated investigations into the specific activities of APP. By comparison, insects express only a single APP-related protein (APP-Like, or APPL) that contains the same protein interaction domains identified in APP...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27932417/molecular-pathways-the-necrosome-a-target-for-cancer-therapy
#5
Lena Seifert, George Miller
Necroptosis is a caspase 8-independent cell death that requires co-activation of receptor-interacting protein (RIP) 1 and RIP 3 kinases. The necrosome is a complex consisting of RIP1, RIP3 and Fas-associated protein with death domain (FADD) leading to activation of the pseudokinase mixed lineage kinase like (MLKL) followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns (DAMPs) and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma and several hematological malignancies...
December 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27931083/the-therapeutic-potential-of-t-cell-metabolism
#6
Ali Zarrinpar, Steven J Bensinger
Transplant rejection mediated by the adaptive immune system remains a major barrier to achieving long-term tolerance and graft survival. Emerging evidence indicates that lymphocytes rapidly shift their metabolic programs in response to activation, co-stimulatory, and cytokine signals to support required effector cell differentiation and function. These observations have led to the hypothesis that manipulating the metabolic programs of immune cells could serve as a powerful therapeutic strategy for attenuating deleterious immune responses and facilitating durable tolerance in the setting of allogeneic solid organ or bone marrow transplant...
December 8, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27930322/casitas-b-cell-lymphoma-cbl-proteins-protect-mammary-epithelial-cells-from-proteotoxicity-of-active-c-src-accumulation
#7
Chandrani Mukhopadhyay, Aleata Triplett, Tom Bargar, Carol Heckman, Kay-Uwe Wagner, Mayumi Naramura
Casitas B-cell lymphoma (Cbl) family ubiquitin ligases negatively regulate tyrosine kinase-dependent signal transduction by promoting degradation of active kinases. We and others previously reported that loss of Cbl functions caused hyperproliferation in lymphoid and hematopoietic systems. Unexpectedly, Cbl deletion in Cbl-b-null, Cbl-c-null primary mouse mammary epithelial cells (MECs) (Cbl triple-deficiency) induced rapid cell death despite enhanced MAP kinase and AKT activation. Acute Cbl triple-deficiency elicited distinct transcriptional and biochemical responses with partial overlap with previously described cellular reactions to unfolded proteins and oxidative stress...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27926473/growth-differentiation-factor-15-increases-following-oral-glucose-ingestion-effect-of-meal-composition-and-obesity
#8
Marie Helene Schernthaner-Reiter, Dominik Kasses, Christina Tugendsam, Michaela Riedl, Slobodan Peric, Gerhard Prager, Michael Krebs, Miriam Promintzer-Schifferl, Martin Clodi, Anton Luger, Greisa Vila
OBJECTIVE: Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-β superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. DESIGN: Lean (n = 8) and obese (n = 8) individuals received a carbohydrate- or fat-rich meal, a 75 g oral glucose load (OGTT) or short-term fasting...
December 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27926436/to-work-or-not-to-work-neural-representation-of-cost-and-benefit-of-instrumental-action
#9
N B Kroemer, C Burrasch, L Hellrung
By definition, instrumental actions are performed in order to obtain certain goals. Nevertheless, the attainment of goals typically implies obstacles, and response vigor is known to reflect an integration of subjective benefit and cost. Whereas several brain regions have been associated with cost/benefit ratio decision-making, trial-by-trial fluctuations in motivation are not well understood. We review recent evidence supporting the motivational implications of signal fluctuations in the mesocorticolimbic system...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27925291/herbivore-perception-decreases-photosynthetic-carbon-assimilation-and-reduces-stomatal-conductance-by-engaging-12-oxo-phytodienoic-acid-mitogen-activated-protein-kinase-4-and-cytokinin-perception
#10
Ivan D Meza-Canales, Stefan Meldau, Jorge A Zavala, Ian T Baldwin
Herbivory-induced changes in photosynthesis have been documented in many plant species, however the complexity of photosynthetic regulation and analysis has thwarted progress in understanding the mechanism involved, particularly those elicited by herbivore-specific elicitors. Here we analyzed the early photosynthetic gas-exchange responses in Nicotiana attenuata plants after wounding and elicitation with Manduca sexta oral-secretions, and the pathways regulating these responses. Elicitation with M. sexta oral-secretions rapidly decreased photosynthetic carbon-assimilation (AC ) in treated and systemic (untreated, vascularly connected) leaves, which were associated with changes in stomatal conductance, rather than with changes in Rubisco activity and RuBP-turnover...
December 7, 2016: Plant, Cell & Environment
https://www.readbyqxmd.com/read/27925187/depletion-of-cd52-positive-cells-inhibits-the-development-of-cns-autoimmune-disease-but-deletes-an-immune-tolerance-promoting-cd8-t-cell-population-implications-for-secondary-autoimmunity-of-alemtuzumab-in-multiple-sclerosis
#11
Stephanie von Kutzleben, Gareth Pryce, Gavin Giovannoni, David Baker
The objective was to determine whether CD52 lymphocyte depletion can act to promote immunological tolerance induction via intravenous antigen administration such that it could be used to either: improve efficiency of inhibition of MS or to inhibit secondary autoimmunities that may occur following alemtuzumab use in multiple sclerosis. Relapsing experimental autoimmune encephalomyelitis was induced in ABH mice and immune cell depletion was therapeutically applied using mouse CD52 or CD4 (in conjunction with CD8 or CD20) depleting monoclonal antibodies...
December 7, 2016: Immunology
https://www.readbyqxmd.com/read/27924107/newborn-healthcare-in-urban-india
#12
REVIEW
J Sharma, D Osrin, B Patil, S B Neogi, M Chauhan, R Khanna, R Kumar, V K Paul, S Zodpey
The rapid population growth in urban India has outpaced the municipal capacity to build essential infrastructures that make life in cities safe and healthy. Local and national governments alike are grappling with the challenges of urbanization with thousands migrating from villages to cities. Thus, urbanization in India has been accompanied by a concentration of poverty and urban public healthcare has emerged as one of the most pressing priorities facing our country. Newborn mortality rates in urban settings are lower than rural areas, early neonatal deaths account for greater proportion than late neonatal deaths...
December 2016: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/27923919/quorum-sensing-coordinates-cooperative-expression-of-pyruvate-metabolism-genes-to-maintain-a-sustainable-environment-for-population-stability
#13
Lisa A Hawver, Jennifer M Giulietti, James D Baleja, Wai-Leung Ng
: Quorum sensing (QS) is a microbial cell-cell communication system that regulates gene expression in response to population density to coordinate collective behaviors. Yet, the role of QS in resolving the stresses caused by the accumulation of toxic metabolic by-products at high cell density is not well defined. In response to cell density, QS could be involved in reprogramming of the metabolic network to maintain population stability. Using unbiased metabolomics, we discovered that Vibrio cholerae mutants genetically locked in a low cell density (LCD) QS state are unable to alter the pyruvate flux to convert fermentable carbon sources into neutral acetoin and 2,3-butanediol molecules to offset organic acid production...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27923742/neuronal-adaptation-in-the-somatosensory-system-of-rodents
#14
REVIEW
I Lampl, Y Katz
The sensory systems in animals constantly monitor the environment and process salient and relevant features while subtracting background activity. This process requires continuous recalibration of neuronal gain based on recent history. Adaptation has been postulated to be the key mechanism by which neurons rapidly tune their response curves to represent the entire dynamic range of external inputs. Rodents heavily rely on their vibrissa system while gathering information about their surroundings using whisking...
December 3, 2016: Neuroscience
https://www.readbyqxmd.com/read/27923644/s-and-n-alkylating-agents-diminish-the-fluorescence-of-fluorescent-dye-stained-dna
#15
Robert Giesche, Harald John, Kai Kehe, Annette Schmidt, Tanja Popp, Frank Balzuweit, Horst Thiermann, Thomas Gudermann, Dirk Steinritz
Sulfur mustard (SM), a chemical warfare agent, causes DNA alkylation, which is believed to be the main cause of its toxicity. SM DNA adducts are commonly used to verify exposure to this vesicant. However, the required analytical state-of-the-art mass-spectrometry methods are complex, use delicate instruments, are not mobile, and require laboratory infrastructure that is most likely not available in conflict zones. Attempts have thus been made to develop rapid detection methods that can be used in the field...
December 3, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27923422/first-responders-and-prehospital-care-for-road-traffic-injuries-in-malawi
#16
Linda Chokotho, Wakisa Mulwafu, Isaac Singini, Yasin Njalale, Limbika Maliwichi-Senganimalunje, Kathryn H Jacobsen
: Introduction Road traffic collisions are a common cause of injuries and injury-related deaths in sub-Saharan Africa (SSA). Basic prehospital care can be the difference between life and death for injured drivers, passengers, and pedestrians. Problem This study examined the challenges associated with current first response practices in Malawi. METHODS: In April 2014, focus groups were conducted in two areas of Malawi: Karonga (in the Northern Region) and Blantyre (in the Southern Region; both are along the M1 highway), and a qualitative synthesis approach was used to identify themes...
December 7, 2016: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/27921082/global-role-of-cyclic-amp-signaling-in-ph-dependent-responses-in-candida-albicans
#17
Jeffrey M Hollomon, Nora Grahl, Sven D Willger, Katja Koeppen, Deborah A Hogan
Candida albicans behaviors are affected by pH, an important environmental variable. Filamentous growth is a pH-responsive behavior, where alkaline conditions favor hyphal growth and acid conditions favor growth as yeast. We employed filamentous growth as a tool to study the impact of pH on the hyphal growth regulator Cyr1, and we report that downregulation of cyclic AMP (cAMP) signaling by acidic pH contributes to the inhibition of hyphal growth in minimal medium with GlcNAc. Ras1 and Cyr1 are generally required for efficient hyphal growth, and the effects of low pH on Ras1 proteolysis and GTP binding are consistent with diminished cAMP output...
November 2016: MSphere
https://www.readbyqxmd.com/read/27920759/immune-responses-to-influenza-virus-and-its-correlation-to-age-and-inherited-factors
#18
REVIEW
Azadeh Bahadoran, Sau H Lee, Seok M Wang, Rishya Manikam, Jayakumar Rajarajeswaran, Chandramathi S Raju, Shamala D Sekaran
Influenza viruses belong to the family Orthomyxoviridae of enveloped viruses and are an important cause of respiratory infections worldwide. The influenza virus is able to infect a wide variety species as diverse as poultry, marine, pigs, horses, and humans. Upon infection with influenza virus the innate immunity plays a critical role in efficient and rapid control of viral infections as well as in adaptive immunity initiation. The humoral immune system produces antibodies against different influenza antigens, of which the HA-specific antibody is the most important for neutralization of the virus and thus prevention of illness...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27920467/possible-therapeutic-role-of-ige-blockade-in-irritable-bowel-syndrome
#19
EDITORIAL
Eli Magen, Tinatin Chikovani
Omalizumab is a humanized monoclonal antibody that binds to the high-affinity type-I IgE Fc receptors on mast cells (MCs) and basophils, inhibiting the IgE immune pathway. Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder, and dysregulation of the immune system likely contributes to its etiology and/or symptomatology. Colonic biopsies from patients with IBS demonstrate considerable increase in the number of degranulating MCs releasing histamine in proximity to nerves, and this event may underlie the common IBS symptom of abdominal pain...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27920243/between-the-flags-implementing-a-safety-net-system-at-scale-to-recognise-and-manage-deteriorating-patients-in-the-new-south-wales-public-health-system
#20
Charles Pain, Malcolm Green, Colette Duff, Deborah Hyland, Annette Pantle, Kimberley Fitzpatrick, Cliff Hughes
QUALITY PROBLEM: In 2005, the Clinical Excellence Commission (CEC) found that unrecognised patient deterioration remained an important problem in New South Wales (NSW) public hospitals. INITIAL ASSESSMENT: The challenge was to design and implement an effective and sustainable safety-net system in all 225 NSW public hospitals. DESIGNING A SOLUTION: The CEC's system was designed in collaboration with a broad coalition of partners, including clinicians, managers, system administrators and collaborating agencies...
December 4, 2016: International Journal for Quality in Health Care
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