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Over stimulation

Anthony L Cunningham, Nathalie Garçon, Oberdan Leo, Leonard R Friedland, Richard Strugnell, Béatrice Laupèze, Mark Doherty, Peter Stern
In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response...
October 18, 2016: Vaccine
J R Teijaro
Since Isaac's and Lindenmann's seminal experiments over 50 years ago demonstrating a soluble factor generated from heat killed virus-stimulated chicken embryos could inhibit live influenza virus replication, the term interferon has been synonymous with inhibition of virus replication. While the antiviral properties of type 1 interferon (IFN-I) are undeniable, recent studies have reported expanding and somewhat unexpected roles of IFN-I signaling during both acute and persistent viral infections. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses and recruitment of inflammatory innate immune cell populations during acute respiratory viral infections...
2016: Advances in Immunology
Zhujun Ao, Rong Zhu, Xiaoli Tan, Lisa Liu, Liyu Chen, Shuiping Liu, XiaoJian Yao
BACKGROUND: HIV-1 latency is a major obstacle for HIV-1 eradication. Extensive efforts are being directed toward the reactivation of latent HIV reservoirs with the aim of eliminating latently infected cells via the host immune system and/or virus-mediated cell lysis. RESULTS: We screened over 1,500 small molecules and kinase inhibitors and found that a small molecule, PKC412 (midostaurin, a broad-spectrum kinase inhibitor), can stimulate viral transcription and expression from the HIV-1 latently infected ACH2 cell line and primary resting CD4+ T cells...
October 21, 2016: Virology Journal
Whitney Marsh, Heith Copes, Travis Linnemann
BACKGROUND: Because of increased law enforcement and subsequent media attention, methamphetamine users appear in the public's imagination as diseased, zombie-like White trash. We explore methamphetamine users' perceptions about whether the images, people, and situations in anti-methamphetamine campaigns reflect their own lives and experiences using meth. METHODS: To explore these perceptions, we used photo-elicitation interviews with 47 people who used methamphetamine (30 former and 17 active)...
October 18, 2016: International Journal on Drug Policy
Yanna Si, Yuan Zhang, Liu Han, Lihai Chen, Yajie Xu, Fan Sun, Muhuo Ji, Jianjun Yang, Hongguang Bao
BACKGROUND: Previous studies showed that isoflurane-induced cognitive deficits could be alleviated by dexmedetomidine in young animal subjects. In the current study, we examine whether dexmedetomidine could also alleviate isoflurane-induced cognitive deficits in senile animals. METHODS: Senile male C57BL/6 mice (20 months) received dexmedetomidine (50 μg/kg, i.p.) or vehicle 30 minutes prior to isoflurane exposure (1.3% for 4 h). Cognitive function was assessed 19 days later using a 5-day testing regimen with Morris water maze...
2016: PloS One
Klaus Kratochwill, Michael Boehm, Rebecca Herzog, Katharina Gruber, Anton Michael Lichtenauer, Lilian Kuster, Dagmar Csaicsich, Andreas Gleiss, Seth L Alper, Christoph Aufricht, Andreas Vychytil
BACKGROUND: Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysis (PD). Dysfunctional cellular stress responses aggravate peritoneal injury associated with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomized cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamine (AlaGln) addition to glucose-based PDF. METHODS: In a prospective randomized cross-over design, 20 stable PD outpatients underwent paired peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chamber 3...
2016: PloS One
Divya Singh, Ghanshyam Upadhyay, Ananya Sengupta, Mohammed A Biplob, Shaleen Chakyayil, Tiji George, Shireen Saleque
Understanding the production and differentiation of megakaryocytes from progenitors is crucial for realizing the biology and functions of these vital cells. Previous gene ablation studies demonstrated the essential role of the transcriptional repressor Gfi1b (growth factor independence 1b) in the generation of both erythroid and megakaryocytic cells. However, our recent work has demonstrated the down-regulation of this factor during megakaryocytic differentiation. In this study we identify two new gene targets of Gfi1b, the cytoskeletal proteins Kindlin3 and Talin1, and demonstrate the inverse expression and functions of these cytoskeletal targets relative to Gfi1b, during megakaryocytic differentiation...
2016: PloS One
Ellen L Mintz, Juliana A Passipieri, Daniel Y Lovell, George J Christ
Despite the regenerative capacity of skeletal muscle, permanent functional and/or cosmetic deficits (e.g., volumetric muscle loss (VML) resulting from traumatic injury, disease and various congenital, genetic and acquired conditions are quite common. Tissue engineering and regenerative medicine technologies have enormous potential to provide a therapeutic solution. However, utilization of biologically relevant animal models in combination with longitudinal assessments of pertinent functional measures are critical to the development of improved regenerative therapeutics for treatment of VML-like injuries...
October 7, 2016: Journal of Visualized Experiments: JoVE
Lars Marstaller, Hana Burianová, David C Reutens
Safety learning describes the ability to learn that certain cues predict the absence of a dangerous or threatening event. Although incidental observations of activity within the default mode network (DMN) during the processing of safety cues have been reported previously, there is as yet no evidence demonstrating that the DMN plays a functional rather than a corollary role in safety learning. Using functional magnetic resonance imaging and a Pavlovian fear conditioning and extinction paradigm, we investigated the neural correlates of danger and safety learning...
October 21, 2016: Human Brain Mapping
Wei Tuo, Natascha Leleu-Chavain, John Spencer, Supojjanee Sansook, Regis Millet, Philippe Chavatte
Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation. FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2)...
October 21, 2016: Journal of Medicinal Chemistry
Joerg Schiller, Christoph Korallus, Matthias Bethge, Matthias Karst, Marie-Lena Schmalhofer, Christoph Gutenbrunner, Matthias Georg Fink
: In this sham-controlled study, 53 patients received 10 sessions of acupuncture treatment over 5 weeks to investigate the effects of acupuncture on the pain and quality of life of patients with osteoporosis. The results showed significant favorable effects of verum acupuncture on quality of life. Both interventions showed sustained and clinically relevant effects on pain. PURPOSE: Standard analgesic treatment is associated with adverse events in patients with osteoporosis, especially elderly and/or comorbid patients...
December 2016: Archives of Osteoporosis
N Seyed Majidi, M C Verhage, O Donchin, P Holland, M A Frens, J N van der Geest
In this study, the role of the cerebellum in a cognitive learning task using transcranial direct current stimulation (tDCS) was investigated. Using a weather prediction task, subjects had to learn the probabilistic associations between a stimulus (a combination of cards) and an outcome (sun or rain). This task is a variant of a probabilistic classification learning task, for which it has been reported that prefrontal tDCS enhances performance. Using a between-subject design, all 30 subjects learned to improve their performance with increasing accuracies and shortened response times over a series of 500 trials...
October 20, 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Nathan D Nuzum, Ashlee M Hendy, Aaron P Russell, Wei-Peng Teo
Individual responses to transcranial direct current stimulation (tDCS) are varied and therefore potentially limit its application. There is evidence that this variability is related to the contributions of Indirect waves (I-waves) recruited in the cortex. The latency of motor-evoked potentials (MEPs) can be measured through transcranial magnetic stimulation (TMS), allowing an individual's responsiveness to tDCS to be determined. However, this single-pulse method requires several different orientations of the TMS coil, potentially affecting its reliability...
2016: Frontiers in Human Neuroscience
Thibaut Aurore, Russo Cristina, Morales-Quezada Leon, Hurtado-Puerto Aura, Deitos Alícia, Steven Freedman, Carvalho Sandra, Fregni Felipe
Transcranial pulsed current stimulation (tPCS) and transcranial direct current stimulation (tDCS) are two noninvasive neuromodulatory brain stimulation techniques whose effects on human brain and behavior have been studied individually. In the present study we aimed to quantify the effects of tDCS and tPCS, individually and in combination, on cortical activity, sensitivity and pain-related assessments in healthy individuals in order to understand their neurophysiological mechanisms and potential applications in clinical populations...
October 17, 2016: Neuroscience Letters
Jangjin Kim, Mary E Goldsberry, Thomas C Harmon, John H Freeman
Hippocampal development is thought to play a crucial role in the emergence of many forms of learning and memory, but ontogenetic changes in hippocampal activity during learning have not been examined thoroughly. We examined the ontogeny of hippocampal function by recording theta and single neuron activity from the dorsal hippocampal CA1 area while rat pups were trained in associative learning. Three different age groups [postnatal days (P)17-19, P21-23, and P24-26] were trained over six sessions using a tone conditioned stimulus (CS) and a periorbital stimulation unconditioned stimulus (US)...
2016: PloS One
Monika Lindemann, Marina Zaslavskaya, Melanie Fiedler, Benjamin Wilde, Falko M Heinemann, Andreas Heinold, Peter A Horn, Oliver Witzke
Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix(™) , an HBV vaccine containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti-HBs antibodies...
October 20, 2016: Scandinavian Journal of Immunology
Madhukar Pai, Mark P Nicol, Catharina C Boehme
Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement...
October 2016: Microbiology Spectrum
David S Freedman, Joseph B Schroeder, Gregory I Telian, Zhengyang Zhang, Smrithi Sunil, Jason T Ritt
OBJECTIVE: Behavioral neuroscience studies in freely moving rodents require small, light-weight implants to facilitate neural recording and stimulation. Our goal was to develop an integrated package of 3D printed parts and assembly aids for labs to rapidly fabricate, with minimal training, an implant that combines individually positionable microelectrodes, an optical fiber, zero insertion force (ZIF-clip) headstage connection, and secondary recording electrodes, e.g. for electromyography (EMG)...
October 20, 2016: Journal of Neural Engineering
M Voigtlaender, K Holstein, B Spath, C Bokemeyer, F Langer
INTRODUCTION: Despite similar residual factor VIII activity, patients with haemophilia A (HA) show significant interindividual variability with regard to bleeding frequency and severity, suggesting that additional factors modulate thrombin generation and fibrin deposition. Protein disulphide isomerase (PDI) is an abundant oxidoreductase that exerts pleiotropic effects in primary and secondary haemostasis and contributes to thrombosis and vascular inflammation. AIM: We conducted a pilot study to explore a potential role of platelet PDI in patients with HA...
October 20, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
Alberto Campanaro, Raffaella Battaglia, Massimo Galbiati, Ari Sadanandom, Chiara Tonelli, Lucio Conti
SUMOylation and anther growth. During fertilization, stamen elongation needs to be synchronized with pistil growth. The phytohormone gibberellic acid (GA) promotes stamen growth by stimulating the degradation of growth repressing DELLA proteins. DELLA accumulation is negatively regulated by GAs through the ubiquitin-proteasome system. In Arabidopsis thaliana, a proportion of DELLAs is also conjugated to the small ubiquitin-like modifier (SUMO) protein, which stabilizes DELLAs. Increased DELLA levels occur in the SUMO protease-deficient OVERLY TOLERANT TO SALT 1 and 2 (ots1 ots2) double mutants, especially under salt stress conditions...
October 19, 2016: Plant Reproduction
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