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Francesca Rocchi, Margit E Dylla, Peter A Bohlen, Ramnarayan Ramachandran
Detection thresholds for auditory stimuli (signals) increase in the presence of maskers. Natural environments contain maskers/distractors that can have a wide range of spatiotemporal properties relative to the signal. While these parameters have been well explored psychophysically in humans, they have not been well explored in animal models, and their neuronal underpinnings are not well understood. As a precursor to the neuronal measurements, we report the effects of systematically varying the spatial and temporal relationship between signals and noise in macaque monkeys (Macaca mulatta and Macaca radiata)...
October 19, 2016: Hearing Research
Pirow Bekker, Daniel Dairaghi, Lisa Seitz, Manmohan Leleti, Yu Wang, Linda Ertl, Trageen Baumgart, Sarah Shugarts, Lisa Lohr, Ton Dang, Shichang Miao, Yibin Zeng, Pingchen Fan, Penglie Zhang, Daniel Johnson, Jay Powers, Juan Jaen, Israel Charo, Thomas J Schall
The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood...
2016: PloS One
Mieke T Bus, Daniel M De Bruin, Guido M Kamphuis, Patricia J Zondervan, Maria P Laguna Pes, Theo M De Reijke, Ton G Van Leeuwen, Jean J De LA Rosette
BACKGROUND: The applicability of urinary biomarkers and optical diagnostics in upper urinary tract carcinoma (UUTUC) are increasingly debated. To receive insight in the opinion of the urological community involved in this field, a survey was sent out to identify the most promising techniques and understand the need for new diagnostics. Primary objective of this study was to provide an overview of current diagnostics in upper urinary tract urothelial carcinoma. Secondary objectives of this study was to assess the need for additional diagnostic techniques in the current diagnostic work-up for UUT-UC and to assess knowledge of novel techniques...
October 21, 2016: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
Chantal Cossette, Shishir Chourey, Qiuji Ye, Chintam Nagendra Reddy, Vivek Gore, Sylvie Gravel, Irina Slobodchikova, Dajana Vuckovic, Joshua Rokach, William S Powell
The potent eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a 5-lipoxygenase product that acts via the selective OXE receptor, which is present in many species, but not rodents. We previously reported that the indole 230 is a potent human OXE receptor antagonist. The objective of the present study was to determine whether the monkey would be a suitable animal model to investigate its pharmaceutical potential. We found that monkey leukocytes synthesize and respond to 5-oxo-ETE, and that 230 is a potent antagonist of the OXE receptor in monkey eosinophils...
October 21, 2016: Journal of Medicinal Chemistry
Yajie Hu, Jie Song, Longding Liu, Jing Li, Beibei Tang, Jingjing Wang, Xiaolong Zhang, Ying Zhang, Lichun Wang, Yun Liao, Zhanlong He, Qihan Li
Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are the predominant pathogens of hand, foot, and mouth disease (HFMD). Although these viruses exhibit genetic homology, the clinical manifestations caused by the two viruses have some discrepancies. In addition, the underlying mechanisms leading to these differences remain unclear. microRNAs (miRNAs) participate in numerous biological or pathological processes, including host responses to viral infections. Here, we focused on differences in miRNA expression patterns in rhesus monkey peripheral blood mononuclear cells (PBMCs) infected with EV71 and CA16 at various time points using high-throughput sequencing...
October 17, 2016: International Journal of Biochemistry & Cell Biology
Bernhard Reuss, Abdul R Asif, Abdullah Almamy, Christian Schwerk, Horst Schroten, Hiroshi Ishikawa, Charis Drummer, Rüdiger Behr
Prenatal maternal infections with Neisseria gonorrhoeae (NG) correlate with an increased lifetime probability for the offspring to develop psychosis. We could previously demonstrate that in human choroid plexus papilloma cells, anti-NG antibodies (α-NG) bind to mitochondrial proteins HSP60 and ATPB, and interfere with cellular energy metabolism. To assess the in vivo relevance for this, especially during prenatal neural development, we investigated here interactions of NG-specific antisera (α-NG1, α-NG2) with brain, choroid plexus and other non-neural tissues in pre- and perinatal samples of the nonhuman primate (NHP) Callithrix jacchus (CJ), a NHP model for preclinical research...
October 17, 2016: Brain Research
Rufin Vogels
New research published in Neuron describes assignment of cortical layer to single neurons recorded in awake monkeys. Applying the procedure to perirhinal cortex, Koyano et al. (2016) found marked and unsuspected differences among layers in the coding of associative memory signals.
October 19, 2016: Neuron
Shin-Ichi Inaba, Maki Goto, Kaoru Tanaka-Takanaka, Hisako Tanaka, Wataru Tomisato, Hiroshi Yuita, Hiromi Doi-Komuro, Ryotaku Inoue, Keiko Oshima, Takashi Kagari, Takaichi Shimozato, Takashi Izumi
The pharmacokinetic (PK) and pharmacodynamic (PD) modeling was conducted for the reduction of peripheral lymphocytes after oral administration of CS-0777 to healthy rats, monkeys and experimental autoimmune encephalomyelitis (EAE) induced rats. M1, the phosphorylated active metabolite of CS-0777, is a selective sphingosine 1-phosphate receptor-1 modulator. A linear one-and two-compartment model with reversible metabolism process characterized the time courses of CS-0777 and M1 concentrations in rats and monkeys, respectively...
October 20, 2016: Biopharmaceutics & Drug Disposition
Jou-Ku Chung, Eilish Brown, Bob Crooker, Kathleen J Palmieri, Thomas G McCauley
Enzyme replacement therapy with intravenous idursulfase (recombinant iduronate-2-sulfatase) is approved for the treatment of Hunter syndrome. Intravenous administration does not, however, treat the neurological manifestations, due to its low central nervous system bioavailability. Using intrathecal-lumbar administration, iduronate-2-sulfatase is delivered directly to the central nervous system. This study investigates the central nervous system biodistribution of intrathecal-lumbar administered iduronate-2-sulfatase in cynomolgus monkeys...
2016: PloS One
Lisa M Schneper, Jeanne Brooks-Gunn, Daniel A Notterman, Stephen J Suomi
OBJECTIVE: Child-rearing environments have been associated with morbidity in adult rhesus monkeys. We examine whether such links are also seen with leukocyte telomere length. METHODS: To determine telomere length in leukocytes, blood was collected from 11 adult female monkeys aged 7 to 10 years who had been exposed to different rearing environments between birth and 7 months. Four had been reared with their mothers in typical social groups composed of other female monkeys, their offspring, and 1 to 2 adult male monkeys...
October 19, 2016: Psychosomatic Medicine
David F Woodward, Stacey L Wenthur, Tara L Rudebush, Shan Fan, Carol B Toris
PURPOSE: Since all prostanoid receptors affect intraocular pressure (IOP) and endogenous prostanoids are found in ocular tissues, the pressor effects of prostanoid antagonists were comprehensively evaluated. The absence of effects of most of these antagonists was not entirely anticipated. To ensure no false-negative results, ocular biodisposition studies were conducted. METHODS: Monkeys with laser-induced ocular hypertension were used to study antagonist effects on IOP...
October 20, 2016: Journal of Ocular Pharmacology and Therapeutics
Matthew T Kaufman, Jeffrey S Seely, David Sussillo, Stephen I Ryu, Krishna V Shenoy, Mark M Churchland
Neural activity in monkey motor cortex (M1) and dorsal premotor cortex (PMd) can reflect a chosen movement well before that movement begins. The pattern of neural activity then changes profoundly just before movement onset. We considered the prediction, derived from formal considerations, that the transition from preparation to movement might be accompanied by a large overall change in the neural state that reflects when movement is made rather than which movement is made. Specifically, we examined "components" of the population response: time-varying patterns of activity from which each neuron's response is approximately composed...
July 2016: ENeuro
Gregory R Waryasz, Alan H Daniels, Joseph A Gil, Vladimir Suric, Craig P Eberson
Increasing emphasis on maintaining a healthy lifestyle has led many individuals to seek advice on exercise from personal trainers. There are few studies to date that evaluate personal trainer education, practice trends, and injuries they have seen while training clients. A survey was distributed to personal trainers using Survey Monkey® (Palo Alto, CA, USA) with 605 personal trainers accessing the survey. An exercise related bachelor's degree was held by 64.2% of survey participants and a certification in personal training by 89...
September 19, 2016: Orthopedic Reviews
Akiyoshi Ishikawa, Keita Sakai, Takehiro Maki, Yuri Mizuno, Kimie Niimi, Yasuhiro Oda, Eiki Takahashi
To understand sleep mechanisms and develop treatments for sleep disorders, investigations using animal models are essential. The sleep architecture of rodents differs from that of diurnal mammals including humans and non-human primates. Sleep studies have been conducted in non-human primates; however, these sleep assessments were performed on animals placed in a restraint chair connected via the umbilical area to the recording apparatus. To avoid restraints, cables, and other stressful apparatuses and manipulations, telemetry systems have been developed...
October 18, 2016: Experimental Animals
Encarni Marcos, Satoshi Tsujimoto, Aldo Genovesio
The estimation of space and time can interfere with each other, and neuroimaging studies have shown overlapping activation in the parietal and prefrontal cortical areas. We used duration and distance discrimination tasks to determine whether space and time share resources in prefrontal cortex (PF) neurons. Monkeys were required to report which of 2 stimuli, a red circle or blue square, presented sequentially, was longer and farther, respectively, in the duration and distance tasks. In a previous study, we showed that relative duration and distance are coded by different populations of neurons and that the only common representation is related to goal coding...
October 19, 2016: Journal of Neurophysiology
Tomos Proffitt, Lydia V Luncz, Tiago Falótico, Eduardo B Ottoni, Ignacio de la Torre, Michael Haslam
Our understanding of the emergence of technology shapes how we view the origins of humanity. Sharp-edged stone flakes, struck from larger cores, are the primary evidence for the earliest stone technology. Here we show that wild bearded capuchin monkeys (Sapajus libidinosus) in Brazil deliberately break stones, unintentionally producing recurrent, conchoidally fractured, sharp-edged flakes and cores that have the characteristics and morphology of intentionally produced hominin tools. The production of archaeologically visible cores and flakes is therefore no longer unique to the human lineage, providing a comparative perspective on the emergence of lithic technology...
October 19, 2016: Nature
Scott N Furlan, Benjamin Watkins, Victor Tkachev, Sarah Cooley, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, Daniel J Hunt, John B Schell, Katie Zeleski, Alison Yu, Cindy Giver, Edmund Waller, Jeffrey S Miller, Bruce R Blazar, Leslie S Kean
One of the central challenges of transplantation is the development of alloreactivity despite the use of multi-agent immunoprophylaxis. Effective control of this immune-suppression-resistant T cell activation represents one of the key unmet needs in the fields of both solid organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly-translational non-human primate model to interrogate the transcriptional signature of T cells during Breakthrough Acute GVHD that occurs in the setting of clinically-relevant immune suppression and compared this to the Hyperacute GVHD, that develops in unprophylaxed or sub-optimally prophylaxed transplant recipients...
October 6, 2016: Blood
Caroline M Hostetler, Katherine Hinde, Nicole Maninger, Sally P Mendoza, William A Mason, Douglas J Rowland, Guobao B Wang, David Kukis, Simon R Cherry, Karen L Bales
Pair bonding leads to increases in dopamine D1 receptor (D1R) binding in the nucleus accumbens of monogamous prairie voles. In the current study, we hypothesized that there is similar up-regulation of D1R in a monogamous primate, the titi monkey (Callicebus cupreus). Receptor binding of the D1R antagonist [(11) C]-SCH23390 was measured in male titi monkeys using PET scans before and after pairing with a female. We found that within-subject analyses of pairing show significant increases in D1R binding in the lateral septum, but not the nucleus accumbens, caudate, putamen, or ventral pallidum...
October 18, 2016: American Journal of Primatology
Tomomichi Ishizaka, Yu Yoshimatsu, Yu Maeda, Wataru Takasaki, Katsuyoshi Chiba, Kazuhiko Mori
INTRODUCTION: Load-independent cardiac parameters obtained from the ventricular pressure-volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy.In this study, for better analyses of cardiac risks, load-independent pressure-volume loop parameters were assessed in addition to load-dependent inotropic, hemodynamic and electrocardiographic changes in isoflurane-anesthetized monkeys. METHODS: The animals were given milrinone (a PDE 3 inhibitor), metoprolol (a β-blocker), or dl-sotalol (a β+IKr blocker) intravenously over 10min at two dose levels including clinically relevant doses (n=5/drug)...
October 15, 2016: Journal of Pharmacological and Toxicological Methods
Karyn Colman
It has been long established that not only the species but also the strain and supplier of rodents used in preclinical safety studies can have a significant impact on the outcome of studies due to variability in their genetic background and thus spontaneous pathologic findings. In addition, local husbandry, housing, and other environmental conditions may have effects on the development and expression of comorbidities, particularly in longer-term or chronic studies. More recently, similar effects related to the source, including genetic and environmental variability, have been recognized in cynomolgus macaques (Macaca fascicularis)...
October 17, 2016: Toxicologic Pathology
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