The Role of Fur in Heat Regulation in the Guinea Pig

Author Institution: Kent State University, Kent, Ohio and University of Delaware, Newark, Delawar

Pre-movement changes in sensorimotor beta oscillations predict motor adaptation drive

International audienceBeta frequency oscillations in scalp electroencephalography (EEG) recordings over the primary motor cortex have been associated with the preparation and execution of voluntary movements. Here, we test whether changes in beta frequency are related to the preparation of adapted movements in human, and whether such effects generalise to other species (cat). Eleven healthy adult humans performed a joystick visuomotor adaptation task. Beta (15-25 Hz) scalp EEG signals recorded over the motor cortex during a pre-movement preparatory phase were, on average, significantly reduced in amplitude during early adaptation trials compared to baseline, late adaptation, or aftereffect trials. The changes in beta were not related to measurements of reaction time or reach duration. We also recorded local field potential (LFP) activity within the primary motor cortex of three cats during a prism visuomotor adaptation task. Analysis of these signals revealed similar reductions in motor cortical LFP beta frequencies during early adaptation. This effect was present when controlling for any influence of the reaction time and reach duration. Overall, the results are consistent with a reduction in pre-movement beta oscillations predicting an increase in adaptive drive in upcoming task performance when motor errors are largest in magnitude and the rate of adaptation is greatest

Non-invasive Stimulation of the Cerebellum in Health and Disease

The cerebellum is linked to motor, cognitive and affective functions. Anatomically, the cerebellum is part of an interconnected network including a wide range of other brain structures. This chapter reviews ways in which non-invasive stimulation has been used to activate or inhibit these circuits and how this has contributed to our understanding of cerebellar function in both motor and non-motor domains. The utility of non-invasive stimulation of the cerebellum in the treatment of neurological and psychiatric diseases (Parkinson’s disease, cerebellar ataxia, stroke, depression and schizophrenia) is discussed. The chapter concludes with consideration of the challenges that must be overcome if non-invasive cerebellar stimulation is to be adopted in a wider clinical setting

Oocyte maturation and quality: role of cyclic nucleotides

Advance Publication first posted online on 15 July 2016 - Accepted manuscriptThe cyclic nucleotides, cAMP and cGMP, are the key molecules controlling mammalian oocyte meiosis. Their roles in oocyte biology have been at the forefront of oocyte research for decades and many of the long standing controversies in relation to the regulation of oocyte meiotic maturation are now resolved. It is now clear that the follicle prevents meiotic resumption through the actions of natriuretic peptides and cGMP inhibiting the hydrolysis of intra-oocyte cAMP and that the preovulatory gonadotrophin surge reverses these processes. The gonadotrophin surge also leads to a transient spike in cAMP in the somatic compartment of the follicle; research over the past 2 decades has conclusively demonstrated that this surge in cAMP is important for the subsequent developmental capacity of the oocyte. This is important, as oocyte in vitro maturation (IVM) systems practiced clinically do not recapitulate this cAMP surge in vitro, possibly accounting for the lower efficiency of IVM compared to clinical IVF. This review focuses in particular on this latter aspect - the role of cAMP/cGMP in the regulation of oocyte quality. We conclude that clinical practice of IVM should reflect this new understanding of the role of cyclic nucleotides, thereby creating a new generation of ART and fertility treatment options.Gilchrist RB, Luciano AM, Richani D, Zeng HT, Wang X, De Vos M, Sugimura S, Smitz J, Richard FJ and Thompson J

Slower rates of prism adaptation but intact aftereffects in patients with early to mid-stage Parkinson's disease

There is currently mixed evidence on the effect of Parkinson's disease on motor adaptation. Some studies report that patients display adaptation comparable to age-matched controls, while others report a complete inability to adapt to novel sensory perturbations. Here, early to mid-stage Parkinson's patients were recruited to perform a prism adaptation task. When compared to controls, patients showed slower rates of initial adaptation but intact aftereffects. These results support the suggestion that patients with early to mid-stage Parkinson's disease display intact adaptation driven by sensory prediction errors, as shown by the intact aftereffect. But impaired facilitation of performance through cognitive strategies informed by task error, as shown by the impaired initial adaptation. These results support recent studies that suggest that patients with Parkinson's disease retain the ability to perform visuomotor adaptation, but display altered use of cognitive strategies to aid performance and generalises these previous findings to the classical prism adaptation task

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

Biotransformation of Silver Released from Nanoparticle Coated Titanium Implants Revealed in Regenerating Bone

Antimicrobial silver nanoparticle coatings have attracted interest for reducing prosthetic joint infection. However, few studies report in vivo investigations of the biotransformation of silver nanoparticles within the regenerating tissue and its impact on bone formation. We present a longitudinal investigation of the osseointegration of silver nanoparticle-coated additive manufactured titanium implants in rat tibial defects. Correlative imaging at different time points using nanoscale secondary ion mass spectrometry, transmission electron microscopy (TEM), histomorphometry, and 3D X-ray microcomputed tomography provided quantitative insight from the nano- to macroscales. The quality and quantity of newly formed bone is comparable between the uncoated and silver coated implants. The newly formed bone demonstrates a trabecular morphology with bone being located at the implant surface, and at a distance, at two weeks. Nanoscale elemental mapping of the bone−implant interface showed that silver was present primarily in the osseous tissue and colocalized with sulfur. TEM revealed silver sulfide nanoparticles in the newly regenerated bone, presenting strong evidence that the previously in vitro observed biotransformation of silver to silver sulfide occurs in vivo

Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease

BACKGROUND: Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD). METHODS: Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638). RESULTS: In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction. CONCLUSIONS: Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality

Impact of flavonoid-rich black tea and beetroot juice on postprandial peripheral vascular resistance and glucose homeostasis in obese, insulin-resistant men: a randomized controlled trial.

BACKGROUND: Insulin-stimulated muscle blood flow facilitates plasma glucose disposal after a meal, a mechanism that is impaired in obese, insulin-resistant volunteers. Nitrate- or flavonoid-rich products, through their proposed effects on nitric oxide, may improve postprandial blood flow and, subsequently, glucose disposal. To investigate whether a single dose of nitrate-rich beetroot juice or flavonoid-rich black tea lowers postprandial muscle vascular resistance in obese volunteers and alters postprandial glucose or insulin concentrations. METHOD: In a randomised, controlled, cross-over study, 16 obese, insulin-resistant males consumed 75 g glucose, which was combined with 100 ml black tea, beetroot juice or control (water). Peripheral vascular resistance (VR), calculated as mean arterial pressure divided by blood flow, was assessed in the arm and leg conduit arteries, resistance arteries and muscle microcirculation across 3 h (every 30-min) after the oral glucose load. RESULTS: During control, we found no postprandial response in VR in conduit, resistance and microvessels (all P > 0.05). Black tea decreased VR compared to control in conduit, resistance and microvessels (all P < 0.05). Beetroot juice decreased postprandial VR in resistance vessels, but not in conduit artery and microvessels. Although postprandial glucose response was similar after all interventions, postprandial insulin response was attenuated by ~29 % after tea (P < 0.0005), but not beetroot juice. CONCLUSIONS: A single dose of black tea decreased peripheral VR across upper and lower limbs after a glucose load which was accompanied by a lower insulin response. Future studies in insulin-resistant subjects are warranted to confirm the observed effects and to explore whether long-term regular tea consumption affects glucose homeostasis. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov on 30(th) November 2012 (NCT01746329)