The Role of the Locus Coeruleus and its Effect on Spontaneous Motor Activity in Response to Intraperitoneal Lipopolysaccharide in Rats

The locus coeruleus (LC) is a group of norepinephrine (NE)-containing neurons that shows marked NE depletion when rats are exposed to uncontrollable shock. The depletion of NE in the LC region results in an increase in burst-firing of LC neurons. Evidence indicates that an increase in burst-firing of LC neurons results in a decrease in motor activity. Intraperitoneal (ip) administration of lipopolysaccharide (LPS), cell wall of gram-negative bacteria, also causes an increase in burst-firing of LC neurons, apparently via the induction of interleukin-1 (IL-1) in the brain. Ip LPS also results in a decrease in spontaneous motor activity in rats, a behavior that expressed in “sickness behavior.” However, a causal relationship between an increase in burst-firing of LC neurons and a decrease in spontaneous motor activity after ip LPS has not yet been established. Therefore, this manuscript examines the effect of IL-1 acting within the LC region on producing an aspect of sickness behavior - a decrease in spontaneous motor activity — that is seen after ip LPS. We hypothesize that the decrease in spontaneous motor activity that occurs after an injection of ip LPS is mediated by the induction of IL- 1 in the LC region. Several experiments conducted measured spontaneous motor activity as affected by 1) ip LPS, 2) LPS infused into the LC region or 3) IL-1 infused into the LC or LC surrounding regions. A final experiment tested whether interleukin-1 receptor antagonist (IL-lra) infused into the LC region would block the decrease in spontaneous motor activity in response to an injection of ip LPS. The results showed that a range of ip LPS doses (5-20 pg/kg), a range of LPS doses (0.1-4.0 ng/rat) or a range of IL-lp doses (0.1-40 ng/rat) infused into the LC region all decreased spontaneous motor activity in a dose-dependent manner. Unexpectedly, an infusion of IL-ip (0.4 ng/rat) into LC surrounding regions did not significantly decrease spontaneous motor activity differently from an infusion of IL-ip (0.4 ng/rat) into the LC region. Finally, central IL-lra (40 pg/rat) was unable to block or affect the decrease in spontaneous motor activity seen after an injection of ip LPS (10 pg/kg). Collectively, the findings do not support the hypothesis that the decrease in spontaneous motor activity that occurs after an injection of ip LPS is mediated by the induction of IL-1 in the LC region. Although LPS infused into the LC region or IL-ip infused into the LC region decreased spontaneous motor activity, IL-lra was unable to block the decrease in spontaneous motor activity seen after an injection of ip LPS

Valuing jazz: cross-cultural comparisons of the classical influence in jazz

‘Valuing Jazz: Cross-cultural Comparisons of the Classical Influence in Jazz’ re-examines the interaction of Western classical music and jazz, focussing particularly on developments in North America and Britain in the twentieth century. This dissertation acknowledges and builds on the existing connections that have been drawn between classical music and jazz—both those that underscore the musical differences between the two idioms in order to discredit the latter, and those that acknowledge similarities in order to claim cultural legitimacy for jazz. These existing studies almost universally use outdated evaluative criteria, and I seek to redress this by using contemporary classical-music practices and discourses as my point of reference. By adopting a range of methodologies to investigate both intra- and extra-musical trends, this dissertation offers a thorough and balanced exploration of the topic. Each chosen avenue for exploration is explained with reference to parallel developments in North America, in order to provide a context within accepted jazz history and to highlight the different ways in which jazz developed in Britain. The phenomena under consideration include the emergence of a school of jazz criticism and scholarship that adopted systems of analysis and evaluation from established studies of classical music (Ch. 1); physical characteristics of jazz performance venues and the changing styles of audience reception within (Ch. 2); the adoption by jazz composers of ideologies and musical features from classical repertoire (Ch. 3); and the development of educational establishments and pedagogical systems that mirrored those already present in the classical-music world (Ch. 4). Although by no means exhaustive, these chapter topics provide a range of jazz narratives that provide a clear picture of the degree to which the development of jazz in America and Britain has been conditioned by the practices and characteristics of classical music

Valuing jazz: cross-cultural comparisons of the classical influence in jazz

‘Valuing Jazz: Cross-cultural Comparisons of the Classical Influence in Jazz’ re-examines the interaction of Western classical music and jazz, focussing particularly on developments in North America and Britain in the twentieth century. This dissertation acknowledges and builds on the existing connections that have been drawn between classical music and jazz—both those that underscore the musical differences between the two idioms in order to discredit the latter, and those that acknowledge similarities in order to claim cultural legitimacy for jazz. These existing studies almost universally use outdated evaluative criteria, and I seek to redress this by using contemporary classical-music practices and discourses as my point of reference. By adopting a range of methodologies to investigate both intra- and extra-musical trends, this dissertation offers a thorough and balanced exploration of the topic. Each chosen avenue for exploration is explained with reference to parallel developments in North America, in order to provide a context within accepted jazz history and to highlight the different ways in which jazz developed in Britain. The phenomena under consideration include the emergence of a school of jazz criticism and scholarship that adopted systems of analysis and evaluation from established studies of classical music (Ch. 1); physical characteristics of jazz performance venues and the changing styles of audience reception within (Ch. 2); the adoption by jazz composers of ideologies and musical features from classical repertoire (Ch. 3); and the development of educational establishments and pedagogical systems that mirrored those already present in the classical-music world (Ch. 4). Although by no means exhaustive, these chapter topics provide a range of jazz narratives that provide a clear picture of the degree to which the development of jazz in America and Britain has been conditioned by the practices and characteristics of classical music

Detection of siRNA induced mRNA silencing by RT-qPCR: considerations for experimental design

<p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) has been one of the most rapidly expanding areas of biological research in the past decade, revolutionizing the ability to analyze gene function. Thorough validation of siRNA duplexes is required prior to use in experimental systems, ideally by western blotting to show a reduction in protein levels. However, in many cases good antibodies are not available, and researchers must rely on RT-qPCR to detect knockdown of the mRNA species.</p> <p>Findings</p> <p>We have observed a phenomenon that gives a disparity between analyzing small interfering RNA (siRNA) efficacy by western blotting of the protein levels and real-time quantitative PCR (RT-qPCR) measurement of mRNA levels. Detection of this phenomenon was dependent upon the location of the target amplicon for PCR primers within the mRNA.</p> <p>Conclusions</p> <p>Our data suggests that for certain mRNAs, degradation of the 3' mRNA fragment resulting from siRNA mediated cleavage is blocked, leaving an mRNA fragment that can act as a template for cDNA synthesis, giving rise to false negative results and the rejection of a valid siRNA duplex. We show that this phenomenon may be avoided by the careful design of RT-qPCR primers for each individual siRNA experiment.</p

“Great Job Cleaning Your Plate Today!” Determinants of Child-Care Providers’ Use of Controlling Feeding Practices: An Exploratory Examination

Background National early childhood obesity prevention policies recommend that child-care providers avoid controlling feeding practices (CFP) (e.g., pressure-to-eat, food as reward, and praising children for cleaning their plates) with children to prevent unhealthy child eating behaviors and childhood obesity. However, evidence suggests that providers frequently use CFP during mealtimes. Objective Using the Academy of Nutrition and Dietetics (2011) benchmarks for nutrition in child care as a framework, researchers assessed child-care providers’ perspectives regarding their use of mealtime CFP with young children (aged 2 to 5 years). Design Using a qualitative design, individual, face-to-face, semi-structured interviews were conducted with providers until saturation was reached. Participants/setting Providers were selected using maximum variation purposive sampling from varying child-care contexts (Head Start, Child and Adult Care Food Program [CACFP] e-funded centers, non-CACFP programs). All providers were employed full-time in Head Start or state-licensed center-based child-care programs, cared for children (aged 2 to 5 years), and were directly responsible for serving meals and snacks. Main outcome measure Child-care providers’ perspectives regarding CFP. Statistical analyses performed Thematic analysis using NVivo (version 9, 2010, QSR International Pty Ltd) to derive themes. Results Providers’ perspectives showed barriers, motivators, and facilitators regarding their use of mealtime CFP. Providers reported barriers to avoiding CFP such as CFP were effective for encouraging desired behaviors, misconceptions that providers were encouraging but not controlling children’s eating, and fear of parents’ negative reaction if their child did not eat. Providers who did not practice CFP were motivated to avoid CFP because they were unnecessary for encouraging children to eat, and they resulted in negative child outcomes and obesity. Facilitators as an alternative to CFP included practicing healthful feeding practices such as role modeling, peer modeling, and sensory exploration of foods. Conclusions Training providers about negative child outcomes associated with CFP, children’s ability to self-regulate energy intake, and differentiating between controlling and healthful feeding strategies may help providers to avoid CFP

“Great Job Cleaning Your Plate Today!” Determinants of Child-Care Providers’ Use of Controlling Feeding Practices: An Exploratory Examination

Background National early childhood obesity prevention policies recommend that child-care providers avoid controlling feeding practices (CFP) (e.g., pressure-to-eat, food as reward, and praising children for cleaning their plates) with children to prevent unhealthy child eating behaviors and childhood obesity. However, evidence suggests that providers frequently use CFP during mealtimes. Objective Using the Academy of Nutrition and Dietetics (2011) benchmarks for nutrition in child care as a framework, researchers assessed child-care providers’ perspectives regarding their use of mealtime CFP with young children (aged 2 to 5 years). Design Using a qualitative design, individual, face-to-face, semi-structured interviews were conducted with providers until saturation was reached. Participants/setting Providers were selected using maximum variation purposive sampling from varying child-care contexts (Head Start, Child and Adult Care Food Program [CACFP] e-funded centers, non-CACFP programs). All providers were employed full-time in Head Start or state-licensed center-based child-care programs, cared for children (aged 2 to 5 years), and were directly responsible for serving meals and snacks. Main outcome measure Child-care providers’ perspectives regarding CFP. Statistical analyses performed Thematic analysis using NVivo (version 9, 2010, QSR International Pty Ltd) to derive themes. Results Providers’ perspectives showed barriers, motivators, and facilitators regarding their use of mealtime CFP. Providers reported barriers to avoiding CFP such as CFP were effective for encouraging desired behaviors, misconceptions that providers were encouraging but not controlling children’s eating, and fear of parents’ negative reaction if their child did not eat. Providers who did not practice CFP were motivated to avoid CFP because they were unnecessary for encouraging children to eat, and they resulted in negative child outcomes and obesity. Facilitators as an alternative to CFP included practicing healthful feeding practices such as role modeling, peer modeling, and sensory exploration of foods. Conclusions Training providers about negative child outcomes associated with CFP, children’s ability to self-regulate energy intake, and differentiating between controlling and healthful feeding strategies may help providers to avoid CFP

Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson's disease applied retrospectively in a large cohort study of recent onset cases

Objective: To examine the utility of the new Movement Disorder Society (MDS) diagnostic criteria in a large cohort of Parkinson's disease (PD) patients. Methods: Recently diagnosed (&lt;3.5 years) PD cases fulfilling United Kingdom (UK) brain bank criteria in Tracking Parkinson's, a UK multicenter prospective natural history study were assessed by retrospective application of the MDS criteria. Results: In 2000 cases, 1835 (91.7%) met MDS criteria for PD, either clinically established (n = 1261, 63.1%) or clinically probable (n = 574, 28.7%), leaving 165 (8.3%) not fulfilling criteria. Clinically established cases were significantly more likely to have limb rest tremor (89.3%), a good l-dopa response (79.5%), and olfactory loss (71.1%), than clinically probable cases (60.6%, 44.4%, and 34.5% respectively), but differences between probable PD and ‘not PD’ cases were less evident. In cases not fulfilling criteria, the mean MDS UPDRS3 score (25.1, SD 13.2) was significantly higher than in probable PD (22.3, SD 12.7, p = 0.016) but not established PD (22.9, SD 12.0, p = 0.066). The l-dopa equivalent daily dose of 341 mg (SD 261) in non-PD cases was significantly higher than in probable PD (250 mg, SD 214, p &lt; 0.001) and established PD (308 mg, SD 199, p = 0.025). After 30 months' follow-up, 89.5% of clinically established cases at baseline remained as PD (established/probable), and 86.9% of those categorized as clinically probable at baseline remained as PD (established/probable). Cases not fulfilling PD criteria had more severe parkinsonism, in particular relating to postural instability, gait problems, and cognitive impairment. Conclusion: Over 90% of cases clinically diagnosed as early PD fulfilled the MDS criteria for PD. Those not fulfilling criteria may have an atypical parkinsonian disorder or secondary parkinsonism that is not correctly identified by the UK Brain Bank criteria, but possibly by the new criteria

Comparative quasi-static mechanical characterization of fresh and stored porcine trachea specimens

Abstract: Tissues of the upper airways of critically ill patients are particularly vulnerable to mechanical damage associated with the use of ventilators. Ventilation is known to disrupt the structural integrity of respiratory tissues and their function. This damage contributes to the vulnerability of these tissues to infection. We are currently developing tissue models of damage and infection to the upper airways. As part of our studies, we have compared how tissue storage conditions affect mechanical properties of excised respiratory tissues using a quasi-static platform. Data presented here show considerable differences in mechanical responses of stored specimens compared to freshly excised specimens. These data indicate that implementation of storage and maintenance procedures that minimize rapid degradation of tissue structure are essential for retaining the material properties in our tissue trauma models

An Unidentified Filarial Species and its Impact on Fitness in Wild Populations of the Black-Footed Ferret (\u3ci\u3eMustela nigripes\u3c/i\u3e)

Disease can threaten the restoration of endangered species directly by substantially decreasing host survival or indirectly via incremental decreases in survival and reproduction. During a biomedical survey of reintroduced populations of the highly endangered black-footed ferret from 2002 to 2005, microfilariae discovered in the blood were putatively identified as Dirofilaria immitis, and widespread screening was initiated using a commercially available antigen-based ELISA test. A subset of animals (n = 16) was screened for D. immitis using a highly sensitive PCR-based assay. Microfilariae were also molecularly and morphologically characterized. Of 198 animals at six reintroduction sites, 12% had positive results using the ELISA test. No antigen-positive animals which were screened via PCR (n = 11) had positive PCR results, and all antigen-positive animals (n=24) were asymptomatic. No significant differences were found in body mass of antigen-positive (male: 1223±82 g [mean±SD], female: 726±75 g) vs. antigen-negative (male: 1,198±119 g, female: 710±53 g) individuals (P=0.4). Antigen prevalence was lower in juveniles (3%) than adults (12%; P=0.03), and higher in in situ, captive-reared individuals (33%) than wild-born individuals (10%; P=0.005). Morphologic, analysis of microfilariae revealed they were neither D. immitis nor any other previously characterized North American species. PCR amplification of the 5S spacer region of rDNA revealed that the filarial sequence shared only 76% identity with D. immitis. This previously unidentified filarial sequence was present in all antigen positive animals (11 of 11 tested). It appears that black-footed ferrets were infected with a previously undescribed species of filaria whose antigen cross-reacted with the ELISA assay, although further analysis is needed to make a conclusive statement. Nonetheless, this previously undescribed filaria does not appear to threaten recovery for this highly endangered mammal