Does the presence of a vaginal probe alter pelvic floor muscle activation in young,continent women?

Vaginal probes may induce changes in pelvic floor muscle (PFM) recruitment by the very presence of the probes. Fine-wire electrodes allow us to detect muscle activation parameters without altering the natural position and shape of the PFMs. The purpose of this study was to determine whether PFM activation is altered by changes in sensory feedback, muscle length or tissue position caused by two different vaginal probes used to record surface electromyography (EMG). Twelve continent women (30.1 ± 5.4 years), performed PFM maximal voluntary contractions (MVCs) in supine while fine-wire EMG was recorded bilaterally from the PFMs under three conditions: (a) without any probe inserted into the vagina, (b) while a Femiscan? probe was in situ, and (c) while a Periform? vaginal probe was in situ. The reliability of the fine wire EMG data was assessed using intra-class correlation coefficients (ICCs) and coefficients of variation (CV). A repeated measures analysis of variance (ANOVA) model was used to determine if there were differences in EMG amplitude recorded when the different vaginal probes were in situ. For each condition the between-trial reliability was excellent, ICC_(3,1) = 0.93–0.96, (p < 0.001) and CV = 11.2–21.8%. There were no differences in peak EMG amplitude recorded during the MVCs across the three conditions (no probe 63.4 ± 48.4 μV, Femiscan? 55.3 ± 42.4 μV, Periform? 59.4 ± 42.2 μV, p = 0.178). These results suggest that women produce consistent MVCs over multiple contractions, and that PFM muscle activation is not affected by different probes inserted into the vagina.     

Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export

The microtubule-associated protein tau has risk alleles for both Alzheimer's disease and Parkinson's disease and mutations that cause brain degenerative diseases termed tauopathies. Aggregated tau forms neurofibrillary tangles in these pathologies, but little is certain about the function of tau or its mode of involvement in pathogenesis. Neuronal iron accumulation has been observed pathologically in the cortex in Alzheimer's disease, the substantia nigra (SN) in Parkinson's disease and various brain regions in the tauopathies. Here we report that tau-knockout mice develop age-dependent brain atrophy, iron accumulation and SN neuronal loss, with concomitant cognitive deficits and parkinsonism. These changes are prevented by oral treatment with a moderate iron chelator, clioquinol. Amyloid precursor protein (APP) ferroxidase activity couples with surface ferroportin to export iron, but its activity is inhibited in Alzheimer's disease, thereby causing neuronal iron accumulation. In primary neuronal culture, we found loss of tau also causes iron retention, by decreasing surface trafficking of APP. Soluble tau levels fall in affected brain regions in Alzheimer's disease and tauopathies, and we found a similar decrease of soluble tau in the SN in both Parkinson's disease and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. These data suggest that the loss of soluble tau could contribute to toxic neuronal iron accumulation in Alzheimer's disease, Parkinson's disease and tauopathies, and that it can be rescued pharmacologically.     

Processing of Chlamydia abortus Polymorphic Membrane Protein 18D during the Chlamydial Developmental Cycle

Background

Chlamydia possess a unique family of autotransporter proteins known as the Polymorphic membrane proteins (Pmps). While the total number of pmp genes varies between Chlamydia species, all encode a single pmpD gene. In both Chlamydia trachomatis (C. trachomatis) and C. pneumoniae, the PmpD protein is proteolytically cleaved on the cell surface. The current study was carried out to determine the cleavage patterns of the PmpD protein in the animal pathogen C. abortus (termed Pmp18D).

Methodology/Principal Findings

Using antibodies directed against different regions of Pmp18D, proteomic techniques revealed that the mature protein was cleaved on the cell surface, resulting in a100 kDa N-terminal product and a 60 kDa carboxy-terminal protein. The N-terminal protein was further processed into 84, 76 and 73 kDa products. Clustering analysis resolved PmpD proteins into three distinct clades with C. abortus Pmp18D, being most similar to those originating from C. psittaci, C. felis and C. caviae.

Conclusions/Significance

This study indicates that C. abortus Pmp18D is proteolytically processed at the cell surface similar to the proteins of C. trachomatis and C. pneumoniae. However, patterns of cleavage are species-specific, with low sequence conservation of PmpD across the genus. The absence of conserved domains indicates that the function of the PmpD molecule in chlamydia remains to be elucidated.     

The interplay of plant and animal disease in a changing landscape: the role of sudden aspen decline in moderating Sin Nombre virus prevalence in natural deer mouse populations

We examined how climate-mediated forest dieback regulates zoonotic disease prevalence using the relationship between sudden aspen decline (SAD) and Sin Nombre virus (SNV) as a model system. We compared understory plant community structure, small mammal community composition, and SNV prevalence on 12 study sites within aspen forests experiencing levels of SAD ranging from <10.0% crown fade to >95.0% crown fade. Our results show that sites with the highest levels of SAD had reduced canopy cover, stand density, and basal area, and these differences were reflected by reductions in understory vegetation cover. Conversely, sites with the highest levels of SAD had greater understory standing biomass, suggesting that vegetation on these sites was highly clustered. Changes in forest and understory vegetation structure likely resulted in shifts in small mammal community composition across the SAD gradient, as we found reduced species diversity and higher densities of deer mice, the primary host for SNV, on sites with the highest levels of SAD. Sites with the highest levels of SAD also had significantly greater SNV prevalence compared to sites with lower levels of SAD, which is likely a result of their abundance of deer mice. Collectively, results of our research provide strong evidence to show SAD has considerable impacts on vegetation community structure, small mammal density and biodiversity and the prevalence of SNV.     

Spatial and Temporal Analysis of Contact Rates in Female White-Tailed Deer

Abstract: White-tailed deer (Odocoileus virginianus) are important game mammals and potential reservoirs of diseases of domestic livestock; thus, diseases of deer are of great concern to wildlife managers. Contact, either direct or indirect, is necessary for disease transmission, but we know little about the ecological contexts that promote intrasexual contact among deer. Using pair-wise direct contacts estimated from Global Positioning System collar locations and joint utilization distributions (JUDs), we assessed habitats in which contacts occur to test whether direct contact rates among female white-tailed deer in different social groups differs among land-cover types. We also tested whether contact rates differed among seasons, lunar phases, and times of day. We obtained locations from 27 female deer for periods of 0.5–17 months during 2002–2006. We designated any simultaneous pair of locations for 2 deer <25 m apart as a direct contact. For each season, we used compositional analysis to compare land-cover types where 2 deer had contact to available land-cover weighted by their JUD. We used mixed-model logistic regression to test for effects of season, lunar phase, and time of day on contact rates. Contact rates during the gestation season were greater than expected from random use in forest and grassland cover, whereas contact rates during the fawning period were greater in agricultural fields than in other land-cover types. Contact rates were greatest during the rut and lowest in summer. Diel patterns of contact rates varied with season, and contact rates were elevated during full moon compared to other lunar periods. Both spatial and temporal analyses suggest that contact between female deer in different social groups occurs mainly during feeding, which highlights the potential impact of food distribution and habitat on contact rates among deer. By using methods to associate contacts and land-cover, we have created beneficial tools for more elaborate and detailed studies of disease transmission. Our methods can offer information necessary to develop spatially realistic models of disease transmission in deer.     

Relationships between lamb carcass quality traits measured by X-ray computed tomography and current UK hill sheep breeding goals

Genetic parameters were estimated between current UK hill sheep breeding goals and lamb carcass composition and muscularity traits derived using X-ray computed tomography (CT). To produce these estimates, a total of 648 lambs from two hill farms were CT scanned at weaning (ca 120 days of age), over 3 years, and total weights of carcass muscle (MUSC), fat (CFAT) and bone (BONE) and internal fat (IFAT) were predicted. Previously derived muscularity indices were also calculated for the hind leg (HLMI) and lumbar (LRMI) regions, to assess muscle shape. Data for current breeding goals (lamb performance and maternal traits) were also included from a total of 10 297 lamb records and 12 704 ewe records. Heritabilities were estimated for each trait and genetic and phenotypic correlations were calculated between each CT trait and other lamb or ewe traits. Moderate to high positive genetic correlations were found between CT-predicted tissue weights and breeding goals, which were also weights (lamb weaning weight, carcass weight, mature ewe weight, average weight of lambs reared by the ewe). CFAT was positively genetically correlated with ultrasound backfat depth at weaning (UFD) and subjective fatness grade at slaughter (MLCF), suggesting that carcass fat could be decreased using selection on any of these predictors. Ultrasound muscle depth at weaning (UMD) and subjective conformation score at slaughter (MLCC) had high genetic correlations with the muscularity indices (HLMI and LRMI), but correlations with MUSC were not significantly different from zero. This implies that selection to improve MLCC is likely to be increasing the 'roundness' of muscle shape in the high-priced carcass region, but having little impact on total lean meat yield. Correlations of CT traits with the other ewe traits (number of lambs weaned, number of lambs lost, longevity, fleece weight) were generally small or not significantly different from zero. The genetic parameters generated in this study can now be used in selection index calculations to assess the benefits of including lamb CT traits in future selection programmes for hill sheep.     

Reciprocal control of pyruvate dehydrogenase kinase and phosphatase by inositol phosphoglycans. Dynamic state set by "push-pull" system

Reversible phosphorylation of proteins regulates numerous aspects of cell function, and abnormal phosphorylation is causal in many diseases. Pyruvate dehydrogenase complex (PDC) is central to the regulation of glucose homeostasis. PDC exists in a dynamic equilibrium between de-phospho-(active) and phosphorylated (inactive) forms controlled by pyruvate dehydrogenase phosphatases (PDP1,2) and pyruvate dehydrogenase kinases (PDK1-4). In contrast to the reciprocal regulation of the phospho-/de-phospho cycle of PDC and at the level of expression of the isoforms of PDK and PDP regulated by hormones and diet, there is scant evidence for regulatory factors acting in vivo as reciprocal "on-off" switches. Here we show that the putative insulin mediator inositol phosphoglycan P-type (IPG-P) has a sigmoidal inhibitory action on PDK in addition to its known linear stimulation of PDP. Thus, at critical levels of IPG-P, this sigmoidal/linear model markedly enhances the switchover from the inactive to the active form of PDC, a "push-pull" system that, combined with the developmental and hormonal control of IPG-P, indicates their powerful regulatory function. The release of IPGs from cell membranes by insulin is significant in relation to diabetes. The chelation of IPGs with Mn2+ and Zn2+ suggests a role as "catalytic chelators" coordinating the traffic of metal ions in cells. Synthetic inositol hexosamine analogues are shown here to have a similar linear/sigmoidal reciprocal action on PDC exerting push-pull effects, suggesting their potential for treatment of metabolic disorders, including diabetes.     

Short-term responses of leaf growth rate to water deficit scale up to whole-plant and crop levels: an integrated modelling approach in maize

Physiological and genetic studies of leaf growth often focus on short-term responses, leaving a gap to whole-plant models that predict biomass accumulation, transpiration and yield at crop scale. To bridge this gap, we developed a model that combines an existing model of leaf 6 expansion in response to short-term environmental variations with a model coordinating the development of all leaves of a plant. The latter was based on: (1) rates of leaf initiation, appearance and end of elongation measured in field experiments; and (2) the hypothesis of an independence of the growth between leaves. The resulting whole-plant leaf model was integrated into the generic crop model APSIM which provided dynamic feedback of environmental conditions to the leaf model and allowed simulation of crop growth at canopy level. The model was tested in 12 field situations with contrasting temperature, evaporative demand and soil water status. In observed and simulated data, high evaporative demand reduced leaf area at the whole-plant level, and short water deficits affected only leaves developing during the stress, either visible or still hidden in the whorl. The model adequately simulated whole-plant profiles of leaf area with a single set of parameters that applied to the same hybrid in all experiments. It was also suitable to predict biomass accumulation and yield of a similar hybrid grown in different conditions. This model extends to field conditions existing knowledge of the environmental controls of leaf elongation, and can be used to simulate how their genetic controls flow through to yield.     

Lauric acid dependent enhancement in hepatic SCPx protein requires an insulin deficient environment

Sterol carrier protein X (SCPx) is a peroxisomal protein with both lipid transfer and thiolase activity. Treating with the fatty acid, lauric acid, induced SCPx mRNA levels in rat liver and in rat hepatoma H4IIE cells but enhanced protein levels of SCPx and the thiolase produced as a post-translational modification of SCPx were only seen in H4IIE cells. Further investigation revealed that the presence of insulin can mask lauric acid effects on the SCPx gene especially at the protein level. These data are in agreement with the findings that diabetes, a medical condition characterized by high levels of fatty acids in an insulin deficient environment, enhances the hepatic expression of SCPx.