Age- and Gender-Related Changes in Contractile Properties of Non-Atrophied EDL Muscle

Background: In humans, ageing causes skeletal muscles to become atrophied, weak, and easily fatigued. In rodent studies, ageing has been associated with significant muscle atrophy and changes in the contractile properties of the muscles. However, it is not entirely clear whether these changes in contractile properties can occur before there is significant atrophy, and whether males and females are affected differently. Methods and Results: We investigated various contractile properties of whole isolated fast-twitch EDL muscles from adult (2–6 months-old) and aged (12–22 months-old) male and female mice. Atrophy was not present in the aged mice. Compared with adult mice, EDL muscles of aged mice had significantly lower specific force, longer tetanus relaxation times, and lower fatiguability. In the properties of absolute force and muscle relaxation times, females were affected by ageing to a greater extent than males. Additionally, EDL muscles from a separate group of male mice were subjected to eccentric contractions of 15 % strain, and larger force deficits were found in aged than in adult mice. Conclusion: Our findings provide further insight into the muscle atrophy, weakness and fatiguability experienced by the elderly. We have shown that even in the absence of muscle atrophy, there are definite alterations in the physiological properties of whole fast-twitch muscle from ageing mice, and for some of these properties the alterations are mor

Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns.We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1(st)-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (P<0.001). Western blot concurred in determining that EONS babies had conspicuous Hp&HpRP bands in cord blood ("switch-on pattern") as opposed to non-EONS newborns who had near-absent "switch-off pattern" (P<0.001). Fetal Hp phenotype independently impacted Hp&HpRP. A bayesian latent-class analysis (LCA) was further used for unbiased classification of all 180 cases based on probability of "antenatal IAI exposure" as latent variable. This was then subjected to 2(nd)-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage.Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth

Extracellular chaperones and proteostasis

There is a family of currently untreatable serious human diseases that arise from the inappropriate misfolding and aggregation of extracellular proteins. At present our understanding of mechanisms that operate to maintain proteostasis in extracellular body fluids is limited but has significantly advanced with the discovery of a small but growing family of constitutively secreted extracellular chaperones (ECs). The available evidence strongly suggests that these chaperones act as both sensors and disposal-mediators of misfolded proteins in extracellular fluids, thereby normally protecting us from disease pathologies. It is critically important to further increase our understanding of the mechanisms that operate to effect extracellular proteostasis, as this will be essential knowledge upon which to base the development of effective therapies for some of the world\u27s most debilitating, costly and intractable diseases

Neoliberalism and violence: the Big Society and the changing politics of domestic violence in England

Focusing on the domestic violence sector as a case study, this article examines how the Big Society agenda, coming alongside public spending cuts, is affecting the independence and ability of women’s organizations to engage in progressive policy shaping. By situating the analysis of the Big Society agenda within the broader context of international civil society strengthening programmes, the article considers how the processes currently unfolding in England, share certain similarities to what has happened globally wherever neoliberal policies aimed at instrumentalizing civil society for service delivery have been implemented. It contends that the policies of the Big Society agenda, which are aimed at strengthening the ‘capacity’ of civil society, are instead creating a situation where the independence and ability of civil society organizations to engage in progressive policy making is weakened

Processing and Preparation of Brassica Vegetables and the Fate of Glucosinolates

The healthiness of a vegetable cannot solely be inferred from the amount ofhealth-promoting compounds in the raw materials. Brassica vegetables, forexample, are consumed mostly after processing to improve palatability and toextend the shelf life. However, processing also results to various changes in thecontent of glucosinolates which intakes are associated with a reduced risk ofseveral cancers. The large variety in cooking practices and processing methods affect the glucosinolate content in the vegetables, particularly due to processes that allow for enzymatic hydrolysis and thermal degradation of glucosinolates, and leaching of the bioactive components. Knowledge on the effect of preparation and processing of Brassica vegetables is important to evaluate the healthiness of the consumed product and to investigate mechanisms to retain high glucosinolate levels at the stage of consumption and to increase the intake of health-protective compounds by the consumer. By using a mechanistic approach, the fate of glucosinolates during different processing and preparation methods and conditions can be explained. Boiling and blanching reduce the glucosinolate content significantly particularly because of the mechanisms of leaching following cell lysis and diffusion, and partly due to thermal and enzymatic degradation. Steaming, microwave processing, and stir frying either retain or only slightly reduce the glucosinolate content due to low degrees of leaching. These methods can enhance the accessibility of glucosinolates from the plant tissue. Fermentation reduces the glucosinolate content considerably, the underlying mechanisms are not yet completely clear, but enzymatic breakdown seems to play an important role. Studying the changes of glucosinolates during processing by a mechanistic approach is shown to be valuable to redesign the processing and to reformulate the product for improving health benefits of these compounds