p38 δ

p38δ mitogen activated protein kinase (MAPK) is a unique stress responsive protein kinase. While the p38 MAPK family as a whole has been implicated in a wide variety of biological processes, a specific role for p38δ MAPK in cellular signalling and its contribution to both physiological and pathological conditions are presently lacking. Recent emerging evidence, however, provides some insights into specific p38δ MAPK signalling. Importantly, these studies have helped to highlight functional similarities as well as differences between p38δ MAPK and the other members of the p38 MAPK family of kinases. In this review we discuss the current understanding of the molecular mechanisms underlying p38δ MAPK activity. We outline a role for p38δ MAPK in important cellular processes such as differentiation and apoptosis as well as pathological conditions such as neurodegenerative disorders, diabetes, and inflammatory disease. Interestingly, disparate roles for p38δ MAPK in tumour development have also recently been reported. Thus, we consider evidence which characterises p38δ MAPK as both a tumour promoter and a tumour suppressor. In summary, while our knowledge of p38δ MAPK has progressed somewhat since its identification in 1997, our understanding of this particular isoform in many cellular processes still strikingly lags behind that of its counterparts

Are lay people good at recognising the symptoms of schizophrenia?

©2013 Erritty, Wydell. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Aim: The aim of this study was to explore the general public’s perception of schizophrenia symptoms and the need to seekhelp for symptoms. The recognition (or ‘labelling’) of schizophrenia symptoms, help-seeking behaviours and public awareness of schizophrenia have been suggested as potentially important factors relating to untreated psychosis. Method: Participants were asked to rate to what extent they believe vignettes describing classic symptoms (positive and negative) of schizophrenia indicate mental illness. They were also asked if the individuals depicted in the vignettes required help or treatment and asked to suggest what kind of help or treatment. Results: Only three positive symptoms (i.e., Hallucinatory behaviour, Unusual thought content and Suspiciousness) of schizophrenia were reasonably well perceived (above 70%) as indicating mental illness more than the other positive or negative symptoms. Even when the participants recognised that the symptoms indicated mental illness, not everyone recommended professional help. Conclusion: There may be a need to improve public awareness of schizophrenia and psychosis symptoms, particularly regarding an awareness of the importance of early intervention for psychosis

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I

Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome

Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B. longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. Thus, phylogenetic limiting and resource availability are two factors that control the niche opportunity for AH1206 colonization. These findings suggest that bacterial species and functional genes absent in the gut microbiome of individual humans can be reestablished, providing opportunities for precise and personalized microbiome reconstitution

Living Mercy: Reflecting on the Vocation and Values of Salve Regina University

With this collection of essays, we honor the vocation and spirit of mercy that has enlivened and guided Salve Regina University for the last 75 years. Inspired by the accomplishments of the past and looking forward to the call of the future, these essays provide a starting point for University-wide conversations to support Salve Regina in discerning how it will move into the increasingly complex challenges of the future. Salve\u27s tradition of mercy is rooted in the example of Catherine McAuley, who founded the Sisters of Mercy in 19th-century Dublin, Ireland. It is a model of faith expressed through action and maintains that each person is called to and capable of contributing to the common good by responding to the needs of the day, to respond to the suffering and injustice of each era.Attending to this spirit of mercy that continues to guide our University, this project considers how the six core values of Salve’s Strategic Compass – purpose-driven education, respect and dignity for all, mercy community, integrity, faith and spirituality, and compassionate service and solidarity – relate to our shared mercy, Catholic heritage, and the mercy vocational paradigm. Exploring how to re-root and re-frame these values, we approached the project as a vocationally oriented narrative. This type of narrative focuses on the call and vocation, as well as the patterns of meaning that shape the unique identity of an institution in its founding and how the institution has evolved and changed in response to the claims and context of social and historic dynamics. Thus, these six essays are harmonized by a three-fold critical-creative structure that attends to the dynamic experience of the call and spirit of mercy modeled in the founding of the University, how we presently live this call, and envision the challenges and possibilities that lie on the horizon. We employed the perspectives of Foundations, Living Presence, and Horizons to frame an analogical exploration of the unique character, actions and ideals that have inspired and sustained the vocation and mission of Salve Regina University, and may be creatively transferred to shaping the horizon for future generations of students.Celebrating the 75th anniversary of the founding of Salve Regina University, we invite readers to reflect on this collection of essays and then to join the conversations that are to follow as we continue to discern the path forward as Salve takes its next steps into the future.https://digitalcommons.salve.edu/fac_staff_ebooks/1006/thumbnail.jp

Dietary Compounds Influencing the Sensorial, Volatile and Phytochemical Properties of Bovine Milk

peer-reviewedThe main aim of this study was to evaluate the volatile profile, sensory perception, and phytochemical content of bovine milk produced from cows fed on three distinct feeding systems, namely grass (GRS), grass/clover (CLV), and total mixed ration (TMR). Previous studies have identified that feed type can influence the sensory perception of milk directly via the transfer of volatile aromatic compounds, or indirectly by the transfer of non-volatile substrates that act as precursors for volatile compounds. In the present study, significant differences were observed in the phytochemical profile of the different feed and milk samples. The isoflavone formonoetin was significantly higher in CLV feed samples, but higher in raw GRS milk, while other smaller isoflavones, such as daidzein, genistein, and apigenin were highly correlated to raw CLV milk. This suggests that changes in isoflavone content and concentration in milk relate to diet, but also to metabolism in the rumen. This study also found unique potential volatile biomarkers in milk (dimethyl sulfone) related to feeding systems, or significant differences in the concentration of others (toluene, p-cresol, ethyl and methyl esters) based on feeding systems. TMR milk scored significantly higher for hay-like flavor and white color, while GRS and CLV milk scored significantly higher for a creamy color. Milk samples were easily distinguishable by their volatile profile based on feeding system, storage time, and pasteurization

A critical realist evaluation of a music therapy intervention in palliative care

BACKGROUND: Music therapy is increasingly used as an adjunct therapy to support symptom management in palliative care. However, studies to date have paid little attention to the processes that lead to changes in patient outcomes. To fill this gap, we examined the processes and experiences involved in the introduction of music therapy as an adjunct complementary therapy to palliative care in a hospice setting in the United Kingdom (UK). METHODS: Using a realistic evaluation approach, we conducted a qualitative study using a variety of approaches. These consisted of open text answers from patients (n = 16) on how music therapy helped meet their needs within one hospice in Northern Ireland, UK. We also conducted three focus groups with a range of palliative care practitioners (seven physicians, seven nursing staff, two social workers and three allied health professionals) to help understand their perspectives on music therapy's impact on their work setting, and what influences its successful implementation. This was supplemented with an interview with the music therapist delivering the intervention. RESULTS: Music therapy contains multiple mechanisms that can provide physical, psychological, emotional, expressive, existential and social support. There is also evidence that the hospice context, animated by a holistic approach to healthcare, is an important facilitator of the effects of music therapy. Examination of patients' responses helped identify specific benefits for different types of patients. CONCLUSIONS: There is a synergy between the therapeutic aims of music therapy and those of palliative care, which appealed to a significant proportion of participants, who perceived it as effective

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

Left dorsolateral prefrontal cortex supports context-dependent prioritisation of off-task thought

When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when ‘on-task’ under demanding conditions and ‘off-task’ in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC