Loss of testosterone impairs anti-tumor neutrophil function.

In men, the incidence of melanoma rises rapidly after age 50, and nearly two thirds of melanoma deaths are male. The immune system is known to play a key role in controlling the growth and spread of malignancies, but whether age- and sex-dependent changes in immune cell function account for this effect remains unknown. Here, we show that in castrated male mice, neutrophil maturation and function are impaired, leading to elevated metastatic burden in two models of melanoma. Replacement of testosterone effectively normalized the tumor burden in castrated male mice. Further, the aberrant neutrophil phenotype was also observed in prostate cancer patients receiving androgen deprivation therapy, highlighting the evolutionary conservation and clinical relevance of the phenotype. Taken together, these results provide a better understanding of the role of androgen signaling in neutrophil function and the impact of this biology on immune control of malignancies

Antecedents and outcomes of consumer environmentally friendly attitudes and behaviour

With the intensification of problems relating to the environment, a growing number of consumers are becoming more ecologically conscious in their preferences and purchases of goods. This paper presents the results of a study conducted among 500 Cypriot consumers, focusing on the factors that shape consumer environmental attitudes and behaviour, as well as on the resulting outcomes. The findings confirmed that both the inward and outward environmental attitudes of a consumer are positively influenced by his/her degree of collectivism, long-term orientation, political involvement, deontology, and law obedience, but have no connection with liberalism. The adoption of an inward environmental attitude was also found to be conducive to green purchasing behaviour that ultimately leads to high product satisfaction. On the other hand, an outward environmental attitude facilitates the adoption of a general environmental behaviour, which is responsible for greater satisfaction with life. The findings of the study have important implications for shaping effective company offerings to consumers in target markets, as well as formulating appropriate policies at the governmental level to enhance environmental sensitivity among citizens

Service evaluation of a nurse-led dental anxiety management service for adult patients

Objective: Evaluate patients’ and professionals’ experiences of a Nurse-led Dental Anxiety Management Service (NDAMS). Design: Service evaluation. Setting: The NDAMS operates as part of Sheffield Salaried Primary Dental Care Service. Subjects and methods: Questionnaire survey of anxious patients and qualitative interviews with patients and professionals Interventions: Dental nurses delivered low-level psychological interventions as part of an Integrated Care Pathway (ICP) for dental anxiety. Main outcome Measures: Dental anxiety and oral health-related quality of life (OHRQoL) questionnaires were completed by patients prior to and following NDAM. Results: A total of 187 patients were assessed as suitable for NDAM (mean age= 33.7, 77% female) and 33 had completed it at the time of the service evaluation. Of those patients who had completed the intervention significant improvements in dental anxiety and OHRQoL were reported. Professionals highlighted the importance of integrated working, adequate support and training and assessing the suitability of patients for NDAM. Conclusion: ICPs that combine pharmacological and psychological management approaches can help meet the needs of dentally anxious patients, however, early identification of patients most likely to benefit from psychological intervention should be a priority

Utilising daily diaries to examine oral health experiences associated with dentine hypersensitivity

Background: The current investigation examined the determinants of oral health experiences associated with dentine hypersensitivity using prospective diary methodology. Methods: Staff and students from a large UK university who had self-diagnosed dentine hypersensitivity completed an online daily diary and text survey for two weeks recording their mood, oral health-related coping behaviours, coping and pain appraisals, pain experiences and functional limitations. Cross sectional and lagged path analyses were employed to examine relationships. Results: 101 participants took part in the diary study. Participants had a mean age of 26.3 years (range=18-63) and most were female (N=69). Individuals who used more oral health-related coping behaviours predicted and experienced greater levels of pain on subsequent days. Negative mood also predicted worse pain outcomes. The daily diary method provided a useful avenue for investigating variations in oral health experiences and relationships between variables that can fluctuate daily. Conclusions: Psychological variables such as coping and mood play an important role in the pain experiences of people with dentine hypersensitivity. The study highlights the benefits of using prospective methods to elucidate the experiences of people with oral condition

Nonprofits and business:toward a subfield of nonprofit studies

Although the field of nonprofit studies now encompasses a substantial body of literature on the relationship between governmental and nonprofit organizations, the relationship between the business and nonprofit sectors has been less addressed by specialist nonprofit scholars. This Research Note aims to encourage further studies by nonprofit scholars of the business-nonprofit sector relationship. It looks at descriptive evidence to date, proposes a tentative resource-based framework for understanding how nonprofits and business relate to each other in practice and suggests some initial directions for developing a subfield within nonprofit studies

The halfway house: democracy, complexity, and the limits to markets in green political economy

The argument of the Austrian school of economists that markets are indispensable in the face of social and economic complexity is of defining importance for the modern day case for markets. The dominant paradigm in green political economy accepts this view, whilst proposing that markets be combined with a thick layer of democratic, non-market institutions to ensure environmental sustainability. Closer attention to the relationship between the Austrian and green arguments reveals important implications for both. The Austrian thesis raises significant challenges for the 'halfway house' combination of market and non-market that greens propose. Also, potential responses to the Austrians emerge from green thought. New light is shed upon the problem of complexity and the how it might be addressed by non-market political institutions

Osteopontin depletion in macrophages perturbs proteostasis via regulating UCHL1-UPS axis and mitochondria-mediated apoptosis

IntroductionOsteopontin (OPN; also known as SPP1), an immunomodulatory cytokine highly expressed in bone marrow-derived macrophages (BMMΦ), is known to regulate diverse cellular and molecular immune responses. We previously revealed that glatiramer acetate (GA) stimulation of BMMΦ upregulates OPN expression, promoting an anti-inflammatory, pro-healing phenotype, whereas OPN inhibition triggers a pro-inflammatory phenotype. However, the precise role of OPN in macrophage activation state is unknown.MethodsHere, we applied global proteome profiling via mass spectrometry (MS) analysis to gain a mechanistic understanding of OPN suppression versus induction in primary macrophage cultures. We analyzed protein networks and immune-related functional pathways in BMMΦ either with OPN knockout (OPNKO) or GA-mediated OPN induction compared with wild type (WT) macrophages. The most significant differentially expressed proteins (DEPs) were validated using immunocytochemistry, western blot, and immunoprecipitation assays.Results and discussionWe identified 631 DEPs in OPNKO or GA-stimulated macrophages as compared to WT macrophages. The two topmost downregulated DEPs in OPNKO macrophages were ubiquitin C-terminal hydrolase L1 (UCHL1), a crucial component of the ubiquitin-proteasome system (UPS), and the anti-inflammatory Heme oxygenase 1 (HMOX-1), whereas GA stimulation upregulated their expression. We found that UCHL1, previously described as a neuron-specific protein, is expressed by BMMΦ and its regulation in macrophages was OPN-dependent. Moreover, UCHL1 interacted with OPN in a protein complex. The effects of GA activation on inducing UCHL1 and anti-inflammatory macrophage profiles were mediated by OPN. Functional pathway analyses revealed two inversely regulated pathways in OPN-deficient macrophages: activated oxidative stress and lysosome-mitochondria-mediated apoptosis (e.g., ROS, Lamp1-2, ATP-synthase subunits, cathepsins, and cytochrome C and B subunits) and inhibited translation and proteolytic pathways (e.g., 60S and 40S ribosomal subunits and UPS proteins). In agreement with the proteome-bioinformatics data, western blot and immunocytochemical analyses revealed that OPN deficiency perturbs protein homeostasis in macrophages—inhibiting translation and protein turnover and inducing apoptosis—whereas OPN induction by GA restores cellular proteostasis. Taken together, OPN is essential for macrophage homeostatic balance via the regulation of protein synthesis, UCHL1-UPS axis, and mitochondria-mediated apoptotic processes, indicating its potential application in immune-based therapies

Fluidal pyroclasts reveal the intensity of peralkaline rhyolite pumice cone eruptions

This work is a contribution to the Natural Environment Research Council (NERC) funded RiftVolc project (NE/L013932/1, Rift volcanism: past, present and future) through which several of the authors are supported. In addition, Clarke was funded by a NERC doctoral training partnership grant (NE/L002558/1).Peralkaline rhyolites are medium to low viscosity, volatile-rich magmas typically associated with rift zones and extensional settings. The dynamics of peralkaline rhyolite eruptions remain elusive with no direct observations recorded, significantly hindering the assessment of hazard and risk. Here we describe uniquely-preserved, fluidal-shaped pyroclasts found within pumice cone deposits at Aluto, a peralkaline rhyolite caldera in the Main Ethiopian Rift. We use a combination of field-observations, geochemistry, X-ray computed microtomography (XCT) and thermal-modelling to investigate how these pyroclasts are formed. We find that they deform during flight and, depending on size, quench prior to deposition or continue to inflate then quench in-situ. These findings reveal important characteristics of the eruptions that gave rise to them: that despite the relatively low viscosity of these magmas, and similarities to basaltic scoria-cone deposits, moderate to intense, unstable, eruption columns are developed; meaning that such eruptions can generate extensive tephra-fall and pyroclastic density currents.Publisher PDFPeer reviewe