Inhibitory Effects of Ethanol on the NLRP3 Inflammasome

Immunosuppression is a major complication of alcoholism and contributes to increased rates of opportunistic infections and sepsis associated with the addiction. The NLRP3 inflammasome is a central intracellular pattern recognition receptor within the innate immune system, which leads to the cleavage and secretion of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Ethanol has been reported to inhibit IL-1β secretion, and here we verify that the alcohol can specifically inhibit activation of the NLRP3 inflammasome resulting in attenuated IL-1β and caspase-1 cleavage and secretion, as well as ASC secretion in response to several agonists. These results were found to be independent of the activation of GABAA receptors or the inhibition of NMDA receptors. Ethanol was only partially able to prevent IL-1β secretion subsequent to NLRC4 activation and was incapable of preventing NLRP1b dependent IL-1β secretion, which are both largely independent of the adapter protein ASC, and ethanol was shown to prevent the formation of ASC specks. Treatment of cells with ethanol resulted in markedly decreased global tyrosine phosphorylation, while administration of the tyrosine phosphatase inhibitor sodium orthovanadate prior to ethanol restored IL-1β secretion. Multiple alcohol containing organic compounds exerted inhibitory effects on the NLRP3 inflammasome parallel to ethanol; however, isoamyl alcohol’s non-alcohol analog, 2-methylbutane, did not. Together, these results show that ethanol antagonizes the NLRP3 inflammasome at an apical event in its activation potentially through the stimulation of protein tyrosine phosphatases. As other short chain alcohols retain this ability, this effect could be dependent on the hydroxyl group of these compounds

A Just and Sustainable Solution to the Boat People Predicament in Australia?

Since the year 2000, there have been close to two thousand deaths of asylum seekers at sea as a result of foiled attempts to travel to Australia in order to seek protection under the United Nations Convention and Protocol on the Status of Refugees.[1] Many thousands more have made it to shore. Growing numbers of irregular or unauthorized migrants attempting to reach the United States and the European Union has long been known as a contentious policy issue in these states, but perhaps less known is the situation on the other side of the Pacific. Australia is the eight-largest recipient of asylum seekers in the industrialized world, receiving around 4% of the global applications for asylum, a relatively minimal amount considering that the state has the capacity to take on a much greater burden of the international refugee crisis.[2] In addition, the policies that are currently in place are primarily seeking to deter the arrival of ‘boat people’ and associated people smuggling activity, rather than to constructively manage the flow while upholding the individual rights of those seeking refuge under international law. This paper deconstructs the restrictive policies of the Australian government and proposes a more sustainable solution, drawing widely from research literature, government publications and media reports that use both primary and secondary sources to build a strong case for an alternative program. The policy that I found best balances the costs and benefits for both the asylum seekers in question as well as the Australian government is a combination of short-term onshore detention and community-based processing and integration. There is a robust debate in Australia over refugees and asylum policy, but in order for such a bill to be feasible in the Australian context, a major transformation of the public’s attitude is essential. [1] The study sponsored by Monash University has compiled a database of border deaths, and has found that 1911 deaths have occurred at sea since 2000, how the true numbers are not known as there is no official government database that has been published. See: Macleod, Kenneth. Deadly Voyages: Border Related Deaths Associated with Australia. SBS News. April 23, 2015, and Australian Border Deaths Database. Monash University: The Border Crossing Observatory. October, 2014 and Bullock, Chris. Asylum Seekers: Drowning on Our Watch. ABC Radio National. September 1, 2013.[2] Australia Asylum: Why Is It Controversial? - BBC News. BBC News. December 5, 2014

A Framework for Integrating Oncology Palliative Care in Doctor of Nursing Practice (DNP) Education

Doctor of Nursing Practice (DNP) faculty play a critical role in preparing students to meet the complex needs of the nation as the number of cancer rates and survivors rise (National Cancer Institute, 2018) and as an unprecedented number of older Americans enter into the healthcare system with complicated comorbidities (Whitehead, 2016). Palliative care has dramatically expanded over the past decade and has been increasingly accepted as a standard of care for people with cancer and other serious, chronic, or life-limiting illnesses. Advanced practice registered nurses (APRNs) are recognized as important providers of palliative care (Walling et al., 2017). A 2-day course was held with support from the National Cancer Institute to enhance integration of palliative oncology care into DNP curriculum. The course participants (N = 183), consisting of DNP faculty or deans, practicing DNP clinicians, and students, received detailed annotated slides, case studies, and suggested activities to increase student engagement with the learning process. Course content was developed and delivered by palliative care experts and DNP faculty skilled in curriculum design. Participants were required to develop goals on how to enhance their school\u27s DNP curriculum with the course content. They provided updates regarding their progress at integrating the content into their school\u27s curriculum at 6, 12, and 18 months post course. Results demonstrated an increase in incorporating oncology palliative care in DNP scholarly projects and clinical opportunities. Challenges to inclusion of this content in DNP curricula included lack of: perceived time in curriculum; faculty educated in palliative care; and available clinical sites

Italy: Delayed adaptation of social institutions to changes in family behaviour

Considering its very low fertility and high age at childbearing, Italy stands alone in the European context and can hardly be compared with other countries, even those in the Southern region. The fertility decline occurred without any radical change in family formation. Individuals still choose (religious) marriage for leaving their parental home and rates of marital dissolution and subsequent step-family formation are low. Marriage is being postponed and fewer people marry. The behaviours of young people are particularly alarming. There is a delay in all life cycle stages: end of education, entry into the labour market, exit from the parental family, entry into union, and managing an independent household. Changes in family formation and childbearing are constrained and slowed down by a substantial delay (or even failure) with which the institutional and cultural framework has adapted to changes in economic and social conditions, in particular to the growth of the service sector, the increase in female employment and the female level of education. In a Catholic country that has been led for almost half a century by a political party with a Catholic ideology, the paucity of attention to childhood and youth seems incomprehensible. Social policies focus on marriage-based families already formed and on the phases of life related to pregnancy, delivery, and the first months of a newborn’s life, while forming a family and childbearing choices are considered private affairs and neglected.adaptations, childbearing, Europe, family, fertility, Italy

Fight for a Future

Non-fiction by Laura Rose Holderma

Intrasexual selection and warning color evolution in an aposematic poison dart frog

textFlamboyant colors are widespread throughout the animal kingdom. While many of these traits arise through sexual selection, bright coloration can also evolve through natural selection. Many aposematic species, for example, use conspicuous warning coloration to communicate their noxiousness to predators. Recent research suggests these signals can also function in the context of mate choice. Studies of warning color evolution can therefore provide new insights into how the interplay of natural and sexual selection impact the trajectory of conspicuous signal evolution. For my dissertation, I investigated the potential for male-male competition to impact the warning color evolution of a species of poison frog. I focused my work on an exceptionally bright and toxic population of the strawberry poison frog (Oophaga pumilio) where males are brighter than females, a classic signature of sexual selection. In Chapter 1, I used theoretical models of predator and frog visual systems to determine which can see the variation in bright warning coloration within this population. I found that birds, the presumed major predator, likely cannot see this variation, indicating that sexual selection can work under the radar of predators in this species. In Chapter 2, I tested the aggressive responses of males using a two-way choice paradigm that manipulated the perceived brightness of stimulus males. I found that males directed more of their behaviors to bright stimulus frogs, and brighter focal frogs more readily approached stimuli and directed more of their attention to the brighter rival. In Chapter 3, I tested the outcomes of dyadic interactions between males of varying brightness and observed male reactions to simulated intruders in their territories. I found that brighter males initiated aggressive interactions with rivals more readily, and brightness asymmetries between males settled interactions in a way that is consistent with classic hypotheses about male sexual signals. In Chapter 4 I sought to describe physiological correlates of male warning color brightness. While male brightness did not co-vary with classic measures of body condition (circulating testosterone and skin carotenoids), it did correlate with toxins sequestered from the diet and thus appears to be a reliable signal of toxicity in this population.Ecology, Evolution and Behavio

An acoustic analysis of pharyngeal and emphatic consonants in Iraqi Arabic

Emphatic consonants in Arabic are coronal obstruents with a secondary articulation. The exact place of the secondary constriction is debated, though these consonants are often said to be pharyngealized. The emphatic consonants contrast with plain coronal obstruents and pharyngeal fricatives. Emphatic consonants also affect adjacent and non-adjacent vowels through a process of emphasis spread, usually by F1 raising and F2 lowering. A production experiment in Iraqi Arabic examined the acoustic patterns of plain, emphatic, and pharyngeal consonants and adjacent vowels. Acoustic measurements of the first and second formants of the low vowel /a/ and the high front vowel /i/ before and after the consonant were analyzed, as well as center of gravity of the fricatives. This experiment found that F1 was higher adjacent to pharyngeal and emphatic consonants than adjacent to plain consonants. F2 was lower adjacent to emphatic consonants than adjacent to plain and pharyngeal consonants. These results suggest some similarities in the articulation of pharyngeal and emphatic consonants, but that emphatic consonants have a slightly different constriction for the secondary articulation than the constriction for pharyngeal consonants. Vowels adjacent to pharyngeal consonants also did not have the characteristic F2 lowering associated with emphatic consonants and emphasis spread. The center of gravity of pharyngeal /ħ/ was lower than the center of gravity for plain /s/ and emphatic /sˤ/, but there was no difference in the center of gravity values for the plain and emphatic fricatives. Combined with the F2 lowering of vowels adjacent to emphatic consonants, this suggests that the perception of emphatic consonants may be primarily triggered by the adjacent vowel, not the consonant itself. The results of this experiment motivate future analyses of the relationship between the effects of emphatic consonants on adjacent vowels and the perception of emphatic consonants.Linguistic

Gary, Indiana and the US Steel Corporation: An Examination of Race, Class, and Environmental Injustice in Early Twentieth Century Urban Planning

Gary, Indiana was widely regarded as one of the most successful and promising industrial American cities of its time. Gary was founded by the United States Steel Corporation to be a model industrial city created by a private corporation. Gary is unique in that the city was conceptualized, planned, and constructed by a private entity, with little public or governmental input, for the purpose of serving the US Steel industry. As groundbreaking and innovative as the urban planning of Gary was supposed to be, conditions of segregation in the city caused by a divide between the premiere steel mills and a lack of scientifically planned housing subdivisions, proved to be an interesting catalyst for issues of class conflict, racial conflict, and severe environmental damage This thesis, argues that the United States Steel Corporation, as a private entity overseeing the urban planning of Gary, Indiana is culpable in the segregation and racism that occurred in early twentieth century Gary and in the environmental racism that occurred in the city due to US Steel having full control over the planning, construction, and the political-economic ethos over the city and its residents

Policymakers\u27 Decision-Making: A Critical Policy Analysis on Performance-Based Funding

Over the last three decades, state governments have been challenged by financial recessions. With limited resources, it is not surprising that taxpayers demanded greater accountability over state funds, and neoliberalism, a political ideology that prefaces a strong economy and individual marketplace choices, spread. Scholars have argued that performance based funding (PBF) policies for higher education, which ties financial resources to specific metrics of achievement, is a result of that spread. In contemporary literature, scholars are examining the impacts of PBF and limitations, especially for community colleges, Historically Black Colleges and Universities, and Minority-Serving Institutions. Research on the PBF policy making process, however, has been limited, especially from a critical perspective. From the Critical Theory research paradigm and a Critical Policy Analysis theoretical lens, this qualitative case study critically examined how policymakers approach their decisions on PBF and how they understand PBF. This study utilized Kingdon’s (1984) agenda setting theory and Stones’ (2012) approach to policy decision making to situate the nuances of policymaking. This case study (Merriam, 1998) included interviewing policymakers across five states and reviewing PBF policy-related documents. The final analysis presented four narratives and included a critical examination of issues related to power and equity. In the findings, policymakers described themselves as influencers, who balance control over higher education in order to solve problems. They practiced decision-making under feelings of urgency and tension, but with clear goals for accountability and the economy. Interestingly, policymakers described PBF as a tool designed to be flexible in order to distribute resources based on specific performances, which can include equity. Neoliberalist-based words were frequently used in goal-setting decisions for education and institutions. In contrast, equity-based words were sparingly used. Policymakers felt PBF supports their state plans for a thriving economy and disclosed an active discussion on equity for underrepresented students. However, a gap existed between dialogue and practice. Though they were aware of policy feedback on equity-based concerns for institutional types, they revealed divergent views on whether or not institutions that serve underrepresented students deserve special protection. In these discussions, no policy alternatives were offered, but a policy window (Kingdon, 1984) may open