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A PDK-1 allosteric agonist improves spatial learning and memory in a βAPP/PS-1 transgenic mouse-high fat diet intervention model of Alzheimer\u27s disease
No full textDiabetes mellitus (DM), peripheral insulin resistance (IR) and obesity are clear risk factors for Alzheimer\u27s disease. Several anti-diabetic drugs and insulin have been tested in rodents and humans with MCI or AD, yielding promising but inconclusive results. The PDK-1/Akt axis, essential to the action of insulin, has not however been pharmacologically interrogated to a similar degree. Our previous cell culture and in vitro studies point to such an approach. Double transgenic APPsw/PSENdE9 mice, a model for Alzheimer\u27s disease, were used to test the oral administration of PS48, a PDK-1 agonist, on preventing the expected decline in learning and memory in the Morris Water Maze (MWM). Mice were raised on either standard (SD) or high fat (HFD) diets, dosed beginning 10 months age and tested at an advanced age of 14 months. PS48 had positive effects on learning the spatial location of a hidden platform in the TG animals, on either SD or HFD, compared to vehicle diet and WT animals. On several measures of spatial memory following successful acquisition (probe trials), the drug also proved significantly beneficial to animals on either diet. The PS48 treatment-effect size was more pronounced in the TG animals on HFD compared to on SD in several of the probe measures. HFD produced some of the intended metabolic effects of weight gain and hyperglycemia, as well as accelerating cognitive impairment in the TG animals. PS48 was found to have added value in modestly reducing body weights and improving OGTT responses in TG groups although results were not definitive. PS48 was well tolerated without obvious clinical signs or symptoms and did not itself affect longevity. These results recommend a larger preclinical study before human trial
Over One Million DNA and Protein Events Through Ultra-Stable Chemically-Tuned Solid-State Nanopores
No full textStability, long lifetime, resilience against clogging, low noise, and low cost are five critical cornerstones of solid-state nanopore technology. Here, a fabrication protocol is described wherein \u3e1 million events are obtained from a single solid-state nanopore with both DNA and protein at the highest available lowpass filter (LPF, 100 kHz) of the Axopatch 200B–the highest event count mentioned in literature. Moreover, a total of ≈8.1 million events are reported in this work encompassing the two analyte classes. With the 100 kHz LPF, the temporally attenuated population is negligible while with the more ubiquitous 10 kHz, ≈91% of the events are attenuated. With DNA experiments, the pores are operational for hours (typically \u3e7 h) while the average pore growth is merely ≈0.16 ± 0.1 nm h−1. The current noise is exceptionally stable with traces typically showing \u3c10 pA h−1 increase in noise. Furthermore, a real-time method to clean and revive pores clogged with analyte with the added benefit of minimal pore growth during cleaning (\u3c 5% of the original diameter) is showcased. The enormity of the data collected herein presents a significant advancement to solid-state pore performance and will be useful for future ventures such as machine learning where large amounts of pristine data are a prerequisite
Bridge-Mediated Metal-to-Metal Electron and Hole Transfer in a Supermolecular Dinuclear Complex: A Computational Study Using Quantum Electron-Nuclear Dynamics
No full textBimetallic electron donor-acceptor complexes can facilitate electron and energy transfer with excellent structural control through synthetic design. In this work, we investigate the photochemical dynamics in a Ru-Cu bimetallic complex after photoexcitation of the Ru-centered charge transfer state. The physical underpinnings of the metal-to-metal directional charge transfer process are unraveled via analyses of the quantum electronic dynamics and electron-nuclear trajectories. The effects of molecular vibrations in the photoexcited state on the charge transfer processes are also analyzed
Taking stock: Is recovery of a depleted population possible in a changing climate?
No full textAs the impacts of climate change become more severe throughout the global oceans, fisheries managers will be increasingly challenged to rebuild stocks exhibiting declining productivity. In such cases, detailed knowledge of species life history will be necessary to both restrict harvest and manage other environmental conditions, where possible, that impact survivorship. A current example of these challenges, the Southern New England/Mid-Atlantic Bight winter flounder stock remains in a persistently depleted state due to a combination of past harvest and the effects of climate change mediated through increased predation. To explore the recovery capacity of a subpopulation of this stock, a life-cycle model was fit to 29 year classes of stage-specific winter flounder data from surveys conducted in Narragansett Bay, Rhode Island and used to project future subpopulation abundance. Supporting a prevailing hypothesis, the results indicated that environmental factors influencing juvenile mortality were largely responsible for inhibiting recovery. Furthermore, recovery of the subpopulation to past levels of abundance was determined to be unlikely even under optimistic future conditions resulting from aggressive management interventions. Taken together, the findings of this work pose important questions regarding the realism of assessing climate-challenged populations against biological reference points set under past environmental regimes and the degree to which harvest restrictions to promote recovery of such stocks should be allowed to limit warm-water fisheries thriving in a warming ocean
The Process of Sexual Misconduct by Male Teachers and Staff in K-12 Institutions
Get PDFDespite the increased media attention of teachers who engage in sexual misconduct with their students, research on such incidents remains limited, specifically on how these incidents are initiated and evolve. The purpose of the current study was to examine the nature of sexual abuse incidents by K-12 teachers who engaged in sexual misconduct with students by focusing on the onset, progression, and conclusion of these cases. Data included 10 secondary narrative interviews with male sex offenders who used their position as school employees to target and engage in sexual misconduct with their students in 2014 in a southern state. All offenders were interviewed and assessed for risk and community notification purposes, and the narrative interviews were obtained from the offenders\u27 correctional casefile. Based on narratives from both victims and offenders, the manner in which sexual misconduct is initiated varies by the victim\u27s age. Incidents of sexual misconduct began through the use of technology among older students. For younger students, incidents of sexual misconduct started with inappropriate sexual contact in the classroom. Incidents continued to progress through manipulated opportunities to be alone with the victim and bribery. Incidents were likely to end when reported to law enforcement or school administration. Overall, findings can help inform educational policy regarding recognition and appropriate responses to prevent future sexual misconduct incidents
Uptake of Per- and Polyfluoroalkyl Substances by Fish, Mussel, and Passive Samplers in Mobile-Laboratory Exposures Using Groundwater from a Contamination Plume at a Historical Fire Training Area, Cape Cod, Massachusetts
Get PDFAqueous film-forming foams historically were used during fire training activities on Joint Base Cape Cod, Massachusetts, and created an extensive per- and polyfluoroalkyl substances (PFAS) groundwater contamination plume. The potential for PFAS bioconcentration from exposure to the contaminated groundwater, which discharges to surface water bodies, was assessed with mobile-laboratory experiments using groundwater from the contamination plume and a nearby reference location. The on-site continuous-flow 21-day exposures used male and female fathead minnows, freshwater mussels, polar organic chemical integrative samplers (POCIS), and polyethylene tube samplers (PETS) to evaluate biotic and abiotic uptake. The composition of the PFAS-contaminated groundwater was complex and 9 PFAS were detected in the reference groundwater and 17 PFAS were detected in the contaminated groundwater. The summed PFAS concentrations ranged from 120 to 140 ng L–1 in reference groundwater and 6100 to 15,000 ng L–1 in contaminated groundwater. Biotic concentration factors (CFb) for individual PFAS were species, sex, source, and compound-specific and ranged from 2.9 to 1000 L kg–1 in whole-body male fish exposed to contaminated groundwater for 21 days. The fish and mussel CFb generally increased with increasing fluorocarbon chain length and were greater for sulfonates than for carboxylates. The exception was perfluorohexane sulfonate, which deviated from the linear trend and had a 10-fold difference in CFb between sites, possibly because of biotransformation of precursors such as perfluorohexane sulfonamide. Uptake for most PFAS in male fish was linear over time, whereas female fish had bilinear uptake indicated by an initial increase in tissue concentrations followed by a decrease. Uptake of PFAS was less for mussels (maximum CFb = 200) than for fish, and mussel uptake of most PFAS also was bilinear. Although abiotic concentration factors were greater than CFb, and values for POCIS were greater than for PETS, passive samplers were useful for assessing PFAS that potentially bioconcentrate in fish but are present at concentrations below method quantitation limits in water. Passive samplers also accumulate short-chain PFAS that are not bioconcentrated
Exploring critical media health literacy (CMHL) in the online classroom.
Get PDFCritical media health literacy (CMHL) is concerned with identifying healthrelated messages in the media, acknowledging the potential effects on health behaviours, critically analyzing the content of the message, and the subsequent application of the message to one’s health behaviours (Levin-Zamir & Bertschi, 2018). This exploratory research examined the CMHL skills of students (n = 120) in an entry-level, online asynchronous health and wellness course, by examining their ability to think critically about health-related themes presented in news media articles online and apply course-based knowledge during a Twitter event. Employing a content analysis of tweets from the event, students were found to illustrate CMHL skills when interacting with peers on Twitter, more than when directly assessing online news media. The findings suggest that the course curriculum be altered to include CMHL skills, to better equip students with the ability to identify accurate health information in the media
’90s “It Girls”: Britpop at the Postfeminist Intermezzo
Get PDFIn considering the Britpop genre of music and its moment of popularity in the mid/late-1990s, the few female-fronted Britpop groups created space for more compelling articulations of existential matters than were to be found in standard Britpop fare. This article argues these articulations are most appropriately read as arising from a moment of feminist thought in transition: a premature “victory,” under the sign of postfeminism, in which the struggles of Second Wave feminists could be seen to have delivered equality. This moment results in an encroaching and contested sense of entry into maturity, and a loss of youth. The groups examined in this article—Elastica, Echobelly and particularly Sleeper—articulate something of the lived condition of postfeminism and a sense of its concerns and uncertainties (emotional, ethical, existential) in this short-lived period. Additionally, the article tracks the development in the movement from the “wild child,” “It Girl” of the early 1990s through the figure of the ladette (which found a resonance in female-fronted Britpop groups), and thereafter to the emergence of a sexualized celebrity feminism, under the sign of Third Wave feminism
Criticizing Paywall Publishing, or Integrating Open Access into the Feminist Movement
Get PDFDominant scholarly publishing models, reliant on expensive paywalls, remain preferential throughout higher education’s landscape. This essay engages paywall publishing from a feminist communicative perspective by asking, how can publishing extend or prohibit feminist movements? Or, as Nancy Fraser (2013) asks, “which modes of feminist theorizing should be incorporated into the new political imaginaries now being invented by new generations” (2)? With these questions in mind, we integrate feminist epistemologies into publishing practices to argue that open access is integral to the feminist movement. The argument unfolds in three parts: first, we conduct a feminist criticism of paywall publishing by arguing that status quo practices constitute a dominant public based on onto-epistemological foundations of exclusion that systematically subordinate potentially liberatory knowledge. Second, we consider open access as a feminist re-tooling that creates new political imaginaries. In this section, we place open access in conversation with bell hooks’s conception of literacy and Fraser’s counterpublic theory. We conclude by considering how to live feminist lives with these criticisms and re-toolings in mind