Endoplasmic Reticulum-Dependent Redox Reactions Control Endoplasmic Reticulum-Associated Degradation and Pathogen Entry

Abstract Significance: Protein misfolding within the endoplasmic reticulum (ER) is managed by an ER quality control system that retro-translocates aberrant proteins into the cytosol for proteasomal destruction. This process, known as ER-associated degradation, utilizes the action of ER redox enzymes to accommodate the disulfide-bonded nature of misfolded proteins. Strikingly, various pathogenic viruses and toxins co-opt these redox components to reach the cytosol during entry. These redox factors thus regulate critical cellular homeostasis and host?pathogen interactions. Recent Advances: Recent studies identify specific members of the protein disulfide isomerase (PDI) family, which use their chaperone and catalytic activities, in engaging both misfolded ER proteins and pathogens. Critical Issues: The precise molecular mechanism by which a dedicated PDI family member disrupts the disulfide bonds in the misfolded ER proteins and pathogens, as well as how they act to unfold these substrates to promote their ER-to-cytosol membrane transport, remain poorly characterized. Future Directions: How PDI family members distinguish folded versus misfolded ER substrates remains enigmatic. What physical characteristics surrounding a substrate's disulfide bond instruct PDI that it is mispaired or native? For the pathogens, as their disulfide bonds normally serve a critical role in providing physical support, what conformational changes experienced in the host enable their disulfide bonds to be disrupted? A combination of more rigorous biochemical and high-resolution structural studies should begin to address these questions. Antioxid. Redox Signal. 16, 809?818.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98492/1/ars%2E2011%2E4425.pd

Transit Photometry as an Exoplanet Discovery Method

Photometry with the transit method has arguably been the most successful exoplanet discovery method to date. A short overview about the rise of that method to its present status is given. The method's strength is the rich set of parameters that can be obtained from transiting planets, in particular in combination with radial velocity observations; the basic principles of these parameters are given. The method has however also drawbacks, which are the low probability that transits appear in randomly oriented planet systems, and the presence of astrophysical phenomena that may mimic transits and give rise to false detection positives. In the second part we outline the main factors that determine the design of transit surveys, such as the size of the survey sample, the temporal coverage, the detection precision, the sample brightness and the methods to extract transit events from observed light curves. Lastly, an overview over past, current and future transit surveys is given. For these surveys we indicate their basic instrument configuration and their planet catch, including the ranges of planet sizes and stellar magnitudes that were encountered. Current and future transit detection experiments concentrate primarily on bright or special targets, and we expect that the transit method remains a principal driver of exoplanet science, through new discoveries to be made and through the development of new generations of instruments.Comment: Review chapte

Violent video games and morality: a meta-ethical approach

This paper considers what it is about violent video games that leads one reasonably minded person to declare "That is immoral" while another denies it. Three interpretations of video game content a re discussed: reductionist, narrow, and broad. It is argued that a broad interpretation is required for a moral objection to be justified. It is further argued that understanding the meaning of moral utterances – like "x is immoral" – is important to an understanding of why there is a lack of moral consensus when it comes to the content of violent video games. Constructive ecumenical expressivism is presented as a means of explaining what it is that we are doing when we make moral pronouncements and why, when it comes to video game content, differing moral attitudes abound. Constructive ecumenical expressivism is also presented as a means of illuminating what would be required for moral consensus to be achieved

Aquatic community response to volcanic eruptions on the Ecuadorian Andean flank: evidence from the palaeoecological record

Aquatic ecosystems in the tropical Andes are under increasing pressure from human modification of the landscape (deforestation and dams) and climatic change (increase of extreme events and 1.5 °C on average temperatures are projected for AD 2100). However, the resilience of these ecosystems to perturbations is poorly understood. Here we use a multi-proxy palaeoecological approach to assess the response of aquatic ecosystems to a major mechanism for natural disturbance, volcanic ash deposition. Specifically, we present data from two Neotropical lakes located on the eastern Andean flank of Ecuador. Laguna Pindo (1°27.132′S–78°04.847′W) is a tectonically formed closed basin surrounded by a dense mid-elevation forest, whereas Laguna Baños (0°19.328′S–78°09.175′W) is a glacially formed lake with an inflow and outflow in high Andean Páramo grasslands. In each lake we examined the dynamics of chironomids and other aquatic and semi-aquatic organisms to explore the effect of thick (> 5 cm) volcanic deposits on the aquatic communities in these two systems with different catchment features. In both lakes past volcanic ash deposition was evident from four large tephras dated to c.850 cal year BP (Pindo), and 4600, 3600 and 1500 cal year BP (Baños). Examination of the chironomid and aquatic assemblages before and after the ash depositions revealed no shift in composition at Pindo, but a major change at Baños occurred after the last event around 1500 cal year BP. Chironomids at Baños changed from an assemblage dominated by Pseudochironomus and Polypedilum nubifer-type to Cricotopus/Paratrichocladius type-II, and such a dominance lasted for approximately 380 years. We suggest that, despite potential changes in the water chemistry, the major effect on the chironomid community resulted from the thickness of the tephra being deposited, which acted to shallow the water body beyond a depth threshold. Changes in the aquatic flora and fauna at the base of the trophic chain can promote cascade effects that may deteriorate the ecosystem, especially when already influenced by human activities, such as deforestation and dams, which is frequent in the high Andes

The signature of orbital motion from the dayside of the planet tau Bootis b

The giant planet orbiting tau Bootis was among the first extrasolar planets to be discovered through the reflex motion of its host star. It is one of the brightest known and most nearby planets with an orbital period of just a few days. Over the course of more than a decade, measurements of its orbital inclination have been announced and refuted, and have subsequently remained elusive until now. Here we report on the detection of carbon monoxide absorption in the thermal day-side spectrum of tau Bootis b. At a spectral resolution of R~100,000, we trace the change in the radial velocity of the planet over a large range in phase, determining an orbital inclination of i=44.5+-1.5 degrees and a true planet mass of 5.95+-0.28 MJup. This result extends atmospheric characterisation to non-transiting planets. The strong absorption signal points to an atmosphere with a temperature that is decreasing towards higher altitudes. This is a stark contrast to the temperature inversion invoked for other highly irradiated planets, and supports models in which the absorbing compounds believed to cause such atmospheric inversions are destroyed by the ultraviolet emission from the active host star.Comment: To appear in the June 28 issue of Nature: main article + supplementary informatio

A Spectrum of an Extrasolar Planet

Of the over 200 known extrasolar planets, 14 exhibit transits in front of their parent stars as seen from Earth. Spectroscopic observations of the transiting planets can probe the physical conditions of their atmospheres. One such technique can be used to derive the planetary spectrum by subtracting the stellar spectrum measured during eclipse (planet hidden behind star) from the combined-light spectrum measured outside eclipse (star + planet). Although several attempts have been made from Earth-based observatories, no spectrum has yet been measured for any of the established extrasolar planets. Here we report a measurement of the infrared spectrum (7.5--13.2 micron) of the transiting extrasolar planet HD209458b. Our observations reveal a hot thermal continuum for the planetary spectrum, with approximately constant ratio to the stellar flux over this wavelength range. Superposed on this continuum is a broad emission peak centered near 9.65 micron that we attribute to emission by silicate clouds. We also find a narrow, unidentified emission feature at 7.78 micron. Models of these ``hot Jupiter'' planets predict a flux peak near 10 micron, where thermal emission from the deep atmosphere emerges relatively unimpeded by water absorption, but models dominated by water fit the observed spectrum poorly

“Beyond words”: a researcher’s guide to using photo elicitation in psychology

The use of photo elicitation is limited within the field of psychology despite its theoretical and practical potential. It offers significant benefits as a qualitative method that could present a new and interesting way of exploring previously understood topics within the discipline. Within our discussions, we present a Step-by-Step guide in which we outline the key practical stages, as well as ethical assurances involved in photo elicitation research, using our ongoing research as an illustrative example. It is intended that this could be used as a model of good practice for developing research paradigms beyond those typically used within the psychology discipline

Well-being in residency training: a survey examining resident physician satisfaction both within and outside of residency training and mental health in Alberta

BACKGROUND: Despite the critical importance of well-being during residency training, only a few Canadian studies have examined stress in residency and none have examined well-being resources. No recent studies have reported any significant concerns with respect to perceived stress levels in residency. We investigated the level of perceived stress, mental health and understanding and need for well-being resources among resident physicians in training programs in Alberta, Canada. METHODS: A mail questionnaire was distributed to the entire resident membership of PARA during 2003 academic year. PARA represents each of the two medical schools in the province of Alberta. RESULTS: In total 415 (51 %) residents participated in the study. Thirty-four percent of residents who responded to the survey reported their life as being stressful. Females reported stress more frequently than males (40% vs. 27%, p < 0.02). Time pressure was reported as the number one factor contributing to stress (44% of males and 57% of females). A considerable proportion of residents would change their specialty program (14%) and even more would not pursue medicine (22%) if given the opportunity to relive their career. Up to 55% of residents reported experiencing intimidation and harassment. Intimidation and harassment was strongly related to gender (12% of males and 38% of females). Many residents (17%) rated their mental health as fair or poor. This was more than double the amount reported in the Canadian Community Health Survey from the province (8%) or the country (7%). Residents highly valued their colleagues (67%), program directors (60%) and external psychiatrist/psychologist (49%) as well-being resources. Over one third of residents wished to have a career counselor (39%) and financial counselor (38%). CONCLUSION: Many Albertan residents experience significant stressors and emotional and mental health problems. Some of which differ among genders. This study can serve as a basis for future resource application, research and advocacy for overall improvements to well-being during residency training

Reliability of Transcriptional Cycles and the Yeast Cell-Cycle Oscillator

A recently published transcriptional oscillator associated with the yeast cell cycle provides clues and raises questions about the mechanisms underlying autonomous cyclic processes in cells. Unlike other biological and synthetic oscillatory networks in the literature, this one does not seem to rely on a constitutive signal or positive auto-regulation, but rather to operate through stable transmission of a pulse on a slow positive feedback loop that determines its period. We construct a continuous-time Boolean model of this network, which permits the modeling of noise through small fluctuations in the timing of events, and show that it can sustain stable oscillations. Analysis of simpler network models shows how a few building blocks can be arranged to provide stability against fluctuations. Our findings suggest that the transcriptional oscillator in yeast belongs to a new class of biological oscillators

Mental Health and Wellbeing Implications of the COVID-19 Quarantine for Disabled and Disadvantaged Children and Young People: Evidence from a Cross-cultural Study in Zambia and Sierra Leone

Background The mental health impact of the COVID-19 pandemic and quarantining on children and young people (CYP) living in low- and middle-income countries (LMICs) has yet to be fully comprehended. CYP in LMICs are at utmost risk, given the COVID-19-related restrictions and social distancing measures, resulting in reduced access to school-based services for nutritional and mental health needs. This study examined mental health of CYP during the first COVID-19 lockdown in Zambia and Sierra Leone. Method A total of 468 disabled and disadvantaged CYP aged 12 to 25 completed a planning tool that comprised the short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), as well as open-ended questions covering social connectedness, physical distancing and educational challenges during the lockdown. The community coaches screened individuals and families who could be eligible to receive emergency aid, and based on a convenience sample following distribution of aid, recipients were invited to complete the online planning tool. Results The data showed that participants in the global south have increasing anxieties and fears centred on accessing offline educational resources and income loss in the family effecting food security and their ability to return to education. Mean (SD) SWEMWBS scores for all participants in Zambia and Sierra Leone, were 19.61 (3.45) and 21.65 (2.84), respectively. Mental well-being scores were lower in females, children aged 12-14 and participants with two or more disabilities. Factors significantly associated with poor mental wellbeing in the sample were: type of disability, nationality, peer relationships, connection to others during the pandemic, knowledge about COVID-19, worry about the long-term impact of COVID-19, and the types of self-isolating. Conclusion The study shows that participants who self-reported low levels of COVID-19 health literacy also scored low on the mental wellbeing self-assessment. Yet, despite undoubted limited resources, these CYP are doing well in identifying their needs and maintaining hope in the face of the problems associated with COVID-19 in countries where stigma persists around mental ill-health