Stressor reflections, sleep, and psychological well-being: A pre-registered experimental test of self-distanced versus self-immersed reflections

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: All data and analysis code are publicly available via our OSF project (https://osf.io/ue9jm/). We pre-registered the design and analysis plan for this experiment via the OSF (https://osf.io/jyf69). Deviations from our registered protocol are reported in the manuscript in the section ‘Deviations from Pre-Registered Protocol’.Evidence supports the effectiveness of cuing people to analyse negative autobiographical experiences from self-distanced rather than self-immersed perspectives. However, the evidence on which this expectation resides is limited largely to static snapshots of mean levels of cognitive and emotional factors. Via a pre-registered, randomised controlled trial (N = 257), we examined the differential effectiveness of self-distanced relative to self-immersed reflections on mean levels and within-person variability of sleep duration and quality as well as psychological well-being over a 5-day working week. Except for sleep quality, we found that reflecting from a psychologically distanced perspective, overall, was no more effective for mean levels and within-person variability of sleep duration, well-being, and stress-related factors than when the current self is fully immersed in the experiential reality of the event. We consider several substantive and methodological considerations (e.g., dosage, salience of stressor event) that require interrogation in future research via experimental and longitudinal observational methods

Animal contests and microplastics: evidence of disrupted behaviour in hermit crabs Pagurus bernhardus

Microplastics are ubiquitous in global marine systems and may have negative impacts on a vast range of species. Recently, microplastics were shown to impair shell selection assessments in hermit crabs, an essential behaviour for their survival. Hermit crabs also engage in 'rapping' contests over shells, based on cognitive assessments of shell quality and opponent fighting ability and, hence, are a useful model species for examining the effects of microplastics on fitness-relevant behaviour in marine systems. Here, we investigated how a 5-day microplastic exposure (25 microplastics/litre) affected the dynamics and outcome of 120 staged hermit crab contests. Using a 2 x 2 factorial design, we examined how microplastics (i.e. presence or absence) and contestant role (i.e. attacker or defender) affected various behavioural variables. Significantly higher raps per bout were needed to evict microplastic-treated defenders when attackers were pre-exposed to control conditions (i.e. no plastic). Also, significantly longer durations of rapping bouts were needed to evict control-treated defenders when attackers were pre-exposed to microplastics. We suggest that microplastics impaired defenders' ability to identify resource holding potential and also affected attackers' rapping strength and intensity during contests. These impacts on animal contests indicate that microplastics have broader deleterious effects on marine biota than currently recognized

Impact of hiatal hernia on histological pattern of non-erosive reflux disease

BACKGROUND: Hiatus hernia (HH) has major pathophysiological effects favoring gastroesophageal reflux and hence contributing to esophageal mucosa injury, especially in patients with severe gastroesophageal disease. However, prospective studies investigating the impact of HH on the esophageal mucosa in non-erosive reflux disease (NERD) are lacking. This study evaluated the association between the presence of (HH) and the histological findings in symptomatic patients with NERD. METHODS: Fifty consecutive patients with gastroesophageal reflux disease (GERD) were enrolled. After conventional endoscopy, Lugol solution was applied and biopsy specimens were obtained. Histological parameters including basal zone hyperplasia, papillary length and cellular infiltration were evaluated. The chi-square test with Yates' correlation was used for comparing discrete parameters between groups. However, Fisher's exact probability test was used where the expected frequencies were lower than 5. Wilcoxon's test for unpaired samples was preferred in cases of semi-quantitative parameters. RESULTS: The presence of HH along with more severe findings (0.01 <P < 0.05) was confirmed in 18 patients. NERD was observed in 29 (58%) patients. Basal zone hyperplasia and loss of glycogen accompanied HH in all cases, and the correlation was significant in NERD (P < 0.001). The remaining histological patterns were similar between erosive reflux disease and NERD in the presence of HH. CONCLUSION: The presence of HH is correlated with more severe endoscopy findings, and predisposes for severe histological abnormality in cases of NERD

Buffered memory: a hypothesis for the maintenance of functional, virus-specific CD8(+) T cells during cytomegalovirus infection.

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and both CD4(+) and CD8(+) CMV-specific T cells are essential. These virus-specific T cells persist in exceptionally large numbers during the infection, traffic into peripheral tissues and remain functional, making CMV an attractive vaccine vector for driving CMV-like T cell responses against recombinant antigens of choice. However, the mechanisms by which these T cells persist and differentiate while remaining functional are still poorly understood, and we have no means to promote their development in immune-compromised patients at risk for CMV disease. In this review, I will briefly summarize our current knowledge of CMV-specific CD8(+) T cells and propose a mechanism that may explain their maintenance and preservation of function during chronic infection

NYESO-1/LAGE-1s and PRAME Are Targets for Antigen Specific T Cells in Chondrosarcoma following Treatment with 5-Aza-2-Deoxycitabine

Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA) family that have been identified as promising targets for T cell therapy. LAGE-1 is a cancer testis antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5-Aza-2-Deoxycitabine (5-Aza-dC) in other cancers. We sought to evaluate the feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME specific T cells using 5-Aza-dC to induce antigen expression.We used 11 flash frozen tumors from the University of Washington tumor bank to test for the expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors. Using four chondrosarcoma cell lines we tested the expression of these CTA's with and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME specific effectors that we generated from sarcoma patients, we evaluated the ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in vitro both with and without 5-Aza-dC treatment.A minority (36%) of chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our reference value and none expressed PRAME at that level. However, in all four of the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be induced following treatment with 5-Aza-dC including in cell lines where expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and PRAME specific CD8+ effector T cells were able to specifically recognize and lyse A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment.These data suggest that adoptive immunotherapy in combination with 5-Aza-dC may be a potential strategy to treat unresectable or metastatic chondrosarcoma patients where no proven systemic therapies exist

Análise do impacto do tênis e coturno fornecidos pelo Exército Brasileiro durante a marcha

O objetivo do presente estudo foi comparar a absorção de impacto durante a marcha descalço e com tênis e coturno fornecidos pelo Exército Brasileiro. A amostra foi composta por 20 soldados saudáveis recém-incorporados sem sintomas ou lesões musculoesqueléticas ou neurológicas que interferissem na marcha. Os sujeitos foram instruídos a caminhar em uma plataforma de madeira de 10 metros de comprimento por um metro de largura, com duas plataformas de força (Bertec, EUA) embutidas no centro. O componente vertical da força de reação do solo foi avaliado durante a marcha nas situações tênis, coturno e descalço. O sistema de cinemetria (Qualysis, Suécia) foi utilizado para medir a velocidade da marcha em cada situação de teste. O primeiro pico de força (PPF), o tempo para atingir o PPF (T_PPF), pico transiente de impacto (IPF) e a taxa de aceitação do peso (TAP) entre 10% e 30%, 30% e 50%, 50% e 70%, 70% e 90% e 10% e 90% do PPF foram avaliadas. O T_PPF foi em média 1s menor (p < 0,0001), o IPF e a TAP entre 10% e 30% do PPF foram maiores (p < 0,0001, ambos) descalço comparados a marcha com tênis e coturno. Não foi observado diferença estatística nas outras variáveis estudadas nas três condições de teste, bem como em nenhuma variável na comparação entre tênis e coturno. Os calçados avaliados são eficientes em reduzir o impacto durante a marcha por atrasar em média 1 s o tempo em que o PPF foi atingido, reduzir o IPF e a TAP nos primeiros 30% do PPF

Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice

10.1038/srep03754Scientific Reports4

Discovering privileged topologies of molecular knots with self-assembling models

Despite the several available strategies to build complex supramolecular constructs, only a handful of different molecular knots have been synthesised so far. Here, in response to the quest for further designable topologies, we use Monte Carlo sampling and molecular dynamics simulations, informed by general principles of supramolecular assembly, as a discovery tool for thermodynamically and kinetically accessible knot types made of helical templates. By combining this approach with the exhaustive enumeration of molecular braiding patterns applicable to more general template geometries, we find that only few selected shapes have the closed, symmetric and quasi-planar character typical of synthetic knots. The corresponding collection of admissible topologies is extremely restricted. It covers all known molecular knots but it especially includes a limited set of novel complex ones that have not yet been obtained experimentally, such as 10124 and 15n41185, making them privileged targets for future self-assembling experiments

Congo Basin peatlands: threats and conservation priorities

The recent publication of the first spatially explicit map of peatlands in the Cuvette Centrale, central Congo Basin, reveals it to be the most extensive tropical peatland complex, at ca. 145,500 km2. With an estimated 30.6 Pg of carbon stored in these peatlands, there are now questions about whether these carbon stocks are under threat and, if so, what can be done to protect them. Here, we analyse the potential threats to Congo Basin peat carbon stocks and identify knowledge gaps in relation to these threats, and to how the peatland systems might respond. Climate change emerges as a particularly pressing concern, given its potential to destabilise carbon stocks across the whole area. Socio-economic developments are increasing across central Africa and, whilst much of the peatland area is protected on paper by some form of conservation designation, the potential exists for hydrocarbon exploration, logging, plantations and other forms of disturbance to significantly damage the peatland ecosystems. The low level of human intervention at present suggests that the opportunity still exists to protect the peatlands in a largely intact state, possibly drawing on climate change mitigation funding, which can be used not only to protect the peat carbon pool but also to improve the livelihoods of people living in and around these peatlands

Systemic hematogenous maintenance of memory inflation by MCMV infection.

Several low-grade persistent viral infections induce and sustain very large numbers of virus-specific effector T cells. This was first described as a response to cytomegalovirus (CMV), a herpesvirus that establishes a life-long persistent/latent infection, and sustains the largest known effector T cell populations in healthy people. These T cells remain functional and traffic systemically, which has led to the recent exploration of CMV as a persistent vaccine vector. However, the maintenance of this remarkable response is not understood. Current models propose that reservoirs of viral antigen and/or latently infected cells in lymph nodes stimulate T cell proliferation and effector differentiation, followed by migration of progeny to non-lymphoid tissues where they control CMV reactivation. We tested this model using murine CMV (MCMV), a natural mouse pathogen and homologue of human CMV (HCMV). While T cells within draining lymph nodes divided at a higher rate than cells elsewhere, antigen-dependent proliferation of MCMV-specific effector T cells was observed systemically. Strikingly, inhibition of T cell egress from lymph nodes failed to eliminate systemic T cell division, and did not prevent the maintenance of the inflationary populations. In fact, we found that the vast majority of inflationary cells, including most cells undergoing antigen-driven division, had not migrated into the parenchyma of non-lymphoid tissues but were instead exposed to the blood supply. Indeed, the immunodominance and effector phenotype of inflationary cells, both of which are primary hallmarks of memory inflation, were largely confined to blood-localized T cells. Together these results support a new model of MCMV-driven memory inflation in which most immune surveillance occurs in circulation, and in which most inflationary effector T cells are produced in response to viral antigen presented by cells that are accessible to the blood supply