The neural correlates of emotion regulation by implementation intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency

High-level production of animal-free recombinant transferrin from saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Animal-free recombinant proteins provide a safe and effective alternative to tissue or serum-derived products for both therapeutic and biomanufacturing applications. While recombinant insulin and albumin already exist to replace their human counterparts in cell culture media, until recently there has been no equivalent for serum transferrin.</p> <p>Results</p> <p>The first microbial system for the high-level secretion of a recombinant transferrin (rTf) has been developed from <it>Saccharomyces cerevisiae </it>strains originally engineered for the commercial production of recombinant human albumin (Novozymes' Recombumin^®USP-NF) and albumin fusion proteins (Novozymes' albufuse^®). A full-length non-N-linked glycosylated rTf was secreted at levels around ten-fold higher than from commonly used laboratory strains. Modification of the yeast 2 μm-based expression vector to allow overexpression of the ER chaperone, protein disulphide isomerase, further increased the secretion of rTf approximately twelve-fold in high cell density fermentation. The rTf produced was functionally equivalent to plasma-derived transferrin.</p> <p>Conclusions</p> <p>A <it>Saccharomyces cerevisiae </it>expression system has enabled the cGMP manufacture of an animal-free rTf for industrial cell culture application without the risk of prion and viral contamination, and provides a high-quality platform for the development of transferrin-based therapeutics.</p

Salinity control of thermal evolution of late summer melt ponds on Arctic sea ice

The thermal evolution of melt ponds on Arctic sea ice was investigated through a combination of autonomous observations and two‐dimensional high‐resolution fluid dynamics simulations. We observed one relatively fresh pond and one saline pond on the same ice floe, with similar depth. The comparison of observations and simulations indicates that thermal convection dominates in relatively fresh ponds, but conductive heat transfer dominates in salt‐stratified ponds. Using a parameterized surface energy balance, we estimate that the heat flux to the ice is larger under the saline pond than the freshwater pond when averaged over the observational period. The deviation is sensitive to assumed wind, varying between 3 and 14 W/m2 for winds from 0 to 5 m/s. If this effect persists as conditions evolve through the melt season, our results suggest that this imbalance potentially has a climatologically significant impact on sea‐ice evolution

Influenza A virus challenge models in cynomolgus macaques using the authentic inhaled aerosol and intra-nasal routes of infection

Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (&gt; 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections

Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD

RATIONALE: Pulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms. METHODS: Bronchoalveolar lavage proteome and lipidome were characterised in ex-smoking mild/moderate COPD subjects (n=26) and healthy ex-smoking (n=20) and never-smoking (n=16) controls using mass spectrometry. Serum surfactant protein analysis was performed. RESULTS: Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, surfactant protein (SP)-B, SP-A and SP-D concentrations were lower in COPD versus controls (log2 fold change (log2FC) -2.0, -2.2, -1.5, -0.5, -0.7 and -0.5 (adjusted p<0.02), respectively) and correlated with lung function. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D, napsin A and CD44 inversely correlated with computed tomography small airways disease measures (expiratory to inspiratory mean lung density) (r= -0.56, r= -0.58, r= -0.45, r= -0.36, r= -0.44, r= -0.37, r= -0.40 and r= -0.39 (adjusted p<0.05)). Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D and NAPSA inversely correlated with emphysema (% low-attenuation areas): r= -0.55, r= -0.61, r= -0.48, r= -0.51, r= -0.41, r= -0.31 and r= -0.34, respectively (adjusted p<0.05). Neutrophil elastase, known to degrade SP-A and SP-D, was elevated in COPD versus controls (log2FC 0.40, adjusted p=0.0390), and inversely correlated with SP-A and SP-D. Serum SP-D was increased in COPD versus healthy ex-smoking volunteers, and predicted COPD status (area under the curve 0.85). CONCLUSIONS: Using a multiomics approach, we demonstrate, for the first time, global surfactant dysregulation in COPD that was associated with emphysema, giving new insights into potential mechanisms underlying the cause or consequence of disease

Psychometric evaluation of a short measure of social capital at work

BACKGROUND: Prior studies on social capital and health have assessed social capital in residential neighbourhoods and communities, but the question whether the concept should also be applicable in workplaces has been raised. The present study reports on the psychometric properties of an 8-item measure of social capital at work. METHODS: Data were derived from the Finnish Public Sector Study (N = 48,592) collected in 2000–2002. Based on face validity, an expert unfamiliar with the data selected 8 questionnaire items from the available items for a scale of social capital. Reliability analysis included tests of internal consistency, item-total correlations, and within-unit (interrater) agreement by r(wg )index. The associations with theoretically related and unrelated constructs were examined to assess convergent and divergent validity (construct validity). Criterion-related validity was explored with respect to self-rated health using multilevel logistic regression models. The effects of individual level and work unit level social capital were modelled on self-rated health. RESULTS: The internal consistency of the scale was good (Cronbach's alpha = 0.88). The r(wg )index was 0.88, which indicates a significant within-unit agreement. The scale was associated with, but not redundant to, conceptually close constructs such as procedural justice, job control, and effort-reward imbalance. Its associations with conceptually more distant concepts, such as trait anxiety and magnitude of change in work, were weaker. In multilevel models, significantly elevated age adjusted odds ratios (ORs) of poor self-rated health (OR = 2.42, 95% confidence interval (CI): 2.24–2.61 for the women and OR = 2.99, 95% CI: 2.56–3.50 for the men) were observed for the employees in the lowest vs. highest quartile of individual level social capital. In addition, low social capital at the work unit level was associated with a higher likelihood of poor self-rated health. CONCLUSION: Psychometric techniques show our 8-item measure of social capital to be a valid tool reflecting the construct and displaying the postulated links with other variables

Localised climate change defines ant communities in human‐modified tropical landscapes

Funder: Sime Darby FoundationFunder: Sir Philip Reckitt Educational TrustFunder: Czech Science Foundation; Id: http://dx.doi.org/10.13039/501100001824Abstract: Logging and habitat conversion create hotter microclimates in tropical forest landscapes, representing a powerful form of localised anthropogenic climate change. It is widely believed that these emergent conditions are responsible for driving changes in communities of organisms found in modified tropical forests, although the empirical evidence base for this is lacking. Here we investigated how interactions between the physiological traits of genera and the environmental temperatures they experience lead to functional and compositional changes in communities of ants, a key organism in tropical forest ecosystems. We found that the abundance and activity of ant genera along a gradient of forest disturbance in Sabah, Malaysian Borneo, was defined by an interaction between their thermal tolerance (CTmax) and environmental temperature. In more disturbed, warmer habitats, genera with high CTmax had increased relative abundance and functional activity, and those with low CTmax had decreased relative abundance and functional activity. This interaction determined abundance changes between primary and logged forest that differed in daily maximum temperature by a modest 1.1°C, and strengthened as the change in microclimate increased with disturbance. Between habitats that differed by 5.6°C (primary forest to oil palm) and 4.5°C (logged forest to oil palm), a 1°C difference in CTmax among genera led to a 23% and 16% change in relative abundance, and a 22% and 17% difference in functional activity. CTmax was negatively correlated with body size and trophic position, with ants becoming significantly smaller and less predatory as microclimate temperatures increased. Our results provide evidence to support the widely held, but never directly tested, assumption that physiological tolerances underpin the influence of disturbance‐induced microclimate change on the abundance and function of invertebrates in tropical landscapes. A free Plain Language Summary can be found within the Supporting Information of this article

TBVAC2020: Advancing tuberculosis vaccines from discovery to clinical development

TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage. The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal

Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations

BACKGROUND AND PURPOSE: Currently, there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently used to treat anticoagulant anomalies in COVID-19 patients. Additionally, in the United Kingdom, Brazil and Australia, nebulised unfractionated heparin (UFH) is being trialled in COVID-19 patients as a potential treatment. A systematic comparison of the potential antiviral effect of various heparin preparations on live wild type SARS-CoV-2, in vitro, is needed.EXPERIMENTAL APPROACH: Seven different heparin preparations including UFH and low MW heparins (LMWH) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Australia/VIC01/2020) using a plaque inhibition assay with Vero E6 cells. Interaction of heparin with spike protein RBD was studied using differential scanning fluorimetry and the inhibition of RBD binding to human ACE2 protein using elisa assays was examined.KEY RESULTS: All the UFH preparations had potent antiviral effects, with IC50 values ranging between 25 and 41 μg·ml-1 , whereas LMWHs were less inhibitory by ~150-fold (IC50 range 3.4-7.8 mg·ml-1 ). Mechanistically, we observed that heparin binds and destabilizes the RBD protein and furthermore, we show heparin directly inhibits the binding of RBD to the human ACE2 protein receptor.CONCLUSION AND IMPLICATIONS: This comparison of clinically relevant heparins shows that UFH has significantly stronger SARS-CoV-2 antiviral activity compared to LMWHs. UFH acts to directly inhibit binding of spike protein to the human ACE2 protein receptor. Overall, the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19.</p