Cytosolic Phospholipase A2α and Eicosanoids Regulate Expression of Genes in Macrophages Involved in Host Defense and Inflammation

Acknowledgments: We thank Dr. Robert Barkley and Charis Uhlson for mass spectrometry analysis. Funding: This work was supported by grants from the National Institutes of Health HL34303 (to C.C.L., R.C.M. and D.L.B), DK54741 (to J.V.B.), GM5322 (to D.L.W.) and the Wellcome Trust (to N.A.R.G. and G.D.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The effect of distance on reaction time in aiming movements

Target distance affects movement duration in aiming tasks but its effect on reaction time (RT) is poorly documented. RT is a function of both preparation and initiation. Experiment 1 pre-cued movement (allowing advanced preparation) and found no influence of distance on RT. Thus, target distance does not affect initiation time. Experiment 2 removed pre-cue information and found that preparing a movement of increased distance lengthens RT. Experiment 3 explored movements to targets of cued size at non-cued distances and found size altered peak speed and movement duration but RT was influenced by distance alone. Thus, amplitude influences preparation time (for reasons other than altered duration) but not initiation time. We hypothesise that the RT distance effect might be due to the increased number of possible trajectories associated with further targets: a hypothesis that can be tested in future experiments

The 2020 Five Domains Model: Including Human-Animal Interactions in Assessments of Animal Welfare

Throughout its 25-year history, the Five Domains Model for animal welfare assessment has been regularly updated to include at each stage the latest authenticated developments in animal welfare science thinking. The domains of the most up-to-date Model described here are: 1 Nutrition, 2 Physical Environment, 3 Health, 4 Behavioural Interactions and 5 Mental State. The first four domains focus attention on factors that give rise to specific negative or positive subjective experiences (affects), which contribute to the animal’s mental state, as evaluated in Domain 5. More specifically, the first three domains focus mainly on factors that disturb or disrupt particular features of the body’s internal stability. Each disturbed or disrupted feature generates sensory inputs which are processed by the brain to form specific negative affects. These affects are associated with behaviours that act to restore the body’s internal stability. Each such behaviour is essential for the survival of the animal

Powerful-synergies: Gender Equality, Economic Development and Environmental Sustainability

This is a collection of evidence-based papers by scholars and practitioners that explore the interconnections between gender equality and sustainable development across a range of sectors and global development issues such as energy, health, education, food security, climate change, human rights, consumption and production patterns, and urbanization. The publication provides evidence from various sectors and regions on how women's equal access and control over resources not only improves the lives of individuals, families and nations, but also helps ensure the sustainability of the environment

Investigating the Psychosocial Determinants of Physical Activity in Older Adults: A Qualitative Approach

Objective: Despite the benefits of physical activity (PA), only one-third of older adults meet the recommended levels. The present study focused on psychosocial determinants of PA following retirement. Social cognitive theory (SCT) was used to better understand pre- and post-retirement adults’ thoughts about PA, the reasons why some individuals are more active than others, and how PA is incorporated into daily life after retirement. Design: Seven focus groups of older adults (N = 37, M = 64, SD = 5.20; males = 20) representing a range of PA levels and retirement length participated in one of seven focus groups. Results: Aligned with SCT, self-efficacy beliefs along with perceptions about barriers and benefits of PA were among the major determinants of PA. Findings highlighted the importance of social support, positive outcome expectations and self-regulatory strategies as motivators. The lack of structure in retirement was a hindrance to incorporating PA into daily routine but, when incorporated, PA provided a sense of purpose in the lives of retired individuals. Conclusion: It is important to understand the meaning of retirement as a life transition and how it affects beliefs about PA to inform SCT-based health promotion interventions targeting individuals in retirement age

Regulation of Cytosolic Phospholipase A 2 Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor

Phagocytosis of non-opsonized microorganisms by macrophages initiates innate immune responses for host defense against infection. Cytosolic phospholipase A(2) is activated during phagocytosis, releasing arachidonic acid for production of eicosanoids, which initiate acute inflammation. Our objective was to identify pattern recognition receptors that stimulate arachidonic acid release and cyclooxygenase 2 (COX2) expression in macrophages by pathogenic yeast and yeast cell walls. Zymosan- and Candida albicans-stimulated arachidonic acid release from resident mouse peritoneal macrophages was blocked by soluble glucan phosphate. In RAW264.7 cells arachidonic acid release, COX2 expression, and prostaglandin production were enhanced by overexpressing the beta-glucan receptor, dectin-1, but not dectin-1 lacking the cytoplasmic tail. Pure particulate (1, 3)-beta-D-glucan stimulated arachidonic acid release and COX2 expression, which were augmented in a Toll-like receptor 2 (TLR2)-dependent manner by macrophage-activating lipopeptide-2. However, arachidonic acid release and leukotriene C(4) production stimulated by zymosan and C. albicans were TLR2-independent, whereas COX2 expression and prostaglandin production were partially blunted in TLR2(-/-) macrophages. Inhibition of Syk tyrosine kinase blocked arachidonic acid release and COX2 expression in response to zymosan, C. albicans, and particulate (1, 3)-beta-D-glucan. The results suggest that cytosolic phospholipase A(2) activation triggered by the beta-glucan component of yeast is dependent on the immunoreceptor tyrosine-based activation motif-like domain of dectin-1 and activation of Syk kinase, whereas both TLR2 and Syk kinase regulate COX2 expression

Regulation of Cytosolic Phospholipase a\u3csub\u3e2\u3c/sub\u3e Activation and Cyclooxygenase 2 Expression in Macrophages by the β-Glucan Receptor

Phagocytosis of non-opsonized microorganisms bymacrophages initiates innate immune responses for host defense against infection. Cytosolic phospholipase A2 is activated during phagocytosis, releasing arachidonic acid for production of eicosanoids, which initiate acute inflammation. Our objective was to identify pattern recognition receptors that stimulate arachidonic acid release and cyclooxygenase 2 (COX2) expression in macrophages by pathogenic yeast and yeast cell walls. Zymosan- and Candida albicans-stimulated arachidonic acid release from resident mouse peritoneal macrophages was blocked by soluble glucan phosphate. In RAW264.7 cells arachidonic acid release, COX2 expression, and prostaglandin production were enhanced by overexpressing the β-glucan receptor, dectin-1, but not dectin-1 lacking the cytoplasmic tail. Pure particulate (1, 3)-β-D-glucan stimulated arachidonic acid release and COX2 expression, which were augmented in a Toll-like receptor 2 (TLR2)-dependent manner by macrophage-activating lipopeptide-2. However, arachidonic acid release and leukotriene C4 production stimulated by zymosan and C. albicans were TLR2-independent, whereas COX2 expression and prostaglandin production were partially blunted in TLR2-/- macrophages. Inhibition of Syk tyrosine kinase blocked arachidonic acid release and COX2 expression in response to zymosan, C. albicans, and particulate (1, 3)-β-D-glucan. The results suggest that cytosolic phospholipase A2 activation triggered by the β-glucan component of yeast is dependent on the immunoreceptor tyrosine-based activation motif-like domain of dectin-1 and activation of Syk kinase, whereas both TLR2 and Syk kinase regulate COX2 expression

JWST and ALMA imaging of dust-obscured, massive substructures in a typical z∼3z \sim 3 star-forming disk galaxy

We present an identification of dust-attenuated star-forming galactic-disk substructures in a typical star-forming galaxy (SFG), UDF2, at $z = 2.696$. To date, substructures containing significant buildup of stellar mass and actively forming stars have yet to be found in typical (i.e., main-sequence) SFGs at $z > 2$. This is due to the strong dust attenuation common in massive galaxies at the epoch and the scarcity of high-resolution, high-sensitivity extinction-independent imaging. To search for disk substructures, we subtracted the central stellar-mass disk from the JWST/NIRCam rest-frame 1.2 $\mu$m image ($0.13''$ resolution) and subtracted, in the visibility plane, the central starburst disk from ALMA rest-frame 240 $\mu$m observations ($0.03''$ resolution). The residual images revealed substructures at rest-frame 1.2 $\mu$m co-located with those found at rest-frame 240 $\mu$m, $\simeq 2$ kpc away from the galactic center. The largest substructure contains $\simeq20$% of the total stellar mass and $\simeq5$% of the total SFR of the galaxy. While UDF2 exhibits a kinematically-ordered velocity field of molecular gas consistent with a secularly evolving disk, more sensitive observations are required to characterize the nature and the origin of this substructure (spiral arms, minor merger, or other types of disk instabilities). UDF2 resides in an overdense region ($N \geqslant 4$ massive galaxies within 70 kpc projected distance at $z=2.690-2.697$) and the substructures may be associated with interaction-induced instabilities. Importantly, a statistical sample of such substructures identified with JWST and ALMA could play a key role in bridging the gap between the bulge-forming starburst and the rest of the galaxy.Comment: 7 pages, 5 figures; ApJL, accepte

Barriers and enablers of physical activity engagement for patients with COPD in primary care

Maria-Christina Kosteli,1 Nicola R Heneghan,1 Carolyn Roskell,1 Sarah E Williams,1 Peymane Adab,2 Andrew P Dickens,2 Alexandra Enocson,2 David A Fitzmaurice,2 Kate Jolly,2 Rachel Jordan,2 Sheila Greenfield,2 Jennifer Cumming1 1School of Sport, Exercise and Rehabilitation Sciences, 2Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, UK Background: Given that physical activity (PA) has a positive impact on COPD symptoms and prognosis, this study examined the factors that both encourage and limit participation in PA for individuals with COPD in a primary care setting from the perspective of social cognitive theory.Methods: A purposive sample of 26 individuals with a range of COPD severity (age range: 50–89 years; males =15) were recruited from primary care to participate in one of four focus groups. Thematic analysis was undertaken to identify key concepts related to their self-efficacy beliefs.Results: Several barriers and enablers closely related to self-efficacy beliefs and symptom severity were identified. The main barriers were health related (fatigue, mobility problems, breathing issues caused by the weather), psychological (embarrassment, fear, frustration/disappointment), attitudinal (feeling in control of their condition, PA perception, older age perception), and motivational. The main enabling factors were related to motivation (autonomous or controlled), attitudes, self-regulation, and performance accomplishments.Clinical implications: When designing interventions for individuals with COPD, it is important to understand the patient-specific social cognitive influences on PA participation. This information can then inform individually tailored management planning. Keywords: COPD, social cognitive theory, self-efficacy, barriers, enablers, primary car

Influence of Comorbidity on Racial Differences in Receipt of Surgery Among US Veterans With Early-Stage Non–Small-Cell Lung Cancer

It is unclear why racial differences exist in the frequency of surgery for lung cancer treatment. Comorbidity is an important consideration in selection of patients for lung cancer treatment, including surgery. To assess whether comorbidity contributes to the observed racial differences, we evaluated racial differences in the prevalence of comorbidity and their impact on receipt of surgery