Azithromycin Augments Bacterial Uptake and Anti-Inflammatory Macrophage Polarization in Cystic Fibrosis.

BACKGROUND: Azithromycin (AZM) is widely being used for treating patients with cystic fibrosis (pwCF) following clinical trials demonstrating improved lung function and fewer incidents of pulmonary exacerba-tions. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. METHODS: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs), were differentiated into monocyte-derived macrophages (MDMs) and subsequently infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. RESULTS: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected; however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM d'd not restore endocytosis in CF, another essential feature of M2 macrophages. CONCLUSIONS: This study highlights the cellular functions and molecular targets of AZM which may involve an improved uptake of both Gram-positive and Gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.

A Review of Pollen Counting Networks: From the Nineteenth Century into the Twenty-first Century.

PURPOSE OF REVIEW: Pollen is enormously important to the human experience. As pollen became germane to human health in the late nineteenth century, methods for pollen collection and measurement were developed. Techniques were standardized and pollen counting networks were established in many parts of the world during the middle to late part of the twentieth century. With some notable exceptions, the technology of the 1950s and 1960s is presently employed to create the current pollen counting networks. Pollen counting networks in the past faced substantial challenges. Pollen counting networks using the same technology as the past face the same challenges. RECENT FINDINGS: As we move into the twenty-first century, automated pollen counting technology enables pollen counting networks to be robust, available, scalable, self-perpetuating, and able to meet modern demands. Automated pollen measurement networks present a promising path towards a more informed, data-driven, and effective approach to managing allergens, improving crop yields, and minimizing human suffering caused by pollen. By empowering individuals with comprehensive pollen data, a feat not possible with manual counting, we can help people make informed decisions and take proactive measures to minimize exposure to allergens and improve their well-being.

Assessing Validity and Bias of Within-Person Variability in Affect and Personality.

Within-person variability in affect (e.g., Neuroticism) and personality have been linked to well-being. These are measured either by asking people to report how variable they are or to give multiple reports on the construct and calculating a within-person standard deviation adjusted for confounding by the person-level mean. The two measures are weakly correlated with one another and the links of variability with well-being depend on which measure researchers use. Recent research suggests that people's repeated ratings may be biased by response styles. In a 7-day study (N = 399) with up to five measurements per day, we confirmed that the measures of variability lacked sufficient convergent validity to be used interchangeably. We found only 1 significant correlation (of 10) between variability in repeated ratings of affect or personality and variability in repeated ratings of a theoretically unrelated construct (i.e., features of images). There was very little evidence supporting the response styles hypothesis.

Brief Report: Does the Number of Response Options Matter for the BFI-2? Conceptual Replication and Extension.

We evaluated how the number of response options affects the psychometric properties of the Big Five Inventory-2 (BFI-2). Using two large samples collected from a market research company (Ns = 893 and 1,213), we tested how different response options of the BFI-2 influenced scale score distributions, internal consistency estimates, convergent validity correlations, and criterion validity correlations. Results suggest that score distributions were impacted by the number of response options such that ceiling and floor effects were more common when using two or three response options than when using more options. Estimates of Cronbach's alpha were generally lower with fewer scale points as compared with more scale points, but these effects disappeared when ordinal alpha was used. There were no systematic effects of response options on convergent validity and criterion validity correlations. Given these results, there seems to be few psychometric reasons for deciding whether to administer personality items with five, six, or seven scale points.

Describing Broad Categories with Narrow Terms: the Problems with Emotional Well-Being.

The target article proposes a new term-emotional well-being-and a new definition of that term, which are meant to bring clarity to a broad set of psychological constructs that relate to well-being. Although we appreciate the goal of improving scientific communication through the clarification of terms and definitions, both the chosen terminology and definition are too narrow to capture the broad range of constructs that researchers in these areas study. This imprecision will likely impede rather than aid effective scientific communication. In this commentary, we consider whether it is necessary or even useful to try to define and label the broad category that is the focus of the target article, and we conclude the potential for confusion outweighs the limited benefits that would result.

Toward a roadmap for space-based observations of the land sector for the UNFCCC global stocktake.

Space-based remote sensing can make an important contribution toward monitoring greenhouse gas emissions and removals from the agriculture, forestry, and other land use (AFOLU) sector, and to understanding and addressing human-caused climate change through the UNFCCC Paris Agreement. Space agencies have begun to coordinate their efforts to identify needs, collect and harmonize available data and efforts, and plan and maintain a long-term roadmap for observations. International cooperation is crucial in developing and realizing the roadmap, and the Committee on Earth Observation Satellites (CEOS) is a key coordinating driver of this effort. Here, we first identify the data and information that will be useful to support the global stocktake (GST) of the Paris Agreement. Then, the paper explains how existing and planned space-based capabilities and products can be used and combined, particularly in the land use sector, and provides a workflow for their harmonization and contribution to greenhouse gas inventories and assessments at the national and global level.

TLR4 phosphorylation at tyrosine 672 activates the ERK/c-FOS signaling module for LPS-induced cytokine responses in macrophages.

TLRs engage numerous adaptor proteins and signaling molecules, enabling a complex series of post-translational modifications (PTMs) to mount inflammatory responses. TLRs themselves are post-translationally modified following ligand-induced activation, with this being required to relay the full spectrum of proinflammatory signaling responses. Here, we reveal indispensable roles for TLR4 Y672 and Y749 phosphorylation in mounting optimal LPS-inducible inflammatory responses in primary mouse macrophages. LPS promotes phosphorylation at both tyrosine residues, with Y749 phosphorylation being required for maintenance of total TLR4 protein levels and Y672 phosphorylation exerting its pro-inflammatory effects more selectively by initiating ERK1/2 and c-FOS phosphorylation. Our data also support a role for the TLR4-interacting membrane proteins SCIMP and the SYK kinase axis in mediating TLR4 Y672 phosphorylation to permit downstream inflammatory responses in murine macrophages. The corresponding residue in human TLR4 (Y674) is also required for optimal LPS signaling responses. Our study, thus, reveals how a single PTM on one of the most widely studied innate immune receptors orchestrates downstream inflammatory responses.

Towards European automatic bioaerosol monitoring: Comparison of 9 automatic pollen observational instruments with classic Hirst-type traps.

To benefit allergy patients and the medical practitioners, pollen information should be available in both a reliable and timely manner; the latter is only recently possible due to automatic monitoring. To evaluate the performance of all currently available automatic instruments, an international intercomparison campaign was jointly organised by the EUMETNET AutoPollen Programme and the ADOPT COST Action in Munich, Germany (March-July 2021). The automatic systems (hardware plus identification algorithms) were compared with manual Hirst-type traps. Measurements were aggregated into 3-hourly or daily values to allow comparison across all devices. We report results for total pollen as well as for Betula, Fraxinus, Poaceae, and Quercus, for all instruments that provided these data. The results for daily averages compared better with Hirst observations than the 3-hourly values. For total pollen, there was a considerable spread among systems, with some reaching R2 > 0.6 (3 h) and R2 > 0.75 (daily) compared with Hirst-type traps, whilst other systems were not suitable to sample total pollen efficiently (R2 < 0.3). For individual pollen types, results similar to the Hirst were frequently shown by a small group of systems. For Betula, almost all systems performed well (R2 > 0.75 for 9 systems for 3-hourly data). Results for Fraxinus and Quercus were not as good for most systems, while for Poaceae (with some exceptions), the performance was weakest. For all pollen types and for most measurement systems, false positive classifications were observed outside of the main pollen season. Different algorithms applied to the same device also showed different results, highlighting the importance of this aspect of the measurement system. Overall, given the 30 % error on daily concentrations that is currently accepted for Hirst-type traps, several automatic systems are currently capable of being used operationally to provide real-time observations at high temporal resolutions. They provide distinct advantages compared to the manual Hirst-type measurements.

ERK1/2 in immune signalling.

Extracellular signal-related kinases 1 and 2 (ERK1/2) are the final components of the mitogen-activated protein kinase (MAPK) phosphorylation cascade, an integral module in a diverse array of signalling pathways for shaping cell behaviour and fate. More recently, studies have shown that ERK1/2 plays an essential role downstream of immune receptors to elicit inflammatory gene expression in response to infection and cell or tissue damage. Much of this work has studied ERK1/2 activation in Toll-like receptor (TLR) pathways, providing mechanistic insights into its recruitment, compartmentalisation and activation in cells of the innate immune system. In this review, we summarise the typical activation of ERK1/2 in growth factor receptor pathways before discussing its known roles in immune cell signalling with a focus downstream of TLRs. We examine emerging research uncovering evidence of dysfunctional ERK1/2 signalling in inflammatory diseases and discuss the potential therapeutic benefit of targeting ERK1/2 pathways in inflammation.

A globally relevant change taxonomy and evidence-based change framework for land monitoring.

A globally relevant and standardized taxonomy and framework for consistently describing land cover change based on evidence is presented, which makes use of structured land cover taxonomies and is underpinned by the Driver-Pressure-State-Impact-Response (DPSIR) framework. The Global Change Taxonomy currently lists 246 classes based on the notation 'impact (pressure)', with this encompassing the consequence of observed change and associated reason(s), and uses scale-independent terms that factor in time. Evidence for different impacts is gathered through temporal comparison (e.g., days, decades apart) of land cover classes constructed and described from Environmental Descriptors (EDs; state indicators) with pre-defined measurement units (e.g., m, %) or categories (e.g., species type). Evidence for pressures, whether abiotic, biotic or human-influenced, is similarly accumulated, but EDs often differ from those used to determine impacts. Each impact and pressure term is defined separately, allowing flexible combination into 'impact (pressure)' categories, and all are listed in an openly accessible glossary to ensure consistent use and common understanding. The taxonomy and framework are globally relevant and can reference EDs quantified on the ground, retrieved/classified remotely (from ground-based, airborne or spaceborne sensors) or predicted through modelling. By providing capacity to more consistently describe change processes-including land degradation, desertification and ecosystem restoration-the overall framework addresses a wide and diverse range of local to international needs including those relevant to policy, socioeconomics and land management. Actions in response to impacts and pressures and monitoring towards targets are also supported to assist future planning, including impact mitigation actions.

The lunar nodal cycle controls mangrove canopy cover on the Australian continent.

Long-phase (interannual) tidal cycles have been shown to influence coastal flooding and sedimentation, but their role in shaping the extent and condition of tidal wetlands has received little attention. Here, we show that the 18.61-year lunar nodal cycle, popularly termed the "lunar wobble," is a dominant control over the expansion and contraction of mangrove canopy cover over much of the Australian continent. Furthermore, the contrasting phasing of the 18.61-year lunar nodal cycle between diurnal and semidiurnal tidal settings has mediated the severity of drought impacts in northern bioregions. Long-phase tidal cycles regulate maximum tide heights, are an important control over mangrove canopy cover, and may influence mangrove ecosystem services including forest productivity and carbon sequestration at regional scales.

Trajectories of adolescent life satisfaction.

Increasing global policy interest in measuring and improving population wellbeing has prompted academic investigations into the dynamics of lifespan life satisfaction. Yet little research has assessed the complete adolescent age range, although it harbours developmental changes that could affect wellbeing far into adulthood. This study investigates how life satisfaction develops throughout the whole of adolescence, and compares this development to that in adulthood, by applying exploratory and confirmatory latent growth curve modelling to UK and German data, respectively (37 076 participants, 10-24 years). We find a near universal decrease in life satisfaction during adolescence. This decrease is steeper than at any other point across adulthood. Further, our findings suggest that adolescent girls' life satisfaction is lower than boys', but that this difference does not extend into adulthood. The study highlights the importance of studying adolescent subjective wellbeing trajectories to inform research, policy and practice.

High-resolution mapping of losses and gains of Earth's tidal wetlands.

Tidal wetlands are expected to respond dynamically to global environmental change, but the extent to which wetland losses have been offset by gains remains poorly understood. We developed a global analysis of satellite data to simultaneously monitor change in three highly interconnected intertidal ecosystem types-tidal flats, tidal marshes, and mangroves-from 1999 to 2019. Globally, 13,700 square kilometers of tidal wetlands have been lost, but these have been substantially offset by gains of 9700 km2, leading to a net change of -4000 km2 over two decades. We found that 27% of these losses and gains were associated with direct human activities such as conversion to agriculture and restoration of lost wetlands. All other changes were attributed to indirect drivers, including the effects of coastal processes and climate change.

The transmembrane adapter SCIMP recruits tyrosine kinase Syk to phosphorylate Toll-like receptors to mediate selective inflammatory outputs.

Innate immune signaling by Toll-like receptors (TLRs) involves receptor phosphorylation, which helps to shape and drive key inflammatory outputs, yet our understanding of the kinases and mechanisms that mediate TLR phosphorylation is incomplete. Spleen tyrosine kinase (Syk) is a nonreceptor protein tyrosine kinase, which is known to relay adaptive and innate immune signaling, including from TLRs. However, TLRs do not contain the conserved dual immunoreceptor tyrosine-based activation motifs that typically recruit Syk to many other receptors. One possibility is that the Syk-TLR association is indirect, relying on an intermediary scaffolding protein. We previously identified a role for the palmitoylated transmembrane adapter protein SCIMP in scaffolding the Src tyrosine kinase Lyn, for TLR phosphorylation, but the role of SCIMP in mediating the interaction between Syk and TLRs has not yet been investigated. Here, we show that SCIMP recruits Syk in response to lipopolysaccharide-mediated TLR4 activation. We also show that Syk contributes to the phosphorylation of SCIMP and TLR4 to enhance their binding. Further evidence pinpoints two specific phosphorylation sites in SCIMP critical for its interaction with Syk-SH2 domains in the absence of immunoreceptor tyrosine-based activation motifs. Finally, using inhibitors and primary macrophages from SCIMP-/- mice, we confirm a functional role for SCIMP-mediated Syk interaction in modulating TLR4 phosphorylation, signaling, and cytokine outputs. In conclusion, we identify SCIMP as a novel, immune-specific Syk scaffold, which can contribute to inflammation through selective TLR-driven inflammatory responses.

Editorial.

In this brief article, the new editor-in-chief of the Journal of Personality and Social Psychology (JPSP): Personality Processes and Individual Differences (PPID) states that he looks forward to building on the success of his predecessor in the next 6 years. His editorial team has three primary goals: To continue to improve transparency and openness of the research published; to further diversify the journal (including diversity in authors of the papers published, the editors and reviewers who evaluate that work, the samples of participants who take part in these studies, and the methods used); and to attract and publish solid scientific studies that make important new contributions to the understanding of PPID. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Happiness Singled Out: Bidirectional Associations Between Singlehood and Life Satisfaction.

Despite constituting a large portion of society, single people-and their satisfaction with singlehood and life-are rarely examined in their own right. How happy are single people and does their happiness change over time? In 3,439 people followed over 10 years, we found that people reported being more satisfied than not, but both singlehood satisfaction and life satisfaction declined over time. Older adults, men, and highly educated people, and people with worse health reported lower singlehood satisfaction. Constrained random-intercept cross-lagged panel models suggested that singlehood and life satisfaction had lagged bidirectional influences with each other. Results are discussed in the context of the origins of singlehood satisfaction and life satisfaction.

Loved and lost or never loved at all? Lifelong marital histories and their links with subjective well-being.

Marriage has been linked to higher well-being. However, previous research has generally examined marital status at one point in time or over a relatively short window of time. In order to determine if different marital histories have unique impacts on well-being in later life, we conducted a marital sequence analysis of 7,532 participants from the Panel Study of Income Dynamics (54.2% women; M age = 66.68, SD = 8.50; 68.7% White/Caucasian). Three different marital sequence types emerged: a "consistently-married" group (79%), a "consistently-single" group (8%), and a "varied histories" group (13%), in which individuals had moved in and out of various relationships throughout life. The consistently-married group was slightly higher in well-being at the end of life than the consistently-single and varied histories groups; the latter two groups did not differ in their well-being. The results are discussed in the context of why marriage is linked to well-being across the lifespan.

SCIMP is a spatiotemporal transmembrane scaffold for Erk1/2 to direct pro-inflammatory signaling in TLR-activated macrophages.

Immune cells are armed with Toll-like receptors (TLRs) for sensing and responding to pathogens and other danger cues. The role of extracellular-signal-regulated kinases 1/2 (Erk1/2) in TLR signaling remains enigmatic, with both pro- and anti-inflammatory functions described. We reveal here that the immune-specific transmembrane adaptor SCIMP is a direct scaffold for Erk1/2 in TLR pathways, with high-resolution, live-cell imaging revealing that SCIMP guides the spatial and temporal recruitment of Erk2 to membrane ruffles and macropinosomes for pro-inflammatory TLR4 signaling. SCIMP-deficient mice display defects in Erk1/2 recruitment to TLR4, c-Fos activation, and pro-inflammatory cytokine production, with these effects being phenocopied by Erk1/2 signaling inhibition. Our findings thus delineate a selective role for SCIMP as a key scaffold for the membrane recruitment of Erk1/2 kinase to initiate TLR-mediated pro-inflammatory responses in macrophages.

Detecting Endogenous Rab8 Activation.

The family of Rab GTPases switch between GDP- and GTP-bound forms to interact with effectors and accessory proteins for the regulation of trafficking and signaling pathways in cells. The activation and recruitment of a specific Rab by stimulants or physiological changes can be detected and assessed by measuring the relative amount of the Rab in its active, "GTP-bound" state versus the inactive "GDP-bound" state. While GTP loading can be measured in vitro, current methods to detect the activation state of endogenous Rabs within a cellular context are limited. Here, we developed two molecular probes, based on domains of known Rab effectors, which can be used to pull down endogenous GTP-bound Rab8 from cell extracts as a measure of Rab8 activation. As a test system, we use the lipopolysaccharide (LPS) induced activation of Rab8 in mouse macrophages. The molecular probes compared for capture of GTP-bound Rab8 are derived from two Rab8 effectors, OCRL and PI3Kγ, with the former assessed as being more efficient. We describe how the OCRL-RBD probe is used to assess activation of Rab8 in cell extracts with a method that should be applicable to assessing GTP-bound Rab8 in other cell and tissue extracts.

Putting the Self in Self-Correction: Findings From the Loss-of-Confidence Project.

Science is often perceived to be a self-correcting enterprise. In principle, the assessment of scientific claims is supposed to proceed in a cumulative fashion, with the reigning theories of the day progressively approximating truth more accurately over time. In practice, however, cumulative self-correction tends to proceed less efficiently than one might naively suppose. Far from evaluating new evidence dispassionately and infallibly, individual scientists often cling stubbornly to prior findings. Here we explore the dynamics of scientific self-correction at an individual rather than collective level. In 13 written statements, researchers from diverse branches of psychology share why and how they have lost confidence in one of their own published findings. We qualitatively characterize these disclosures and explore their implications. A cross-disciplinary survey suggests that such loss-of-confidence sentiments are surprisingly common among members of the broader scientific population yet rarely become part of the public record. We argue that removing barriers to self-correction at the individual level is imperative if the scientific community as a whole is to achieve the ideal of efficient self-correction.