Hidden Mechanisms of Climate Impacts in Western Forests: Integrating Theory and Observation for Climate Adaptation

Fire, insects, and disease are necessary components of forest ecosystems. Yet, climate change is intensifying these tree stressors and creating new interactions that threaten forest survival. This dissertation combined field observations with statistical predictions of changing disturbances in western forests to identify 1) how conventional models may underestimate future forest loss, and 2) how positive relationships between trees may be exploited by managers to prevent forest loss. In Chapter II, I tested whether increasingly extreme weather with climate change increases Pacific yew extinction risk. I found that conventional modeling methods underestimated local extinction risk because trees were adapted to a range in average conditions, but had limited tolerance of extreme drought. In Chapter III, I predicted whether future climate change will alter the strength of competition between species (heterospecifics) versus within species (conspecifics). I found that heterospecific competition is more sensitive to drought than conspecific competition, leading to higher tree mortality during drought than is currently expected. In Chapter IV, I looked at sugar pine tree rings to measure how pines respond to three centuries of fire exclusion, drought, fire, and a bark beetle outbreak. I found that fire suppression led to higher competitive stress, which decreased pines’ resilience to fire, and consequently, decreased pines’ survival during a subsequent bark beetle outbreak. Woody species diversity, however, was able to increase pine survival following fire and bark beetles by allowing higher pine growth and defenses. In Chapter V, I tested whether beneficial relationships between trees and mutualistic fungi could help trees survive across regional differences in climate, environmental conditions, and disturbances. I found that woody species diversity increased large-diameter tree resistance to insects and disease, but only if those species shared a mycorrhizal network. Large trees comprising 17 common western species across three canonical forest types showed this pattern –– despite residing in different topographic positions and climatological contexts. I identified how biodiversity can increase forest resistance and resilience to disturbances, but also found climate change to be weakening the processes responsible for maintaining biodiversity. Managers must take a more active approach to cultivating and preserving forest tree biodiversity to ensure forests are able to continue provisioning essential services, such as carbon storage, in the future. These four long-term studies of spatially explicit, cause-specific tree mortality provided useful insights into tree survival and forest change that will improve vegetation model accuracy and inform management of mature forests in western North America

Shrub Communities, Spatial Patterns, and Shrub-Mediated Tree Mortality following Reintroduced Fire in Yosemite National Park, California, USA

Shrubs contribute to the forest fuel load; their distribution is important to tree mortality and regeneration, and vertebrate occupancy. We used a method new to fire ecology—extensive continuous mapping of trees and shrub patches within a single large (25.6 ha) study site—to identify changes in shrub area, biomass, and spatial pattern due to fire reintroduction by a backfire following a century of fire exclusion in lower montane forests of the Sierra Nevada, California, USA. We examined whether trees in close proximity to shrubs prior to fire experienced higher mortality rates than trees in areas without shrubs. We calculated shrub biomass using demography subplots and existing allometric equations, and we developed new equations for beaked hazel (Corylus cornuta ssp. californica [A. de Candolle] E. Murray) from full dissection of 50 stems. Fire decreased shrub patch area from 15.1 % to 0.9 %, reduced live shrub biomass from 3.49 Mg ha−1 to 0.27 Mg ha−1, and consumed 4.41 Mg ha−1 of living and dead shrubs. Distinct (non-overlapping) shrub patches decreased from 47 ha−1 to 6 ha−1. The mean distance between shrub patches increased 135 %. Distances between montane chaparral patches increased 285 %, compared to a 54 % increase in distances between riparian shrub patches and an increase of 267 % between generalist shrub patches. Fire-related tree mortality within shrub patches was marginally lower (67.6 % versus 71.8 %), showing a contrasting effect of shrubs on tree mortality between this forest ecosystem and chaparral-dominated ecosystems in which most trees are killed by fire

Large-Diameter Trees Dominate Snag and Surface Biomass Following Reintroduced Fire

The reintroduction of fire to landscapes where it was once common is considered a priority to restore historical forest dynamics, including reducing tree density and decreasing levels of woody biomass on the forest floor. However, reintroducing fire causes tree mortality that can have unintended ecological outcomes related to woody biomass, with potential impacts to fuel accumulation, carbon sequestration, subsequent fire severity, and forest management. In this study, we examine the interplay between fire and carbon dynamics by asking how reintroduced fire impacts fuel accumulation, carbon sequestration, and subsequent fire severity potential. Beginning pre-fire, and continuing 6 years post-fire, we tracked all live, dead, and fallen trees ≥ 1 cm in diameter and mapped all pieces of deadwood (downed woody debris) originating from tree boles ≥ 10 cm diameter and ≥ 1 m in length in 25.6 ha of an Abies concolor/Pinus lambertiana forest in the central Sierra Nevada, California, USA. We also tracked surface fuels along 2240 m of planar transects pre-fire, immediately post-fire, and 6 years post-fire. Six years after moderate-severity fire, deadwood ≥ 10 cm diameter was 73 Mg ha−1, comprised of 32 Mg ha−1 that persisted through fire and 41 Mg ha−1 of newly fallen wood (compared to 72 Mg ha−1 pre-fire). Woody surface fuel loading was spatially heterogeneous, with mass varying almost four orders of magnitude at the scale of 20 m × 20 m quadrats (minimum, 0.1 Mg ha−1; mean, 73 Mg ha−1; maximum, 497 Mg ha−1). Wood from large-diameter trees (≥ 60 cm diameter) comprised 57% of surface fuel in 2019, but was 75% of snag biomass, indicating high contributions to current and future fuel loading. Reintroduction of fire does not consume all large-diameter fuel and generates high levels of surface fuels ≥ 10 cm diameter within 6 years. Repeated fires are needed to reduce surface fuel loading

Src Kinases Are Required for a Balanced Production of IL-12/IL-23 in Human Dendritic Cells Activated by Toll-Like Receptor Agonists

BACKGROUND: Pathogen recognition by dendritic cells (DC) is crucial for the initiation of both innate and adaptive immune responses. Activation of Toll-like Receptors (TLRs) by microbial molecular patterns leads to the maturation of DC, which present the antigen and activate T cells in secondary lymphoid tissues. Cytokine production by DC is critical for shaping the adaptive immune response by regulating T helper cell differentiation. It was previously shown by our group that Src kinases play a key role in cytokines production during TLR4 activation in human DC. PRINCIPAL FINDINGS: In this work we investigated the role of Src kinases during different TLRs triggering in human monocyte-derived DC (MoDC). We found that Src family kinases are important for a balanced production of inflammatory cytokines by human MoDC upon stimulation of TLR3 and 8 with their respective agonists. Disruption of this equilibrium through pharmacological inhibition of Src kinases alters the DC maturation pattern. In particular, while expression of IL-12 and other inflammatory cytokines depend on Src kinases, the induction of IL-23 and co-stimulatory molecules do not. Accordingly, DC treated with Src inhibitors are not compromised in their ability to induce CD4 T cell proliferation and to promote the Th17 subset survival but are less efficient in inducing Th1 differentiation. CONCLUSIONS: We suggest that the pharmacological modulation of DC maturation has the potential to shape the quality of the adaptive immune response and could be exploited for the treatment of inflammation-related diseases

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Mutations in Protein-Binding Hot-Spots on the Hub Protein Smad3 Differentially Affect Its Protein Interactions and Smad3-Regulated Gene Expression

Hub proteins are connected through binding interactions to many other proteins. Smad3, a mediator of signal transduction induced by transforming growth factor beta (TGF-β), serves as a hub protein for over 50 protein-protein interactions. Different cellular responses mediated by Smad3 are the product of cell-type and context dependent Smad3-nucleated protein complexes acting in concert. Our hypothesis is that perturbation of this spectrum of protein complexes by mutation of single protein-binding hot-spots on Smad3 will have distinct consequences on Smad3-mediated responses.We mutated 28 amino acids on the surface of the Smad3 MH2 domain and identified 22 Smad3 variants with reduced binding to subsets of 17 Smad3-binding proteins including Smad4, SARA, Ski, Smurf2 and SIP1. Mutations defective in binding to Smad4, e.g., D408H, or defective in nucleocytoplasmic shuttling, e.g., W406A, were compromised in modulating the expression levels of a Smad3-dependent reporter gene or six endogenous Smad3-responsive genes: Mmp9, IL11, Tnfaip6, Fermt1, Olfm2 and Wnt11. However, the Smad3 mutants Y226A, Y297A, W326A, K341A, and E267A had distinct differences on TGF-β signaling. For example, K341A and Y226A both reduced the Smad3-mediated activation of the reporter gene by ∼50% but K341A only reduced the TGF-β inducibilty of Olfm2 in contrast to Y226A which reduced the TGF-β inducibility of all six endogenous genes as severely as the W406A mutation. E267A had increased protein binding but reduced TGF-β inducibility because it caused higher basal levels of expression. Y297A had increased TGF-β inducibility because it caused lower Smad3-induced basal levels of gene expression.Mutations in protein binding hot-spots on Smad3 reduced the binding to different subsets of interacting proteins and caused a range of quantitative changes in the expression of genes induced by Smad3. This approach should be useful for unraveling which Smad3 protein complexes are critical for specific biological responses

Genetically predicted cortisol levels and risk of venous thromboembolism

Introduction - In observational studies, venous thromboembolism (VTE) has been associated with Cushing’s syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization. Methods - Three genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed. Results - Genetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62–0.87, p Conclusions - This study provides evidence that genetically predicted plasma cortisol levels in the high end of the normal range are associated with a decreased risk of VTE and that this association may be mediated by blood pressure. This study has implications for the planning of observational studies of cortisol and VTE, suggesting that blood pressure traits should be measured and accounted for

The influences of nursing transformational leadership style on the quality of nurses’ working lives in Taiwan: a cross-sectional quantitative study

- Background: Taiwan’s NHI system is one of the most successful health care models for countries around the globe. However, little research has demonstrated the mental health issues associated with nursing transformational leadership style under the NHI system, especially in the quality of nurses’ working lives in Taiwan. It is important to know the relationship between transformational leadership style and the mental health of nurses, organisational commitment and job satisfaction. The research aimed to understand the influences of nursing transformational leadership style on the quality of nurses’ working lives in Taiwan. The research hypothesis was that transformational leadership styles would have positive influence on the quality of nurses’ working lives. - Methods: This was a cross-sectional quantitative study. Nurses from each type of hospital ownership (private, public and religious) were recruited. Participation was voluntary and signed informed consent was obtained. The inclusion criteria were nurses with at least one year’s work experience in the hospitals. Self-administrated questionnaires were used. A total of 807 participants were contacted and 651 questionnaires were fully completed (response rate 80.7 %). A theory driven model was used to test the research hypotheses using structural equation modelling performed with AMOS 16.0. - Results: Transformational leadership contributes significantly to supervisor support. Workplace support, particularly from the supervisor, is an important mediator variable that explains the relationship between transformational leadership and job satisfaction. Organisational commitment was the strongest factor relevant to the general health well-being in Taiwanese nurses than job satisfaction. The hypothesized positive relationships between transformational leadership and all variables were supported by the data. - Conclusions: Our findings have important consequences for organisational health. Our model demonstrates a complete picture of the work relationships on the quality of nurses’ working lives. The results provided information about the subordinates’ perceptions of transformational nursing leadership styles and mental health outcomes in different hospital settings, as well as identified organisational factors that could improve the quality of nurses’ working lives

Performance of the ALICE experiment at the CERN LHC

ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables