ABSTRACT
Bipedal locomotion is one of the key adaptations that define the hominin clade. Evidence of bipedalism is known from postcranial remains of late Miocene hominins as early as 6 million years ago (Ma) in eastern Africa1-4. Bipedality of Sahelanthropus tchadensis was hitherto inferred about 7 Ma in central Africa (Chad) based on cranial evidence5-7. Here we present postcranial evidence of the locomotor behaviour of S. tchadensis, with new insights into bipedalism at the early stage of hominin evolutionary history. The original material was discovered at locality TM 266 of the Toros-Ménalla fossiliferous area and consists of one left femur and two, right and left, ulnae. The morphology of the femur is most parsimonious with habitual bipedality, and the ulnae preserve evidence of substantial arboreal behaviour. Taken together, these findings suggest that hominins were already bipeds at around 7 Ma but also suggest that arboreal clambering was probably a significant part of their locomotor repertoire.
Subject(s)
Biological Evolution , Gait , Hominidae , Skull , Animals , Chad , Fossils , Hominidae/anatomy & histology , Hominidae/physiology , Skull/anatomy & histology , TreesABSTRACT
Improved understanding of the shared genetic architecture between psychiatric disorders and brain white matter may provide mechanistic insights for observed phenotypic associations. Our objective is to characterize the shared genetic architecture of bipolar disorder (BD), major depression (MD), and schizophrenia (SZ) with white matter fractional anisotropy (FA) and identify shared genetic loci to uncover biological underpinnings. We used genome-wide association study (GWAS) summary statistics for BD (n = 413,466), MD (n = 420,359), SZ (n = 320,404), and white matter FA (n = 33,292) to uncover the genetic architecture (i.e., polygenicity and discoverability) of each phenotype and their genetic overlap (i.e., genetic correlations, overlapping trait-influencing variants, and shared loci). This revealed that BD, MD, and SZ are at least 7-times more polygenic and less genetically discoverable than average FA. Even in the presence of weak genetic correlations (range = -0.05 to -0.09), average FA shared an estimated 42.5%, 43.0%, and 90.7% of trait-influencing variants as well as 12, 4, and 28 shared loci with BD, MD, and SZ, respectively. Shared variants were mapped to genes and tested for enrichment among gene-sets which implicated neurodevelopmental expression, neural cell types, myelin, and cell adhesion molecules. For BD and SZ, case vs control tract-level differences in FA associated with genetic correlations between those same tracts and the respective disorder (rBD = 0.83, p = 4.99e-7 and rSZ = 0.65, p = 5.79e-4). Genetic overlap at the tract-level was consistent with average FA results. Overall, these findings suggest a genetic basis for the involvement of brain white matter aberrations in the pathophysiology of psychiatric disorders.
Subject(s)
Bipolar Disorder , Depressive Disorder, Major , White Matter , Humans , Genome-Wide Association Study , Diffusion Tensor Imaging/methods , Bipolar Disorder/genetics , Depressive Disorder, Major/geneticsABSTRACT
Psychiatric disorders and common epilepsies are heritable disorders with a high comorbidity and overlapping symptoms. However, the causative mechanisms underlying this relationship are poorly understood. Here we aimed to identify overlapping genetic loci between epilepsy and psychiatric disorders to gain a better understanding of their comorbidity and shared clinical features. We analysed genome-wide association study data for all epilepsies (n = 44 889), genetic generalized epilepsy (n = 33 446), focal epilepsy (n = 39 348), schizophrenia (n = 77 096), bipolar disorder (n = 406 405), depression (n = 500 199), attention deficit hyperactivity disorder (n = 53 293) and autism spectrum disorder (n = 46 350). First, we applied the MiXeR tool to estimate the total number of causal variants influencing the disorders. Next, we used the conjunctional false discovery rate statistical framework to improve power to discover shared genomic loci. Additionally, we assessed the validity of the findings in independent cohorts, and functionally characterized the identified loci. The epilepsy phenotypes were considerably less polygenic (1.0 K to 3.4 K causal variants) than the psychiatric disorders (5.6 K to 13.9 K causal variants), with focal epilepsy being the least polygenic (1.0 K variants), and depression having the highest polygenicity (13.9 K variants). We observed cross-trait genetic enrichment between genetic generalized epilepsy and all psychiatric disorders and between all epilepsies and schizophrenia and depression. Using conjunctional false discovery rate analysis, we identified 40 distinct loci jointly associated with epilepsies and psychiatric disorders at conjunctional false discovery rate <0.05, four of which were associated with all epilepsies and 39 with genetic generalized epilepsy. Most epilepsy risk loci were shared with schizophrenia (n = 31). Among the identified loci, 32 were novel for genetic generalized epilepsy, and two were novel for all epilepsies. There was a mixture of concordant and discordant allelic effects in the shared loci. The sign concordance of the identified variants was highly consistent between the discovery and independent datasets for all disorders, supporting the validity of the findings. Gene-set analysis for the shared loci between schizophrenia and genetic generalized epilepsy implicated biological processes related to cell cycle regulation, protein phosphatase activity, and membrane and vesicle function; the gene-set analyses for the other loci were underpowered. The extensive genetic overlap with mixed effect directions between psychiatric disorders and common epilepsies demonstrates a complex genetic relationship between these disorders, in line with their bi-directional relationship, and indicates that overlapping genetic risk may contribute to shared pathophysiological and clinical features between epilepsy and psychiatric disorders.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Epilepsies, Partial , Epilepsy, Generalized , Humans , Autism Spectrum Disorder/genetics , Genome-Wide Association Study , Epilepsies, Partial/genetics , Genomics , Epilepsy, Generalized/genetics , Genetic Loci/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/geneticsABSTRACT
Two fruit fly (Diptera: Tephritidae) species of economic importance: Ceratitis rosa Karsch and Ceratitis quilicii De Meyer, Mwatawala & Virgilio are present in South Africa. The two species were considered as one species prior to 2016, but were subsequently separated. In this study, the distribution and abundance of the two species were quantified in seven provinces in South Africa through trapping with Enriched Ginger Oil as an attractant. Trapping was conducted over three seasons across two years (2020 and 2021): late summer, autumn-winter, and spring-early summer. Host ranges of the two species were investigated by fruit sampling in and outside of trapping sites. Ceratitis quilicii was more widely distributed than C. rosa with the latter being recorded in only three north-eastern provinces. There were geographical limits for both species with no records of them in Northern Cape Province. Catches of C. quilicii were higher in summer with average temperatures varying from 15 to 27°C while for C. rosa, catches remained low and consistent between seasons. Ceratitis quilicii catches decreased at lower rates than those of C. rosa at temperatures below 15°C. The two species were reared from 13 plant species from nine families. Four of these hosts were infested by both C. quilicii and C. rosa in the same province where they occurred. Preferred hosts of the two species belonged to the Myrtaceae family. The characterisation of the distribution, abundance and host ranges of these pests will provide a baseline for pest status determination and implementation of management actions.
ABSTRACT
BACKGROUND: Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of regulated cell death (including apoptosis and necroptosis) and inflammation, both drivers of COPD pathogenesis. We aimed to define the contribution of RIPK1 kinase-dependent cell death and inflammation in the pathogenesis of COPD. METHODS: We assessed RIPK1 expression in single-cell RNA sequencing (RNA-seq) data from human and mouse lungs, and validated RIPK1 levels in lung tissue of COPD patients via immunohistochemistry. Next, we assessed the consequences of genetic and pharmacological inhibition of RIPK1 kinase activity in experimental COPD, using Ripk1 S25D/S25D kinase-deficient mice and the RIPK1 kinase inhibitor GSK'547. RESULTS: RIPK1 expression increased in alveolar type 1 (AT1), AT2, ciliated and neuroendocrine cells in human COPD. RIPK1 protein levels were significantly increased in airway epithelium of COPD patients compared with never-smokers and smokers without airflow limitation. In mice, exposure to cigarette smoke (CS) increased Ripk1 expression similarly in AT2 cells, and further in alveolar macrophages and T-cells. Genetic and/or pharmacological inhibition of RIPK1 kinase activity significantly attenuated airway inflammation upon acute and subacute CS exposure, as well as airway remodelling, emphysema, and apoptotic and necroptotic cell death upon chronic CS exposure. Similarly, pharmacological RIPK1 kinase inhibition significantly attenuated elastase-induced emphysema and lung function decline. Finally, RNA-seq on lung tissue of CS-exposed mice revealed downregulation of cell death and inflammatory pathways upon pharmacological RIPK1 kinase inhibition. CONCLUSIONS: RIPK1 kinase inhibition is protective in experimental models of COPD and may represent a novel promising therapeutic approach.
Subject(s)
Emphysema , Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Humans , Mice , Animals , Lung , Cell Death , Inflammation/metabolism , Mice, Inbred C57BL , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/metabolismABSTRACT
If trees minimize self-shading, new foliage in shaded parts of the crown should remain minimal. However, many species have abundant foliage on short shoots inside their crown. In this paper, we test the hypothesis that short shoots allow trees to densify their foliage in self-shaded parts of the crown thanks to reduced costs. Using 30 woody species in Mediterranean and tropical biomes, we estimated the contribution of short shoots to total plant foliage, calculated their costs relative to long shoots including wood cost and used 3D plant simulations calibrated with field measurements to quantify their light interception, self-shading and yield. In species with short shoots, leaves on short shoots account for the majority of leaf area. The reduced cost of short stems enables the production of leaf area with 36% less biomass. Simulations show that although short shoots are more self-shaded, they benefit the plant because they cost less. Lastly, the morphological properties of short shoots have major implications for whole plant architecture. Taken together, our results question the validity of only assessing leaf costs to understand leaf economics and call for more integrated observations at the crown scale to understand light capture strategies in woody plants.
Subject(s)
Ecosystem , Wood , Plant Shoots/anatomy & histology , Cost-Benefit Analysis , Biomass , Trees/anatomy & histology , Plant Leaves/anatomy & histologyABSTRACT
BACKGROUND: Isolate features of the coronary anatomy have been associated with the pathophysiology of atherosclerotic disease. Computational methods have been described to allow precise quantification of the complex three-dimensional (3D) coronary geometry. The present study tested whether quantitative parameters that describe the spatial 3D coronary geometry is associated with the extension and composition of the underlying coronary artery disease (CAD). METHODS: Patients with CAD scheduled for percutaneous intervention were investigated with coronary computed tomography angiography (CCTA), and invasive coronary angiography, and virtual histology intravascular ultrasound (IVUS-VH). For all target vessels, 3D centerlines were extracted from CCTA images and processed to quantify 23 geometric indexes, grouped into 3 main categories as follows: (i) length-based; (ii) curvature-based, torsion-based, and curvature/torsion-combined; (iii) vessel path-based. The geometric variables were compared with IVUS-VH parameters assessing the extent and composition of coronary atherosclerosis. RESULTS: A total of 36 coronary patients (99 vessels) comprised the study population. From the 23 geometric indexes, 18 parameters were significantly (p < 0.05) associated with at least 1 IVUS-VH parameter at a univariate analysis. All three main geometric categories provided parameters significantly related with atherosclerosis variables. The 3D geometric indexes were associated with the degree of atherosclerotic extension, as well as with plaque composition. Geometric features remained significantly associated with all IVUS-VH parameters even after multivariate adjustment for clinical characteristics. CONCLUSIONS: Quantitative 3D vessel morphology emerges as a relevant factor associated with atherosclerosis in patients with established CAD.
Subject(s)
Atherosclerosis , Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Ultrasonography, Interventional/methods , Treatment Outcome , Coronary Artery Disease/pathology , Coronary Angiography/methods , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Predictive Value of TestsABSTRACT
Recent assessment reports by the Intergovernmental Panel on Climate Change (IPCC) and the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) have highlighted the risks to humanity arising from the unsustainable use of natural resources. Thus far, land, freshwater, and ocean exploitation have been the chief causes of biodiversity loss. Climate change is projected to be a rapidly increasing additional driver for biodiversity loss. Since climate change and biodiversity loss impact human societies everywhere, bold solutions are required that integrate environmental and societal objectives. As yet, most existing international biodiversity targets have overlooked climate change impacts. At the same time, climate change mitigation measures themselves may harm biodiversity directly. The Convention on Biological Diversity's post-2020 framework offers the important opportunity to address the interactions between climate change and biodiversity and revise biodiversity targets accordingly by better aligning these with the United Nations Framework Convention on Climate Change Paris Agreement and the Sustainable Development Goals. We identify the considerable number of existing and proposed post-2020 biodiversity targets that risk being severely compromised due to climate change, even if other barriers to their achievement were removed. Our analysis suggests that the next set of biodiversity targets explicitly addresses climate change-related risks since many aspirational goals will not be feasible under even lower-end projections of future warming. Adopting more flexible and dynamic approaches to conservation, rather than static goals, would allow us to respond flexibly to changes in habitats, genetic resources, species composition, and ecosystem functioning and leverage biodiversity's capacity to contribute to climate change mitigation and adaptation.
Subject(s)
Biodiversity , Climate Change , Carbon Dioxide/analysis , Conservation of Natural Resources , FeedbackABSTRACT
BACKGROUND: Candidates for transcatheter aortic valve implantation (TAVI) are currently evaluated using computed tomography angiography and invasive cardiac catheterization as an essential part of case selection and pre-procedure interventional planning. However, both imaging methods utilize iodinated agents, which may cause contrast-induced nephropathy, particularly in patients with baseline renal dysfunction. This study aimed to describe a zero-contrast imaging protocol for pre-TAVI evaluation in patients with advanced renal impairment. METHODS: The pre-TAVI zero-contrast scheme consisted of the following multi-modality combinations: (1) gadolinium-free magnetic resonance imaging (three-dimensional navigator-echo with electrocardiogram-gated steady-state free-precession series); (2) iodinated-free multislice computed tomography electrocardiogram-gated; (3) lower limb arterial duplex scan ultrasound; and (4) transesophageal echocardiography. Ultimately, TAVI was performed for those deemed good candidates, and contrast was allowed during the intervention; however, operators were strongly advised to utilize the least volume possible of iodinated agents. This pilot survey included ten patients with symptomatic aortic stenosis and renal dysfunction who underwent zero-contrast multi-modality imaging. RESULTS: All the patients ultimately underwent TAVI. The intervention was successful in all cases, without ≥ moderate residual aortic regurgitation, prosthesis embolization, annulus rupture, major vascular complications, stroke, or death during index hospitalization. The creatinine clearance remained stable throughout the observation period (baseline: 26.85 ± 12.55 mL/min; after multi-modality imaging: 26.76 ± 11.51 mL/min; post-TAVI at discharge: 29.84 ± 13.98 mL/min; p = 0.3 all). CONCLUSION: The proposed contrast-free imaging protocol appears to be a promising clinical tool for pre-TAVI evaluation in patients with severe renal dysfunction.
Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Heart Valve Prosthesis Implantation/methods , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Multidetector Computed Tomography , Cardiac Catheterization/methodsABSTRACT
Aloidendron dichotomum appears to be undergoing the early stages of a range shift in response to anthropogenic climate change in south-western Africa. High mortality has been recorded in warmer populations, while population expansions have been recorded in cooler poleward parts of its range. This study aimed to determine the key environmental controls on A. dichotomum photosynthesis in areas of population expansion, to inform the potential attribution of directional population expansion to anthropogenic warming. Nocturnal acid accumulation and CO2 assimilation were measured in individuals growing under a range of temperature and watering treatments in a greenhouse experiment. In addition, nocturnal acid accumulation and phosphoenolpyruvate carboxylase activity were quantified in two wild populations at the most southerly and south-easterly range extents. Multiple lines of evidence confirmed that A. dichotomum performs Crassulacean acid metabolism. Total nocturnal acid accumulation was highest at night-time temperatures of ~21.5 °C, regardless of soil water availability, and night-time CO2 assimilation rates increased with leaf temperature, suggesting a causal link to the cool southern range limit. Leaf acidity at the start of the dark period was highly predictive of nocturnal acid accumulation in all individuals, implicating light availability during the day as an important determinant of nocturnal acid accumulation.
Subject(s)
Trees , South AfricaABSTRACT
The two most urgent and interlinked environmental challenges humanity faces are climate change and biodiversity loss. We are entering a pivotal decade for both the international biodiversity and climate change agendas with the sharpening of ambitious strategies and targets by the Convention on Biological Diversity and the United Nations Framework Convention on Climate Change. Within their respective Conventions, the biodiversity and climate interlinked challenges have largely been addressed separately. There is evidence that conservation actions that halt, slow or reverse biodiversity loss can simultaneously slow anthropogenic mediated climate change significantly. This review highlights conservation actions which have the largest potential for mitigation of climate change. We note that conservation actions have mainly synergistic benefits and few antagonistic trade-offs with climate change mitigation. Specifically, we identify direct co-benefits in 14 out of the 21 action targets of the draft post-2020 global biodiversity framework of the Convention on Biological Diversity, notwithstanding the many indirect links that can also support both biodiversity conservation and climate change mitigation. These relationships are context and scale-dependent; therefore, we showcase examples of local biodiversity conservation actions that can be incentivized, guided and prioritized by global objectives and targets. The close interlinkages between biodiversity, climate change mitigation, other nature's contributions to people and good quality of life are seldom as integrated as they should be in management and policy. This review aims to re-emphasize the vital relationships between biodiversity conservation actions and climate change mitigation in a timely manner, in support to major Conferences of Parties that are about to negotiate strategic frameworks and international goals for the decades to come.
Subject(s)
Conservation of Natural Resources , Quality of Life , Biodiversity , Climate Change , Ecosystem , HumansABSTRACT
Africa's protected areas (PAs) are the last stronghold of the continent's unique biodiversity, but they appear increasingly threatened by climate change, substantial human population growth, and land-use change. Conservation planning is challenged by uncertainty about how strongly and where these drivers will interact over the next few decades. We investigated the combined future impacts of climate-driven vegetation changes inside African PAs and human population densities and land use in their surroundings for 2 scenarios until the end of the 21st century. We used the following 2 combinations of the shared socioeconomic pathways (SSPs) and representative greenhouse gas concentration pathways (RCPs): the "middle-of-the-road" scenario SSP2-RCP4.5 and the resource-intensive "fossil-fueled development" scenario SSP5-RCP8.5. Climate change impacts on tree cover and biome type (i.e., desert, grassland, savanna, and forest) were simulated with the adaptive dynamic global vegetation model (aDGVM). Under both scenarios, most PAs were adversely affected by at least 1 of the drivers, but the co-occurrence of drivers was largely region and scenario specific. The aDGVM projections suggest considerable climate-driven tree cover increases in PAs in today's grasslands and savannas. For PAs in West Africa, the analyses revealed climate-driven vegetation changes combined with hotspots of high future population and land-use pressure. Except for many PAs in North Africa, future decreases in population and land-use pressures were rare. At the continental scale, SSP5-RCP8.5 led to higher climate-driven changes in tree cover and higher land-use pressure, whereas SSP2-RCP4.5 was characterized by higher future population pressure. Both SSP-RCP scenarios implied increasing challenges for conserving Africa's biodiversity in PAs. Our findings underline the importance of developing and implementing region-specific conservation responses. Strong mitigation of future climate change and equitable development scenarios would reduce ecosystem impacts and sustain the effectiveness of conservation in Africa.
Las áreas protegidas (AP) de África son el último bastión de la biodiversidad distintiva del continente, pero cada vez están más amenazadas por el cambio climático, crecimiento sustancial de la población humana y cambio de uso de suelo. La planificación de la conservación enfrenta el reto de la incertidumbre de cuan fuerte y donde interactuarán estos factores a lo largo de las siguientes décadas. Investigamos los impactos futuros combinados de los cambios en la vegetación impulsados por el clima dentro de AP africanas y las densidades de población humana y el uso de suelo en sus alrededores en 2 escenarios hasta el final del siglo 21. Utilizamos las siguientes 2 combinaciones de las trayectorias socioeconómicas compartidas (SSP) y las trayectorias representativas de concentración de gases de invernadero (RCP): el escenario de "mitad del camino" SSP2-RCP4.5 y el escenario recurso intensivo "desarrollo impulsado por combustibles fósiles" SSP5-RCP8.5. Los impactos del cambio climático sobre la cobertura de árboles y el tipo de bioma (i. e., desierto, pastizal, sabana y bosque) fueron simulados con el modelo vegetación global dinámica adaptativo (aDGVM). En ambos escenarios, la mayoría de las AP fueron afectadas adversamente por lo menos por 1 de los factores, pero la coocurrencia de los factores fue mayoritariamente específica por región y escenario. Las proyecciones de MVGDa sugieren incrementos considerables en la cobertura de árboles impulsados por el clima en las AP en pastizales y sabanas actuales. Para AP en África Occidental, los análisis revelaron cambios en la vegetación impulsados por el clima combinados con sitios clave con numerosa población y gran presión de uso de suelo en el futuro. Excepto en muchos PA de África del Norte, los decrementos en la población y presiones de uso de suelo en el futuro fueron raros. A escala continental, SSP5-RCP8.5 condujo a mayores cambios impulsados por el clima en la cobertura arbórea y en la presión de cambio de uso de suelo, mientras que SSP5-RCP8.5 se caracterizó por una mayor presión demográfica en el futuro. Ambos escenarios SSP-RCP implicaron mayores retos para la conservación de la biodiversidad en AP africanas. Nuestros hallazgos subrayan la importancia de desarrollar e implementar respuestas de conservación específicas para cada región. Medidas sólidas para la mitigación del cambio climático así como escenarios de desarrollo equitativo podrían reducir los impactos en el ecosistema y sustentar la efectividad de la conservación en África.
Subject(s)
Conservation of Natural Resources , Ecosystem , Humans , Climate Change , Biodiversity , Trees , Socioeconomic FactorsABSTRACT
Since microRNA (miR)-223-3p modulates inflammatory responses and chronic obstructive pulmonary disease (COPD) is associated with amplified pulmonary inflammation, we hypothesized that miR-223-3p plays a role in COPD pathogenesis. Expression of miR-223-3p was measured in lung tissue of two independent cohorts with patients with GOLD stage II-IV COPD, never smokers, and smokers without COPD. The functional role of miR-223-3p was studied in deficient mice and on overexpression in airway epithelial cells from COPD and controls. We observed higher miR-223-3p levels in patients with COPD stage II-IV compared with (non)-smoking controls, and levels were associated with higher neutrophil numbers in bronchial biopsies of patients with COPD. MiR-223-3p expression was also increased in lungs and bronchoalveolar lavage of cigarette smoke (CS)-exposed mice. CS-induced neutrophil and monocyte lung infiltration was stronger in miR-223-deficient mice on acute (5 days) exposure, but attenuated on subchronic (4 wk) exposure. Additionally, miR-223 deficiency attenuated acute and subchronic CS-induced lung infiltration of dendritic cells and T lymphocytes. Finally, in vitro overexpression of miR-223-3p in non-COPD airway epithelial cells suppressed C-X-C motif chemokine ligand 8 (CXCL8) and granulocyte monocyte-colony stimulation factor (GM-CSF) secretion and gene expression of the proinflammatory transcription factor TRAF6. Importantly, this suppressive effect of miR-223-3p was compromised in COPD-derived cultures. In conclusion, we demonstrate that miR-223-3p is increased in lungs of patients with COPD and CS-exposed mice and is associated with neutrophilic inflammation. In vivo data indicate that miR-223 acts as negative regulator of acute CS-induced neutrophilic and monocytic inflammation. In vitro data suggest that miR-223-3p does so by suppressing proinflammatory airway epithelial responses, which is less effective in COPD epithelium.
Subject(s)
Cigarette Smoking/adverse effects , Lung/pathology , MicroRNAs/genetics , Pneumonia/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Aged , Animals , Cytokines/metabolism , Female , Humans , Lung/drug effects , Lung/metabolism , Male , Mice , Mice, Knockout , Middle Aged , Neutrophils/drug effects , Neutrophils/immunology , Neutrophils/metabolism , Pneumonia/chemically induced , Pneumonia/genetics , Pneumonia/metabolism , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/metabolismABSTRACT
BACKGROUND: SSMD are used to enhance transparency, improve quality and facilitate patient choice. The use of SSMD is controversial, but patients' views on such data are largely unknown. OBJECTIVES: The aim of this study was therefore to explore the views of patients and to identify their priorities for outcome reporting in vascular surgery. METHODS: A prospective questionnaire study of 165 patients receiving care in a single academic vascular unit was performed. Data on patients' current understanding and use of SSMD, together with future priorities were collected. RESULTS: Of the 165 patients 80% were unaware of SSMD. 72% thought they should be made aware of the data, although 63% thought they were likely to misinterpret the results. The majority recognized the utility of SSMD to inform treatment (60%) and surgeon (53%) choice. The majority prioritize the patient-surgeon relationship (90%) and past experiences of care (71%) when making treatment decisions. A significant majority (66% vs 49%; P < 0.005) would favour hospital-level to surgeon-level data. The main patient priorities for future outcome reporting were waiting list length (56%), the quality of hospital facilities (55%), and patient satisfaction (54%). CONCLUSIONS: The aims of SSMD reporting are not currently being met, and both patients and healthcare professionals have shared concerns over the nature and usefulness of the data. Patients express a preference for hospital-level outcomes and prioritize the experience of receiving care over outcomes when making treatment decisions. Future outcome reporting should include patient-directed hospital-level metrics that are readily accessible and understood by all.
Subject(s)
Patient Reported Outcome Measures , Surveys and Questionnaires , Vascular Surgical Procedures , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Psychometrics , United KingdomABSTRACT
A flexible use of the crassulacean acid metabolism (CAM) has been hypothesised to represent an intermediate stage along a C3 to full CAM evolutionary continuum, when relative contributions of C3 vs CAM metabolism are co-determined by evolutionary history and prevailing environmental constraints. However, evidence for such eco-evolutionary interdependencies is lacking. We studied these interdependencies for the leaf-succulent genus Drosanthemum (Aizoaceae, Southern African Succulent Karoo) by testing for relationships between leaf δ13 C diagnostic for CAM dependence (i.e. contribution of C3 and CAM to net carbon gain), and climatic variables related to temperature and precipitation and their temporal variation. We further quantified the effects of shared phylogenetic ancestry on CAM dependence and its relation to climate. CAM dependence is predicted by rainfall and its temporal variation, with high predictive power of rainfall constancy (temporal entropy). The predictive power of rainfall seasonality and temperature-related variables was negligible. Evolutionary history of the tested clades significantly affected the relationship between rainfall constancy and CAM dependence. We argue that higher CAM dependence might provide an adaptive advantage in increasingly unpredictable rainfall environments when the anatomic exaptation (succulence) is already present. These observations might shed light on the evolution of full CAM.
Subject(s)
Crassulacean Acid Metabolism , Photosynthesis , Carbon Dioxide , Phylogeny , Plant LeavesABSTRACT
Anthropogenic climate change is expected to impact ecosystem structure, biodiversity and ecosystem services in Africa profoundly. We used the adaptive Dynamic Global Vegetation Model (aDGVM), which was originally developed and tested for Africa, to quantify sources of uncertainties in simulated African potential natural vegetation towards the end of the 21st century. We forced the aDGVM with regionally downscaled high-resolution climate scenarios based on an ensemble of six general circulation models (GCMs) under two representative concentration pathways (RCPs 4.5 and 8.5). Our study assessed the direct effects of climate change and elevated CO2 on vegetation change and its plant-physiological drivers. Total increase in carbon in aboveground biomass in Africa until the end of the century was between 18% to 43% (RCP4.5) and 37% to 61% (RCP8.5) and was associated with woody encroachment into grasslands and increased woody cover in savannas. When direct effects of CO2 on plants were omitted, woody encroachment was muted and carbon in aboveground vegetation changed between -8 to 11% (RCP 4.5) and -22 to -6% (RCP8.5). Simulated biome changes lacked consistent large-scale geographical patterns of change across scenarios. In Ethiopia and the Sahara/Sahel transition zone, the biome changes forecast by the aDGVM were consistent across GCMs and RCPs. Direct effects from elevated CO2 were associated with substantial increases in water use efficiency, primarily driven by photosynthesis enhancement, which may relieve soil moisture limitations to plant productivity. At the ecosystem level, interactions between fire and woody plant demography further promoted woody encroachment. We conclude that substantial future biome changes due to climate and CO2 changes are likely across Africa. Because of the large uncertainties in future projections, adaptation strategies must be highly flexible. Focused research on CO2 effects, and improved model representations of these effects will be necessary to reduce these uncertainties.
Subject(s)
Climate Change , Ecosystem , Africa , Africa, Northern , BiodiversityABSTRACT
BACKGROUND AND AIMS: Global plant trait datasets commonly identify trait relationships that are interpreted to reflect fundamental trade-offs associated with plant strategies, but often these trait relationships are not identified when evaluating them at smaller taxonomic and spatial scales. In this study we evaluate trait relationships measured on individual plants for five widespread Protea species in South Africa to determine whether broad-scale patterns of structural trait (e.g. leaf area) and physiological trait (e.g. photosynthetic rates) relationships can be detected within natural populations, and if these traits are themselves related to plant fitness. METHODS: We evaluated the variance structure (i.e. the proportional intraspecific trait variation relative to among-species variation) for nine structural traits and six physiological traits measured in wild populations. We used a multivariate path model to evaluate the relationships between structural traits and physiological traits, and the relationship between these traits and plant size and reproductive effort. KEY RESULTS: While intraspecific trait variation is relatively low for structural traits, it accounts for between 50 and 100 % of the variation in physiological traits. Furthermore, we identified few trait associations between any one structural trait and physiological trait, but multivariate regressions revealed clear associations between combinations of structural traits and physiological performance (R2 = 0.37-0.64), and almost all traits had detectable associations with plant fitness. CONCLUSIONS: Intraspecific variation in structural traits leads to predictable differences in individual-level physiological performance in a multivariate framework, even though the relationship of any particular structural trait to physiological performance may be weak or undetectable. Furthermore, intraspecific variation in both structural and physiological traits leads to differences in plant size and fitness. These results demonstrate the importance of considering measurements of multivariate phenotypes on individual plants when evaluating trait relationships and how trait variation influences predictions of ecological and evolutionary outcomes.
Subject(s)
Proteaceae , Biological Evolution , Phenotype , Plant Leaves , Proteaceae/genetics , South AfricaABSTRACT
BACKGROUND: Occupational asthma, induced by workplace exposures to low molecular weight agents such as toluene 2,4-diisocyanate (TDI), causes a significant burden to patients and society. Little is known about innate lymphoid cells (ILCs) in TDI-induced asthma. A critical regulator of ILC function is microRNA-155, a microRNA associated with asthma. OBJECTIVE: To determine whether TDI exposure modifies the number of ILCs in the lung and whether microRNA-155 contributes to TDI-induced airway inflammation and hyperresponsiveness. METHODS: C57BL/6 wild-type and microRNA-155 knockout mice were sensitised and challenged with TDI or vehicle. Intracellular cytokine expression in ILCs and T-cells was evaluated in bronchoalveolar lavage (BAL) fluid using flow cytometry. Peribronchial eosinophilia and goblet cells were evaluated on lung tissue, and airway hyperresponsiveness was measured using the forced oscillation technique. Putative type 2 ILCs (ILC2) were identified in bronchial biopsies of subjects with TDI-induced occupational asthma using immunohistochemistry. Human bronchial epithelial cells were exposed to TDI or vehicle. RESULTS: TDI-exposed mice had higher numbers of airway goblet cells, BAL eosinophils, CD4+ T-cells and ILCs, with a predominant type 2 response, and tended to have airway hyperresponsiveness. In TDI-exposed microRNA-155 knockout mice, inflammation and airway hyperresponsiveness were attenuated. TDI exposure induced IL-33 expression in human bronchial epithelial cells and in murine lungs, which was microRNA-155 dependent in mice. GATA3+CD3- cells, presumably ILC2, were present in bronchial biopsies. CONCLUSION: TDI exposure is associated with increased numbers of ILCs. The proinflammatory microRNA-155 is crucial in a murine model of TDI asthma, suggesting its involvement in the pathogenesis of occupational asthma due to low molecular weight agents.
Subject(s)
MicroRNAs , Toluene 2,4-Diisocyanate , Animals , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Humans , Immunity, Innate , Lymphocytes , Mice , Mice, Inbred C57BL , Toluene 2,4-Diisocyanate/toxicityABSTRACT
Biomes are constructs for organising knowledge on the structure and functioning of the world's ecosystems, and serve as useful units for monitoring how the biosphere responds to anthropogenic drivers, including climate change. The current practice of delimiting biomes relies on expert knowledge. Recent studies have questioned the value of such biome maps for comparative ecology and global-change research, partly due to their subjective origin. Here we propose a flexible method for developing biome maps objectively. The method uses range modelling of several thousands of plant species to reveal spatial attractors for different growth-form assemblages that define biomes. The workflow is illustrated using distribution data from 23 500 African plant species. In an example application, we create a biome map for Africa and use the fitted species models to project biome shifts. In a second example, we map gradients of growth-form suitability that can be used to identify sites for comparative ecology. This method provides a flexible framework that (1) allows a range of biome types to be defined according to user needs and (2) enables projections of biome changes that emerge purely from the individualistic responses of plant species to environmental changes.
Subject(s)
Ecology , Ecosystem , Africa , Climate Change , PlantsABSTRACT
We propose a unified new approach to describe polarized and unpolarized quark distributions in the proton based on the gauge-gravity correspondence, light-front holography, and the generalized Veneziano model. We find that the spin-dependent quark distributions are uniquely determined in terms of the unpolarized distributions by chirality separation without the introduction of additional free parameters. The predictions are consistent with existing experimental data and agree with perturbative QCD constraints at large longitudinal momentum x. In particular, we predict the sign reversal of the polarized down-quark distribution in the proton at x=0.8±0.03, a key property of nucleon substructure which will be tested very soon in upcoming experiments.