Global relationships between plant functional traits and environment in grasslands

In order to understand how ecosystems are likely to respond to global anthropogenic change it is first necessary to identify general patterns and processes that can explain how they are created and maintained. Plant traits potentially provide a mechanistic explanation for the differences in growth and survival that explain a species niche that can scale up from individual to biome. In this thesis I investigate the relationships between grass functional traits and the biotic and abiotic environment, and test whether the predictions made by community ecological theory are more broadly applicable at continental and global scales. I provide evidence that at the global scale soil nutrients is more important than climate in explaining the distribution of traits that reflect different strategies of resource use but that evolutionary history provides a stronger explanation for global trait distribution than contemporary environment. I then show the functional traits that are associated with gradients of grazing and fire and identify functional groups that have diverging responses to grazing across Sub-Saharan Africa. Finally I investigate species response to drought and identify traits which can explain a species hydrological niche. The findings of this work provide evidence that trade-offs between carbon and nitrogen acquisition and use (leaf nitrogen content and C/N ratio) could provide a foundation for predicting plant responses to changes in climate, soil nutrients and disturbance at global scales. However, I also show that traits often used to reflect differences in leaf growth and longevity (ie. specific leaf area and leaf tensile strength) are not able to strongly predict response to either resource availability or disturbance at macro-ecological scales. This highlights the need to identify other axis of variation and organs beyond the leaf economic spectrum, for example root architecture, that are potentially important in explaining the differing aspects of a species niche and how vegetation may respond to global change

How Collections End: Objects, Meaning and Loss in Laboratories and Museums

Collections are made and maintained for pleasure, status, nation or empire building, cultural capital, as a substrate for knowledge production, and everything in between. In asking how collections end, we shift the focus from acquisition and growth to erosion, loss and decay, and expose the intellectual, material and curatorial labour required to maintain collections. In this introductory essay, we draw together insights from the history of science and from science and technology studies to investigate the dispersal, destruction, absorption, repurposing and repatriation of the diverse scientific collections discussed in the papers that make up this issue of BJHS Themes, and many other collections besides. We develop a distinction first suggested by the bibliographer John Willis Clark between ‘working’ collections of objects valued for the information they hold or produce, and ‘unique’ collections of objects valued for their historical singularity. We show that in many cases, the ‘end’ of an object or collection is merely a shift in the dominant account of its cultural value from ‘working’ to ‘unique’ or vice versa. Moving between the laboratory, the museum, and difficult-to-classify spaces in between, we argue that ‘ending’ is not anathema to ‘collecting’ but is always present as a threat, or as an everyday reality, or even as a necessary part of a collection’s continued existence. A focus on ending draws attention not only to the complex internal dynamics and social contexts of collections, but also to their roles in producing scientific knowledge

Cardiovascular outcomes reported in hemodialysis trials

Patients on long-term hemodialysis are at very high risk for cardiovascular disease but are usually excluded from clinical trials conducted in the general population or in at-risk populations. There are no universally agreed cardiovascular outcomes for trials conducted specifically in the hemodialysis population. In this review, we highlight that trials reporting cardiovascular outcomes in hemodialysis patients are usually of short duration (median 3 to 6 months) and are small (59% of trials have \u3c100 participants). Overall, the cardiovascular outcomes are very heterogeneous and may not reflect outcomes that are meaningful to patients and clinicians in supporting decision making, as they are often surrogates of uncertain clinical importance. Composite outcomes used in different trials rarely share the same components. In a field in which a single trial is often insufficiently powered to fully assess the clinical and economic impact of interventions, differences in outcome reporting across trials make the task of meta-analysis and interpretation of all the available evidence challenging. Core outcome sets are now being established across many specialties in health care to prevent these problems. Through the global Standardized Outcomes in Nephrology-Hemodialysis initiative, cardiovascular disease was identified as a critically important core domain to be reported in all trials in hemodialysis. Informed by the current state of reporting of cardiovascular outcomes, a core outcome measure for cardiovascular disease is currently being established with involvement of patients, caregivers, and health professionals. Consistent reporting of cardiovascular outcomes that are critically important to hemodialysis patients and clinicians will strengthen the evidence base to inform care in this very high-risk population

Dual role of USP 30 in controlling basal pexophagy and mitophagy

USP 30 is an integral protein of the outer mitochondrial membrane that counteracts PINK 1 and Parkin‐dependent mitophagy following acute mitochondrial depolarisation. Here, we use two distinct mitophagy reporter systems to reveal tonic suppression by USP 30, of a PINK 1‐dependent component of basal mitophagy in cells lacking detectable Parkin. We propose that USP 30 acts upstream of PINK 1 through modulation of PINK 1‐substrate availability and thereby determines the potential for mitophagy initiation. We further show that a fraction of endogenous USP 30 is independently targeted to peroxisomes where it regulates basal pexophagy in a PINK 1‐ and Parkin‐independent manner. Thus, we reveal a critical role of USP 30 in the clearance of the two major sources of ROS in mammalian cells and in the regulation of both a PINK 1‐dependent and a PINK 1‐independent selective autophagy pathway

The evolution of cellular deficiency in GATA2 mutation.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageConstitutive heterozygous GATA2 mutation is associated with deafness, lymphedema, mononuclear cytopenias, infection, myelodysplasia (MDS), and acute myeloid leukemia. In this study, we describe a cross-sectional analysis of 24 patients and 6 relatives with 14 different frameshift or substitution mutations of GATA2. A pattern of dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency (DCML deficiency) with elevated Fms-like tyrosine kinase 3 ligand (Flt3L) was observed in all 20 patients phenotyped, including patients with Emberger syndrome, monocytopenia with Mycobacterium avium complex (MonoMAC), and MDS. Four unaffected relatives had a normal phenotype indicating that cellular deficiency may evolve over time or is incompletely penetrant, while 2 developed subclinical cytopenias or elevated Flt3L. Patients with GATA2 mutation maintained higher hemoglobin, neutrophils, and platelets and were younger than controls with acquired MDS and wild-type GATA2. Frameshift mutations were associated with earlier age of clinical presentation than substitution mutations. Elevated Flt3L, loss of bone marrow progenitors, and clonal myelopoiesis were early signs of disease evolution. Clinical progression was associated with increasingly elevated Flt3L, depletion of transitional B cells, CD56(bright) NK cells, naïve T cells, and accumulation of terminally differentiated NK and CD8(+) memory T cells. These studies provide a framework for clinical and laboratory monitoring of patients with GATA2 mutation and may inform therapeutic decision-making.Lymphoma and Leukaemia Research British Society of Hematology Bright Red George Walker Trust Wellcome Trus

Single-cell multi-omics analysis of the immune response in COVID-19

Peer reviewedPublisher PD

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice