Grassland biodiversity restoration increases resistance of carbon fluxes to drought

Evidence suggests that the restoration of plant diversity in grasslands not only brings benefits for biodiversity conservation, but also the delivery of ecosystem services. While biodiversity-function experiments show that greater plant diversity increases resistance of plant productivity to climate extremes, it is not known whether real-world management options for grassland restoration likewise stabilize ecosystem responses to extreme climate events. We used a long-term (23 year) field experiment in northern England to test the hypothesis that management aimed at biodiversity restoration increases the resistance and recovery of ecosystem carbon (C) fluxes to short-term summer drought. This was tested by measuring plant, soil and microbial responses to a simulated drought in experimental grassland plots where fertilizer application and seed addition have been managed to enhance plant species diversity. The cessation of fertilizer application brought about small increases in plant species richness. Additionally, cessation of fertilizer application reduced overall plant productivity and promoted hemi-parasitic plants at the expense of grasses and forbs. Resistance of CO 2 fluxes to drought, measured as ecosystem respiration, was greater in non-fertilized plots, as lower plant biomass reduced water demand, likely aided by proportionally more hemi-parasitic plants further reducing plant biomass. Additionally, legumes increased under drought, thereby contributing to overall resistance of plant productivity. Recovery of soil microbial C and nitrogen was more rapid after rewetting than soil microbial community composition, irrespective of restoration treatment, suggesting high resilience of soil microbial communities to drought. Synthesis and applications. This study shows that while grassland diversity restoration management increases the resistance of carbon fluxes to drought, it also reduces agricultural yields, revealing a trade-off for land managers. Furthermore legumes, promoted through long-term restoration treatments, can help to maintain plant community productivity under drought by increasing their biomass. As such, grassland management strategies not only have consequences for ecosystem processes, but also the capacity to withstand extreme weather events

Phenotypic spectrum in osteogenesis imperfecta due to mutations in TMEM38B: unravelling a complex cellular defect.

Context: Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Objectives: Clinical and bone material phenotype description and osteoblast differentiation studies. Design and Setting: Natural history study in paediatric research centres. Patients: Eight patients with type XIV OI. Main Outcome Measures: Clinical examinations included: bone mineral density, radiographs, echocardiography and muscle biopsy. Bone biopsy samples (n=3) were analysed using histomorphometry, quantitative backscattered electron microscopy and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Results: The clinical phenotype of type XIV OI ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband L1-L4 bone density Z-score was reduced (median -3.3 [range -4.77 to +0.1; n=7]), and increased by +1.7 (1.17 to 3.0; n=3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased late and mineralization-related markers. Predominance of TRIC-B over TRIC-A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. Conclusions: OI type XIV has a bone histology, matrix mineralization and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities

Spin polarization and magneto-luminescence of confined electron-hole systems

A BCS-like variational wave-function, which is exact in the infinite field limit, is used to study the interplay among Zeeman energies, lateral confinement and particle correlations induced by the Coulomb interactions in strongly pumped neutral quantum dots. Band mixing effects are partially incorporated by means of field-dependent masses and g-factors. The spin polarization and the magneto-luminescence are computed as functions of the number of electron-hole pairs present in the dot and the applied magnetic field.Comment: To appear in Phys. Rev.

Multiple Imputation for Incomplete Data in Epidemiologic Studies

Epidemiologic studies are frequently susceptible to missing information. Omitting observations with missing variables remains a common strategy in epidemiologic studies, yet this simple approach can often severely bias parameter estimates of interest if the values are not missing completely at random. Even when missingness is completely random, complete-case analysis can reduce the efficiency of estimated parameters, because large amounts of available data are simply tossed out with the incomplete observations. Alternative methods for mitigating the influence of missing information, such as multiple imputation, are becoming an increasing popular strategy in order to retain all available information, reduce potential bias, and improve efficiency in parameter estimation. In this paper, we describe the theoretical underpinnings of multiple imputation, and we illustrate application of this method as part of a collaborative challenge to assess the performance of various techniques for dealing with missing data (Am J Epidemiol. 2018;187(3):568–575). We detail the steps necessary to perform multiple imputation on a subset of data from the Collaborative Perinatal Project (1959–1974), where the goal is to estimate the odds of spontaneous abortion associated with smoking during pregnancy

Principled Approaches to Missing Data in Epidemiologic Studies

Principled methods with which to appropriately analyze missing data have long existed; however, broad implementation of these methods remains challenging. In this and 2 companion papers (Am J Epidemiol. 2018;187(3):576–584 and Am J Epidemiol. 2018;187(3):585–591), we discuss issues pertaining to missing data in the epidemiologic literature. We provide details regarding missing-data mechanisms and nomenclature and encourage the conduct of principled analyses through a detailed comparison of multiple imputation and inverse probability weighting. Data from the Collaborative Perinatal Project, a multisite US study conducted from 1959 to 1974, are used to create a masked data-analytical challenge with missing data induced by known mechanisms. We illustrate the deleterious effects of missing data with naive methods and show how principled methods can sometimes mitigate such effects. For example, when data were missing at random, naive methods showed a spurious protective effect of smoking on the risk of spontaneous abortion (odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.19, 0.93), while implementation of principled methods multiple imputation (OR = 1.30, 95% CI: 0.95, 1.77) or augmented inverse probability weighting (OR = 1.40, 95% CI: 1.00, 1.97) provided estimates closer to the “true” full-data effect (OR = 1.31, 95% CI: 1.05, 1.64). We call for greater acknowledgement of and attention to missing data and for the broad use of principled missing-data methods in epidemiologic research

Inverse-Probability-Weighted Estimation for Monotone and Nonmonotone Missing Data

Missing data is a common occurrence in epidemiologic research. In this paper, 3 data sets with induced missing values from the Collaborative Perinatal Project, a multisite US study conducted from 1959 to 1974, are provided as examples of prototypical epidemiologic studies with missing data. Our goal was to estimate the association of maternal smoking behavior with spontaneous abortion while adjusting for numerous confounders. At the same time, we did not necessarily wish to evaluate the joint distribution among potentially unobserved covariates, which is seldom the subject of substantive scientific interest. The inverse probability weighting (IPW) approach preserves the semiparametric structure of the underlying model of substantive interest and clearly separates the model of substantive interest from the model used to account for the missing data. However, IPW often will not result in valid inference if the missing-data pattern is nonmonotone, even if the data are missing at random. We describe a recently proposed approach to modeling nonmonotone missing-data mechanisms under missingness at random to use in constructing the weights in IPW complete-case estimation, and we illustrate the approach using 3 data sets described in a companion article (Am J Epidemiol. 2018;187(3):568–575)

Terminal regions confer plasticity to the tetrameric assembly of human HspB2 and HspB3

Heterogeneity in small heat shock proteins (sHsps) spans multiple spatiotemporal regimes – from fast fluctuations of part of the protein, to conformational variability of tertiary structure, plasticity of the interfaces, and polydispersity of the inter-converting, and co-assembling oligomers. This heterogeneity and dynamic nature of sHsps has significantly hindered their structural characterisation. Atomic-coordinates are particularly lacking for vertebrate sHsps, where most available structures are of extensively truncated homomers. sHsps play important roles in maintaining protein levels in the cell and therefore in organismal health and disease. HspB2 and HspB3 are vertebrate sHsps that are found co-assembled in neuromuscular cells, and variants thereof are associated with disease. Here, we present the structure of human HspB2/B3, which crystallised as a hetero-tetramer in a 3:1 ratio. In the HspB2/B3 tetramer, the four a-crystallin domains (ACDs) assemble into a flattened tetrahedron which is pierced by two non-intersecting approximate dyads. Assembly is mediated by flexible “nuts and bolts” involving IXI/V motifs from terminal regions filling ACD pockets. Parts of the N-terminal region bind in an unfolded conformation into the anti-parallel shared ACD dimer grooves. Tracts of the terminal regions are not resolved, most likely due to their disorder in the crystal lattice. This first structure of a full-length human sHsp heteromer reveals the heterogeneous interactions of the terminal regions and suggests a plasticity that is important for the cytoprotective functions of sHsps

Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3

Objective: Genome-wide association studies (GWAS) of BMI are mostly undertaken under the assumption that "kg/m2" is an index of weight fully adjusted for height, but in general this is not true. The aim here was to assess the contribution of common genetic variation to a adjusted version of that phenotype which appropriately accounts for covariation in height in children. Methods: A GWAS of height-adjusted BMI (BMI[x]=weight/heightx), calculated to be uncorrelated with height, in 5809 participants (mean age 9.9 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC) was performed. Results: GWAS based on BMI[x] yielded marked differences in genomewide results profile. SNPs in ADCY3 (adenylate cyclase 3) were associated at genome-wide significance level (rs11676272 (0.28 kg/m3.1 change per allele G (0.19, 0.38), P=6 × 10-9). In contrast, they showed marginal evidence of association with conventional BMI [rs11676272 (0.25 kg/m2 (0.15, 0.35), P=6 × 10-7)]. Results were replicated in an independent sample, the Generation R study. Conclusions: Analysis of BMI[x] showed differences to that of conventional BMI. The association signal at ADCY3 appeared to be driven by a missense variant and it was strongly correlated with expression of this gene. Our work highlights the importance of well understood phenotype use (and the danger of convention) in characterising genetic contributions to complex traits

Striatal mRNA expression patterns underlying peak dose L-DOPA-induced dyskinesia in the 6-OHDA hemiparkinsonian rat

L-DOPA is the primary pharmacological treatment for relief of the motor symptoms of Parkinson’s disease (PD). With prolonged treatment (⩾5 years) the majority of patients will develop abnormal involuntary movements as a result of L-DOPA treatment, known as L-DOPA-induced dyskinesia. Understanding the underlying mechanisms of dyskinesia is a crucial step toward developing treatments for this debilitating side effect. We used the 6-hydroxydopamine (6-OHDA) rat model of PD treated with a three-week dosing regimen of L-DOPA plus the dopa decarboxylase inhibitor benserazide (4 mg/kg and 7.5 mg/kg s.c., respectively) to induce dyskinesia in 50% of individuals. We then used RNA-seq to investigate the differences in mRNA expression in the striatum of dyskinetic animals, non-dyskinetic animals, and untreated parkinsonian controls at the peak of dyskinesia expression, 60 min after L-DOPA administration. Overall, 255 genes were differentially expressed; with significant differences in mRNA expression observed between all three groups. In dyskinetic animals 129 genes were more highly expressed and 14 less highly expressed when compared with non-dyskinetic and untreated parkinsonian controls. In L-DOPA treated animals 42 genes were more highly expressed and 95 less highly expressed when compared with untreated parkinsonian controls. Gene set cluster analysis revealed an increase in expression of genes associated with the cytoskeleton and phosphoproteins in dyskinetic animals compared with non-dyskinetic animals, which is consistent with recent studies documenting an increase in synapses in dyskinetic animals. These genes may be potential targets for drugs to ameliorate L-DOPA-induced dyskinesia or as an adjunct treatment to prevent their occurrence

Measurement of the ratio B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) and the time-integrated CP asymmetry in D0->pi+pi-pi0

We report a high-statistics measurement of the relative branching fraction B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) using a 532 fb^{-1} data sample collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. The measured value of the relative branching fraction is B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) = (10.12 +/- 0.04(stat) +/- 0.18(syst))x10^{-2} which has an accuracy comparable to the world average. We also present a measurement of the time-integrated CP asymmetry in D0->pi+pi-pi0 decay. The result, A_{CP} = (0.43 +/- 1.30)%, shows no significant CP violation.Comment: 15 pages, 11 figures, submitted to Physics Letters