Chain‐Length‐Dependent Termination of Vinyl Acetate and Vinyl Pivalate Bulk Homopolymerizations Studied by SP‐PLP‐EPR

Bulk homopolymerizations of vinyl acetate and vinyl pivalate are studied by EPR experiments between ?65 °C and 60 °C with dicumyl peroxide acting as the photoinitiator. No mid‐chain radicals are seen, which demonstrates that backbiting plays no role. The chain‐length dependence of the termination rate coefficients measured up to 13% monomer conversion is adequately represented by the composite model. The power‐law exponents α_s and α_l for short‐chain and long‐chain radicals are: α_s(VAc) = 0.57 ± 0.05, α_s(VPi) = 0.67 ± 0.15, α_l(VAc) = 0.16 ± 0.07, and α_l(VPi) = 0.16 ± 0.07. The crossover chain lengths differ largely: i_c(VAc) = 20 ± 10 and i_c(VPi) = 110 ± 30. The rate coefficient for termination of two radicals of chain length unity, , which is the fourth composite‐model parameter, depends on temperature, as does the monomer fluidity.

     

A New Workflow for Whole‐Genome Sequencing of Single Human Cells

Unbiased amplification of the whole‐genome amplification (WGA) of single cells is crucial to study cancer evolution and genetic heterogeneity, but is challenging due to the high complexity of the human genome. Here, we present a new workflow combining an efficient adapter‐linker PCR‐based WGA method with second‐generation sequencing. This approach allows comparison of single cells at base pair resolution. Amplification recovered up to 74% of the human genome. Copy‐number variants and loss of heterozygosity detected in single cell genomes showed concordance of up to 99% to pooled genomic DNA. Allele frequencies of mutations could be determined accurately due to an allele dropout rate of only 2%, clearly demonstrating the low bias of our PCR‐based WGA approach. Sequencing with paired‐end reads allowed genome‐wide analysis of structural variants. By direct comparison to other WGA methods, we further endorse its suitability to analyze genetic heterogeneity.     

Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease

The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.     

Temperature drives global patterns in forest biomass distribution in leaves,stems, and roots

Whether the fraction of total forest biomass distributed in roots, stems, or leaves varies systematically across geographic gradients remains unknown despite its importance for understanding forest ecology and modeling global carbon cycles. It has been hypothesized that plants should maintain proportionally more biomass in the organ that acquires the most limiting resource. Accordingly, we hypothesize greater biomass distribution in roots and less in stems and foliage in increasingly arid climates and in colder environments at high latitudes. Such a strategy would increase uptake of soil water in dry conditions and of soil nutrients in cold soils, where they are at low supply and are less mobile. We use a large global biomass dataset (>6,200 forests from 61 countries, across a 40 °C gradient in mean annual temperature) to address these questions. Climate metrics involving temperature were better predictors of biomass partitioning than those involving moisture availability, because, surprisingly, fractional distribution of biomass to roots or foliage was unrelated to aridity. In contrast, in increasingly cold climates, the proportion of total forest biomass in roots was greater and in foliage was smaller for both angiosperm and gymnosperm forests. These findings support hypotheses about adaptive strategies of forest trees to temperature and provide biogeographically explicit relationships to improve ecosystem and earth system models. They also will allow, for the first time to our knowledge, representations of root carbon pools that consider biogeographic differences, which are useful for quantifying whole-ecosystem carbon stocks and cycles and for assessing the impact of climate change on forest carbon dynamics.After acquisition via photosynthesis (gross primary production), new plant carbon (C) is respired, transferred to mycorrhizal symbionts, exuded, or converted into new biomass (net primary production). The new biomass can be foliage, stems (including boles, branches, and bark), roots, or reproductive parts. The proportional allocation of new C to these four plant biomass pools, when combined with their turnover rates, results in the proportional distribution of standing biomass among these pools. Such processes can be influenced by plant size, resource supply, and/or climate (1–10). Although simple in concept, our understanding of these processes and our ability to quantify and predict them remain surprisingly rudimentary (3–13).The general lack of knowledge about C partitioning is important for a number of reasons, including its implications for the accuracy of global C cycle modeling and accounting. A recent study (11) concluded

different carbon partitioning schemes resulted in large variations in estimates of global woody carbon flux and storage, indicating that stand-level controls on carbon partitioning are not yet accurately represented in ecosystem models.

Uncertainty about C partitioning in relation to biogeography and environmental effects is a particularly critical knowledge gap, because the direct and indirect influence of temperature or moisture availability on biomass partitioning could be important to growth, nutrient cycling, productivity, ecosystem fluxes, and other key plant and ecosystem processes (5, 7–10, 12). Additionally, uncertainty about belowground C allocation and biomass dynamics represents a major information gap that hampers efforts to estimate belowground C pools at continental to global scales (cf. 13 and 14).Some of the limited evidence available supports the hypothesis that under low temperatures both selection and phenotypic plasticity should promote a relatively greater fraction of forest biomass in roots (5, 7, 8, 12, 15–18), as a result of adaptation to low nutrient supply (7, 19–22) driven by low nutrient cycling rates and limited soil solution movement. Cold environments also are often periodically dry and exhibit low plant production (19–26). Belowground resource limitations obviously also rise with increasing shortage of rainfall relative to evaporative demand, which can influence biomass distribution as well (4, 5, 17). Uncertainties include whether there are differences across climate gradients in the fraction of gross primary production respired vs. converted into new biomass; how new biomass is partitioned to foliage, stems, and roots; what the turnover rates are for these different tissues; and what are the consequences of the biomass distribution in foliage, stem, and root. In this study we focus on the last uncertainty—biomass distributions in standing pools—which is a direct consequence of new biomass allocation and subsequent turnover rate. Following optimal partitioning theory (1–4), we posit that the fraction of total forest biomass in roots should increase and in foliage should decrease when belowground resources are scarce.We use a large dataset based on more than 6,200 observations of forest stands in 61 countries (Tables S1–S3 and Fig. 1) to test the following hypotheses: (i) with increasing temperature, proportional biomass distribution (i.e., fraction of total biomass) should decrease in roots and increase in foliage; (ii) with increasing water shortage (estimated by an index of rainfall to evaporative demand), proportional biomass distribution should increase in roots and decrease in foliage; and (iii) gymnosperm and angiosperm forests should follow similar patterns. The dataset comprises data entries for individual stands including total foliage mass per hectare (M_fol), total stem mass per hectare (M_stem), total root mass per hectare (M_root), and, where available, total mass per hectare (M_tot = M_fol + M_stem + M_root). Forests were either naturally regenerated or plantations. Stands were classified as gymnosperm or angiosperm based on whichever represented a greater fraction of basal area or biomass; almost all native forests were of mixed species.Open in a separate windowFig. 1.Map showing location of all stands in the assembled database (see Tables S1 and S2 for additional information specific to those with root, foliage, and stem biomass data or with foliage and stem biomass data) across color-coded ranges of MAT.The sampled forests varied widely in age (from 3–400 y) and size (with M_tot ranging from near zero to 300 Mg/ha). Differences in biomass (which we refer to as size) reflect differences in productivity, density, and especially the range of ages of sampled stands. Because tree-size scaling is allometric (3, 4, 7, 9), we use an allometric approach to account for size-related changes in biomass partitioning in examining broad biogeographic patterns. Forests with high biomass have larger trees on average than forests with low biomass (given that tree density typically is lower in the former), so the forest size allometry characterized herein likely has its roots at the individual tree scale, but our analyses use stand M_tot, not individual tree biomass. We also examine biogeographic differences in the fraction of M_tot in foliage (F_fol), stem (F_stem), and root (F_root).The term “allocation” has been used historically to describe both the onward distribution, or flux, of newly acquired substances (usually C or biomass) to different plant functions and differences in how those pools are distributed at any point in time. To minimize confusion about these different measures. we hereafter use the term “allocation” along with “new biomass” or “new C” only to indicate the former and discuss either the proportion of biomass or the fraction of biomass distributed in foliage, stems, or roots to indicate the latter.The sampled forests varied widely geographically and in mean annual temperature (MAT) (from −13 to 29 °C) and mean annual precipitation (MAP) (from 20–420 cm) (Tables S1 and S2 and Fig. 1). Because a number of seasonal and annual climatic factors covary, it is difficult to ascertain which are responsible for the observed patterns (Materials and Methods and SI Materials and Methods). Because MAP is strongly correlated with MAT and is not a good global measure of water availability, we used an aridity index, the ratio of MAP to annual potential evapotranspiration (MAP/PET) (27) as a measure of relative water availability. MAP/PET ranged from <0.5 in cold, high-latitude zones to >3 in temperate and tropical rainforests. The forests ranged from sea level to >4,000 m elevation, with the large majority at <1,000 m elevation. More sampled forests were from Asia and Europe than other continents, and more were boreal and temperate than tropical. Thus, inferences from these data are likely to be most reliable across the gradient from subtropical to cold boreal forests.     

Successful treatment of a paravalvular leak with balloon cracking and valve‐in‐valve TAVR

Transcatheter heart valve implantation into degenerated bioprosthetic valves (ViV‐THV implantation) has become an established procedure for high risk patients. In general, paravalvular leak (PVL) is a contraindication for valve‐in‐valve‐TAVR (ViV‐TAVR). Herein, we report on a 81‐year‐old patient presenting with acute heart failure for a failing aortic bioprosthesis (Medtronic Mosaic 27 mm). Intraoperative transesophageal echocardiography during urgent ViV‐TAVR revealed a PVL previously not detected. After transfemoral implantation of a 26 mm‐Evolut‐R, balloon‐fracturing of the bioprosthetic ring was performed using a 24 mm True Dilatation balloon for treatment of the PVL. Afterward, left ventricular to aortic peak‐to‐peak pressure gradient measured 2–4mmHg. Transesophageal echocardiography merely revealed trace PVL. Aortic root angiography showed no PVL. At discharge, echocardiography measured a transprosthetic mean gradient of 5mmHg detecting no PVL. Intentional ring‐fracturing of an aortic valve prostheses may prove not only to be effective in lowering transvalvular gradients after valve‐in‐valve‐TAVR, but may also be a tool to treat PVL alongside degenerated surgical aortic bioprostheses in certain patients.     

Preserved function of regulatory T cells in chronic HIV-1 infection despite decreased numbers in blood and tissue

Regulatory T cells (Tregs) are potent immune modulators, but their role in human immunodeficiency virus type 1 (HIV-1) pathogenesis remains poorly understood. We performed a detailed analysis of the frequency and function of Tregs in a large cohort of HIV-1-infected individuals and HIV-1 negative controls. While HIV "elite controllers" and uninfected individuals had similar Treg numbers and frequencies, the absolute numbers of Tregs declined in blood and gut-associated lymphoid tissue in patients with chronic progressive HIV-1 infection. Despite quantitative changes in Tregs, HIV-1 infection was not associated with an impairment of ex vivo suppressive function of flow-sorted Tregs in both HIV controllers and untreated chronic progressors.