R code for a model of phytoplankton community structure under multiple frequencies of pulsed nutrient supply.

Dataset: Modeling phytoplankton under multiple frequencies of nutrient supplyR code for a model of phytoplankton community structure under multiple frequencies of pulsed nutrient supply. For a complete list of measurements, refer to the full dataset description in the supplemental file 'Dataset_description.pdf'. The most current version of this dataset is available at: https://www.bco-dmo.org/dataset/820488NSF Division of Ocean Sciences (NSF OCE) OCE-155935

Local adaptation constrains drought tolerance in a tropical foundation tree

Plant species with broad climatic ranges might be more vulnerable to climate change than previously appreciated due to intraspecific variation in climatic stress tolerance. In tropical forests, drought is increasingly frequent and severe, causing widespread declines and altering community dynamics. Yet, little is known about whether foundation tropical trees vary in drought tolerance throughout their distributions, and how intraspecific variation in drought tolerance might contribute to their vulnerability to climate changE. We tested for local adaptation in seedling emergence and establishment with a full-factorial reciprocal transplant experiment including 27 populations and 109,350 seeds along a 3,500 mm precipitation gradient for a widespread tropical foundation tree, Metrosideros polymorpha, in Hawaii. To more precisely relate seedling performance to soil moisture, we conducted a complementary greenhouse experiment to test responses of the same focal populations to simulated drought. In the reciprocal transplant experiment, we observed significant variation among populations and sites in germination and seedling establishment rates. Overall, there was a significant link between historical rainfall of populations and their performance under current rainfall at the study sites consistent with local adaptation. In particular, populations from historically wet sites demonstrated lower germination rates in currently dry sites compared to wet field sites, while populations from historically dry sites germinated well across all sites, with particularly high germination in dry sites. In the greenhouse, seedlings from wet populations survived fewer days without water, and succumbed at wetter soil conditions than populations from historically dry sites, corroborating results from the field experiment. Synthesis. While climate change models project the greatest drying trends for historically dry areas in Hawaii, even moderate drying of wet sites could significantly reduce Metrosideros polymorpha recruitment given the sensitivity of seedlings to very slight changes in water regimes. Thus, although M. polymorpha demonstrates high seedling drought tolerance in some populations, providing evidence of resilience at the species-scale, there are nonetheless vulnerable populations that will likely decline under climate change. Our approach demonstrates that even trees with high dispersal abilities can show significant clines in drought tolerance, and suggests that similar intraspecific variation might be an important consideration for other tropical foundational tree species

A Meta-Analysis Of Resource Pulse-Consumer Interactions

Resource Pulses are infrequent, large-magnitude, and short-duration events of increased resource availability. They include a diverse set of extreme events in a wide range of ecosystems, but identifying general patterns among the diversity of pulsed resource phenomena in nature remains an important challenge. Here we present a meta-analysis of resource pulse-consumer interactions that addresses four key questions: (1) Which characteristics of pulsed resources best predict their effects on consumers? (2) Which characteristics of consumers best predict their responses to resource pulses? (3) How do the effects of resource Pulses differ in different ecosystems? (4) What are the indirect effects of resource pulses in communities\u27? To investigate these questions, we built a data set of diverse Pulsed resource-consumer interactions from around the world, developed metrics to compare the effects of resource pulses across disparate systems, and conducted multilevel regression analyses to examine the manner in which variation in the characteristics of resource pulse-consumer interactions affects important aspects Of Consumer responses. Resource pulse magnitude, resource trophic level, resource Pulse duration, ecosystem type and subtype, consumer response mechanisms, and consumer body mass were found to be key. explanatory factors predicting the magnitude, duration, and timing of consumer responses. Larger consumers showed more persistent responses to resource pulses, and reproductive responses were more persistent than aggregative responses. Aquatic systems showed shorter temporal lags between peaks of resource availability and consumer response compared to terrestrial systems, and temporal lags were also shorter for smaller consumers compared to larger consumers. The magnitude of consumer responses relative to their resource pulses was generally smaller for the direct consumers of primary resource pulses, compared to consumers at greater trophic distances from the initial resource pulse. In specific systems, this data set showed both attenuating and amplifying indirect effects. We consider the mechanistic processes behind these patterns and their implications for the ecology of resource pulses

Cautionary Tale of Using Tris(alkyl)phosphine Reducing Agents with NAD+-Dependent Enzymes

Protein biochemistry protocols typically include disulfide bond reducing agents to guard against unwanted thiol oxidation and protein aggregation. Commonly used disulfide bond reducing agents include dithiothreitol, β-mercaptoethanol, glutathione, and the tris(alkyl)phosphine compounds tris(2-carboxyethyl)phosphine (TCEP) and tris(3-hydroxypropyl)phosphine (THPP). While studying the catalytic activity of the NAD(P)H-dependent enzyme Δ1-pyrroline-5-carboxylate reductase, we unexpectedly observed a rapid non-enzymatic chemical reaction between NAD+ and the reducing agents TCEP and THPP. The product of the reaction exhibits a maximum ultraviolet absorbance peak at 334 nm and forms with an apparent association rate constant of 231–491 M−1 s−1. The reaction is reversible, and nuclear magnetic resonance characterization (1H, 13C, and 31P) of the product revealed a covalent adduct between the phosphorus of the tris(alkyl)phosphine reducing agent and the C4 atom of the nicotinamide ring of NAD+. We also report a 1.45 Å resolution crystal structure of short-chain dehydrogenase/reductase with the NADP+–TCEP reaction product bound in the cofactor binding site, which shows that the adduct can potentially inhibit enzymes. These findings serve to caution researchers when using TCEP or THPP in experimental protocols with NAD(P)+. Because NAD(P)+-dependent oxidoreductases are widespread in nature, our results may be broadly relevant

Selective Affimers Recognise the BCL‐2 Family Proteins BCL‐xL and MCL‐1 through Noncanonical Structural Motifs

The BCL‐2 family is a challenging group of proteins to target selectively due to sequence and structural homologies across the family. Selective ligands for the BCL‐2 family regulators of apoptosis are useful as probes to understand cell biology and apoptotic signalling pathways, and as starting points for inhibitor design. We have used phage display to isolate Affimer reagents (non‐antibody‐binding proteins based on a conserved scaffold) to identify ligands for MCL‐1, BCL‐xL, BCL‐2, BAK and BAX, then used multiple biophysical characterisation methods to probe the interactions. We established that purified Affimers elicit selective recognition of their target BCL‐2 protein. For anti‐apoptotic targets BCL‐xL and MCL‐1, competitive inhibition of their canonical protein‐protein interactions is demonstrated. Co‐crystal structures reveal an unprecedented mode of molecular recognition; where a BH3 helix is normally bound, flexible loops from the Affimer dock into the BH3 binding cleft. Moreover, the Affimers induce a change in the target proteins towards a desirable drug‐bound‐like conformation. These proof‐of‐concept studies indicate that Affimers could be used as alternative templates to inspire the design of selective BCL‐2 family modulators and more generally other protein‐protein interaction inhibitors

Clinical Science A better prognosis for Merkel cell carcinoma of unknown primary origin

Abstract BACKGROUND: There is limited evidence that Merkel cell carcinoma (MCC) arising from a nodal basin without evidence of a primary cutaneous (PC) site has better prognosis. We present our experience at 2 tertiary care referral centers with stage III MCC with and without a PC site. METHODS: Fifty stage III MCC patients were identified between 1996 and 2011. Clinical data were analyzed, with primary endpoints being disease-free survival and overall survival. RESULTS: Of stage III patients, 34 patients presented with a PC site and 16 patients with an unknown primary (UP) site. Treatment strategies varied; of patients with UP vs PC sites, 25% vs 44% underwent combined regional lymphadenectomy and radiation, with an additional 25% vs 15% receiving chemotherapy. The median disease-free survival for a UP site was not reached vs 15 months for a PC site (hazards ratio 5 .48, P 5 .18). The median overall survival for a UP site was not reached vs 21 months for a PC site (hazards ratio 5 .34, P 5 .03). Multivariate analysis showed that UP status was a significant factor in overall survival (P 5 .002). CONCLUSIONS: Stage III MCC with a UP site portends a better prognosis than MCC with a PC site

A comprehensive transcript index of the human genome generated using microarrays and computational approaches

BACKGROUND: Computational and microarray-based experimental approaches were used to generate a comprehensive transcript index for the human genome. Oligonucleotide probes designed from approximately 50,000 known and predicted transcript sequences from the human genome were used to survey transcription from a diverse set of 60 tissues and cell lines using ink-jet microarrays. Further, expression activity over at least six conditions was more generally assessed using genomic tiling arrays consisting of probes tiled through a repeat-masked version of the genomic sequence making up chromosomes 20 and 22. RESULTS: The combination of microarray data with extensive genome annotations resulted in a set of 28,456 experimentally supported transcripts. This set of high-confidence transcripts represents the first experimentally driven annotation of the human genome. In addition, the results from genomic tiling suggest that a large amount of transcription exists outside of annotated regions of the genome and serves as an example of how this activity could be measured on a genome-wide scale. CONCLUSIONS: These data represent one of the most comprehensive assessments of transcriptional activity in the human genome and provide an atlas of human gene expression over a unique set of gene predictions. Before the annotation of the human genome is considered complete, however, the previously unannotated transcriptional activity throughout the genome must be fully characterized

Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People

The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics—European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document

Quadrupole Anisotropy in Dihadron Azimuthal Correlations in Central dd++Au Collisions at sNN\sqrt{s_{_{NN}}}=200 GeV

The PHENIX collaboration at the Relativistic Heavy Ion Collider (RHIC) reports measurements of azimuthal dihadron correlations near midrapidity in $d$$+$Au collisions at $\sqrt{s_{_{NN}}}$=200 GeV. These measurements complement recent analyses by experiments at the Large Hadron Collider (LHC) involving central $p$$+$Pb collisions at $\sqrt{s_{_{NN}}}$=5.02 TeV, which have indicated strong anisotropic long-range correlations in angular distributions of hadron pairs. The origin of these anisotropies is currently unknown. Various competing explanations include parton saturation and hydrodynamic flow. We observe qualitatively similar, but larger, anisotropies in $d$$+$Au collisions compared to those seen in $p$$+$Pb collisions at the LHC. The larger extracted $v_2$ values in $d$$+$Au collisions at RHIC are consistent with expectations from hydrodynamic calculations owing to the larger expected initial-state eccentricity compared with that from $p$$+$Pb collisions. When both are divided by an estimate of the initial-state eccentricity the scaled anisotropies follow a common trend with multiplicity that may extend to heavy ion data at RHIC and the LHC, where the anisotropies are widely thought to arise from hydrodynamic flow.Comment: 375 authors, 7 pages, 5 figures. Published in Phys. Rev. Lett. v2 has minor changes to text and figures in response to PRL referee suggestions. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm