bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying forest growth uncertainty on carbon payback times in a simple biomass carbon model
Authors: Rolls Will , Forster Piers M 
Published: March 2020

AbstractIn 2018 Stermanet al(2018a) published a simple dynamic lifecycle analysis (DLCA) model for forest-sourced bioenergy. The model has been widely cited since its publication, including widespread reporting of the model’s headline results within the media. In adapting a successful replication of the Stermanet al(2018a) model with open-source software, we identified a number of changes to input parameters which improved the fit of the model’s forest site growth function with its training data. These relatively small changes to the input parameters result in relatively large changes to the model predictions of forest site carbon uptake: up to 92 tC.ha−1or 18% of total site carbon at year 500. This change in estimated site carbon resulted in calculated payback periods (carbon sequestration parity) which differed by up to 54 years in a clear-fell scenario when compared with results obtained using previously published parameters. Notably, this uncertainty was confined to forests which were slower growing and where the model’s training dataset was not sufficiently long for forests to reach maturity. We provide improved parameterisations for all forest types used within the original Stermanet al(2018a) paper, and propose that these provide better fits to the underlying data. We also provide margins of error for the generated growth curves to indicate the wide range of possible results possible with the model for some forest types. We conclude that, while the revised model is able to reproduce the earlier Stermanet al(2018a) results, the headline figures from that paper depend heavily on how the forest growth curve is fitted to the training data. The resulting uncertainty in payback periods could be reduced by either obtaining more extensive training data (including mature forests of all types) or by modification of the forest growth function.
Computer-generated STOPP/START recommendations for hospitalised older adults: evaluation of the relationship between clinical relevance and rate of implementation in the SENATOR trial
Authors: Dalton Kieran , Curtin Denis , O’Mahony Denis , Byrne Stephen 
Published: March 2020

Abstract

Background
findings from a recent qualitative study indicate that the perceived clinical relevance of computer-generated STOPP/START recommendations was a key factor affecting their implementation by physician prescribers caring for hospitalised older adults in the SENATOR trial.

Aim
to systematically evaluate the clinical relevance of these recommendations and to establish if clinical relevance significantly affected the implementation rate.

Methods
a pharmacist–physician pair retrospectively reviewed the case records for all SENATOR trial intervention patients at Cork University Hospital and assigned a degree of clinical relevance for each STOPP/START recommendation based on a previously validated six-point scale. The chi-square test was used to quantify the differences in prescriber implementation rates between recommendations of varying clinical relevance, with statistical significance set at P &lt; 0.05.

Results
in 204 intervention patients, the SENATOR software produced 925 STOPP/START recommendations. Nearly three quarters of recommendations were judged to be clinically relevant (73.6%); however, nearly half of these were deemed of ‘possibly low relevance’ (320/681; 47%). Recommendations deemed of higher clinical relevance were significantly more likely to be implemented than those of lower clinical relevance (P &lt; 0.05).

Conclusions
a large proportion (61%) of the computer-generated STOPP/START recommendations provided were of potential ‘adverse significance’, of ‘no clinical relevance’ or of ‘possibly low relevance’. The adjudicated clinical relevance of computer-generated medication recommendations significantly affects their implementation. Meticulous software refinement is required for future interventions of this type to increase the proportion of recommendations that are of high clinical relevance. This should facilitate their implementation, resulting in prescribing optimisation and improved clinical outcomes for multimorbid older adults.
Ancient vases in modern vitrines: the sensory dynamics and social implications of museum display
Authors: Meyer Caspar 
Published: March 2020

AbstractThis contribution explores the changing sensory priorities underpinning the display of Greek painted pottery in European collections. The focus is on the introduction of glass-fronted cabinets in the purpose-designed public museums of art and archaeology of the mid-nineteenth century. Contrary to expectations, the contemporaneous debates surrounding the use of gallery furniture show that the museum stakeholders were less worried about the safety of the objects than the prospect of middle- and working-class visitors being exposed to the sexualized imagery on Athenian pottery. A survey of the different traditions of display in Britain and continental Europe highlights the shift from the multisensory engagements in early modern elite collections with vases as evidence of ancient custom to the selective viewing of the objects’ painted decoration as works of art whose proper interpretation called for classical education.
DeCoDe: degenerate codon design for complete protein-coding DNA libraries
Authors: Shimko Tyler C , Fordyce Polly M , Orenstein Yaron 
Published: March 2020

Abstract

Motivation
High-throughput protein screening is a critical technique for dissecting and designing protein function. Libraries for these assays can be created through a number of means, including targeted or random mutagenesis of a template protein sequence or direct DNA synthesis. However, mutagenic library construction methods often yield vastly more nonfunctional than functional variants and, despite advances in large-scale DNA synthesis, individual synthesis of each desired DNA template is often prohibitively expensive. Consequently, many protein-screening libraries rely on the use of degenerate codons (DCs), mixtures of DNA bases incorporated at specific positions during DNA synthesis, to generate highly diverse protein-variant pools from only a few low-cost synthesis reactions. However, selecting DCs for sets of sequences that covary at multiple positions dramatically increases the difficulty of designing a DC library and leads to the creation of many undesired variants that can quickly outstrip screening capacity.

Results
We introduce a novel algorithm for total DC library optimization, degenerate codon design (DeCoDe), based on integer linear programming. DeCoDe significantly outperforms state-of-the-art DC optimization algorithms and scales well to more than a hundred proteins sharing complex patterns of covariation (e.g. the lab-derived avGFP lineage). Moreover, DeCoDe is, to our knowledge, the first DC design algorithm with the capability to encode mixed-length protein libraries. We anticipate DeCoDe to be broadly useful for a variety of library generation problems, ranging from protein engineering attempts that leverage mutual information to the reconstruction of ancestral protein states.

Availability and implementation
github.com/OrensteinLab/DeCoDe.

Contact
yaronore@bgu.ac.il

Supplementary information
Supplementary data are available at Bioinformatics online.
FMNL3 regulates FASCIN for actin-mediated spindle migration and cytokinesis in mouse oocytes†
Authors: Pan Meng-Hao , Wan Xiang , Wang Hong-Hui , Pan Zhen-Nan , Zhang Yu , Sun Shao-Chen 
Published: March 2020

Abstract
Formin-like 3 (FMNL3) is a member of the formin-likes (FMNLs), which belong to the formin family. As an F-actin nucleator, FMNL3 is essential for several cellular functions, such as polarity control, invasion, and migration. However, the roles of FMNL3 during oocytes meiosis remain unclear. In this study, we investigated the functions of FMNL3 during mouse oocyte maturation. Our results showed that FMNL3 mainly concentrated in the oocyte cortex and spindle periphery. Depleting FMNL3 led to the failure of polar body extrusion, and we also found large polar bodies in the FMNL3-deleted oocytes, indicating the occurrence of symmetric meiotic division. There was no effect of FMNL3 on spindle organization; however, we observed spindle migration defects at late metaphase I, which might be due to the decreased cytoplasmic actin. Microinjecting Fmnl3-EGFP mRNA into Fmnl3-depleted oocytes significantly rescued these defects. In addition, the results of co-immunoprecipitation and the perturbation of protein expression experiments suggested that FMNL3 interacted with the actin-binding protein FASCIN for the regulation of actin filaments in oocytes. Thus, our results provide the evidence that FMNL3 regulates FASCIN for actin-mediated spindle migration and cytokinesis during mouse oocyte meiosis.
Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFβ signalling
Authors: Ebeid David E , Khalafalla Farid G , Broughton Kathleen M , Monsanto Megan M , Esquer Carolina Y , Sacchi Veronica , Hariharan Nirmala , Korski Kelli I , Moshref Maryam , Emathinger Jacqueline , Cottage Christopher T , Quijada Pearl J , Nguyen Jonathan H , Alvarez Roberto , Völkers Mirko , Konstandin Mathias H , Wang Bingyan J , Firouzi Fareheh , Navarrete Julian M , Gude Natalie A , Goumans Marie-Jose , Sussman Mark A 
Published: March 2020

Abstract

Aims
Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere length is the transforming growth factor beta (TGFβ) signalling pathway where inhibiting TGFβ signalling maintains telomere length. The relationship between Pim1 and TGFβ has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGFβ signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes.

Methods and results
Telomere length was maintained by lentiviral-mediated overexpression of PIM1 and inhibition of TGFβ signalling in A549 cells. Telomere length maintenance was further demonstrated in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1 and by pharmacological inhibition of TGFβ signalling. Mechanistically, Pim1 inhibited phosphorylation of Smad2, preventing its translocation into the nucleus and repressing expression of TGFβ pathway genes.

Conclusion
Pim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGFβ pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase. Findings from this study demonstrate a novel mechanism of telomere length maintenance and provide a potential target for preserving cardiac function.
Lymphocyte Activation Gene (LAG)-3 Is Associated With Mucosal Inflammation and Disease Activity in Ulcerative Colitis
Authors: Slevin Stephanie M , Garner Lucy C , Lahiff Conor , Tan Malcolm , Wang Lai Mun , Ferry Helen , Greenaway Borgel , Lynch Kate , Geremia Alessandra , Hughes Stephen , Leavens Karen , Krull David , Marks Daniel J B , Nevin Katherine , Page Kevin , Srinivasan Naren , Tarzi Ruth , Klenerman Paul , Travis Simon , Arancibia-Cárcamo Carolina V , Keshav Satish 
Published: March 2020

AbstractBackground and AimsLymphocyte activation gene [LAG]-3 is an immune checkpoint and its expression identifies recently activated lymphocytes that may contribute to inflammation. We investigated the role of LAG-3 by analysing its expression and function in immune cells from blood and tissue of patients with ulcerative colitis [UC].MethodsThe phenotypic properties of LAG-3+ T cells were determined by flow cytometry, qRT-PCR and single-cell RNA-sequencing. LAG-3+ cells were quantified and correlated with disease activity. The functional effects of LAG-3+ cells were tested using a depleting anti-LAG-3 monoclonal antibody [mAb] in a mixed lymphocyte reaction [MLR].ResultsLAG-3+ cells in the blood were negligible. LAG-3+ lymphocytes were markedly increased in inflamed mucosal tissue and both frequencies of LAG-3+ T cells and transcript levels of LAG3 correlated with endoscopic severity. LAG-3 expression was predominantly on effector memory T cells, and single-cell RNA-sequencing revealed LAG3 expression in activated and cytokine-producing T cell subsets. Foxp3+CD25hi Tregs also expressed LAG-3, although most mucosal Tregs were LAG-3−. Mucosal LAG-3+ cells produced mainly interferon γ [IFNγ] and interleukin-17A. LAG-3+ cell numbers decreased in patients who responded to biologics, and remained elevated in non-responders. Treatment with a depleting anti-LAG-3 mAb led to a reduction in proliferation and IFNγ production in an MLR.ConclusionsLAG-3+ cells are increased in the inflamed mucosa, predominantly on effector memory T cells with an activated phenotype and their cell numbers positively correlate with disease activity. Depleting LAG-3 eliminates activated proliferating T cells, and hence LAG-3 could be a therapeutic target in UC.
From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases
Authors: Landmesser Ulf , Poller Wolfgang , Tsimikas Sotirios , Most Patrick , Paneni Francesco , Lüscher Thomas F 
Published: March 2020

Abstract
Nucleic acid-based therapeutics are currently developed at large scale for prevention and management of cardiovascular diseases (CVDs), since: (i) genetic studies have highlighted novel therapeutic targets suggested to be causal for CVD; (ii) there is a substantial recent progress in delivery, efficacy, and safety of nucleic acid-based therapies; (iii) they enable effective modulation of therapeutic targets that cannot be sufficiently or optimally addressed using traditional small molecule drugs or antibodies. Nucleic acid-based therapeutics include (i) RNA-targeted therapeutics for gene silencing; (ii) microRNA-modulating and epigenetic therapies; (iii) gene therapies; and (iv) genome-editing approaches (e.g. CRISPR-Cas-based):
(i) RNA-targeted therapeutics: several large-scale clinical development programmes, using antisense oligonucleotides (ASO) or short interfering RNA (siRNA) therapeutics for prevention and management of CVD have been initiated. These include ASO and/or siRNA molecules to lower apolipoprotein (a) [apo(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoCIII, ANGPTL3, or transthyretin (TTR) for prevention and treatment of patients with atherosclerotic CVD or TTR amyloidosis.
(ii) MicroRNA-modulating and epigenetic therapies: novel potential therapeutic targets are continually arising from human non-coding genome and epigenetic research. First microRNA-based therapeutics or therapies targeting epigenetic regulatory pathways are in clinical studies.
(iii) Gene therapies: EMA/FDA have approved gene therapies for non-cardiac monogenic diseases and LDL receptor gene therapy is currently being examined in patients with homozygous hypercholesterolaemia. In experimental studies, gene therapy has significantly improved cardiac function in heart failure animal models.
(iv) Genome editing approaches: these technologies, such as using CRISPR-Cas, have proven powerful in stem cells, however, important challenges are remaining, e.g. low rates of homology-directed repair in somatic cells such as cardiomyocytes. In summary, RNA-targeted therapies (e.g. apo(a)-ASO and PCSK9-siRNA) are now in large-scale clinical outcome trials and will most likely become a novel effective and safe therapeutic option for CVD in the near future. MicroRNA-modulating, epigenetic, and gene therapies are tested in early clinical studies for CVD. CRISPR-Cas-mediated genome editing is highly effective in stem cells, but major challenges are remaining in somatic cells, however, this field is rapidly advancing.
Assessing the long-term impact of agricultural research on productivity: evidence from France
Authors: Lemarié Stéphane , Orozco Valérie , Butault Jean-Pierre , Musolesi Antonio , Simioni Michel , Schmitt Bertrand 
Published: March 2020

Abstract
This paper analyses the economic impact of agricultural research on productivity in France over the period 1959–2012. Adopting a dynamic time series model, we provide evidence that the impact of French agricultural research is in the range of values estimated for other countries, with the estimated long-run elasticity being 0.16, which corresponds to an internal rate of return of 22%. The estimated elasticity decreases at the beginning of the 1970s. Complementary analyses are developed to take into account the evolution of the priorities of public agricultural research (reorientation towards more fundamental objectives and focus on broader objective than productivity enhancement).
Resource availability drives bacterial succession during leaf-litter decomposition in a bromeliad ecosystem
Authors: Carrias Jean-François , Gerphagnon Mélanie , Rodríguez-Pérez Héctor , Borrel Guillaume , Loiseau Camille , Corbara Bruno , Céréghino Régis , Mary Isabelle , Leroy Céline 
Published: March 2020

ABSTRACT
Despite the growing number of investigations on microbial succession during the last decade, most of our knowledge on primary succession of bacteria in natural environments comes from conceptual models and/or studies of chronosequences. Successional patterns of litter-degrading bacteria remain poorly documented, especially in undisturbed environments. Here we conducted an experiment with tank bromeliads as natural freshwater microcosms to assess major trends in bacterial succession on two leaf-litter species incubated with or without animal exclusion. We used amplicon sequencing and a co-occurrence network to assess changes in bacterial community structure according to treatments. Alpha-diversity and community complexity displayed the same trends regardless of the treatments, highlighting that primary succession of detrital-bacteria is subject to resource limitation and biological interactions, much like macro-organisms. Shifts in bacterial assemblages along the succession were characterized by an increase in uncharacterized taxa and potential N-fixing bacteria, the latter being involved in positive co-occurrence between taxa. These findings support the hypothesis of interdependence between taxa as a significant niche-based process shaping bacterial communities during the advanced stage of succession.
Natural extract and its fractions isolated from the marine bacterium Pseudoalteromonas flavipulchra STILL-33 have antioxidant and antiaging activities in Schizosaccharomyces pombe
Authors: Prastya Muhammad Eka , Astuti Rika Indri , Batubara Irmanida , Takagi Hiroshi , Wahyudi Aris Tri 
Published: March 2020

ABSTRACT
Investigations into the potential for pharmacological inhibition of the aging process and the onset of age-related disease are increasingly garnering attention. Here, we analyzed the antiaging properties of natural compounds derived from several marine bacteria in vitro and in vivo using the fission yeast Schizosaccharomyces pombe. The Pseudoalteromonas flavipulchra STILL-33 extract exhibited high antioxidant and antiglycation activities in vitro. We then characterized two antioxidant active fractions isolated from this extract. In addition, we showed that the P. flavipulchra STILL-33 extract or either of its two active fractions (Fractions 1 and 2) could extend the longevity of fission yeast. Moreover, the particular extract and two active fractions were found to induce mitochondrial activity and to delay the G1 phase of the fission yeast cell cycle, perhaps by improving the aging process. The P. flavipulchra STILL-33 extract and Fraction 1 also increased the expression of the catalase-encoding ctt1+ gene and thereby decreased the reactive oxygen species level. Structural analysis showed that Fraction 1 was dominated by l-arginine and ipriflavone, and we showed indeed that the two corresponding commercial products increase the fission yeast lifespan. As for Fraction 2 was identified as the putative structure of butamben. Together, these results should facilitate the discovery of additional antiaging compounds from P. flavipulchra and ultimately the development of novel antiaging compounds for pharmaceutical use.
The Limits to Estimating Population-Genetic Parameters with Temporal Data
Authors: Lynch Michael , Ho Wei-Chin 
Published: March 2020

AbstractThe ability to obtain genome-wide sequences of very large numbers of individuals from natural populations raises questions about optimal sampling designs and the limits to extracting information on key population-genetic parameters from temporal-survey data. Methods are introduced for evaluating whether observed temporal fluctuations in allele frequencies are consistent with the hypothesis of random genetic drift, and expressions for the expected sampling variances for the relevant statistics are given in terms of sample sizes and numbers. Estimation methods and aspects of statistical reliability are also presented for the mean and temporal variance of selection coefficients. For nucleotide sites that pass the test of neutrality, the current effective population size can be estimated by a method of moments, and expressions for its sampling variance provide insight into the degree to which such methodology can yield meaningful results under alternative sampling schemes. Finally, some caveats are raised regarding the use of the temporal covariance of allele-frequency change to infer selection. Taken together, these results provide a statistical view of the limits to population-genetic inference in even the simplest case of a closed population.