bluuebunny/crossref_metadata_2025_split huggingface dataset:
Closing the gap between rocks and clocks using total-evidence dating
Authors: Ronquist Fredrik , Lartillot Nicolas , Phillips Matthew J. 
Published: June 2016

Total-evidence dating (TED) allows evolutionary biologists to incorporate a wide range of dating information into a unified statistical analysis. One might expect this to improve the agreement between rocks and clocks but this is not necessarily the case. We explore the reasons for such discordance using a mammalian dataset with rich molecular, morphological and fossil information. There is strong conflict in this dataset between morphology and molecules under standard stochastic models. This causes TED to push divergence events back in time when using inadequate models or vague priors, a phenomenon we term ‘deep root attraction’ (DRA). We identify several causes of DRA. Failure to account for diversified sampling results in dramatic DRA, but this can be addressed using existing techniques. Inadequate morphological models also appear to be a major contributor to DRA. The major reason seems to be that current models do not account for dependencies among morphological characters, causing distorted topology and branch length estimates. This is particularly problematic for huge morphological datasets, which may contain large numbers of correlated characters. Finally, diversification and fossil sampling priors that do not incorporate all the available background information can contribute to DRA, but these priors can also be used to compensate for DRA. Specifically, we show that DRA in the mammalian dataset can be addressed by introducing a modest extra penalty for ghost lineages that are unobserved in the fossil record, for instance by assuming rapid diversification, rare extinction or high fossil sampling rate; any of these assumptions produces highly congruent divergence time estimates with a minimal gap between rocks and clocks. Under these conditions, fossils have a stabilizing influence on divergence time estimates and significantly increase the precision of those estimates, which are generally close to the dates suggested by palaeontologists.
This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Tectonic blocks and molecular clocks
Authors: De Baets Kenneth , Antonelli Alexandre , Donoghue Philip C. J. 
Published: June 2016

Evolutionary timescales have mainly used fossils for calibrating molecular clocks, though fossils only really provide minimum clade age constraints. In their place, phylogenetic trees can be calibrated by precisely dated geological events that have shaped biogeography. However, tectonic episodes are protracted, their role in vicariance is rarely justified, the biogeography of living clades and their antecedents may differ, and the impact of such events is contingent on ecology. Biogeographic calibrations are no panacea for the shortcomings of fossil calibrations, but their associated uncertainties can be accommodated. We provide examples of how biogeographic calibrations based on geological data can be established for the fragmentation of the Pangaean supercontinent: (i) for the uplift of the Isthmus of Panama, (ii) the separation of New Zealand from Gondwana, and (iii) for the opening of the Atlantic Ocean. Biogeographic and fossil calibrations are complementary, not competing, approaches to constraining molecular clock analyses, providing alternative constraints on the age of clades that are vital to avoiding circularity in investigating the role of biogeographic mechanisms in shaping modern biodiversity.This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Genomic insights into temperature-dependent transcriptional responses ofKosmotoga olearia, a deep-biosphere bacterium that can grow from 20°C to 79°C
Authors: Pollo Stephen M. J. , Adebusuyi Abigail A. , Straub Timothy J. , Foght Julia M. , Zhaxybayeva Olga , Nesbø Camilla L. 
Published: June 2016

AbstractTemperature is one of the defining parameters of an ecological niche. Most organisms thrive within a temperature range that rarely exceeds ∼ 30°C, but the deep subsurface bacteriumKosmotoga oleariacan grow over a temperature range of 59°C (20°C -79°C). To identify genes correlated with this flexible phenotype, we compared transcriptomes ofK. oleariacultures grown at its optimal 65°C to those at 30°C, 40°C, and 77°C. The temperature treatments affected expression of 573 of 2,224K. oleariagenes. Notably, this transcriptional response elicits re-modeling of the cellular membrane and changes in metabolism, with increased expression of genes involved in energy and carbohydrate metabolism at high temperatures and up-regulation of amino acid metabolism at lower temperatures. At sub-optimal temperatures, many transcriptional changes were similar to those observed in mesophilic bacteria at physiologically low temperatures, including up-regulation of typical cold stress genes and ribosomal proteins. Comparative genomic analysis of additional Thermotogae genomes, indicate that one ofK. olearia's strategies for low temperature growth is increased copy number of some typical cold response genes through duplication and/or lateral acquisition. At 77°C one third of the up-regulated genes are of hypothetical function, indicating that many features of high temperature growth are unknown.
Evolutionary genomics of peach and almond domestication
Authors: Velasco Dianne , Hough Josh , Aradhya Mallikarjuna , Ross-Ibarra Jeffrey 
Published: June 2016

AbstractThe domesticated almond [Prunus dulcis (L.) Batsch] and peach [P. persica (Mill.) D. A. Webb] originate on opposite sides of Asia and were independently domesticated approximately 5000 years ago. While interfertile, they possess alternate mating systems and differ in a number of morpholog-ical and physiological traits. Here we evaluated patterns of genome-wide diversity in both almond and peach to better understand the impacts of mating system, adaptation, and domestication on the evolution of these taxa. Almond has ∼7X the genetic diversity of peach, and high genome-wide FSTvalues support their status as separate species. We estimated a divergence time of approximately 8 Mya, coinciding with an active period of uplift in the northeast Tibetan Plateau and subsequent Asian climate change. We see no evidence of bottleneck during domestication of either species, but identify a number of regions showing signatures of selection during domestication and a significant overlap in candidate regions between peach and almond. While we expected gene expression in fruit to overlap with candidate selected regions, instead we find enrichment for loci highly differentiated between the species, consistent with recent fossil evidence suggesting fruit divergence long preceded domestication. Taken together this study tells us how closely related tree species evolve and are domesticated, the impact of these events on their genomes, and the utility of genomic information for long-lived species. Further exploration of this data will contribute to the genetic knowledge of these species and provide information regarding targets of selection for breeding application and further the understanding of evolution in these species.
Prioritizing 2nd order interactions via support vector ranking using sensitivity indices on time series Wnt measurements†
Authors: sinha shriprakash 
Published: June 2016

AbstractIt is widely known that the sensitivity analysis plays a major role in computing the strength of the influence of involved factors in any phenomena under investigation. When applied to expression profiles of various intra/extracellular factors that form an integral part of a signaling pathway, the variance and density based analysis yields a range of sensitivity indices for individual as well as various combinations of factors. These combinations denote the higher order interactions among the involved factors, that might be of interest in the working mechanism of the pathway. For example, there are 19 types of WNTs and 10 FZDs with their 2ndorder combinations high enough and it is not possible to know which one to test first (except for those for which wet lab validations have been confirmed). But the effect of these combinations vary over time as measurements of fold changes and deviations in fold changes vary. In this work, after estimating the individual effects of factors for a higher order combination, the individual indices are considered as discriminative features. A combination, then is a multivariate feature set in higher order (>=2). With an excessively large number of factors involved in the pathway, it is difficult to search for important combinations in a wide search space over different orders. Exploiting the analogy of prioritizing webpages using ranking algorithms, for a particular order, a full set of combinations of interactions can then be prioritized based on these features using a powerful ranking algorithm via support vectors. Recording the changing rankings of the combinations over time points and durations, reveals how higher order interactions behave within the pathway and when and where an intervention might be necessary to influence the pathway. This could lead to development of time based therapeutic interventions. Based on a small dataset in time, we were able to generate the rankings of the 2ndorder combinations between WNTs and FZDs at different time snap shots and for different duration or time periods. Code has been made available on Google drive athttps://drive.google.com/folderview?id=0B7Kkv8wlhPU-V1Fkd1dMSTd5ak0&usp=sharingSignificanceThe search and wet lab testing of unknown biological hypotheses in the form of combinations of various intra/extracellular factors that are involved in a signaling pathway, costs a lot in terms of time, investment and energy. To reduce this cost of search in a vast combinatorial space, a pipeline has been developed that prioritises these list of combinations so that a biologist can narrow down their investigation. The pipeline uses kernel based sensitivity indices to capture the influence of the factors in a pathway and employs powerful support vector ranking algorithm. The generic workflow and future improvements are bound to cut down the cost for many wet lab experiments and reveal unknown/untested biological hypothesis.
Moss Chloroplasts Are Surrounded by a Peptidoglycan Wall Containing D-Amino Acids
Authors: Hirano Takayuki , Tanidokoro Koji , Shimizu Yasuhiro , Kawarabayasi Yutaka , Ohshima Toshihisa , Sato Momo , Tadano Shinji , Ishikawa Hayato , Takio Susumu , Takechi Katsuaki , Takano Hiroyoshi 
Published: June 2016

AbstractIt is believed that the plastids in green plants lost peptidoglycan (i.e., a bacterial cell wall-containing d-amino acids) during their evolution from an endosymbiotic cyanobacterium. Although wall-like structures could not be detected in the plastids of green plants, the moss Physcomitrella patens has the genes required to generate peptidoglycan (Mur genes), and knocking out these genes causes defects in chloroplast division. Here, we generated P. patens knockout lines (∆Pp-ddl) for a homolog of the bacterial peptidoglycan-synthetic gene encoding d-Ala:d-Ala ligase. ∆Pp-ddl had a macrochloroplast phenotype, similar to other Mur knockout lines. The addition of d-Ala-d-Ala (DA-DA) to the medium suppressed the appearance of giant chloroplasts in ∆Pp-ddl, but the addition of l-Ala-l-Ala (LA-LA), DA-LA, LA-DA, or d-Ala did not. Recently, a metabolic method for labeling bacterial peptidoglycan was established using ethynyl-DA-DA (EDA-DA) and click chemistry to attach an azide-modified fluorophore to the ethynyl group. The ∆Pp-ddl line complemented with EDA-DA showed that moss chloroplasts are completely surrounded by peptidoglycan. Our findings strongly suggest that the moss plastids have a peptidoglycan wall containing d-amino acids. By contrast, no plastid phenotypes were observed in the T-DNA tagged ddl mutant lines of Arabidopsis thaliana.
Antecedents of ERP systems implementation success: a study on Jordanian healthcare sector
Authors: Almajali Dmaithan Abdelkarim , Masa'deh Ra'ed , Tarhini Ali 
Published: June 2016

Purpose– Most small- and medium-sized enterprises (SMEs) use some business management software to manage their daily operations. Ultimately they consider transitioning to an enterprise resources planning (ERP) system. However, implementing ERP system successfully is costly and complex, and often shows high disappointment rates or even abandonment due to need of fit with the business or social culture. In Jordan, large businesses have been using the ERP system for a long time, but SMEs usage of the system is relatively new. The purpose of this paper is to study the effect of ERP implementation success antecedents which consists of training, supportive leadership and ease of use on ERP implementation success itself through a mediating effect of user satisfaction.Design/methodology/approach– Empirical data were collected using a survey questionnaire which was distributed to ERP users in Jordanian healthcare organizations. A total of 175 responses were collected and analyzed using structure equation modeling.Findings– A significant relationship was found between these antecedents and ERP implementation success. Furthermore, user satisfaction plays a significant mediating role between ease of use and ERP implementation success.Practical implications– The outcomes of this study are useful to ERP users as they would be able to strategize future ERP system implementation in different sectors such as education, manufacturing and insurance industry. Finally, the findings may be useful to ERP system adopters in different developing countries.Originality/value– This is one of the first studies which adequately covers the relationships between antecedents of user satisfaction and ERP implementation success which consists of training, supportive leadership and ease of use on ERP implementation success itself through a mediating effect of user satisfaction.
Following momentum and avoiding the “Minsky Moment” evidence from investors on the Financial Instability Hypothesis
Authors: Pirie Scott , Chan Ronald King To 
Published: June 2016

Purpose
This study aims to find out how institutional investors use momentum in making investment decisions, and whether their actions are consistent with the Financial Instability Hypothesis of Hyman Minsky.

Design/methodology/approach
The study discusses the findings of interviews with 25 professional investors from the Hong Kong offices of five global financial institutions. All of the participants have several years of practical experience in global and regional markets.

Findings
Nearly all the managers interviewed said they use momentum in making investment decisions, and they do this in ways that are consistent with the Financial Instability Hypothesis, in which markets alternate between stable and unstable states. The participants are aware they may contribute to this, but they cannot avoid doing it because of short-term constraints in the present financial system.

Originality/value
This study adds to our knowledge of how professional investors use momentum in their investment strategies. It complements findings of quantitative studies that show momentum strategies have been profitable in many market settings. It also adds evidence that supports the Financial Instability Hypothesis.
Thin section magnetic resonance diffusion‐weighted imaging in the detection of acute infratentorial stroke
Authors: Entwisle Tom , Perchyonok Yuliya , Fitt Greg 
Published: June 2016

AbstractIntroductionMagnetic resonance diffusion‐weighted imaging (DWI) is the most accurate technique available for demonstrating acute infarction; however, false‐negative DWI is higher in the infratentorium due to the limited spatial resolution with conventional 5 mm DWI. The aim of this study was to compare 5 mm DWI with 3 mm DWI in the detection of acute infratentorial infarction.MethodsA 3 mm DWI sequence of the infratentorium was incorporated into the conventional MRI stroke protocol for the evaluation of patients with vertebrobasilar stroke‐like deficits. The 5 mm and 3 mm DWI sequences were assessed by two neuroradiologists who were blinded to the clinical findings. Sensitivity and specificity analysis was then performed against the final clinical diagnosis.ResultsThe sensitivity for detection of infratentorial infarction was 81.1% for 5 mm DWI and 94.6% for 3 mm DWI and the specificity was 100% for 5 mm DWI and 97.7% for 3‐mm DWI. The false‐negative rate in detection of infratentorial infarcts was 5.6% for the 5‐mm sequence and 1.6% for the 3‐mm sequence. The six 5‐mm DWI false‐negative cases (4.8%) were less than 9 mm in diameter (3–8 mm, average 4.67 mm) and located in the brainstem. This supports the hypothesis that small lesions may not be detected on 5 mm DWI due to partial volume averaging.ConclusionWhere there is clinical suspicion of infratentorial infarction, 3 mm DWI of the infratentorium adds sensitivity compared to 5 mm DWI with only a small reduction in specificity.
Significance of different response evaluation criteria in predicting progression‐free survival of lung cancer with certain imaging characteristics
Authors: Yang Dengxia , Woodard Gavitt , Zhou Chan , Wang Xinyue , Liu Zhujun , Ye Zhaoxiang , Li Kai 
Published: June 2016

BackgroundCertain radiographic signs of a treatment response, such as cavitation, changes in density, or tumor change along a short axis, are not considered by Response Evaluation Criteria in Solid Tumors (RECIST). This study evaluates what additional prognostic information can be obtained by including these criteria in tumor assessment.MethodsData of 105 patients were included. Tumor cavitation was observed in 51 patients at baseline. An additional 23 patients developed tumor cavitation during treatment. A change in tumor density was the only radiographic treatment response observed in 22 patients. The only measureable treatment response in nine patients was a decrease along the short axis size of the tumor. Tumor response was assessed using various criteria.ResultsIn patients with basic tumor cavitation, RECIST1.1 scores accurately predicted differences in progression‐free survival (PFS; P = 0.076) while modified (m) RECIST did not (P = 0.550). mRECIST detected a significant difference between PFS in patients with post‐therapeutic cavitation with different responses, but no significant difference using RECIST1.1 (P = 0.004 vs. P = 0.477). In patients with only tumor density changes, there was no significant difference in PFS when either RECIST1.1 or density criteria were used (P = 0.419). In patients with a change in size along the tumor's short axis, short axis criteria could predict significant difference in PFS (P = 0.004).Conclusions
RECIST1.1 provides the best assessment of tumor response and prediction of PFS in patients with basic tumor cavitation. mRECIST provides better PFS prognostic information in patients with post‐therapeutic cavitation. Short axis criteria provides better PFS prognostic information in patients with changes in the short axis of tumor diameter. Changes in tumor density were not a useful prognostic sign.
Role of OCT2 and MATE1 in renal disposition and toxicity of nitidine chloride
Authors: Li L P , Song F F , Weng Y Y , Yang X , Wang K , Lei H M , Ma J , Zhou H , Jiang H D 
Published: June 2016

Background and PurposeNitidine chloride (NC), a benzophenanthridine alkaloid, has various biological properties including anticancer and analgesic activities. The aim of the present study was to evaluate the role of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion 1 (MATE1) in the renal disposition and nephrotoxicity of NC.Experimental ApproachMDCK cells stably expressing human OCT2 and/or hMATE1 were used to investigate the OCT2‐ and MATE1‐mediated transport of NC. In addition, the accumulation of NC and its potential toxicity were studied in rat primary‐cultured proximal tubular (rPCPT) cells and in rats in vivo.Key ResultsNC was found to be a high‐affinity substrate of both OCT2 and MATE1 with high cytotoxicity in MDCK‐hOCT2/hMATE1 and MDCK‐hOCT2 compared to mock cells. The OCT2 inhibitors, cimetidine and (+)‐tetrahydropalmatine ((+)‐THP), significantly reduced NC accumulation and cytotoxicity in MDCK‐hOCT2, MDCK‐hOCT2/hMATE1 and rPCPT cells. Severe kidney damage with high levels of blood urea nitrogen and lactate dehydrogenase (LDH), reduced levels of alkaline phosphatase (ALP) and pathological changes were found in rats after 20 days of successive i.v. doses of NC (5 mg·kg−1·day−1). Concomitantly, the concentration of NC in the kidney reached similar high levels at 2 h after the last dose of the 20 day treatment as those observed at 0.5 h after a single i.v. dose of 5 mg·kg−1.Conclusions and ImplicationsOur data indicate that NC‐induced nephrotoxicity might be mainly attributed to OCT2‐mediated extensive renal uptake and weak tubular secretion by MATE1.
Magel2‐null mice are hyper‐responsive to setmelanotide, a melanocortin 4 receptor agonist
Authors: Bischof Jocelyn M , Van Der Ploeg Lex H T , Colmers William F , Wevrick Rachel 
Published: June 2016

Background and Purposeα‐ and β‐melanocyte‐stimulating hormones (MSH) are derived from pro‐opiomelanocortin (POMC) and are the natural agonist ligands of the melanocortin 4 receptor, a key regulator of energy homeostasis. Recent rodent and human data have implicated the MAGEL2 gene, which may regulate activation of POMC neurons, as a significant contributor to the metabolic symptoms observed in Prader–Willi Syndrome (PWS). Firstly, patients with protein truncating mutations in MAGEL2 exhibit numerous clinical characteristics of PWS. Secondly, Magel2‐null mice may not normally activate MC4 receptors, as they are defective in the activation of their POMC neurons and hence may fail to normally release the POMC‐derived MC4 receptor agonist ligands α‐ and β‐MSH. Magel2‐null mice represent a tractable animal model for the metabolic and appetitive imbalance seen in patients with PWS.Experimental ApproachWe tested a dose titration of the MC4 receptor agonist setmelanotide, in development for rare monogenic forms of obesity, in Magel2‐null mice.Key ResultsWe show that Magel2‐null mice are hypersensitive to the appetite suppressing and metabolic effects of setmelanotide.Conclusion and ImplicationsSetmelanotide may be a useful investigational hormone/neuropeptide replacement therapy for PWS and rare monogenic forms of obesity exhibiting impaired function of POMC neurons.