bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular phylogeny and biogeography of Holcoglossum (Orchidaceae: Aeridinae) based on nuclear ITS, and chloroplast trnL-F and matK
Authors: Fan Jie , Qin Hai-Ning , Li De-Zhu , Jin Xiao-Hua
Published: February 2019

The phylogenetic relationships and biogeography of the Asiatic orchid genus Holcoglossum (Vandeae, Aeridinae) were inferred from sequences of chloroplast matK and trnL‐F genes and nuclear ITS regions of 25 taxa (12 Holcoglossum, 11 Aeridinae, 2 outgroups). Analysis of combined datasets with parsimony and Bayesian methods revealed that Holcoglossum is highly supported as monophyletic, including two debatable species, H. amesianum and H. subulifolium, and consists of three well‐supported major subclades which agree well with biodiversity centers of Holcoglossum: one tropical subclade comprising four species, another forming a polytomy comprising six species restricted to the temperate alpine region of the Hengduan Mountains, and the third with two species somewhat distributed between the first two regions. However, these three major subclades are only partly in accordance with previous infrageneric classifications based on morphological characters. The lip lamella, long and conical spur and tapering stipe seem to have evolved at least twice in Holcoglossum, similarly the pollination system shift has occurred at least twice. Vicariance analyses and molecular phylogeny suggest that Holcoglossum dispersed from tropical regions to the Hengduan Mountains and then radiated there as a result of the uplift of Qinghai‐Tibetan Plateau.
Molecular phylogeny and biogeography of Gentiana sect. Cruciata (Gentianaceae) based on four chloroplast DNA datasets
Authors: Zhang Xiao-Lan , Wang Yu-Jin , Ge Xue-Jun , Yuan Yong-Ming , Yang Hui-Ling , Liu Jian-Quan
Published: February 2019

Gentiana sect. Cruciata is mainly found on alpine mountains across Eurasia, with the greatest species diversity occurring on the Qinghai‐Tibetan Plateau (QTP). In this study, we determined the phylogenetic relationships between species within the Cruciata section to further elucidate the biogeographical processes governing these relationships. Phylogenetic reconstructions, based on both parsimony and Bayesian methods, were applied to data from four cpDNA fragments (> 3,000 bp) that were obtained for 39 accessions belonging to Cruciata and related sections or outgroups. Our results suggested that all the species sampled within this section comprise a monophyletic group, but rejected all previous hypotheses regarding intra‐sectional classifications based on gross morphology. Five clades were identified. The basal clade comprised three species that were endemic to the QTP. The clade that diverged second comprised three Central Asian species. The European clade, containing only G. cruciata, was grouped with the remaining two clades containing species from the QTP and central Asia. The biogeographic analyses and divergence estimates suggested that this section diversified initially on the QTP within four million years. Given the low genetic differentiation, most species/clades may be the result of more recent differentiation. These results together confirmed the long‐standing hypothesis that alpine plants in Central Asia and Europe originated from the QTP and/or West China and diversified extensively after the Pliocene when global temperatures decreased.
Forensic analysis of flash flood response
Authors: Borga Marco , Comiti Francesco , Ruin Isabelle , Marra Francesco
Published: February 2019

The last decade has witnessed the development of methodologies for the post‐flood documentation of both hydrogeomorphological and social response to extreme precipitation. These investigations are particularly interesting for the case of flash floods, whose space–time scales make their observations by conventional hydrometeorological monitoring networks particularly challenging. Effective flash flood documentation requires post‐flood survey strategies encompassing accurate radar estimation of rainfall, field and remote‐sensing observations of the geomorphic processes, indirect reconstruction of peak discharges—as well eyewitness interviews. These latter can give valuable information on both flood dynamics and the related individual and collective responses. This study describes methods for post‐flood surveys based on interdisciplinary collaborations between natural and social scientists. These surveys may help to better understand the links between hydrometeorological dynamics and geomorphic processes as well as the relationship between flood dynamics and behavioral response in the context of fast space–time changes of flooding conditions.

This article is categorized under:

Science of Water > Methods

Science of Water > Hydrological Processes
Effects of external recirculation on a two‐stage mainstream anaerobic‐anammox treatment system
Authors: Li Xiaojin , He Zhen
Published: February 2019

Nitritation‐anammox treatment can be a potentially energy‐ and resource‐efficient technology for treating mainstream wastewater. However, the issue of nitrate residue from anammox treatment remains to be addressed. Herein, external recirculation of the anammox effluent to a hybrid anaerobic reactor (HAR), which was also to provide a continuous flow with low COD/N for the nitritation‐anammox reactor, was employed to decrease the residue compounds. The recirculation ratio of 50% was observed to be the optimal to achieve the best overall performance with potential savings in energy demand. Specifically, in the operation scenario of R = 50%, the highest COD removal of ~90% by the HAR was achieved. Meanwhile, the lowest COD/NH4+‐N ratio of ~2.0 in the HAR effluent ensured the lowest observed NO3−‐N/NH4+‐N ratio of ~14% in the nitritation‐anammox reactor. These results have demonstrated the feasibility of applying external recirculation for nitrate residue removal via denitrification in the anaerobic pretreatment stage.

Practitioner points

Nitritation‐anammox treatment is an attractive method for mainstream wastewater treatment.

Nitrate residue from anammox processes contributes to total nitrogen in the final effluent.

Recirculation of anammox effluent to an anaerobic reactor can decrease nitrate residue.

A recirculation ratio of 50% results in a low COD/NH4+ ratio of 2 that benefits the subsequent anammox.
Network Analysis to Model and Analyse Roman Transport and Mobility
Authors: de Soto Pau
Published: February 2019

The analysis of Roman infrastructures, which helps to understand the transport costs, the commercial routes and the territorial configuration, is an indispensable way to know the benefits and shortcomings of the transportation system created in Roman times. It is well known that the Roman Empire built the first big transport network in Western Europe, parts of Eastern Europe, the Middle East and Northern Africa. In this paper, we show our attempt to reconstruct the Roman transport conditions in Hispania by valuating its connectivity and by modelling the travel costs and times. All of these calculations have been made based in a highly digitized transport network and Network Science applications. The results of such methodologies provide us with new information to understand the Iberian territorial organisation, the distribution of commodities, product competition and problems of stagnation in ancient economies such as that of Ancient Rome.
Broad and Coarse: Modelling Demography, Subsistence and Transportation in Roman England
Authors: Franconi Tyler , Green Chris
Published: February 2019

The English Landscape and Identities project (EngLaId), which ran from 2011 to 2016 (ERC grant number 269797), was designed to take a long-term perspective on English archaeology from the Middle Bronze Age (c. 1500 BCE) to the Domesday survey (1086 CE). It was a legacy data project that collated an immense number of records of English archaeology from a large number of different public and academic sources. Within this mountain of material, the Roman period (43 to 410/411 CE) stood out as being particularly fecund, accounting for 40% of the data (by record count) coming from only 15% of the total timespan of the project. This paper examines the ways in which the EngLaId project approached the modelling and analysis of its data for Roman England. We focus here on the three themes of demography, subsistence economy and transportation. Overall, EngLaId provides an interesting contrast to the possibilities and limitations of the other projects presented in this volume because of its large spatiotemporal scale and its (thus necessary) broad-brush approaches to data analysis and modelling. It is also this large spatiotemporal scale that helps situate the Roman period within a much longer span of history, making evident what was unique to this time period and what was constant across multiple periods.
The Economic Archaeology of Roman Economic Performance
Authors: Jongman Willem M.
Published: February 2019

Recent years have witnessed a paradigm shift in the study of the Roman economy. Methodologically modern economic analysis is now far more acceptable than it once was, and archaeology has become the major source of empirical data for many questions. On the substantive side there is now a far clearer appreciation of the major changes that the Roman economy underwent, with substantial growth of population and aggregate production and even some improvements in standard of living, but followed by equally dramatic decline. This economic success was not limited to the imperial core, but also extended to the provinces.
Precision study of GeV-scale resonant leptogenesis
Authors: Ghiglieri J. , Laine M.
Published: February 2019

Abstract

Low-scale leptogenesis is most efficient in the limit of an extreme mass degeneracy of right-handed neutrino flavours. Two variants of this situation are of particular interest: large neutrino Yukawa couplings, which boost the prospects of experimental scrutiny, and small ones, which may lead to large lepton asymmetries surviving down to T < 5 GeV. We study benchmarks of these cases within a “complete” framework which tracks both helicity states of right-handed neutrinos as well as their kinetic non-equilibrium, and includes a number of effects not accounted for previously. For two right-handed flavours with GeV-scale masses, Yukawa couplings up to |h| ∼ 0.7×10−5 are found to be viable for baryogenesis, with ΔM/M ∼ 10−8 as the optimal degeneracy. Late-time lepton asymmetries are most favourably produced with ΔM/M ∼ 10−11. We show that the system reaches a stationary state at T < 15 GeV, in which lepton asymmetries can be more than 103 times larger than the baryon asymmetry, reach flavour equilibrium, and balance against helicity asymmetries.
Perturbative classical conformal blocks as Steiner trees on the hyperbolic disk
Authors: Alkalaev Konstantin , Pavlov Mikhail
Published: February 2019

Abstract

We consider the Steiner tree problem in hyperbolic geometry in the context of the AdS/CFT duality between large-c conformal blocks on the boundary and particle motions in the bulk. The Steiner trees are weighted graphs on the Poincare disk with a number of endpoints and trivalent vertices connected to each other by edges in such a way that an overall length is minimum. We specify a particular class of Steiner trees that we call holographic. Their characteristic property is that a holographic Steiner tree with N endpoints can be inscribed into an N-gon with N − 1 ideal vertices. The holographic Steiner trees are dual to large-c conformal blocks. Particular examples of N = 2, 3, 4 Steiner trees as well as their dual conformal blocks are explicitly calculated. We discuss geometric properties of the holographic Steiner trees and their realization in CFT terms. It is shown that connectivity and cuts of the Steiner trees encode the factorization properties of large-c conformal blocks.
The factor structure of a Polish language version of the hospital anxiety depression scale (HADS)
Authors: Nezlek John B. , Rusanowska Marzena , Holas Paweł , Krejtz Izabela
Published: February 2019

The Hospital Anxiety Depression Scale (HADS) is widely used as a screening measure for psychological distress. Nevertheless, there is disagreement among researchers about the extent to which the HADS provides separate measures of anxiety and depression or a single measure of affectively based distress, and the present study was designed to contribute to this discussion. Participants (n = 951) who were psychologically distressed, but not hospitalized, completed a Polish language version of the HADS. A confirmatory factor analysis of participants’ responses confirmed a model with two correlated factors with one cross-loaded item. The estimated correlation between the factors was .68. These results suggest that the Polish version of the HADS consists of two correlated measures of affectively focused distress, depression and anxiety. Nevertheless, analysts and practitioners need to be cautious and take into account the possibility that the discriminant validity of these two scales may be somewhat limited given the correlation between the subscales and the possible cross-loadings of items.
Ocean Commons, Law of the Sea and Rights for the Sea
Authors: De Lucia Vito
Published: February 2019

The aim of this paper is to re-activate certain layers of normative meaning that have been obscured, forgotten or rendered inoperative by the predominant traditions that engaged, from Grotius onwards, with the concept of res communes omnium. The hope and the purpose is that of offering a novel perspective on matters such as the protection and preservation of ocean commons that are of great urgency and importance today. Re-activating or ‘remembering’ the full scope of the concept of res communes omnium may produce some effects on the broader discourse of ocean environmental protection. It may, perhaps, help carve novel space for re-imagining the terms of the problems, and the array of available solutions that can be entertained and discussed, having particularly in mind the debates currently ongoing in the context of the negotiations towards a new global treaty on marine biodiversity in areas beyond national jurisdiction.
ITP, ISP, AND SCH
Authors: HACHTMAN SHERWOOD , SINAPOVA DIMA
Published: February 2019

$ISP$ cannot hold at the first or second successor of a singular strong limit of countable cofinality; on the other hand, we force a failure of “strong ${\rm{SCH}}$” across a cardinal where $ITP$ holds. We also show that $ITP$ does not imply that there are stationary many internally unbounded models.
Sectoral Influence on Competition Legislation: Evidence from the Cartel Registers, 1920–2000
Authors: Fellman Susanna , Shanahan Martin
Published: February 2019

Legislation that required the registration of firms’ anticompetitive agreements (cartel registers) to reveal, and sometimes regulate, anticompetitive behavior was relatively common in many nations before 1975. Examining the introduction of these registers in sixteen mostly OECD countries between 1920 and 2000 reveals which industries and sectors appeared to minimize successfully the impact of the legislation in their jurisdiction. We find considerable variation, but in most countries, the agriculture and export sectors were especially successful in avoiding or delaying the application of a register in their areas of interest.
MISQUOTING SOPHOCLES’ OEDIPVS TYRANNVS. A NEW PROOF OF THE INAUTHENTICITY OF PS.-ARISTOTLE, ON THE COSMOS
Authors: Galzerano Manuel
Published: February 2019

Chapters 6 and 7 of the pseudo-Aristotelian treatise On the Cosmos (Περὶ κόσμου = De mundo) display ‘a series of well-crafted and carefully organized analogies’ in order to represent the power of god pervading the whole universe. The last analogy (400b14–28), which is by far the most important in this section, compares the rule of god over the world to the rule of the law in a Greek city (ὁ τῆς πόλεως νόμος). As shown by the author in the previous analogies, the perfect order of the universe is the result of the continuous creation and dissolution of single things: this process—based upon the harmony of opposites—is the keystone of the eternity and equilibrium of our world. Similarly, the law is the unmoved (ἀκίνητος) mover of every activity and experience in the city: both positive and negative situations involving single citizens contribute to the supreme order and stability of the city. Positive examples include the activity of rulers, officials and members of the assemblies (ἄρχοντες, θεσμοθέται, βουλευταί, ἐκκλησιασταί), whereas negative examples include those who go to trial defending themselves (ὁ δὲ πρὸς τοὺς δικαστὰς ἀπολογησόμενος) and those who are imprisoned and destined to capital punishment (ὁ δὲ εἰς τὸ δεσμωτήριον ἀποθανούμενος). In spite of their difference, all of these actions are due to one single order (κατὰ μίαν πρόσταξιν), that is, the civic law, which ensures the stability of the city. To stress and illustrate this concordia discors, which characterizes both the city and the universe, the author of the treatise closes the passage with a quotation from Sophocles’ Oedipus Tyrannus (lines 4–5):πόλις δ' ὁμοῦ μὲν θυμιαμάτων γέμει,ὁμοῦ δὲ παιάνων τε καὶ στεναγμάτωνThe author reads these verses as a perfect example of a context characterized by opposite situations: in fact, the city is full of paeans (παιάνων), which are interpreted as ‘songs of joy and relief’, and, at the same time, it is also full of laments and mourns (στεναγμάτων). The same interpretation can be found in the Latin translation of the treatise, which gives even more emphasis to the opposition between life and death: uideasque illam ciuitatem pariter spirantem Panchaeis odoribus et graueolentibus caenis, resonantem hymnis et carminibus et canticis, eandem etiam lamentis et ploratibus heiulantem.
Effects of rehabilitation pruning and agroforestry on cacao tree development and yield in an older full-sun plantation
Authors: Riedel Judith , Kägi Nora , Armengot Laura , Schneider Monika
Published: February 2019

Overaged full-sun cacao plantations and the need for sustainable production systems call for combining rehabilitation of plantations with the establishment of agroforestry. We tested the effect of drastic rehabilitation pruning of old cacao tree stock and the introduction of both high- and low-diversity agroforestry on survival, growth and yield of T. cacao in a commercial plantation in peninsular Malaysia over a period of 5 years. We further determined the incidence of pests and diseases of cacao pods and assessed the performance of the whole system for smallholder farmers, including yields of by-crops. Rehabilitation pruning negatively affected cacao tree development and short-term yield. No more effects of pruning on cacao yield were observed starting in the third year on in the monoculture and starting in the fourth year on in low-diversity agroforestry. We found similar cacao tree development and yield in the low-diversity agroforestry and a common practice monoculture, suggesting that the implementation of agroforestry is a commercially feasible strategy, due to additional income generated through timber production. Reduced cacao tree development and yield in the high-diversity agroforestry were compensated by additional harvests of cassava and banana compared to monoculture. Incidence of cocoa pod borer (Conopomorpha cramerella) was lower in the agroforestry systems, especially the high-diversity system, while the incidence of black pod disease (Phytophthora spp.) did not differ between agroforestry and monoculture. The findings highlight the potential of agroforestry to reconcile ecologically sustainable land use with natural, cost-effective pest management. While pruning needs to be done with timing and disease pressure in mind to minimize short-term yield losses, this measure proved to be a feasible strategy for establishing agroforestry on extant plantations.
Defending heaven's desirability
Authors: NEPTUNE CLINTON
Published: February 2019

Bernard Williams famously argued that immortality would lead to intolerable tedium. If his conclusion is true, then we ought not desire any sort of blissful-type afterlife (heaven) that precludes death. I reconstruct Williams's argument and examine three possible defeaters for his premises: the possibility of infinite activity kinds, the inability to prefer justifiably non-existence over the enduring of suffering, and the existence of inexhaustible pleasures such as the deepening love relationship between family, friends, and God, if God exists. I will show that further attempts to reboot Williams's argument also fail to rule out the desirability of heaven.
How Procurement Judges The Value of Medical Technologies: A Review of Healthcare Tenders
Authors: Miller Fiona A. , Lehoux Pascale , Peacock Stuart , Rac Valeria E. , Neukomm Jeff , Barg Carolyn , Bytautas Jessica P. , Krahn Murray
Published: February 2019

Objectives

Procurement's important role in healthcare decision making has encouraged criticism and calls for greater collaboration with health technology assessment (HTA), and necessitates detailed analysis of how procurement approaches the decision task.

Methods

We reviewed tender documents that solicit medical technologies for patient care in Canada, focusing on request for proposal (RFP) tenders that assess quality and cost, supplemented by a census of all tender types. We extracted data to assess (i) use of group purchasing organizations (GPOs) as buyers, (ii) evaluation criteria and rubrics, and (iii) contract terms, as indicators of supplier type and market conditions.

Results

GPOs were dominant buyers for RFPs (54/97) and all tender types (120/226), and RFPs were the most common tender (92/226), with few price-only tenders (11/226). Evaluation criteria for quality were technical, including clinical or material specifications, as well as vendor experience and qualifications; “total cost” was frequently referenced (83/97), but inconsistently used. The most common (47/97) evaluative rubric was summed scores, or summed scores after excluding those below a mandatory minimum (22/97), with majority weight (64.1 percent, 62.9 percent) assigned to quality criteria. Where specified, expected contract lengths with successful suppliers were high (mean, 3.93 years; average renewal, 2.14 years), and most buyers (37/42) expected to award to a single supplier.

Conclusions

Procurement's evaluative approach is distinctive. While aiming to go beyond price in the acquisition of most medical technologies, it adopts a narrow approach to assessing quality and costs, but also attends to factors little considered by HTA, suggesting opportunities for mutual lesson learning.
Maritime Anomaly Detection using Density-based Clustering and Recurrent Neural Network
Authors: Zhao Liangbin , Shi Guoyou
Published: February 2019

Maritime anomaly detection can improve the situational awareness of vessel traffic supervisors and reduce maritime accidents. In order to better detect anomalous behaviour of a vessel in real time, a method that consists of a Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm and a recurrent neural network is presented. In the method presented, the parameters of the DBSCAN algorithm were determined through statistical analysis, and the results of clustering were taken as the traffic patterns to train a recurrent neural network composed of Long Short-Term Memory (LSTM) units. The neural network was applied as a vessel trajectory predictor to conduct real-time maritime anomaly detection. Based on data from the Chinese Zhoushan Islands, experiments verified the applicability of the proposed method. The results show that the proposed method can detect anomalous behaviours of a vessel regarding speed, course and route quickly.
Understanding the nature of associations between family instability, unsupportive parenting, and children's externalizing symptoms
Authors: Coe Jesse L. , Davies Patrick T. , Hentges Rochelle F. , Sturge-Apple Melissa L.
Published: February 2019

This study examined the mediating role of maternal unsupportive parenting in explaining associations between family instability and children's externalizing symptoms during the transition to formal schooling in early childhood. Participants included 243 preschool children (M age = 4.60 years) and their parents. Findings from cross-lagged autoregressive models conducted with multimethod (survey and observations), multi-informant (parent, teacher, and observer), longitudinal (three annual waves of data collection) data indicated that experiences with heightened family instability predicted decreases in supportive parenting, which in turn predicted increases in children's externalizing symptoms. Analyses also revealed a bidirectional association between parenting and family instability over time, such that higher levels of instability predicted decreases in supportive parenting, which in turn predicted increases in family instability.
Hybrid procedure of right ventricle outflow tract stenting in small infants with pulmonary atresia and ventricular septal defect: early and mid-term results from a single centre
Authors: Bondanza Sara , Calevo Maria Grazia , Derchi Maria Elena , Santoro Francesco , Marasini Maurizio
Published: February 2019

Introduction

Pulmonary atresia, ventricular septal defect, major aorto-pulmonary collateral arteries, and pulmonary arteries hypoplasia are rare and complex congenital defects that require early interventions to relieve cyanosis and enhance the growth of native pulmonary arteries. The treatment of these patients is still controversial. Surgical techniques require cardiopulmonary bypass which is poorly tolerated by small infants. Percutaneous techniques such as radiofrequency perforation can be challenging. The hybrid technique consists of perventricular stenting of the right ventricle outflow tract through medial sternotomy, to restore native pulmonary flow.

Methods

We retrospectively reviewed the cardiovascular database of our centre in order to analyse our experience in hybrid procedure. We detected six patients who underwent hybrid first approach between November 2007 and December 2015. We report our early results and mid-term outcomes.

Results

Median age at the procedure was 26 days, median weight was 3150 g, and median Nakata index was 52 mm2/m2. All procedures were successful except for one: this patient underwent a surgical shunt. No immediate and early deaths or major complications occurred and oxygen saturation levels increased in all the patients. Patients were followed up for a period of 12–103 months, and four of them underwent a procedure of unifocalisation at the mean age of 12.5 months.

Conclusions

We reported data from the largest series of patients who underwent this hybrid procedure. Our experience demonstrated encouraging results to expand the use of this approach to bridge high-risk patients with diminutive pulmonary arteries to a second step of surgical repair.
Food security of food recipients of a food pantry and soup kitchen
Authors: Mousa Tamara Y , Freeland-Graves Jeanne H
Published: February 2019

Objective

To discern the impact of food donations provided by a food pantry and soup kitchen on food security.

Design

In this cross-sectional study, participants completed a demographic questionnaire, core food security module, FFQ and list of food donations. The FFQ was utilized to assess diet quality as estimated via the 2010 Healthy Eating Index.

Setting

Clients were selected randomly from a food pantry and soup kitchen in Central Texas, USA.

Participants

A total of 222 adults.

Results

Approximately 73 % of participants lacked food security. Compared with the food secure, the food insecure consisted of 61 % men, 42 % Caucasians, 56 % single and 67 % homeless. Also, of the food insecure, 60 % were soup kitchen clients and 64 % had an annual income <$US 1000 (P<0·01). The probability of food insecurity was reduced by ≥1·17-fold when the total dietary intake included the food donations, as these were rich in fruits, total vegetables and grains, dairy and protein foods (P<0·05).

Conclusions

Food insecurity was quite prevalent in this sample of individuals who visited food pantries and soup kitchens. The addition of food donations improved the quality of the participants’ total diet and had a positive influence on food security. Thus, community organizations should financially support these food assistance agencies and strive to offer a variety of healthy and tasty foods in adequate quantities to provide optimum diet quality.
Future Mars Rover Named for DNA Pioneer Rosalind Franklin
Authors: Cartier Kimberly
Published: February 2019

The rover will explore a once water rich region on Mars’s surface and search for evidence of current and past life.
Decidual RANKL/RANK interaction promotes the residence and polarization of TGF-β1-producing regulatory γδ T cells
Authors: Chang Rui-Qi , Shao Jun , Meng Yu-Han , Wang Jian , Li Da-Jin , Li Ming-Qing
Published: February 2019

Abstact

Decidual γδΤ (dγδΤ) cells play an essential role during successful pregnancy; however, the residence and polarization of γδΤ cells in decidua remain unclear. In this study, we observed higher levels of receptor activator for nuclear factor-κ B ligand (RANKL) on decidual stromal cells (DSCs), and its receptor RANK on dγδΤ cells in decidua from normal pregnancy compared with patients with recurrent spontaneous abortion (RSA). RANKL expressed by DSCs can induce the polarization of peripheral blood γδΤ (pγδΤ) and dγδΤ cells to Foxp3 + γδΤ cells, and upregulate the expression of transforming growth factor (TGF)-β1. This process is mediated through activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In addition, RANKL promotes the adhesion of dγδΤ cells to DSCs in vitro, which is associated with the upregulation of ICAM-1 and VCAM-1 on DSCs and integrins on dγδΤ cells. RANKL knockout leads to the decreased numbers of uterus total γδΤ cells, Foxp3+γδΤ cells and the expression of TGF-β1, and the increased pregnancy loss in mice. These results suggest that RANKL is a pivotal regulator of maternal-fetal tolerance by triggering the polarization and residence of TGF-β1-producing Foxp3+γδΤ cells in early pregnancy. The abnormal low level of RANKL/RANK results in pregnancy loss because of the dialogue disorder between DSCs and dγδΤ cells. This observation provides a scientific basis on which a potential marker can be detected to early warning of pregnancy loss.
The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer
Authors: Tang Weimei , Zhou Weijie , Xiang Li , Wu Xiaosheng , Zhang Pei , Wang Jing , Liu Guangnan , Zhang Wenjing , Peng Ying , Huang Xiaoting , Cai Jianqun , Bai Yang , Bai Lan , Zhu Wei , Gu Hongxiang , Xiong Jing , Ye Chen , Li Aimin , Liu Side , Wang Jide
Published: February 2019

The biological role of miR-500a-5p has not yet been reported in the context of colorectal cancer (CRC). Here, we show that miR-500a-5p expression is decreased in CRC tissues compared with adjacent normal tissues. Low miR-500a-5p expression is associated with malignant progression. Moreover, transfection of CRC cells with miR-500a-5p induces G0/G1 cell cycle arrest and inhibits their growth and migration. Mechanistically, miR-500a-5p directly targets HDAC2 and inhibits HDAC2-mediated proliferation in CRC in nude mice. Furthermore, YY1 binds to the promoter of miR-500a-5p and negatively regulates its transcription. Restoration of miR-500a-5p expression is up-regulated via the p300/YY1/HDAC2 complex. Besides, therapeutic delivery of miR-500a-5p significantly suppresses tumour development in a xenograft tumour model and a HDAC2 inhibitor FK228-treated CRC model. Our studies demonstrate that miR-500a-5p functions as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis, which contributes to the development of and provides new potential candidates for CRC therapy.
Fire-derived organic matter retains ammonia through covalent bond formation
Authors: Hestrin Rachel , Torres-Rojas Dorisel , Dynes James J. , Hook James M. , Regier Tom Z. , Gillespie Adam W. , Smernik Ronald J. , Lehmann Johannes
Published: February 2019

Fire-derived organic matter, often referred to as pyrogenic organic matter (PyOM), is present in the Earth’s soil, sediment, atmosphere, and water. We investigated interactions of PyOM with ammonia (NH3) gas, which makes up much of the Earth’s reactive nitrogen (N) pool. Here we show that PyOM’s NH3 retention capacity under ambient conditions can exceed 180 mg N g−1 PyOM–carbon, resulting in a material with a higher N content than any unprocessed plant material and most animal manures. As PyOM is weathered, NH3 retention increases sixfold, with more than half of the N retained through chemisorption rather than physisorption. Near-edge X-ray absorption fine structure and nuclear magnetic resonance spectroscopy reveal that a variety of covalent bonds form between NH3-N and PyOM, more than 10% of which contained heterocyclic structures. We estimate that through these mechanisms soil PyOM stocks could retain more than 600-fold annual NH3 emissions from agriculture, exerting an important control on global N cycling.
Corticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition
Authors: Gräb Jessica , Suárez Isabelle , van Gumpel Edeltraud , Winter Sandra , Schreiber Fynn , Esser Anna , Hölscher Christoph , Fritsch Melanie , Herb Marc , Schramm Michael , Wachsmuth Laurens , Pallasch Christian , Pasparakis Manolis , Kashkar Hamid , Rybniker Jan
Published: February 2019

Corticosteroids are host-directed drugs with proven beneficial effect on survival of tuberculosis (TB) patients, but their precise mechanisms of action in this disease remain largely unknown. Here we show that corticosteroids such as dexamethasone inhibit necrotic cell death of cells infected with Mycobacterium tuberculosis (Mtb) by facilitating mitogen-activated protein kinase phosphatase 1 (MKP-1)-dependent dephosphorylation of p38 MAPK. Characterization of infected mixed lineage kinase domain-like (MLKL) and tumor necrosis factor receptor 1 (TNFR1) knockout cells show that the underlying mechanism is independent from TNFα-signaling and necroptosis. Our results link corticosteroid function and p38 MAPK inhibition to abrogation of necrotic cell death mediated by mitochondrial membrane permeability transition, and open new avenues for research on novel host-directed therapies (HDT).
Population-wide analysis of differences in disease progression patterns in men and women
Authors: Westergaard David , Moseley Pope , Sørup Freja Karuna Hemmingsen , Baldi Pierre , Brunak Søren
Published: February 2019

Sex-stratified medicine is a fundamentally important, yet understudied, facet of modern medical care. A data-driven model for how to systematically analyze population-wide, longitudinal differences in hospital admissions between men and women is needed. Here, we demonstrate a systematic analysis of all diseases and disease co-occurrences in the complete Danish population using the ICD-10 and Global Burden of Disease terminologies. Incidence rates of single diagnoses are different for men and women in most cases. The age at first diagnosis is typically lower for men, compared to women. Men and women share many disease co-occurrences. However, many sex-associated incongruities not linked directly to anatomical or genomic differences are also found. Analysis of multi-step trajectories uncover differences in longitudinal patterns, for example concerning injuries and substance abuse, cancer, and osteoporosis. The results point towards the need for an increased focus on sex-stratified medicine to elucidate the origins of the socio-economic and ethological differences.
Ecosystem structural changes controlled by altered rainfall climatology in tropical savannas
Authors: Zhang Wenmin , Brandt Martin , Penuelas Josep , Guichard Françoise , Tong Xiaoye , Tian Feng , Fensholt Rasmus
Published: February 2019

Tropical savannas comprise mixed woodland grassland ecosystems in which trees and grasses compete for water resources thereby maintaining the spatial structuring of this ecosystem. A global change in rainfall climatology may impact the structure of tropical savanna ecosystems by favouring woody plants, relative to herbaceous vegetation. Here we analysed satellite data and observed a relatively higher increase in woody vegetation (5%) as compared to the increase in annual maximum leaf area index (LAImax, an indicator of the total green vegetation production) (3%) in arid and semi-arid savannas over recent decades. We further observed a declining sensitivity of LAImax to annual rainfall over 56% of the tropical savannas, spatially overlapping with areas of increased woody cover and altered rainfall climatology. This suggests a climate-induced shift in the coexistence of woody and herbaceous vegetation in savanna ecosystems, possibly caused by altered hydrological conditions with significance for land cover and associated biophysical effects such as surface albedo and evapotranspiration.
A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration
Authors: Coelho João P. L. , Stahl Matthias , Bloemeke Nicolas , Meighen-Berger Kevin , Alvira Carlos Piedrafita , Zhang Zai-Rong , Sieber Stephan A. , Feige Matthias J.
Published: February 2019

A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Despite this, it remains unclear how cells detect and handle failures in this process. Here we show that single point mutations in the membrane protein connexin 32 (Cx32), which cause Charcot-Marie-Tooth disease, can cause failures in membrane integration. This leads to Cx32 transport defects and rapid degradation. Our data show that multiple chaperones detect and remedy this aberrant behavior: the ER–membrane complex (EMC) aids in membrane integration of low-hydrophobicity transmembrane segments. If they fail to integrate, these are recognized by the ER–lumenal chaperone BiP. Ultimately, the E3 ligase gp78 ubiquitinates Cx32 proteins, targeting them for degradation. Thus, cells use a coordinated system of chaperones for the complex task of membrane protein biogenesis, which can be compromised by single point mutations, causing human disease.
Comparison of adverse events associated with different spacers used with non-extrafine beclometasone dipropionate for asthma
Authors: Ming Simon Wan Yau , Haughney John , Ryan Dermot , Patel Shishir , Ochel Matthias , d’Alcontres Martina Stagno , Thornhill Susannah , Kocks Janwillem W. H. , Price David
Published: February 2019

Co-prescription of Aerochamber® spacer with non-extrafine beclometasone diproprionate (non-EF BDP) is common but unlicensed. We report a comparison of inhaled corticosteroid (ICS)-related adverse events between patients co-prescribed Aerochamber compared to the licensed Volumatic® spacer. We utilised two historical cohorts: questionnaire-based and electronic medical record (EMR)-based, to assess patient-reported and EMR-recorded adverse events in patients with asthma prescribed non-EF BDP. Marginal effect estimate (MEE) was calculated to determine non-inferiority of Aerochamber compared to Volumatic in terms of patient-reported oral thrush and hoarseness with margin of 0.13. Other patient-reported adverse events (sore throat, bruising, weight gain, and coughing), and EMR-recorded adverse events were also assessed. Rate of patient-reported oral adverse events were non-inferior in 385 patients prescribed Aerochamber compared to 155 patients prescribed Volumatic (27.7 vs 29.9%; MEE, −0.043; 95% CI, −0.133 to 0.047). Total patient-reported adverse events did not differ significantly between Aerochamber and Volumatic (53.3 vs 49.7% with ≥1 adverse event). The EMR-based study of 1471 matched pairs of subjects did not show significantly different number of EMR-recorded adverse events between Aerochamber and Volumatic (12.5 vs 12.8% with ≥1 adverse events). Co-prescribing Aerochamber with non-EF BDP does not increase the risk for patient-reported and EMR-recorded ICS-related adverse events compared to co-prescribing Volumatic.
Turning the corner on therapeutic cancer vaccines
Authors: Hollingsworth Robert E. , Jansen Kathrin
Published: February 2019

Recent advances in several areas are rekindling interest and enabling progress in the development of therapeutic cancer vaccines. These advances have been made in target selection, vaccine technology, and methods for reversing the immunosuppressive mechanisms exploited by cancers. Studies testing different tumor antigens have revealed target properties that yield high tumor versus normal cell specificity and adequate immunogenicity to affect clinical efficacy. A few tumor-associated antigens, normal host proteins that are abnormally expressed in cancer cells, have been demonstrated to serve as good targets for immunotherapies, although many do not possess the needed specificity or immunogenicity. Neoantigens, which arise from mutated proteins in cancer cells, are truly cancer-specific and can be highly immunogenic, though the vast majority are unique to each patient’s cancer and thus require development of personalized therapies. Lessons from previous cancer vaccine expeditions are teaching us the type and magnitude of immune responses needed, as well as vaccine technologies that can achieve these responses. For example, we are learning which vaccine approaches elicit the potent, balanced, and durable CD4 plus CD8 T cell expansion necessary for clinical efficacy. Exploration of interactions between the immune system and cancer has elucidated the adaptations that enable cancer cells to suppress and evade immune attack. This has led to breakthroughs in the development of new drugs, and, subsequently, to opportunities to combine these with cancer vaccines and dramatically increase patient responses. Here we review this recent progress, highlighting key steps that are bringing the promise of therapeutic cancer vaccines within reach.
The molecular characterization of fixed inversions breakpoints unveils the ancestral character of the Drosophila guanche chromosomal arrangements
Authors: Orengo Dorcas J. , Puerma Eva , Aguadé Montserrat
Published: February 2019

Cytological studies revealed that the number of chromosomes and their organization varies across species. The increasing availability of whole genome sequences of multiple species across specific phylogenies has confirmed and greatly extended these cytological observations. In the Drosophila genus, the ancestral karyotype consists of five rod-like acrocentric chromosomes (Muller elements A to E) and one dot-like chromosome (element F), each exhibiting a generally conserved gene content. Chromosomal fusions and paracentric inversions are thus the major contributors, respectively, to chromosome number variation among species and to gene order variation within chromosomal element. The subobscura cluster of Drosophila consists in three species that retain the genus ancestral karyotype and differ by a reduced number of fixed inversions. Here, we have used cytological information and the D. guanche genome sequence to identify and molecularly characterize the breakpoints of inversions that became fixed since the D. guanche-D. subobscura split. Our results have led us to propose a modified version of the D. guanche cytological map of its X chromosome, and to establish that (i) most inversions became fixed in the D. subobscura lineage and (ii) the order in which the four X chromosome overlapping inversions occurred and became fixed.
Factorial design-assisted supercritical carbon-dioxide extraction of cytotoxic active principles from Carica papaya leaf juice
Authors: Khaw Kooi-Yeong , Parat Marie-Odile , Shaw Paul Nicholas , Nguyen Thao T. T. , Pandey Saurabh , Thurecht Kristofer J. , Falconer James Robert
Published: February 2019

The aims of this study are to investigate the selective cytotoxic activity of supercritical carbon dioxide (scCO2)-extracted freeze-dried leaf juice (FDLJ) of Carica papaya on squamous cell carcinoma (SCC25) cells, and to delineate the best small scale extraction parameters allowing maximal extract activity. Using scCO2 as a solvent, six operating parameters were studied and the supercritical fluid extraction (SFE) process investigated using a factorial design 26-2. The processing values promoting cytotoxic activity towards SCC-25 are: high pressure (250 bar), low temperature (35 °C), extended processing time (180 minutes), as well as a large amount of starting material (5 g). The factorial experimental design successfully identified the key parameters controlling the SFE of molecules cytotoxic to SCC cells from C. papaya juice. This study also validated the extraction method and showed that the SFE yield was reproducible. The chromatographic and mass spectrometric profiles of the scCO2 extract acquired with high-resolution quadrupole time-of-flight mass spectrometry (LC-QToF-MS) were used to tentatively identify the bioactive compounds using comparative analysis. The principal compounds were likely to be mainly vitamins and phytosterols, some of which are documented to be cytotoxic to cancer cells.
Role of nutrient concentrations and water movement on diatom’s productivity in culture
Authors: Orefice Ida , Musella Margherita , Smerilli Arianna , Sansone Clementina , Chandrasekaran Raghu , Corato Federico , Brunet Christophe
Published: February 2019

Microalgal growth maximization is becoming a duty for enhancing the biotechnological fate of these photosynthetic microorganisms. This study, based on an extensive set of data, aims to revisit diatom’s cultivation in laboratory with the objective to increase growth rate and biomass production. We investigated the growth ability and resource requirements of the coastal diatom Skeletonema marinoi Sarno & Zingone grown in laboratory in the conventional f/2 medium with aeration and in two modified conditions: (i) the same medium with water movement inside and (ii) an enriched medium with the same water movement. Results revealed that, by doubling the concentration of phosphate, silicate, microelements and vitamins, growth rate was successfully enhanced, preventing phosphate or silicate limitation in the f/2 culture medium. Yet, irrespective of the media (f/2 or enriched one), water movement induced an increase of growth efficiency compared to aeration, affecting nutrients’ requirement and consumption by diatoms. This study is an important step for enhancing diatom biomass production, reducing its cost, as required in the blue biotechnology context.
Flunarizine related movement disorders: a nationwide population-based study
Authors: Jhang Kai-Ming , Huang Jing-Yang , Nfor Oswald Ndi , Tung Yu-Chun , Ku Wen-Yuan , Jan Cheng-Feng , Liaw Yung-Po
Published: February 2019

Flunarizine (fz) causes side effects such as movement disorders (MDs). We investigated risk factors associated with fz-related MDs. Participants were recruited from the longitudinal health insurance databases and included patients who took fz for more than 1 month. Patients with one of the underlying diseases, or with concomitant drug use (antipsychotics, metoclopramide or reserpine), and those diagnosed with MDs before fz use were excluded. Fz-related MD was defined as a new diagnosis of parkinsonism or hyperkinetic syndrome including dyskinesia or secondary dystonia during fz use or within 3 months after drug discontinuation. After exposure, 288 individuals had fz-related MDs (parkinsonism, n = 240; hyperkinesia, n = 48). Risk factors associated with these disorders were higher-dose exposure (cumulative defined daily dose [cDDD] ≥87.75, odds ratio [OR]: 3.80; 95% CI: 2.61–5.52), older age (OR: 1.07; 95% CI: 1.06–1.09), history of essential tremor (OR: 6.39; 95% CI: 2.29–17.78) and cardiovascular disease (CVD) (OR: 1.47; 95% CI: 1.14–1.9). The optimal value of cDDD to predict MDs was 58.5 (sensitivity: 0.67, specificity: 0.60), indicating an overall exposure of 585 mg. Higher exposure dose and duration, older age, history of essential tremor, and CVD were associated with fz-associated MDs. Clinicians ought to watch for extrapyramidal side effects when prescribing fz.