bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the pharmacological interactions between the nematodicidal fenbendazole and the flukicidal triclabendazole: In vitro studies with bovine liver microsomes and slices
Authors: Viviani P. , Lifschitz A. L. , Maté M. L. , García J. P. , Lanusse C. E. , Virkel G. L. 
Published: February 2018

Parasitic diseases have a significant impact on livestock production. Nematodicidal drugs, such as fenbendazole (FBZ) or its oxidized metabolite oxfendazole (OFZ), can be used along with the trematodicidal triclabendazole (TCBZ), to broaden the spectrum of anthelmintic activity. However, co‐exposure to these compounds could lead to drug–drug (D‐D) interactions and eventually alter the clinical profile of each active principle. The aim of this study was to assess the presence of such interactions by means of two in vitro models, namely bovine liver microsomal fractions and bovine precision‐cut liver slices (PCLSs). To this end, an in vitro assessment involving incubation of FBZ and TCBZ or a combination of FBZ and TCBZ was carried out. Results with microsomal fractions showed a 78.4% reduction (p = .002) in the rate of OFZ production upon co‐incubation, whereas the sulfoxide metabolite of TCBZ (TCBZSO) exhibited a decreasing tendency. With PCLS, OFZ accumulation in the incubation medium increased 1.8‐fold upon co‐incubation, whereas TCBZSO accumulation decreased by 28%. The accumulation of FBZ and OFZ in the liver tissue increased upon 2‐hr co‐incubation, from 2.1 ± 1.5 to 18.2 ± 6.1 (p = .0009) and from 0.4 ± 0.1 to 1.3 ± 0.3 nmol (p = .0005), respectively. These results confirm the presence of D‐D interactions between FBZ and TCBZ. Further studies are needed to determine the extent of involvement of drug‐metabolizing enzymes and membrane transporters in interactions between compounds largely used in livestock production systems.
Low molecular weight heparin does not increase bleeding and mortality post‐endoscopic variceal band ligation in cirrhotic patients
Authors: Bianchini Marcello , Cavani Giulia , Bonaccorso Ambra , Turco Laura , Vizzutti Francesco , Sartini Alessandro , Gitto Stefano , Merighi Alberto , Banchelli Federico , Villa Erica , Schepis Filippo 
Published: February 2018

AbstractBackground & AimsAnticoagulants are commonly indicated in cirrhotic patients due to high rate of (pro)thrombotic conditions. Low molecular weight heparin (LMWH) is safe in patients with esophageal varices. However, the safety of LMWH is unknown in patients undergoing prophylactic endoscopic variceal ligation (EVL). To define the 4‐week risk of bleeding and death after prophylactic EVL in cirrhotic patients continuously treated with LMWH.MethodsAll EVLs performed at a tertiary Italian Center from 2009 to 2016 were retrospectively reviewed. Patients treated with LMWH were classified as on‐LMWH; the remaining as no‐LMWH. Endoscopic characteristics at first and index EVL (that preceding an endoscopy either showing a bleeding episode or the absence of further treatable varices) and clinical events within 4 weeks from the procedures were recorded.Results and ConclusionsFive hundred fifty‐three EVLs were performed in 265 patients (in 215 as a primary prophylaxis): 169 EVLs in 80 on‐LMWH and 384 in 185 no‐LMWH (4.9 ± 1.1 vs 4.8 ± 1.0 bands/session, respectively; P = .796). Six patients bled (2.2%) without between‐groups difference (3.8% on‐LMWH vs 1.6% no‐LMWH, Log‐rank P = .291). Large varices with red marks (100% vs 51.4%, P = .032), number of bands (5.6 ± 0.5 vs 4.6 ± 1.2, P = .004), underlying portal vein thrombosis (66.7% vs 23.6%, P = .033), and creatinine (2.2 ± 2.7 vs 1.0 ± 0.8 mg/dL, P = .001) at index EVL were significantly different between bleeders and non‐bleeders. Six patients died within 4‐week from index EVL, without between‐groups difference (2.5% on‐LMWH vs 2.2% no‐LMWH, Log‐rank P = .863). LMWH does not increase the risk of post‐procedural bleeding and does not affect survival of cirrhotic patients undergoing prophylactic EVL.
Identification and characterization of acetyltransferase‐type toxin‐antitoxin locus in Klebsiella pneumoniae
Authors: Qian Hongliang , Yao Qingqing , Tai Cui , Deng Zixin , Gan Jianhua , Ou Hong‐Yu 
Published: February 2018

SummaryA type II toxin‐antitoxin (TA) system, in which the toxin contains a Gcn5‐related N‐acetyltransferase (GNAT) domain, has been characterized recently. GNAT toxin acetylates aminoacyl‐tRNA and blocks protein translation. It is abolished by the cognate antitoxin that contains the ribbon‐helix‐helix (RHH) domain. Here, we present an experimental demonstration of the interaction of the GNAT‐RHH complex with TA promoter DNA. First, the GNAT‐RHH TA locus kacAT was found in Klebsiella pneumoniae HS11286, a strain resistant to multiple antibiotics. Overexpression of KacT halted cell growth and resulted in persister cell formation. The crystal structure also indicated that KacT is a typical acetyltransferase toxin. Co‐expression of KacA neutralized KacT toxicity. Expression of the bicistronic kacAT locus was up‐regulated during antibiotic stress. Finally, KacT and KacA formed a heterohexamer that interacted with promoter DNA, resulting in negative autoregulation of kacAT transcription. The N‐terminus region of KacA accounted for specific binding to the palindromic sequence on the operator DNA, whereas its C‐terminus region was essential for the inactivation of the GNAT toxin. These results provide an important insight into the regulation of the GNAT‐RHH family TA system.
2H‐fractionations during the biosynthesis of carbohydrates and lipids imprint a metabolic signal on the δ2H values of plant organic compounds
Authors: Cormier Marc‐André , Werner Roland A. , Sauer Peter E. , Gröcke Darren R. , Leuenberger Markus C. , Wieloch Thomas , Schleucher Jürgen , Kahmen Ansgar 
Published: February 2018

Summary

Hydrogen (H) isotope ratio (δ2H) analyses of plant organic compounds have been applied to assess ecohydrological processes in the environment despite a large part of the δ2H variability observed in plant compounds not being fully elucidated.

We present a conceptual biochemical model based on empirical H isotope data that we generated in two complementary experiments that clarifies a large part of the unexplained variability in the δ2H values of plant organic compounds.

The experiments demonstrate that information recorded in the δ2H values of plant organic compounds goes beyond hydrological signals and can also contain important information on the carbon and energy metabolism of plants. Our model explains where 2H‐fractionations occur in the biosynthesis of plant organic compounds and how these 2H‐fractionations are tightly coupled to a plant's carbon and energy metabolism. Our model also provides a mechanistic basis to introduce H isotopes in plant organic compounds as a new metabolic proxy for the carbon and energy metabolism of plants and ecosystems.

Such a new metabolic proxy has the potential to be applied in a broad range of disciplines, including plant and ecosystem physiology, biogeochemistry and palaeoecology.
Mutational studies of the Aux/IAA proteins in Physcomitrella reveal novel insights into their function
Authors: Tao Sibo , Estelle Mark 
Published: February 2018

Summary

The plant hormone auxin regulates many aspects of plant growth and development. Auxin signaling involves hormone perception by the TRANSPORT INHIBITOR RESPONSE/AUXIN F‐BOX (TIR1/AFB)–Aux/IAA co‐receptor system, and the subsequent degradation of the Aux/IAA transcriptional repressors by the ubiquitin proteasome pathway. This leads to the activation of downstream gene expression and diverse physiological responses. Here, we investigate how the structural elements in the Aux/IAAs determine their function in Auxin perception and transcriptional repression.

We took advantage of the facile genetics of the moss Physcomitrella patens to determine the activity of wild‐type and mutant PpIAA1a proteins in a Δaux/iaa null background. In this way, Aux/IAA function was characterized at the molecular and physiological levels without the interference of genetic redundancy.

We identified and characterized degron variants in Aux/IAAs that affect their stability and Auxin response. We also demonstrated that neither the Aux/IAA EAR motif nor Aux/IAA oligomerization is essential for the repressive function of Aux/IAA.

Our study demonstrates how key elements within the Aux/IAA proteins fine tune stability and repressor activity, as well as the long‐term developmental outcome.
Exploring and exploiting the boundaries of host specificity using the cereal rust and mildew models
Authors: Dracatos Peter Michael , Haghdoust Rouja , Singh Davinder , Park Robert Fraser 
Published: February 2018

SummaryIndividual plants encounter a vast number of microbes including bacteria, viruses, fungi and oomycetes through their growth cycle, yet few of these pathogens are able to infect them. Plant species have diverged over millions of years, co‐evolving with few specific pathogens. The host boundaries of most pathogen species can be clearly defined. In general, the greater the genetic divergence from the preferred host, the less likely that pathogen would be able to infect that plant species. Co‐evolution and divergence also occur within pathogen species, leading to highly specialized subspecies with narrow host ranges. For example, cereal rust and mildew pathogens (Puccinia and Blumeria spp.) display high host specificity as a result of ongoing co‐evolution with a narrow range of grass species. In rare cases, however, some plant species are in a transition from host to nonhost or are intermediate hosts (near nonhost). Barley was reported as a useful model for genetic and molecular studies of nonhost resistance due to rare susceptibility to numerous heterologous rust and mildew fungi. This review evaluates host specificity in numerous Puccinia/Blumeria–cereal pathosystems and discusses various approaches for transferring nonhost resistance (NHR) genes between crop species to reduce the impact of important diseases in food production.
Gibberellin antagonizes jasmonate‐induced defense against Meloidogyne graminicola in rice
Authors: Yimer Henok Zemene , Nahar Kamrun , Kyndt Tina , Haeck Ashley , Van Meulebroek Lieven , Vanhaecke Lynn , Demeestere Kristof , Höfte Monica , Gheysen Godelieve 
Published: February 2018

Summary

Gibberellin (GA) regulates various plant growth and developmental processes, but its role in pathogen attack, and especially nematode–plant interactions, still remains to be elucidated.

An in‐depth characterization of the role of GA in nematode infection was conducted using mutant lines of rice, chemical inhibitors, and phytohormone measurements.

Our results showed that GA influences rice–Meloidogyne graminicola interactions in a concentration‐dependent manner. Foliar spray of plants with a low concentration of gibberellic acid enhanced nematode infection. Biosynthetic and signaling mutants confirmed the importance of gibberellin for rice susceptibility to M. graminicola infection. Our study also demonstrates that GA signaling suppresses jasmonate (JA)‐mediated defense against M. graminicola, and likewise the JA‐induced defense against M. graminicola requires SLENDER RICE1 (SLR1)‐mediated repression of the GA pathway. In contrast to observations from other plant–pathogen interactions, GA plays a dominant role over JA in determining susceptibility to M. graminicola in rice. This GA‐induced nematode susceptibility was largely independent of auxin biosynthesis, but relied on auxin transport.

In conclusion, we showed that GA–JA antagonistic crosstalk is at the forefront of the interaction between rice and M. graminicola, and SLR1 plays a central role in the JA‐mediated defense response in rice against this nematode.
Diversification by host switching and dispersal shaped the diversity and distribution of avian malaria parasites in Amazonia
Authors: Fecchio Alan , Bell Jeffrey Andrew , Collins Michael David , Farias Izeni Pires , Trisos Christopher Harry , Tobias Joseph Andrew , Tkach Vasyl Volodymyr , Weckstein Jason David , Ricklefs Robert Eric , Batalha‐Filho Henrique 
Published: February 2018

Understanding how pathogens and parasites diversify through time and space is fundamental to predicting emerging infectious diseases. Here, we use biogeographic, coevolutionary and phylogenetic analyses to describe the origin, diversity, and distribution of avian malaria parasites in the most diverse avifauna on Earth. We first performed phylogenetic analyses using the mitochondrial cytochrome b (cyt b) gene to determine relationships among parasite lineages. Then, we estimated divergence times and reconstructed ancestral areas to uncover how landscape evolution has shaped the diversification of Parahaemoproteus and Plasmodium in Amazonia. Finally, we assessed the coevolutionary patterns of diversification in this host–parasite system to determine how coevolution may have influenced the contemporary diversity of avian malaria parasites and their distribution among Amazonian birds.Biogeographic analysis of 324 haemosporidian parasite lineages recovered from 4178 individual birds provided strong evidence that these parasites readily disperse across major Amazonian rivers and this has occurred with increasing frequency over the last five million years. We also recovered many duplication events within areas of endemism in Amazonia. Cophylogenetic analyses of these blood parasites and their avian hosts support a diversification history dominated by host switching. The ability of avian malaria parasites to disperse geographically and shift among avian hosts has played a major role in their radiation and has shaped the current distribution and diversity of these parasites across Amazonia.
The concept of sin in the Hebrew Bible
Authors: Lam Joseph 
Published: February 2018

AbstractThis essay offers an introduction to the study of sin as a concept in the Hebrew Bible, first via an overview of past scholarship, then through a discussion of four salient issues in sin's definition based on the biblical texts. Previous approaches can be broadly classified by their emphasis on the terminology of sin in Biblical Hebrew, the theology of sin in the Hebrew Bible, or the history of sin as a concept in ancient Israel, with or without a narrower thematic focus. Since the Hebrew Bible is a composite text preserving a variety of views, a proper approach to the biblical notion of sin needs to account for these competing views. This variety in the biblical discourse on sin can be illustrated with respect to at least four issues: the basis of sin's definition; the nature of sin as an act, a state of guilt, or a propensity toward evil; the role of intentionality in sin; and the interplay between individual and corporate notions of sin. The multiplicity of views on these issues preserved in the Hebrew Bible reflects the conceptual diversity that existed in ancient Israel.
Three‐dimensional photography for the evaluation of facial profiles in obstructive sleep apnoea
Authors: Lin Shih‐Wei , Sutherland Kate , Liao Yu‐Fang , Cistulli Peter A. , Chuang Li‐Pang , Chou Yu‐Ting , Chang Chih‐Hao , Lee Chung‐Shu , Li Li‐Fu , Chen Ning‐Hung 
Published: February 2018

ABSTRACTBackground and objectiveCraniofacial structure is an important determinant of obstructive sleep apnoea (OSA) syndrome risk. Three‐dimensional stereo‐photogrammetry (3dMD) is a novel technique which allows quantification of the craniofacial profile. This study compares the facial images of OSA patients captured by 3dMD to three‐dimensional computed tomography (3‐D CT) and two‐dimensional (2‐D) digital photogrammetry. Measurements were correlated with indices of OSA severity.MethodsThirty‐eight patients diagnosed with OSA were included, and digital photogrammetry, 3dMD and 3‐D CT were performed. Distances, areas, angles and volumes from the images captured by three methods were analysed.ResultsAlmost all measurements captured by 3dMD showed strong agreement with 3‐D CT measurements. Results from 2‐D digital photogrammetry showed poor agreement with 3‐D CT. Mandibular width, neck perimeter size and maxillary volume measurements correlated well with the severity of OSA using all three imaging methods. Mandibular length, facial width, binocular width, neck width, cranial base triangle area, cranial base area 1 and middle cranial fossa volume correlated well with OSA severity using 3dMD and 3‐D CT, but not with 2‐D digital photogrammetry.Conclusion3dMD provided accurate craniofacial measurements of OSA patients, which were highly concordant with those obtained by CT, while avoiding the radiation associated with CT.
Re‐Examining the Role of Structural Change and Nonlinearities in a Phillips Curve Model for South Africa
Authors: Nell Kevin S. 
Published: February 2018

AbstractAlthough studies generally find evidence of a Phillips curve‐type relationship in South Africa, uncertainty remains about the relevance of the model over a relatively long sample period, and whether conventional output gap measures are suitable proxies for demand pressure. This paper reviews research which shows that the Phillips curve model prevails over an extended sample, provided that the benchmark specifications include major structural changes in the balance‐of‐payments and labour market, and account for shifts in the root causes of inflation. When this is done, a linear specification with an output gap in levels correctly predicts the non‐trended inflation pattern over the period 1971(Q1)–1984(Q4), whereas a piecewise concave curve with an output gap in growth rates accurately forecasts the decelerating inflation pattern during 1986(Q1)–2001(Q2). A novel feature of the concave model is that it remains statistically robust and structurally stable when it is estimated until 2015(Q4). The concave model imparts a disinflationary bias, which suggests that monetary policy should be more expansionary during downswing phases of the business cycle and neutral during upswing phases. The analysis also considers how the shape of the Phillips curve might change if the balance‐of‐payments constraint on demand is relaxed in a significant way.
Clinical application research through reflection, interpretation and new understanding – a hermeneutic design
Authors: Lindwall Lillemor , Råholm Maj‐Britt , Lohne Vibeke , Caspari Synnøve , Heggestad Anne Kari Tolo , Sæteren Berit , Slettebø Åshild , Høy Bente , Nåden Dagfinn 
Published: February 2018

The implementation of theoretical knowledge in clinical practice and the implementation of good clinical practice into theory have been of interest in caring science for the last 30 years. The aim of this article was to elaborate and discuss a methodology named clinical application research. The method is grounded in a hermeneutical design inspired by Gadamer's philosophy. The methodology, clinical application research, has been used in a research project A life in dignity and experiences from the researchers forms the bases for the elaboration and discussion. The project was performed in collaboration with residents, family caregivers and healthcare providers at six nursing homes in Scandinavia. The material for this article is based on the previous research, that is the results from 10 different articles showing the meaning of dignity and indignity in daily life in nursing homes. Data were generated from 56 individual interviews and 18 focus‐group interviews with a total of 40 staff members with five to eight participants at every interview session. By reflection, interpretation and new understanding our results provide knowledge about dignity and how to preserve dignity for older people in an appropriate ethical way. The methodology was relevant for the research project A life in dignity and relevant to caring practice in nursing homes as it opens new possibilities and new ways of thinking when performing dignified care to older people.
Endothelial extracellular vesicles modulate the macrophage phenotype: Potential implications in atherosclerosis
Authors: He S. , Wu C. , Xiao J. , Li D. , Sun Z. , Li M. 
Published: February 2018

AbstractEndothelial cells (ECs) and macrophages engage in tight and specific interactions that play critical roles in cardiovascular homeostasis and the pathogenesis of atherosclerosis. Extracellular vesicles (EVs) are circular membrane fragments released from the endosomal compartment as exosomes or shed from the surfaces of the membranes of most cell types. Increasing evidence indicates that EVs play a pivotal role in cell‐to‐cell communication. However, the contribution of EVs, as determine by oxidized low‐density lipoprotein (ox‐LDL)‐exposed and/or Kruppel‐like factor 2 (KLF2)‐transduced ECs in the interaction between vascular ECs and monocytes/macrophages, which is a key event in atherosclerotic plaque development, has remained elusive. This study demonstrates the characteristic impact of EVs from ox‐LDL‐treated and/or KLF2‐transduced ECs on the monocyte/macrophage phenotype in vitro and in vivo.Q‐PCR showed that both the atherosclerosis inducer ox‐LDL and atheroprotective factor KLF2 regulated inflammation‐associated microRNA‐155 (miR‐155) expression in human umbilical vein endothelial cells (HUVECs). Moreover, coculture, immunofluorescence and flow cytometry revealed that miR‐155 was enriched in ox‐LDL‐induced ECs‐EVs and subsequently transferred to human monocytic THP1 cells, in which these vesicles enhance monocyte activation by shifting the monocytes/macrophages balance from anti‐inflammatory M2 macrophages towards proinflammatory M1 macrophages; EVs from KLF2‐expressing ECs suppressed monocyte activation by enhancing immunomodulatory responses and diminishing proinflammatory responses, which indicate the potent anti‐inflammatory activities of these cells. Furthermore, oil red staining showed that atherosclerotic lesions were reduced in mice that received EVs from KLF2‐transduced ECs with decreased proinflammatory M1 macrophages and increased anti‐inflammatory M2 macrophages, and this effect is at least partly due to the decreased expression of inflammation‐associated miR‐155, confirming our in vitro findings. In summary, this study provides novel insights into the pathophysiological effects of altered EV secretion and/or microRNA content and their influence on modulating monocyte activation depending on the environment surrounding EVs‐releasing ECs.
Validity of activity trackers, smartphones, and phone applications to measure steps in various walking conditions
Authors: Höchsmann C. , Knaier R. , Eymann J. , Hintermann J. , Infanger D. , Schmidt‐Trucksäss A. 
Published: February 2018

To examine the validity of popular smartphone accelerometer applications and a consumer activity wristband compared to a widely used research accelerometer while assessing the impact of the phone's position on the accuracy of step detection. Twenty volunteers from 2 different age groups (Group A: 18‐25 years, n = 10; Group B 45‐70 years, n = 10) were equipped with 3 iPhone SE smartphones (placed in pants pocket, shoulder bag, and backpack), 1 Samsung Galaxy S6 Edge (pants pocket), 1 Garmin Vivofit 2 wristband, and 2 ActiGraph wGTX+ devices (worn at wrist and hip) while walking on a treadmill (1.6, 3.2, 4.8, and 6.0 km/h) and completing a walking course. All smartphones included 6 accelerometer applications. Video observation was used as gold standard. Validity was evaluated by comparing each device with the gold standard using mean absolute percentage errors (MAPE). The MAPE of the iPhone SE (all positions) and the Garmin Vivofit was small (<3) for treadmill walking ≥3.2 km/h and for free walking. The Samsung Galaxy and hip‐worn ActiGraph showed small MAPE only for treadmill walking at 4.8 and 6.0 km/h and for free walking. The wrist‐worn ActiGraph showed high MAPE (17‐47) for all walking conditions. The iPhone SE and the Garmin Vivofit 2 are accurate tools for step counting in different age groups and during various walking conditions, even during slow walking. The phone's position does not impact the accuracy of step detection, which substantially improves the versatility for physical activity assessment in clinical and research settings.