bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shenfu Injection attenuates rat myocardial hypertrophy by up-regulating miR-19a-3p expression
Authors: Mao Zhu-Jun , Zhang Quan-Long , Shang Jia , Gao Ting , Yuan Wen-Jun , Qin Lu-Ping 
Published: March 2018

AbstractShenfu Injection (SFI) is a classical Chinese medicine used to treat heart failure. Our previous study demonstrated that miRNAs underwent changes in rats with myocardial hypertrophy induced by abdominal aortic constriction. Interestingly, there was a significant change in miR-19a-3p, whose target gene is known to be associated with MEF2 signaling. However, whether and how SFI regulates miR-19a-3p in the treatment of myocardial hypertrophy has not been investigated. The purpose of the present study was to investigate the regulatory effect of SFI on miR-19a-3p in MEF2 signaling in the rat hypertrophic myocardium. We found that the miR-19a-3p expression level was significantly decreased in the hypertrophic myocardium, and MEF2A was the target gene of miR-19a-3p. The protein expressions of MEF2A, β-MHC, BNP and TRPC1 were significantly increased in hypertrophic cardiomyocytes. MiR-19a-3p was up-regulated after SFI treatment, and the protein expressions of these genes were significantly decreased. In addition, miR-19a-3p over-expression in hypertrophic cardiomyocytes could decrease MEF2A mRNA and protein expressions, and anti-miR-19a-3p showed the opposite result. Our study provided substantial evidence that miR-19a-3p played a functional role in MEF2 signaling in myocardial hypertrophy. SFI attenuated cardiomyocyte hypertrophy probably through up-regulating or maintaining the miR-19a-3p levels and regulating the MEF2 signaling pathway.
An ANOVA approach for statistical comparisons of brain networks
Authors: Fraiman Daniel , Fraiman Ricardo 
Published: March 2018

AbstractThe study of brain networks has developed extensively over the last couple of decades. By contrast, techniques for the statistical analysis of these networks are less developed. In this paper, we focus on the statistical comparison of brain networks in a nonparametric framework and discuss the associated detection and identification problems. We tested network differences between groups with an analysis of variance (ANOVA) test we developed specifically for networks. We also propose and analyse the behaviour of a new statistical procedure designed to identify different subnetworks. As an example, we show the application of this tool in resting-state fMRI data obtained from the Human Connectome Project. We identify, among other variables, that the amount of sleep the days before the scan is a relevant variable that must be controlled. Finally, we discuss the potential bias in neuroimaging findings that is generated by some behavioural and brain structure variables. Our method can also be applied to other kind of networks such as protein interaction networks, gene networks or social networks.
Altitudinal, temporal and trophic partitioning of flower-visitors in Alpine communities
Authors: Lefebvre Vincent , Villemant Claire , Fontaine Colin , Daugeron Christophe 
Published: March 2018

AbstractThe cross-pollination of most alpine plants depends on insects, whose altitudinal distribution is limited by temperature. However, although global warming is causing shifts in temporal and spatial species distribution, we are still largely unaware of how plant-pollinator interactions change with elevation and time along altitudinal gradients. This makes the detection of endangered interactions and species challenging. In this study, we aimed at providing such a reference, and tested if and how the major flower-visiting insect orders and families segregated by altitude, phenology and foraging preferences along an elevational gradient from 970 m to 2700 m in the Alps. Flies were the main potential pollinators from 1500 m, as bees and beetles decreased rapidly above that limit. Diptera, Coleoptera and Hymenoptera differed significantly in the angiosperm assemblages visited. Within Diptera, the predominant group, major families segregated by both phenology and foraging preferences along the gradient. Empidids, muscids and anthomyiids, whose role in pollination has never been investigated, dominated the upper part of the gradient. Our results thus suggest that flies and the peculiar plants they visit might be particularly at risk under global warming, and highlight the blatant lack of studies about critical components of these rich, yet fragile mountain ecosystems.
Trends and Economic Impact of Hip and Knee Arthroplasty in Central Europe: Findings from the Austrian National Database
Authors: Leitner Lukas , Türk Silvia , Heidinger Martin , Stöckl Bernd , Posch Florian , Maurer-Ertl Werner , Leithner Andreas , Sadoghi Patrick 
Published: March 2018

AbstractArthroplasty registers were originally established in Scandinavia to receive clinically relevant information from pooled data, to improve quality and reduce revision surgeries, with socioeconomic benefit. In Austria, where the highest rate of total knee arthroplasties (TKA) per inhabitant of all OECD countries was reached in 2014, arthroplasties are centrally reported since 2009. Study purpose was to perform the first analysis of the Austrian database, aiming to obtain data on trends in arthroplasty in Austria over time in relation to demographic development. Between 2009 and 2015 an almost continuous increase of total hip arthroplasties (THA; 18.052) by 14% and TKA (17.324) by 13% were observed, representing 210 THA and 202 TKA per 100k inhabitants in 2015. A similar increase was found for revision surgeries, with 1.290 re-implanted THA (7.1% of all THA) and 919 re-implanted TKA (5.3% of all TKA) in 2015. Implantation of mega or tumor prosthesis for the knee and hip joint remained constant and was mainly performed in two university hospitals. Patellar resurfacing decreased by 31.6%. Demographic development will further increase the number of primary and revision surgeries. Inclusion of more detailed information on used and revised components was established and will improve efficacy in quality control.
Human relevance of rodent liver tumour formation by constitutive androstane receptor (CAR) activators
Authors: Lake Brian G. 
Published: March 2018

Abstract
A large number of nongenotoxic chemicals have been shown to increase the incidence of liver tumours in rats and/or mice by a mode of action (MOA) involving activation of the constitutive androstane receptor (CAR). Studies with the model CAR activator phenobarbital (PB) and its sodium salt (sodium phenobarbital; NaPB) have demonstrated that the key and associative events for rat and mouse liver tumour formation include CAR activation, increased hepatocyte replicative DNA synthesis (RDS), induction of cytochrome P450 CYP2B subfamily enzymes, liver hypertrophy, increased altered hepatic foci and hepatocellular adenomas/carcinomas. The key species difference between the rat and mouse compared to humans, is that human hepatocytes are refractory to the mitogenic effects of PB/NaPB and other CAR activators. While PB/NaPB and other CAR activators stimulate RDS in rat and mouse hepatocytes in both in vitro and in vivo studies, such compounds do not stimulate RDS in cultured human hepatocytes and in in vivo studies performed in chimeric mice with humanised livers. In terms of species differences in RDS, unlike the rat and mouse, humans are similar to other species such as the Syrian hamster and guinea pig in being nonresponsive to the mitogenic effects of CAR activators. Overall, the MOA for rat and mouse liver tumour formation by PB/NaPB and other CAR activators is considered qualitatively not plausible for humans. This conclusion is supported by data from a number of epidemiological studies, which demonstrate that chronic treatment with PB does not increase the incidence of liver cancer in humans.
Fertilitätserhalt bei Patientinnen mit Mammakarzinom – eine aktuelle Übersicht
Authors: Guenther Veronika , Alkatout Ibrahim , Junkers Wiebe , Bauerschlag Dirk , Maass Nicolai , von Otte Soere 
Published: March 2018

ZusammenfassungBei vielen prämenopausalen Patientinnen, die an einem Mammakarzinom erkranken, ist die Familienplanung noch nicht abgeschlossen, sodass für den Erhalt des fertilen Potenzials Maßnahmen der Fertilitätsprotektion sinnvoll sind. Durch eine Polychemotherapie – unabhängig ob im neoadjuvanten oder adjuvanten Setting – kommt es zu einer irreversiblen Schädigung der Follikel, was unter Umständen zu einer permanenten Infertilität führen kann. Abhängig von den verwendeten Zytostatika und der altersabhängigen Ovarialreserve der Frau, muss das gonadotoxische Risiko als niedrig, mittel oder hoch eingeschätzt werden. Möglichkeiten des Fertilitätserhalts sind: a) die Kryokonservierung von fertilisierten oder unfertilisierten Oozyten. Hierbei werden nach ovarieller Hyperstimulation reife Oozyten mittels transvaginaler Follikelaspiration gewonnen und im Anschluss entweder unfertilisiert oder nach erfolgter IVF- oder ICSI-Behandlung kryokonserviert. Bei b) der Kryokonservierung von Ovarialgewebe wird mithilfe eines laparoskopischen Eingriffs etwa 50 % des Ovarkortex eines Ovars reseziert und kryokonserviert. Die Verwendung von c) GnRH-Agonisten als medikamentöse Therapieoption unternimmt den Versuch einer endokrinen Ovarialsuppression, um Oozyten, Granulosa- und Thekazellen vor dem zytotoxischen Einfluss der Chemotherapie zu schützen.
Frequency of Blood Pressure and Estimated Glomerular Filtration Rate Testing in Type 2 Diabetes Mellitus: A Retrospective Study with 43,509 Patients
Authors: Kostev Karel , Lucas Alexander , Jacob Louis 
Published: March 2018

Abstract
Background The goal of this study was to analyze the frequency of blood pressure (BP) and estimated glomerular filtration rate (eGFR) testing in type 2 diabetes mellitus (T2DM) patients followed in general and diabetological practices in Germany.
Methods The study included individuals who had at least two concultations due to T2DM diagnosis (ICD-10: E11) between January and December 2016. Patients were followed in 557 general and diabetological practices. The primary outcome was the frequency of BP and eGFR testing in T2DM patients in 2016. The association between several demographic and clinical variables and the odds of receiving≥2 BP and≥1 eGFR tests in the year 2016 was analyzed using multivariate logistic regression models.
Results A total of 43,509 individuals were available for analysis. The mean age of the population was 68.6 years (SD=12.4 years). The mean number of measurements was 2.9 (SD=3.5) for BP and 0.4 (SD=1.1) for eGFR. 52.3% of patients were tested at least twice for BP and 15.3% of them at least once for eGFR in 2016. Older patients, individuals followed in diabetological practices, people receiving antihyperglycemic medications, and those affected by chronic conditions (i. e. hypertension, renal complications, or neuropathy) displayed higher odds of receiving≥2 BP and≥1 eGFR tests, whereas patients with a diabetes duration of>1 year displayed lower odds.
Conclusions The frequency of BP and eGFR testing was low in T2DM patients in Germany in 2016. Several demographic and clinical variables were associated with this frequency.
Intravenous Injection of miR-34a Inhibitor Alleviates Diabetes Mellitus-Induced Vascular Endothelial Dysfunction by Targeting NOTCH1
Authors: Zhao Di , Wang Na-Sui , Chen Fu , Li Zheng-Bing , Li Xi-Tao , Zhu Xu-Xin 
Published: March 2018

Abstract
Background miR-34a is a multifunctional post-translational modulator, which is involved in several diabetes-related complications. However, miR-34a remains to be fully elucidated in the diabetic endothelium from rats. In this study, the role of miR-34a/NOTCH1 signaling in the progression of hyperglycemia-vascular endothelial dysfunction was investigated.
Methods In intravenous injection of miR-34a mimics and inhibitors in streptozotocin (STZ)-induced diabetic rats, the biomarkers of endothelial dysfunction was measured. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The mRNA and protein levels were assayed by qRT-PCR and western blotting, respectively. Immunohistochemical staining was performed to measure NOTCH1 expression in the diabetic endothelium.
Results miR-34a was significantly up-regulated, and NOTCH1 down-regulated, in the thoracic aorta from STZ-induced diabetic rats compared with control group. As compared to model group, the mRNA of NOTCH1 was significantly decreased or increased by miR-34a mimics or inhibitors ex vivo, respectively. Bioinformatics methods further demonstrated that NOTCH1 was a potential target of miR-34a, which was confirmed by dual-luciferase reporter assay. Moreover, both serum ET and NO were significantly increased in diabetic rats as compared to control group. miR-34a inhibitors ex vivo treatment resulted in significant down-regulation ofserum ET and NO levels in diabetic rats as compared to model group.
Conclusion These results provide evidence to support the use of miR-34a inhibitors as a therapeutic approach attenuating hyperglycemia-induced vascular endothelial dysfunction.
Nanoscale view of assisted ion transport across the liquid–liquid interface
Authors: Liang Zhu , Bu Wei , Schweighofer Karl J. , Walwark David J. , Harvey Jeffrey S. , Hanlon Glenn R. , Amoanu Daniel , Erol Cem , Benjamin Ilan , Schlossman Mark L. 
Published: March 2018

Significance
The selective separation of targeted metal ions is utilized for environmental remediation, mining of rare earth and base metals, as well as the separation and isolation of long-lived radionuclides from nuclear waste. During the process of solvent extraction, organic extractant molecules complex with metal ions to assist their transfer from an aqueous to an organic phase. The structure of ion–extractant complexes at the interface, as well as the mechanism of ion transport across the interface, are generally unknown but are relevant for improving the kinetics and efficiency of this industrial process. Here, we describe experiments that reveal different ion–extractant complexes for divalent and trivalent ions, and discuss their consequences for the extraction process.
The Great Recession worsened blood pressure and blood glucose levels in American adults
Authors: Seeman Teresa , Thomas Duncan , Merkin Sharon Stein , Moore Kari , Watson Karol , Karlamangla Arun 
Published: March 2018

Significance
Longitudinal data from the Multi-Ethnic Study of Atherosclerosis (MESA) document deleterious health impacts of the economic and social stresses associated with the Great Recession, with significant increases in blood pressure and glucose. Effects are independent of underlying age-related trends in these biomarkers. Larger effects are seen in population subgroups more severely hit by the recession: younger adults (i.e., those more likely still in the labor force) and older homeowners (whose declining home wealth likely reduced a key element of their financial security). Results also reveal greater impacts on blood pressure and glucose among those on medication, and a concomitant reduction in medication use and intensity of treatment—a potential pathway by which the Great Recession affected people on medications more.
Chemical control over membrane-initiated steroid signaling with a DNA nanocapsule
Authors: Veetil Aneesh T. , Jani Maulik S. , Krishnan Yamuna 
Published: March 2018

Significance
Steroids execute their diverse biological functions through both membrane-initiated steroid signaling (MISS) and nuclear-initiated steroid signaling (NISS). NISS is much slower, occurring over hours to days accompanied by transcriptional changes in the nucleus and is well studied. In contrast MISS is more recently discovered––it is rapid, occurs within seconds upon binding the plasma membrane, and is much less studied. Despite its emerging importance, fundamental issues such as second messenger dynamics and downstream signaling molecules are still unknown because of the paucity of technologies available to manipulate signaling steroids. Here we describe a technology that offers a clean and controllable release of signaling steroids under chemical control that enables the study of MISS dynamics.
Reintroductions of birds and mammals involve evolutionarily distinct species at the regional scale
Authors: Thévenin Charles , Mouchet Maud , Robert Alexandre , Kerbiriou Christian , Sarrazin François 
Published: March 2018

Significance
There are general acknowledgements that Earth’s sixth mass extinction event is more severe than perceived when looking at population extirpations (rather than focusing only on species extinctions) and that species extinctions are associated with the rapid loss of evolutionary history. In this study, we investigate how population reintroductions, a major conservation tool used to reverse population extirpations, can contribute to the preservation of evolutionary diversity within birds and mammals. Using data on reintroductions of terrestrial birds and mammals in Europe and North America, we show that, despite strong taxonomic biases leading to a poor representativeness of the regional phylogenetic diversity, reintroduction practitioners seem to have focused on highly evolutionarily distinct species.
Mechanistic basis for the activation of plant membrane receptor kinases by SERK-family coreceptors
Authors: Hohmann Ulrich , Santiago Julia , Nicolet Joël , Olsson Vilde , Spiga Fabio M. , Hothorn Ludwig A. , Butenko Melinka A. , Hothorn Michael 
Published: March 2018

Significance
Plants contain a unique family of membrane receptors, which are different from the ones found in bacteria and animals. These proteins are able to sense very different signals, such as steroid molecules, peptides, and proteins at the cell surface using a spiral-shaped ligand binding domain. Ligand binding allows the receptor to engage with a smaller coreceptor kinase, which is shared among different receptors. Here it is analyzed how one coreceptor protein can contribute to the sensing of two different ligands involved in plant growth and organ abscission and to activation of their cognate receptors.
Four millennia of Iberian biomolecular prehistory illustrate the impact of prehistoric migrations at the far end of Eurasia
Authors: Valdiosera Cristina , Günther Torsten , Vera-Rodríguez Juan Carlos , Ureña Irene , Iriarte Eneko , Rodríguez-Varela Ricardo , Simões Luciana G. , Martínez-Sánchez Rafael M. , Svensson Emma M. , Malmström Helena , Rodríguez Laura , Bermúdez de Castro José-María , Carbonell Eudald , Alday Alfonso , Hernández Vera José Antonio , Götherström Anders , Carretero José-Miguel , Arsuaga Juan Luis , Smith Colin I. , Jakobsson Mattias 
Published: March 2018

Significance
The gene pool of modern Europeans was shaped through prehistoric migrations that reached the Western Mediterranean last. Obtaining biomolecular data has been challenging due to poor preservation related to adverse climatic conditions in this region. Here, we study the impact of prehistoric (Neolithic–Bronze Age) migrations in Iberia by analyzing genomic and dietary data, demonstrating that farming practices were introduced by a population genetically distinct from the first farmers in central and northern Europe. After recovering from a founder bottleneck, these first farmers mixed with local hunter-gatherers. Finally, post-Neolithic migrations had a much smaller impact on the Iberian gene pool than they had in other parts of Europe. Stable isotope analysis reveals a homogenous terrestrial diet throughout this period.
Human diets drive range expansion of megafauna-dispersed fruit species
Authors: van Zonneveld Maarten , Larranaga Nerea , Blonder Benjamin , Coradin Lidio , Hormaza José I. , Hunter Danny 
Published: March 2018

SignificanceNeotropical fruit species once dispersed by megafauna have regained relevance for diversifying human diets to address malnutrition. Little is known about the historic interactions between humans and these fruit species. We quantified the human role in modifying distribution ranges of Neotropical fruit species by comparing the distribution of fruit species that have been part of both human and megafauna diets with fruit species that were exclusively part of megafauna diets. Our results show that human food usage has expanded the distribution of species that would otherwise have suffered range contraction after extinction of megafauna. Our analyses help in identifying range segments of fruit species that may hold key genetic diversity to sustain food systems and to maintain critical ecosystem functions.
Structural changes of TasA in biofilm formation of
Bacillus subtilis
Authors: Diehl Anne , Roske Yvette , Ball Linda , Chowdhury Anup , Hiller Matthias , Molière Noel , Kramer Regina , Stöppler Daniel , Worth Catherine L. , Schlegel Brigitte , Leidert Martina , Cremer Nils , Erdmann Natalja , Lopez Daniel , Stephanowitz Heike , Krause Eberhard , van Rossum Barth-Jan , Schmieder Peter , Heinemann Udo , Turgay Kürşad , Akbey Ümit , Oschkinat Hartmut 
Published: March 2018

Significance
Understanding the formation and structure of protective bacterial biofilms will help to design and identify antimicrobial strategies. Our experiments with the secreted major biofilm protein TasA characterize on a molecular level in vivo the transition of a folded protein into protease-resistant biofilm-stabilizing fibrils. Such conformational changes from a globular state into fibrillar structures are so far not seen for other biofilm-forming proteins. In this context, TasA can serve as a model system to study functional fibril formation from a globular state.
Archaeal acetoacetyl-CoA thiolase/HMG-CoA synthase complex channels the intermediate via a fused CoA-binding site
Authors: Vögeli Bastian , Engilberge Sylvain , Girard Eric , Riobé François , Maury Olivier , Erb Tobias J. , Shima Seigo , Wagner Tristan 
Published: March 2018

Significance
Mevalonate is a building block of archaeal lipids. Three enzymes are involved in its biosynthesis: acetoacetyl-CoA thiolase (thiolase), 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGCS), and HMG-CoA reductase. The thiolase reaction is highly endergonic, which means that archaea have to find a way to overcome this low-flux bottleneck. Our work revealed the presence of a thiolase/HMGCS complex, which directly couples the endergonic thiolase reaction to the exergonic HMGCS reaction. An unexpected third protein spatially connects the thiolase and HMGCS. Strikingly, these two enzymes share the same substrate-binding site. Genomic information indicated that the presence of a thiolase/HMGCS complex is common in most of archaea and many bacteria. Such a natural intermediate-channeling system could lead to new strategies to improve biotechnological mevalonate synthesis.
Noncatalytic aspartate at the exonuclease domain of proofreading DNA polymerases regulates both degradative and synthetic activities
Authors: del Prado Alicia , Franco-Echevarría Elsa , González Beatriz , Blanco Luis , Salas Margarita , de Vega Miguel 
Published: March 2018

Significance
Replicative DNA polymerases (DNAPs) combine two processes to ensure the extremely faithful synthesis of DNA, nucleotide selectivity, and editing of misinserted nucleotides by a 3′-5′ exonuclease activity. The 3′-5′ exonuclease activity is governed by four universally conserved aspartate residues that coordinate the two metal ions responsible for the hydrolysis of the last phosphodiester bond of the primer strand. In this work, we have identified an additional conserved aspartate residue that establishes multiple interactions with residues responsible for the exonucleolysis and for the forward movement of the DNAP along the DNA after inserting a nucleotide, acting as a master organizer for the processive intramolecular proofreading of polymerization errors.