bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalysis of amorpha-4,11-diene synthase unraveled and improved by mutability landscape guided engineering
Authors: Abdallah Ingy I. , van Merkerk Ronald , Klumpenaar Esmée , Quax Wim J. 
Published: June 2018

AbstractAmorpha-4,11-diene synthase (ADS) cyclizes the substrate farnesyl pyrophosphate to produce amorpha-4,11-diene as a major product. This is considered the first committed and rate-limiting step in the biosynthesis of the antimalarial artemisinin. Here, we utilize a reported 3D model of ADS to perform mutability landscape guided enzyme engineering. A mutant library of 258 variants along sixteen active site residues was created then screened for catalytic activity and product profile. This allowed for identification of the role of some of these residues in the mechanism. R262 constrains the released pyrophosphate group along with magnesium ions. The aromatic residues (W271, Y519 and F525) stabilize the intermediate carbocations while T296, G400, G439 and L515 help with the 1,6- and 1,10-ring closures. Finally, W271 is suggested to act as active site base along with T399, which ensures regioselective deprotonation. The mutability landscape also helped determine variants with improved catalytic activity. H448A showed ~4 fold increase in catalytic efficiency and the double mutation T399S/H448A improved kcat by 5 times. This variant can be used to enhance amorphadiene production and in turn artemisinin biosynthesis. Our findings provide the basis for the first step in improving industrial production of artemisinin and they open up possibilities for further engineering and understanding of ADS.
Early alteration of epigenetic-related transcription in Huntington’s disease mouse models
Authors: Hervás-Corpión Irati , Guiretti Deisy , Alcaraz-Iborra Manuel , Olivares Román , Campos-Caro Antonio , Barco Ángel , Valor Luis M. 
Published: June 2018

AbstractTranscriptional dysregulation in Huntington’s disease (HD) affects the expression of genes involved in survival and neuronal functions throughout the progression of the pathology. In recent years, extensive research has focused on epigenetic and chromatin-modifying factors as a causative explanation for such dysregulation, offering attractive targets for pharmacological therapies. In this work, we extensively examined the gene expression profiles in the cortex, striatum, hippocampus and cerebellum of juvenile R6/1 and N171-82Q mice, models of rapidly progressive HD, to retrieve the early transcriptional signatures associated with this pathology. These profiles were largely consistent across HD datasets, contained tissular and neuronal-specific genes and showed significant correspondence with the transcriptional changes in mouse strains deficient for epigenetic regulatory genes. The most prominent cases were the conditional knockout of the lysine acetyltransferase CBP in post-mitotic forebrain neurons, the double knockout of the histone methyltransferases Ezh1 and Ezh2, components of the polycomb repressor complex 2 (PRC2), and the conditional mutants of the histone methyltransferases G9a (Ehmt2) and GLP (Ehmt1). Based on these observations, we propose that the neuronal epigenetic status is compromised in the prodromal stages of HD, leading to an altered transcriptional programme that is prominently involved in neuronal identity.
Earth’s youngest banded iron formation implies ferruginous conditions in the Early Cambrian ocean
Authors: Li Zhi-Quan , Zhang Lian-Chang , Xue Chun-Ji , Zheng Meng-Tian , Zhu Ming-Tian , Robbins Leslie J. , Slack John F. , Planavsky Noah J. , Konhauser Kurt O. 
Published: June 2018

AbstractIt has been proposed that anoxic and iron-rich (ferruginous) marine conditions were common through most of Earth history. This view represents a major shift in our understanding of the evolution of marine chemistry. However, thus far, evidence for ferruginous conditions comes predominantly from Fe-speciation data. Given debate over these records, new evidence for Fe-rich marine conditions is a requisite if we are to shift our view regarding evolution of the marine redox landscape. Here we present strong evidence for ferruginous conditions by describing a suite of Fe-rich chemical sedimentary rocks—banded iron formation (BIF)—-deposited during the Early Cambrian in western China. Specifically, we provide new U-Pb geochronological data that confirm a depositional age of ca. 527 Ma for this unit, as well as rare earth element (REE) data are consistent with anoxic deposition. Similar to many Algoma-type Precambrian iron formations, these Early Cambrian sediments precipitated in a back-arc rift basin setting, where hydrothermally sourced iron drove the deposition of a BIF-like protolith, the youngest ever reported of regional extent without direct links to volcanogenic massive sulphide (VMS) deposits. Their presence indicates that marine environments were still characterized by chemical- and redox-stratification, thus supporting the view that—despite a dearth of modern marine analogues—ferruginous conditions continued to locally be a feature of early Phanerozoic seawater.
Complex Network Geometry and Frustrated Synchronization
Authors: Millán Ana P. , Torres Joaquín J. , Bianconi Ginestra 
Published: June 2018

AbstractThe dynamics of networks of neuronal cultures has been recently shown to be strongly dependent on the network geometry and in particular on their dimensionality. However, this phenomenon has been so far mostly unexplored from the theoretical point of view. Here we reveal the rich interplay between network geometry and synchronization of coupled oscillators in the context of a simplicial complex model of manifolds called Complex Network Manifold. The networks generated by this model combine small world properties (infinite Hausdorff dimension) and a high modular structure with finite and tunable spectral dimension. We show that the networks display frustrated synchronization for a wide range of the coupling strength of the oscillators, and that the synchronization properties are directly affected by the spectral dimension of the network.
The Genome Sequences of 90 Mushrooms
Authors: Li Huiying , Wu Surui , Ma Xiao , Chen Wei , Zhang Jing , Duan Shengchang , Gao Yun , Kui Ling , Huang Wenli , Wu Peng , Shi Ruoyu , Li Yifan , Wang Yuanzhong , Li Jieqing , Guo Xiang , Luo Xiaoli , Li Qiang , Xiong Chuan , Liu Honggao , Gui Mingying , Sheng Jun , Dong Yang 
Published: June 2018

AbstractMacrofungus is defined as the fungus that grows an observable sporocarp. The sporocarps of many species are commonly called mushrooms and consumed by people all around the world as food and/or medicine. Most macrofungi belong to the divisions Basidiomycetes and Ascomycetes, which are estimated to contain more than 80,000 species in total. We report the draft genome assemblies of macrofungi (83 Basidiomycetes species and 7 Ascomycetes species) based on Illumina sequencing. The genome sizes of these species ranged from 27.4 Mb (Hygrophorus russula) to 202.2 MB (Chroogomphus rutilus). The numbers of protein-coding genes were predicted in the range of 9,511 (Hygrophorus russula) to 52,289 (Craterellus lutescens). This study provides the largest genomic dataset for macrofungi species. This resource will facilitate the artificial cultivation of edible mushrooms and the discovery of novel drug candidates.
N-doped catalytic graphitized hard carbon for high-performance lithium/sodium-ion batteries
Authors: Wang Ning , Liu Qinglei , Sun Boya , Gu Jiajun , Yu Boxuan , Zhang Wang , Zhang Di 
Published: June 2018

AbstractHard carbon attracts wide attentions as the anode for high-energy rechargeable batteries due to its low cost and high theoretical capacities. However, the intrinsically disordered microstructure gives it poor electrical conductivity and unsatisfactory rate performance. Here we report a facile synthesis of N-doped graphitized hard carbon via a simple carbonization and activation of a urea-soaked self-crosslinked Co-alginate for the high-performance anode of lithium/sodium-ion batteries. Owing to the catalytic graphitization of Co and the introduction of nitrogen-functional groups, the hard carbon shows structural merits of ordered expanded graphitic layers, hierarchical porous channels, and large surface area. Applying in the anode of lithium/sodium-ion batteries, the large surface area and the existence of nitrogen functional groups can improve the specific capacity by surface adsorption and faradic reaction, while the hierarchical porous channels and expanded graphitic layers can provide facilitate pathways for electrolyte and improve the rate performance. In this way, our hard carbon provides its feasibility to serve as an advanced anode material for high-energy rechargeable lithium/sodium-ion batteries.
Apparent diffusion coefficient histogram in breast cancer brain metastases may predict their biological subtype and progression
Authors: Ahn Sung Jun , Park Mijin , Bang Sungkyu , Cho Eunseo , Ahn Sung Gwe , Suh Sang Hyun , Lee Jong-Min 
Published: June 2018

AbstractOur aims for this study were to investigate the relationship between diffusion weighted image (DWI) parameters of brain metastases (BMs) and biological markers of breast cancer, and moreover, to assess whether DWI parameters accurately predict patient outcomes. DWI data for 34 patients with BMs from breast cancer were retrospectively reviewed. Apparent diffusion coefficient (ADC) histogram parameters were calculated from all measurable BMs. Two region of interest (ROI) methods are used for the analysis: from the largest BM or from all measurable BMs per one patient. ADC histogram parameters were compared between positive and negative groups depending on ER/PR and HER2 statuses. Overall survival analysis after BM (OSBM) and BM-specific progression-free survival (BMPFS) was analyzed with ADC parameters. Regardless of ROI methods, 25th percentile of ADC histogram was significantly lower in the ER/PR-positive group than in the ER/PR-negative group (P < 0.05). Using ROIs from all measurable BMs, Peak location, 50th percentile, 75th percentile, and mean value of ADC histogram were also significantly lower in the ER/PR-positive group than in the ER/PR-negative group (P < 0.05). However, there was no significant difference between HER2-postive and negative group. On univariate analysis, using ROIs from all measurable BMs, lower 25th percentile, 50th percentile and mean of ADC were significant predictors for poor BMPFS. ADC histogram analysis may have a prognostic value over ER/PR status as well as BMPFS.
New dates on dingo bones from Madura Cave provide oldest firm evidence for arrival of the species in Australia
Authors: Balme Jane , O’Connor Sue , Fallon Stewart 
Published: June 2018

AbstractThe dingo is the only placental land mammal aside from murids and bats to have made the water crossings to reach Australia prior to European arrival. It is thought that they arrived as a commensal animal with people, some time in the mid Holocene. However, the timing of their arrival is still a subject of major debate with published age estimates varying widely. This is largely because the age estimates for dingo arrival are based on archaeological deposit dates and genetic divergence estimates, rather than on the dingo bones themselves. Currently, estimates vary from between 5000–4000 years ago, for finds from archaeological contexts, and as much as 18,000 based on DNA age estimates. The timing of dingo arrival is important as post arrival they transformed Indigenous societies across mainland Australia and have been implicated in the extinction of a number of animals including the Tasmanian tiger. Here we present the results of direct dating of dingo bones from their oldest known archaeological context, Madura Cave on the Nullarbor Plain. These dates demonstrate that dingoes were in southern Australia by between 3348 and 3081 years ago. We suggest that following their introduction the dingo may have spread extremely rapidly throughout mainland Australia.
High content screen for identifying small-molecule LC3B-localization modulators in a renal cancer cell line
Authors: Kolla Likhitha , Heo David S. , Rosenberg Daniel P. , Barlow Sara A. , Maximova Anna A. , Cassio Emily E. , Buchser William J. 
Published: June 2018

AbstractForms of selective autophagy have now been recognized to regulate flux in many intracellular processes. Specific pathways and functions have been identified for mitophagy, ERphagy, and other selective autophagies; yet there is no consensus in whether and how autophagy regulates protein maintenance in and around the nucleus. Such processes are of interest for potential degradation of DNA and nuclear envelope proteins in various disease states. The mechanistic details of such nucleus-related autophagic processes remain elusive due to the lack of chemical or genetic regulators to manipulate and follow the process in vitro. Here, we describe a high content screen from which we identified small chemical compounds that can modulate the localization of the autophagy marker MAP1LC3B (LC3) in renal carcinoma cells. We also describe a pipeline designed for the execution and analysis of high content screens. The chemical tools discerned from this screen will allow for the deeper exploration of the mechanism, regulation, and molecular targets of nuclear-localized LC3 in perturbed cellular states.
Intersektorale augenmedizinische Facharztzentren und Versorgung auf dem Land
Authors: Hahn Ursula , Awe Burkhard , Koch Jörg , März Markus 
Published: June 2018

Zusammenfassung
Zielsetzung Große Praxen und Medizinische Einrichtungen tragen unzureichend zur Versorgung in ländlichen Regionen bei, so lautet eine häufig vorgetragene
Kritik. Umfassende öffentlich zugängliche Datenquellen dazu fehlen jedoch, auch die MVZ-Statistik der Kassenärztlichen Bundesvereinigung berichtet nur über
Haupt-, nicht jedoch über die Nebenbetriebsstätten. Beispielhaft wurde daher die Aufstellung für Intersektorale augenmedizinischen Facharztzentren erhoben.
Methodik Für alle im OcuNet Verbund organisierten Zentren wurden in 2016 die Leistungsstandorte mit den jeweiligen Leistungsschwerpunkten erfasst und
Regionstypen der Bedarfs planungsrichtlinie zugeordnet. Für die Zentren, die Standorte über die Grenzen eines Stadtgebietes haben, wurden die absolute und
relative Häufigkeit der Standorte bzw. Leistungsschwerpunkte insgesamt und nach den 5 Regionstypen der Bedarfsplanungsregionen erfasst.
Ergebnisse 15 der 19 Zentren hatten Standorte über die Grenzen eines Stadtgebietes hinaus. Diese Zentren kommen auf insgesamt 155 Leistungsstandorte,
davon wiesen 132 (85 %) ein konservatives Leistungsspektrum auf. Insgesamt 55 Prozent der Leistungsstandorte entfielen auf die Kreistypen 4 („mitversorgte
Bereiche“) und 5 („eigenversorgte Gebiete“); also die Kreistypen ländlicher Regionen, die typischerweise besonders stark von Ärztemangel betroffen sind.
Schlussfolgerung Nahezu ¾ der Intersektoralen augenmedizinischen Facharztzentren des OcuNet Verbundes filialisieren; die Leistungsstandorte dieser Zentren
liegen in der Mehrheit in ländlichen Regionen. Die These der unzureichenden Versorgung in der Fläche lässt sich für die betrachtete Stichprobe nicht
bestätigen.
Prävention und Therapie der Arthrose – Systembiologische Sichtweise
Authors: Dickreiter Bernhard 
Published: June 2018

ZusammenfassungDie Arthrose ist mittlerweile eine Volkskrankheit. Überwiegend wird sie verursacht durch multiple negative Faktoren, die aus der modernen Lebensweise resultieren. Deshalb kann eine medikamentöse Therapie nur symptomatisch wirken. Eine sinnvolle und wirksame Prävention und Therapie von Zivilisationskrankheiten, so auch der Arthrose, muss immer an der gesamten Lebensweise mit Ernährung, Bewegung, Mikronährstoffstatus, Dysstress, Zivilisationsgifte usw. ansetzen. Die Systembiologie zeigt auf, dass bei einem komplexen biologischen System wie einem Gelenk alle „Mangelfaktoren“ für eine erfolgreiche Prävention und ursächliche Therapie behoben werden müssen.
Yamamoto Neue Schädelakupunktur
Authors: Ogal Hans P. 
Published: June 2018

ZusammenfassungDie Yamamoto Neue Schädelakupunktur (YNSA) wurde in den 1960er-Jahren von dem japanischen Anästhesisten und Schmerztherapeuten Dr. med. Toshikatsu Yamamoto (PhD) begründet. Neben der Entdeckung des neuen Mikrosystems am Kopf modifizierte Yamamoto als diagnostische Weiterentwicklung die orientalische Bauchdeckendiagnostik und ordnete die auf ihr beruhenden Reflexzonen den Schädelakupunkturpunkten zu. Die YNSA ist geeignet zur schnellen und effizienten Behandlung aller funktionellen und prinzipiell reversiblen Störungen sowie Schmerzzuständen des Bewegungssystems. Auch für die Schmerztherapie und verbesserte Mobilisation nach Verletzungen und Operationen ist sie indiziert sowie zur Rehabilitation und Behandlung von zentralen und peripheren Lähmungen.
Zum Beitrag der gesundheitsökonomischen Forschung zur medizinischen Versorgung
Authors: Leidl Reiner 
Published: June 2018

ZusammenfassungDie Gesundheitsökonomie kann den optimalen Ressourceneinsatz in der medizinischen Versorgung auf vielfältige Weise unterstützen. Nach einem Blick auf
Entwicklungen in der prozessorientierten, morbiditätsbezogenen Steuerung der Krankenhausversorgung stehen Ergebnisse, speziell die Patientenperspektive und
Patient-Reported Outcomes im Fokus. Näher vorgestellt werden Messansätze und Auswirkungen präferenz- und erfahrungsbasierter Bewertungen der
gesundheitsbezogenen Lebensqualität. Als Basis dienen Bevölkerungsstichproben und routinemäßig erhobene, indikationsspezifische Stichproben. Zum
ergebnisbezogenen Value-based Health Care Ansatz wird der Wertbegriff kritisch beleuchtet. Einen neuen Ansatz zur Integration medizinischer und ökonomischer
Zielsetzungen bildet das Outcome-orientierte Versorgungsmanagement. Dazu werden Entwicklungstrends, ein Managementzyklus und ein Studienbeispiel behandelt.
Outcomes sind ein vielversprechendes Zukunftsthema, mit dem Beiträge der gesundheitsökonomischen Forschung zur medizinischen Versorgung weiter verbessert werden
könnten.
Mechanismenbasierte Therapie neuropathischer Schmerzen
Authors: Tina Mainka , Maier C. , Enax-Krumnova Elena K. 
Published: June 2018

ZUSAMMENFASSUNGNeuropathische Schmerzen entstehen als direkte Folge einer Erkrankung oder Läsion des somatosensorischen Systems. In der Allgemeinbevölkerung haben sie eine Prävalenz von bis zu 10 %, bei Diabetikern bis zu 30 %. Typisch ist das gleichzeitige Auftreten von Plus- (Schmerz, Hyperalgesie) und Minussymptomen (Hypästhesie, Hypoalgesie) für thermische und/oder mechanische Reize, wobei unterschiedliche Symptomkonstellationen unabhängig von der Krankheitsätiologie auftreten. Die genaue Analyse der sensorischen Symptome erlaubt Rückschlüsse über die Mechanismen der Schmerzentstehung (z. B. periphere und zentrale Sensibilisierung, Störung endogener Schmerzhemmung), was zusammen mit der Kenntnis der pharmakologischen Angriffspunkte der üblicherweise eingesetzten Medikamente (Antikonvulsiva, Antidepressiva, Opioide und topisch applizierte Wirkstoffe) eine gezieltere Pharmakotherapie ermöglicht. Einige Studien konnten einen Zusammenhang zwischen dem sensorischen Profil und dem Therapieeffekt verschiedener Medikamente nachweisen. Weitere Studien sind notwendig, um diesbezüglich leitlinienrelevante Empfehlungen für die individuelle Therapieauswahl auszusprechen.
Kosteneffektivität – Validierung ökonomischer Evaluationen auf Basis von Routinedaten
Authors: Potempa Christoph 
Published: June 2018

Achana et al. A methodological framework for assessing agreement between cost-effectiveness outcomes estimated using alternative sources of data on treatment
costs and effects for trial-based economic evaluations. Eur J Health Econ; 2018; 19: 75–86
Die Autoren Achana et al. stellen in ihrer Arbeit ein methodologisches Framework zur Validierung der Endpunkte von Kosten-Effektivitäts-Analysen vor, bei dem
die Behandlungskosten und ökonomischen Auswirkunge n durch die Verwendung alternativer Datenquellen (z. B. durch Routinedatensätze) geschätzt werden können
und veranschaulichen die Methode zusätzlich an einem neonatologischen Fallbeispiel.
Akute Pankreatitis als schwere Komplikation einer Erstmanifestation eines Typ-2-Diabetes
Authors: Gördes Lukas , Roden Michael , Müssig Karsten 
Published: June 2018

ZUSAMMENFASSUNGEs gibt eine Reihe von Erkrankungen, die als Folge des Diabetes bestehen oder begleitend auftreten. Diese zu diagnostizieren und die Ursachen richtig einzuschätzen, ist besonders schwer, wenn der Diabetes im Frühstadium noch undiagnostiziert ist. Häufig genannte schwere Komplikationen, die eventuell eine intensivmedizinische Behandlung benötigen, sind Ketoazidosen bei Typ-1-Diabetes oder ein hyperosmolares Koma bei Typ-2-Diabetes. Insbesondere bei adipösen Patienten kann jedoch die Erstmanifestation eines Typ-2-Diabetes mit weiteren, potenziell schwerwiegenden Komplikationen assoziiert sein – wie das folgende Beispiel eines 32-jährigen Patienten eindrucksvoll belegt.
Histomorphometry and Protein Expression From the Ovary and Uterine Horns of Wistar Strain Albino Rats Treated with Methanol Leave Extract of Parquetina Nigrescens
Authors: Akinjiola Akinwale , Ajala Oluwatoyin , Aina Oluwasanmi , Oyebanji Victor , Olukunle Johnny 
Published: June 2018

Abstract
Background The effects of methanol extract of Parquetina nigrescens were studied on histomorphometry and protein expression (SDS-PAGE) from the ovaries and uteri of wistar rats.
Methods 30 sexually matured rats were used for the study with 10 each in the control and treatment 100 mgkg−1 and 400 mgkg−1 groups. The extract was orally administered for 14 days. Histological sections of tissues collected presented no abnormalities.
Results An increase in the number of developing and matured follicles were observed during the study in the treated groups compared to the control in the follicular and the luteal phases. The corpora lutea in the treated groups were fewer in number to that of the control in the follicular phase and in the luteal phase. Sections of the uterine horns showed significant narrowing in the lumen diameter and increases in epithelial height with increased laydown of the lamina propria in the treated groups. The expression of protein bands fractionated during the study, confirm the presence of proteins expressed repeatedly from the ovary and uterine horns in the follicular and luteal phases at the 70 kDa and 63 kDa regions.
Conclusions The study concluded that the methanol extract of the plant increased folliculogenesis on the ovary, secretory activity in the nuclei of the epithelium and the fibroplasia of the lamina propria while narrowing the lumen of the uterine horns which are similar to the effects of oestrogen or oestrogen-like substances on these reproductive organs and may have an effect on the abundance of protein expressed in the follicular phase.
Defibrination Syndrome Followed by Hypercoagulable State
Authors: Rachmilewitz E. A , Schenker J , Kropatkin M. L 
Published: June 2018

SummaryA 37-year-old woman developed an acute defibrination syndrome with peripheral vascular collapse and a renal shut-down following an operation for uterine prolapse. The bleeding tendency was controlled by treatment with blood, Cohn’s fraction I and EACA. During the period when the levels of the clotting factors reached a peak, the patient developed multiple pulmonary emboli. The patient recovered following administration of heparin and antibiotics. The connection between the defibrination syndrome and the subsequent hypercoagulable state is discussed with special mention of the possible role of therapy - mainly EACA - in the production of the latter. The levels of the various clotting factors were very low at the time of the bleeding, but rose to abnormally high values within the ensuing 8 to 10 days.