bluuebunny/crossref_metadata_2025_split huggingface dataset:
MDM2 Contributes to High Glucose-Induced Glomerular Mesangial Cell Proliferation and Extracellular Matrix Accumulation via Notch1
Authors: Lei Chun-Tao , Tang Hui , Ye Chen , You Chao-Qun , Zhang Jiao , Zhang Chun-Yun , Xiong Wei , Su Hua , Zhang Chun 
Published: August 2017

AbstractMurine double minute 2 (MDM2) is an E3-ubiquitin ligase critical for various biological functions. Previous data have revealed an indispensable role of MDM2 in kidney homeostasis. However, its role in glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) accumulation during hyperglycemia condition remains unclear. In our present study, we found that MDM2 protein level was significantly upregulated in high glucose-treated GMCs, while knocking down MDM2 by siRNA could attenuate high glucose-induced ECM accumulation and GMCs proliferation. Unexpectedly, Nutlin-3a, a MDM2-p53 interaction blocker, had no benefit in protecting diabetic mice from renal impairment in vivo and in alleviating high glucose-induced ECM accumulation in vitro. Intriguingly, we found that Notch1 signaling activation was obviously attenuated by MDM2 depletion in GMCs with high glucose exposure. However, Numb, a substrate of MDM2 which suppresses Notch1 signaling, was found not to be involved in the MDM2 and Notch1 association. Moreover, our findings demonstrated that MDM2 interacted with Notch1 intracellular domain (NICD1) independent of Numb and regulated the ubiquitination status of NICD1. Collectively, our data propose a pivotal role of MDM2 in high glucose-induced GMC proliferation and ECM accumulation, via modulating the activation of Notch1 signaling pathway in an ubiquitination-dependent way.
Modulation of action potentials using PEDOT:PSS conducting polymer microwires
Authors: Thourson Scott B. , Payne Christine K. 
Published: August 2017

AbstractWe describe the use of PEDOT:PSS conducting polymer microwires to modulate action potentials in single cells. PEDOT:PSS conducting polymer microwires are electrochemically synthesized with diameters ranging from 860 nm to 4.5 μm and conductivities of ~30 S/cm. The length of the microwires is controlled by the spacing of the electrodes used for the electrochemical polymerization. We demonstrate the use of these microwires to control the action potentials of cardiomyocytes, showing that the cellular contractions match the frequency of the applied voltage. Membrane integrity assays confirm that the voltage delivered by the wires does not damage cells. We expect the conducting polymer microwires will be useful as minimally invasive devices to control the electrical properties of cells with high spatial precision.
Enhanced Low-temperature Electro-optical Kerr Effect of Stable Cubic Soft Superstructure Enabled by Fluorinated Polymer Stabilization
Authors: Li Xiao , Yang Wei-Qiang , Yuan Cong-Long , Liu Zhen , Zhou Kang , Wang Xiao-Qian , Shen Dong , Zheng Zhi-gang 
Published: August 2017

AbstractAn enhanced electro-optical Kerr effect of the stable self-organized cubic blue phase liquid crystal superstructure at a relatively low temperature down to −50 °C was achieved through a judiciously designed fluorinated polymer stabilization. The fluorinated sample exhibited not only a rather stable cubic structure, but the promoted electro-optical performances of low driving voltage, weak hysteresis and high contrast ratio at such a low-temperature, which were much distinct from the common non-fluorinated polymer stabilized blue phase liquid crystal without conspicuous low-temperature Kerr response behaviours. Kerr constant, which reflects the obviousness of Kerr effect, of the fluorinated sample at −50 °C indicated a spectacular enhancement of two orders of magnitude in contrast to the commonly material, thereby corroborating the high efficiency of polymer fluorination in enhancing low-temperature Kerr effect. Such an enhancement of Kerr effect was probably resulted from the decreasing of interfacial anchoring between liquid crystal and fluorinated polymer network. The fluorinated polymer stabilization not only ensures the stability of self-organized cubic structure of blue phase, but overcomes the challenge and bottleneck problem of low-temperature inapplicability of common blue phase liquid crystal and paves a brilliant and broad way for relevant materials to abundant perspective applications at low temperature.
Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide
Authors: Roeckel Laurie-Anne , Utard Valérie , Reiss David , Mouheiche Jinane , Maurin Hervé , Robé Anne , Audouard Emilie , Wood John N. , Goumon Yannick , Simonin Frédéric , Gaveriaux-Ruff Claire 
Published: August 2017

AbstractOpiates are potent analgesics but their clinical use is limited by side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). The Opiates produce analgesia and other adverse effects through activation of the mu opioid receptor (MOR) encoded by the Oprm1 gene. However, MOR and morphine metabolism involvement in OIH have been little explored. Hence, we examined MOR contribution to OIH by comparing morphine-induced hyperalgesia in wild type (WT) and MOR knockout (KO) mice. We found that repeated morphine administration led to analgesic tolerance and hyperalgesia in WT mice but not in MOR KO mice. The absence of OIH in MOR KO mice was found in both sexes, in two KO global mutant lines, and for mechanical, heat and cold pain modalities. In addition, the morphine metabolite morphine-3beta-D-glucuronide (M3G) elicited hyperalgesia in WT but not in MOR KO animals, as well as in both MOR flox and MOR-Nav1.8 sensory neuron conditional KO mice. M3G displayed significant binding to MOR and G-protein activation when using membranes from MOR-transfected cells or WT mice but not from MOR KO mice. Collectively our results show that MOR is involved in hyperalgesia induced by chronic morphine and its metabolite M3G.
Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma
Authors: Johnsen Kasper Bendix , Burkhart Annette , Melander Fredrik , Kempen Paul Joseph , Vejlebo Jonas Bruun , Siupka Piotr , Nielsen Morten Schallburg , Andresen Thomas Lars , Moos Torben 
Published: August 2017

AbstractDrug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain.
A strategy for the identification of patterns in the biosynthesis of nonribosomal peptides by Betaproteobacteria species
Authors: Baldim João Luiz , da Silva Bruna Lidiane , Chagas-Paula Daniela Aparecida , Lago João Henrique G. , Soares Marisi G. 
Published: August 2017

AbstractNonribosomal peptides have an important pharmacological role due to their extensive biological properties. The singularities in the biosynthesis of these natural products allowed the development of genome-mining strategies which associate them to their original biosynthetic gene clusters. Generally, these compounds present complex architectures that make their identification difficult. Based on these evidences, genomes from species of the class Betaproteobacteria were studied with the purpose of finding biosynthetic similarities ﻿among them﻿. These organisms were applied as templates due to their large number of biosynthetic gene clusters and the natural products isolated from them. The strategy for Rapid Identification of Nonribosomal Peptides Portions (RINPEP) proposed in this work was built by reorganizing the data obtained from antiSMASH and NCBI with a product-centered way. The verification steps of RINPEP comprehended the fragments of existent compounds and predictions obtained in silico with the purpose of finding common subunits expressed by different genomic sequences. The results of this strategy revealed patterns in a global overview of the biosynthesis of nonribosomal peptides by Betaproteobacteria.
Addressing the challenges of applying precision oncology
Authors: Shin Seung Ho , Bode Ann M. , Dong Zigang 
Published: August 2017

AbstractPrecision oncology is described as the matching of the most accurate and effective treatments with the individual cancer patient. Identification of important gene mutations, such as BRCA1/2 that drive carcinogenesis, helped pave the way for precision diagnosis in cancer. Oncoproteins and their signaling pathways have been extensively studied, leading to the development of target-based precision therapies against several types of cancers. Although many challenges exist that could hinder the success of precision oncology, cutting-edge tools for precision diagnosis and precision therapy will assist in overcoming many of these difficulties. Based on the continued rapid progression of genomic analysis, drug development, and clinical trial design, precision oncology will ultimately become the standard of care in cancer therapeutics.
FANTOM5 CAGE profiles of human and mouse reprocessed for GRCh38 and GRCm38 genome assemblies
Authors: Abugessaisa Imad , Noguchi Shuhei , Hasegawa Akira , Harshbarger Jayson , Kondo Atsushi , Lizio Marina , Severin Jessica , Carninci Piero , Kawaji Hideya , Kasukawa Takeya 
Published: August 2017

AbstractThe FANTOM5 consortium described the promoter-level expression atlas of human and mouse by using CAGE (Cap Analysis of Gene Expression) with single molecule sequencing. In the original publications, GRCh37/hg19 and NCBI37/mm9 assemblies were used as the reference genomes of human and mouse respectively; later, the Genome Reference Consortium released newer genome assemblies GRCh38/hg38 and GRCm38/mm10. To increase the utility of the atlas in forthcoming researches, we reprocessed the data to make them available on the recent genome assemblies. The data include observed frequencies of transcription starting sites (TSSs) based on the realignment of CAGE reads, and TSS peaks that are converted from those based on the previous reference. Annotations of the peak names were also updated based on the latest public databases. The reprocessed results enable us to examine frequencies of transcription initiations on the recent genome assemblies and to refer promoters with updated information across the genome assemblies consistently.
Genome-wide expression and response to exposure-based psychological therapy for anxiety disorders
Authors: Roberts S , Wong C C Y , Breen G , Coleman J R I , De Jong S , Jöhren P , Keers R , Curtis C , Lee S H , Margraf J , Schneider S , Teismann T , Wannemüller A , Lester K J , Eley T C 
Published: August 2017

AbstractExposure-based psychological treatments for anxiety have high efficacy. However, a substantial proportion of patients do not respond to therapy. Research examining the potential biological underpinnings of therapy response is still in its infancy, and most studies have focussed on candidate genes. To our knowledge, this study represents the first investigation of genome-wide expression profiles with respect to treatment outcome. Participants (n=102) with panic disorder or specific phobia received exposure-based cognitive behavioural therapy. Treatment outcome was defined as percentage reduction from baseline in clinician-rated severity of their primary anxiety diagnosis at post treatment and 6 month follow-up. Gene expression was determined from whole blood samples at three time points using the Illumina HT-12v4 BeadChip microarray. Linear regression models tested the association between treatment outcome and changes in gene expression from pre-treatment to post treatment, and pre-treatment to follow-up. Network analysis was conducted using weighted gene co-expression network analysis, and change in the detected modules from pre-treatment to post treatment and follow-up was tested for association with treatment outcome. No changes in gene expression were significantly associated with treatment outcomes when correcting for multiple testing (q<0.05), although a small number of genes showed a suggestive association with treatment outcome (q<0.5,n=20). Network analysis showed no association between treatment outcome and change in gene expression for any module. We report suggestive evidence for the role of a small number of genes in treatment outcome. Although preliminary, these findings contribute to a growing body of research suggesting that response to psychological therapies may be associated with changes at a biological level.
Botulismus: Diagnostik und Therapie
Authors: Wendt Sebastian , Eder Ines , Wölfel Roman , Braun Peggy , Lippmann Norman , Rodloff Arne 
Published: August 2017

Zusammenfassung
Hintergrund Botulismus ist eine seltene, lebensbedrohliche, zeitkritische neuroparalytische Erkrankung, die häufig Gegenstand differenzialdiagnostischer Erwägungen ist. Bezüglich Diagnostik und Therapie herrscht aber viel Unsicherheit. Rasche Diagnostik, frühzeitige Antitoxingabe, konsequente Lebensmittelhygiene und die Sensibilisierung der Bevölkerung können dazu beitragen, Inzidenz, Morbidität und Mortalität zu senken.
Methoden Grundlage ist eine epidemiologische Datenabfrage (RKI, ECDC, CDC, WHO) und selektive Literaturrecherche zu Diagnostik- und Therapieempfehlungen (PubMed bis März 2017). Ferner wurden die deutsche Botulismus-S1-Leitlinie (2012) und eigene Erfahrungen in der Diagnostik berücksichtigt.
Ergebnisse Die Inzidenz der durch den ubiquitären Sporenbildner Clostridium botulinum (Hauptvertreter) verursachten Botulinum-Intoxikation beträgt < 0,01/100 000 EU-Einwohner. Der Nahrungsmittelbotulismus ist ein reines Intoxikationssyndrom (häufigste Form) durch unsachgemäß zubereitete bzw. falsch gelagerte Lebensmittel. Wund- und Säuglingsbotulismus sind „Toxiko-Infektionen“. Im Vordergrund der Botulismus-Symptomatik steht die Neuroparalyse mit „bulbärem“ Beginn sowie bei Progredienz eine schlaffe Tetraparese bis hin zur Atemlähmung. Säuglingsbotulismus präsentiert sich unspezifisch und wird symptomatisch behandelt; ein spezielles Human-Antitoxin ist aber über internationale Apotheken erhältlich. Bei Verdacht auf Nahrungsmittel- bzw. Wundbotulismus muss schnellstmöglich Antitoxin verabreicht werden, das auch noch 24 Stunden nach Symptombeginn wirksam sein kann. Adjuvante Maßnahmen sind ohne Evidenz.
Schlussfolgerungen Trotz typischer Symptomatik wird Botulismus oft zu spät diagnostiziert. Frühzeitige Antitoxingabe und Intensivtherapie sind für das Überleben entscheidend. Zur Beratung sollte ein Konsiliarlabor kontaktiert werden.
Regionale Zitratantikoagulation
Authors: Forster Christian , Schley Gunnar , Willam Carsten 
Published: August 2017

ZUSAMMENFASSUNGDie regionale Zitratantikoagulation ist inzwischen zum oftmals bevorzugten Antikoagulationsverfahren in der chirurgischen und anästhesiologischen Intensivmedizin geworden. Dem Nachteil des höheren Aufwandes und der Bedenken wegen Nebenwirkungen stehen die Vorteile gegenüber, weniger Blutverlust zu erleiden, höhere Filterlaufzeiten und konsekutiv höhere Dialysedosen zu erreichen und auch blutungsgefährdete Patienten behandeln zu können. Für die intermittierenden Verfahren gibt es mittlerweile ebenfalls zahlreiche Protokolle, die jedoch als weniger validiert gelten können. Die Weiterentwicklung der Zitratantikoagulation verspricht auch vorteilhaft für den intermittierenden Dialysebereich und der Therapie chronischer Dialysepatienten zu sein.
Die Förderung der Adhärenz durch eine psychoedukative Intervention für psychodynamische Psychotherapien
Authors: Hoffmann Knut , Hollenberg Stefan , Juckel Georg 
Published: August 2017

Zusammenfassung
Anliegen Es wird die Förderung der Adhärenz durch ein psychoedukatives Programm für eine psychodynamisch orientierte stationäre Therapie mittels einer randomisierten Experimentalstudie untersucht.
Methode Ein vollständiger Aufnahmejahrgang einer Maßregelvollzugsklinik wurde randomisiert einer Frühgruppe zugeordnet, die nach einer sechswöchigen Eingangsphase an einem psychoedukativen Programm parallel zu einer psychodynamisch orientierten Therapie teilnahm bzw. einer Spätgruppe, die 3 Monate später an dem gleichen Programm teilnahm.
Ergebnisse Von den Teilnehmern der Frühgruppe sind nach 7 Monaten signifikant mehr in psychodynamischer Behandlung.
Schlussfolgerungen Die Adhärenz für eine psychodynamisch orientierte stationäre Therapie kann bei Maßregelvollzugspatienten durch ein psychoedukatives Programm verbessert werden.
Forschen für uns! Welche Forschungsthemen interessieren von Depression Betroffene?
Authors: Bernges Tabea , Iden Laura , Gielen Reinhard , Scholl Michael , Brütt Anna 
Published: August 2017

Zusammenfassung
Ziel der Studie Identifikation und Priorisierung von Forschungsfragen zu Depressionen durch Betroffene und Angehörige.
Methodik In einer Onlineumfrage konnten Betroffene und Angehörige Forschungsthemen benennen, die von den Autoren zu Forschungsfragen zusammengefasst wurden. Diese wurden auf einer Likert-Skala online bewertet.
Ergebnisse Die Befragten schätzen Forschungsfragen zum Zugang und zur Gestaltung von Versorgung als besonders relevant ein.
Schlussfolgerung Themen aus dem Bereich Selbsthilfe und Zugang zur Versorgung sollten stärker beforscht werden.
Null effects of boot camps and short-format training for PhD students in life sciences
Authors: Feldon David F. , Jeong Soojeong , Peugh James , Roksa Josipa , Maahs-Fladung Cathy , Shenoy Alok , Oliva Michael 
Published: August 2017

SignificanceTo increase the effectiveness of graduate research training, many universities have introduced boot camps and bridge programs lasting several days to several weeks. National Science Foundation and National Institutes of Health currently support such interventions with nearly $28 million in active awards. Previous evidence for the efficacy of this format exists primarily in the form of anecdotes and end-of-course surveys. Here we show that participation in such short-format interventions is not associated with observable benefits related to skill development, scholarly productivity, or socialization into the academic community. Analyzing data from 294 PhD students in life sciences from 53 US institutions, we found no evidence of effectiveness across 115 variables. We conclude that boot camps and other short formats may not durably impact student outcomes.
Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women
Authors: Callahan Benjamin J. , DiGiulio Daniel B. , Goltsman Daniela S. Aliaga , Sun Christine L. , Costello Elizabeth K. , Jeganathan Pratheepa , Biggio Joseph R. , Wong Ronald J. , Druzin Maurice L. , Shaw Gary M. , Stevenson David K. , Holmes Susan P. , Relman David A. 
Published: August 2017

SignificancePremature birth (PTB) is a major global public health burden. Previous studies have suggested an association between altered vaginal microbiota composition and PTB, although findings across studies have been inconsistent. To address these inconsistencies, improve upon our previous signature, and better understand the vaginal microbiota’s role in PTB, we conducted a case-control study in two cohorts of pregnant women: one predominantly Caucasian at low risk of PTB, the second predominantly African American at high risk. With the results, we were able to replicate our signature in the first cohort and refine our signature of PTB for both cohorts. Our findings elucidate the ecology of the vaginal microbiota and advance our ability to predict and understand the causes of PTB.
Rome’s urban history inferred from Pb-contaminated waters trapped in its ancient harbor basins
Authors: Delile Hugo , Keenan-Jones Duncan , Blichert-Toft Janne , Goiran Jean-Philippe , Arnaud-Godet Florent , Albarède Francis 
Published: August 2017

Significance
Isotopic evidence showing that Rome’s lead water pipes were the primary source of lead pollution in the city’s runoff reveals the sedimentary profile of lead pollution in the harbor at Ostia to be a sensitive record of the growth of Rome’s water distribution system and hence, of the city itself. The introduction of this lead pipe network can now be dated to around the second century BC, testifying to a delay of about a century and a half between the introduction of Rome’s aqueduct system and the installation of a piped grid. The diachronic evolution of anthropogenic lead contamination is able to capture the main stages of ancient Rome's urbanization until its peak during the early high empire.
Differential HspBP1 expression accounts for the greater vulnerability of neurons than astrocytes to misfolded proteins
Authors: Zhao Ting , Hong Yan , Yin Peng , Li Shihua , Li Xiao-Jiang 
Published: August 2017

Significance
It remains unclear why astrocytes are affected to a lesser extent than neurons in a variety of neurodegenerative diseases. We report the higher activity of C terminus of Hsp70-interacting protein (CHIP), cochaperone of Hsp70, in astrocytes than in neurons, which not only promotes the degradation of misfolded proteins, but also upregulates levels of basal and stress-induced Hsp70 in astrocytes. Furthermore, the low activity of CHIP in neurons is caused by the abundant expression of HspBP1, an inhibitor of CHIP. Knocking down HspBP1 in neurons prevents the accumulation and aggregation of the Huntington’s disease (HD) protein and ameliorates neuropathology in a HD knockin mouse model. These findings suggest that HspBP1 accounts for differential vulnerabilities of neurons and glia to misfolded proteins.
From coseismic offsets to fault-block mountains
Authors: Thompson George A. , Parsons Tom 
Published: August 2017

Significance
Observations at different times during extensional faulting cycles show dramatically different deformation. Available coseismic and postseismic observations bear little resemblance to the topography of rifted zones, yet this topography is the end result of repeated earthquakes. During earthquakes, and during periods decades later, there is little evidence of rift flank, or range-front deformation, yet strong bending and uplift of these features ultimately define extended terranes. Numerical modeling incorporating gravity and the principle of isostatic balance predicts strong vertical forces during the first decade after a significant earthquake that are preferentially focused beneath range fronts. We conclude these forces are responsible for characteristic rift topography. This hypothesis is testable with intermediate period geodetic observations that are rare for extensional earthquakes.