bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome analysis of Brachypodium during fungal pathogen infection reveals both shared and distinct defense responses with wheat
Authors: Powell Jonathan J. , Carere Jason , Sablok Gaurav , Fitzgerald Timothy L. , Stiller Jiri , Colgrave Michelle L. , Gardiner Donald M. , Manners John M. , Vogel John P. , Henry Robert J. , Kazan Kemal 
Published: December 2017

AbstractFusarium crown rot (FCR) of wheat and barley, predominantly caused by the fungal pathogen Fusarium pseudograminearum, is a disease of economic significance. The quantitative nature of FCR resistance within cultivated wheat germplasm has significantly limited breeding efforts to enhanced FCR resistance in wheat. In this study, we characterized the molecular responses of Brachypodium distachyon (Brachypodium hereafter) to F. pseudograminearum infection using RNA-seq to determine whether Brachypodium can be exploited as a model system towards better understanding of F. pseudograminearum-wheat interaction. The transcriptional response to infection in Brachypodium was strikingly similar to that previously reported in wheat, both in shared expression patterns of wheat homologs of Brachypodium genes and functional overlap revealed through comparative gene ontology analysis in both species. Metabolites produced by various biosynthetic pathways induced in both wheat and Brachypodium were quantified, revealing a high degree of overlap between these two species in metabolic response to infection but also showed Brachypodium does not produce certain defence-related metabolites found in wheat. Functional analyses of candidate genes identified in this study will improve our understanding of resistance mechanisms and may lead to the development of new strategies to protect cereal crops from pathogen infection.
Long Noncoding RNA HOTAIR Modulates MiR-206-mediated Bcl-w Signaling to Facilitate Cell Proliferation in Breast Cancer
Authors: Ding Wei , Ren Jin , Ren Hui , Wang Dan 
Published: December 2017

AbstractLncRNA HOX transcript antisense RNA (HOTAIR) is involved in lots of cancers. The pro-survival protein Bcl-w is frequently found in cancer development. However, the effect of HOTAIR on Bcl-w in breast cancer is not well documented. In this study, we first evaluated the correlation between HOTAIR level and Bcl-w expression in clinical breast cancer tissues. We observed that the expression levels of Bcl-w were much higher in the breast cancer samples than that in their paired noncancerous tissues. Moreover, the levels of HOTAIR were positively associated with those of Bcl-w in clinical breast cancer samples. As expected, we observed that HOTAIR was able to up-regulate the expression of Bcl-w in breast cancer cells. Mechanistically, we found that miR-206 was capable of inhibiting the expression of Bcl-w by directly binding to the 3′UTR of Bcl-w mRNA. Interestingly, HOTAIR could increase the expression of Bcl-w through sequestering miR-206 at post-transcriptional level. Functionally, our data showed that HOTAIR-induced Bcl-w by miR-206 facilitated the proliferation of breast cancer cells. Thus, we conclude that HOTAIR up-regulates Bcl-w to enhance cell proliferation through sequestering miR-206 in breast cancer. Our finding provides new insights into the mechanism of breast cancer mediated by HOTAIR.
Probenecid arrests the progression of pronounced clinical symptoms in a mouse model of multiple sclerosis
Authors: Hainz Nadine , Wolf Sandra , Beck Artjom , Wagenpfeil Stefan , Tschernig Thomas , Meier Carola 
Published: December 2017

AbstractWhile it has been established that Probenecid (PBN) prevents the onset of experimental autoimmune encephalomyelitis (EAE) in mice, it is not clear whether it has any effect on already manifest EAE. The aim of this study was therefore to analyze the therapeutic effect of PBN in pronounced EAE. Mice with manifest clinical symptoms of EAE were either treated with PBN or solvent for 20 days, or they were left untreated. The clinical symptoms were monitored daily. Inflammation, demyelination and oligodendrocyte numbers were determined in the spinal cord. We were able to demonstrate that PBN not only significantly prolonged survival but also prevented the progression of clinical symptoms in the EAE model of multiple sclerosis. In addition, we were able to show that PBN reduced inflammation, T cell infiltration and oligodendrocyte cell loss. PBN was previously shown to inhibit – among other targets – pannexin channels. As pannexin channels provide conduits for ATP, are associated with the inflammasome, and act as “find me-signals” in the process of apoptosis, inhibition of pannexins via PBN might contribute to the PBN-effects observed in this study. The beneficial and therapeutic effects of PBN in the context of EAE demonstrate an intriguing link between PBN and neuroinflammation, which might foster translational interest.
Effect of the preparation of lime putties on their properties
Authors: Navrátilová Eva , Tihlaříková Eva , Neděla Vilém , Rovnaníková Pavla , Pavlík Jaroslav 
Published: December 2017

AbstractIn the study of lime as the basic component of historical mortars and plasters, four lime putties prepared from various kinds of lime of various granulometry and by various ways of preparation were evaluated. The rheological properties and micro-morphologic changes, growing of calcite crystals, and rate of carbonation were monitored. The lime putty prepared from lump lime achieves the best rheological properties, yield stress 214.7 Pa and plastic viscosity 2.6 Pa·s. The suitability of this lime putty was checked by testing the development of calcium hydroxide and calcite crystals using scanning electron microscopy and environmental scanning electron microscopy. The disordered crystals of calcium hydroxide exhibit better carbonation resulting in the large crystals of calcite; therefore, the mortar prepared from the lump lime has the highest flexural strength and compressive strength 0.8/2.5 MPa, its carbonation is the fastest and exhibits the longest durability. Also, thanks to the micro-morphological characterization of samples in their native state by means of environmental scanning electron microscopy, the new way of lime putty preparation by mixing was proven. The preparation consists in the mechanical crash of the lime particles immediately after hydration. This enables the properties of putty prepared from lump lime to be nearly reached.
Structure and Dynamics of Cas9 HNH Domain Catalytic State
Authors: Zuo Zhicheng , Liu Jin 
Published: December 2017

AbstractThe bacterial CRISPR-Cas9 immune system has been harnessed as a powerful and versatile genome-editing tool and holds immense promise for future therapeutic applications. Despite recent advances in understanding Cas9 structures and its functional mechanism, little is known about the catalytic state of the Cas9 HNH nuclease domain, and identifying how the divalent metal ions affect the HNH domain conformational transition remains elusive. A deeper understanding of Cas9 activation and its cleavage mechanism can enable further optimization of Cas9-based genome-editing specificity and efficiency. Using two distinct molecular dynamics simulation techniques, we have obtained a cross-validated catalytically active state of Cas9 HNH domain primed for cutting the target DNA strand. Moreover, herein we demonstrate the essential roles of the catalytic Mg2+ for the active state formation and stability. Importantly, we suggest that the derived catalytic conformation of the HNH domain can be exploited for rational engineering of Cas9 variants with enhanced specificity.
Remote control of resistive switching in TiO2 based resistive random access memory device
Authors: Sahu Dwipak Prasad , Jammalamadaka S. Narayana 
Published: December 2017

AbstractWe report on the magnetic field control of a bipolar resistive switching in Ag/TiO2/FTO based resistive random access memory device through I–V characteristics. Essentially, in the presence of magnetic field and in the low resistance state, an abrupt change in the resistance of the device demands higher voltage, hinting that residual Lorentz force plays a significant role in controlling the resistance state. Endurance characteristics of the device infer that there is no degradation of the device even after repeated cycling, which ensures that the switching of resistance between ‘off’ and ‘on’ states is reproducible, reversible and controllable. Magnetic field control of ‘on’ and ‘off’ states in endurance characteristics suggest that this device can be controlled in a remote way for multi-bit data storage.
Digital-PCR for gene expression: impact from inherent tissue RNA degradation
Authors: Millier Melanie J. , Stamp Lisa K. , Hessian Paul A. 
Published: December 2017

AbstractSubtle molecular differences indicate the heterogeneity present in a number of disease settings. Digital-PCR (dPCR) platforms achieve the necessary levels of sensitivity and accuracy over standard quantitative RT-PCR (qPCR) that promote their use for such situations, detecting low abundance transcript and subtle changes from gene expression. An underlying requisite is good quality RNA, principally dictated by appropriate tissue handling and RNA extraction. Here we consider the application of dPCR to measures of gene expression in pathological tissues with inherent necrosis, focusing on rheumatoid subcutaneous nodules. Variable RNA fragmentation is a feature of RNA from such tissues. Increased presence of transcript fragmentation is reflected in a proportionate decrease in Agilent DV200 metric and downstream, a reduction in endogenous control genes’ expression, measured by RT-dPCR. We show that normalisation of target gene expression to that for endogenous control genes sufficiently corrects for the variable level of fragmented RNA. Recovery of target gene values was achieved in samples comprising as much as 50 percent fragmented RNA, indicating the suitability and appropriate limitation of such data treatment when applied to samples obtained from inherently necrotic tissues.
Longitudinal Associations Across Prematurity, Attention, and Language in School-Age Children
Authors: Mahurin-Smith Jamie , DeThorne Laura S. , Petrill Stephen A. 
Published: December 2017

Purpose
This research note explores the potential role of attention in mediating previously reported associations between language outcomes and prematurity.

Method
As a follow-up investigation to Mahurin Smith, DeThorne, Logan, Channell, and Petrill (2014), we employed multilevel modeling to analyze longitudinal data on language and attention collected when children were, on average, ages of 7, 8, and 10 years. The sample of 114 children taken from the Western Reserve Reading and Math Project was selected to oversample children with a history of prematurity while also controlling for differences in confounding influences such as age, gender, parental education, and race.

Results

As predicted, attention differentially predicted language outcomes based on form of measurement. Specifically, parent and examiner ratings of attention were significantly associated with standardized test performance at all 3 time points (
R
2
= 15.2%–20%). Associations between attention and language sample measures were less consistent across home visits and tended to be smaller in effect size.

Conclusion
Attention abilities are associated with children's language performance even in the absence of an attention-deficit/hyperactivity disorder diagnosis. Clinical implications, particularly as related to assessment, are discussed.
Local growth of dust- and ice-mixed aggregates as cometary building blocks in the solar nebula
Authors: Lorek S. , Lacerda P. , Blum J. 
Published: December 2017

Context.Comet formation by gravitational instability requires aggregates that trigger the streaming instability and cluster in pebble-clouds. These aggregates form as mixtures of dust and ice from (sub-)micrometre-sized dust and ice grains via coagulation in the solar nebula.Aim.We investigate the growth of aggregates from (sub-)micrometre-sized dust and ice monomer grains. We are interested in the properties of these aggregates: whether they might trigger the streaming instability, how they compare to pebbles found on comets, and what the implications are for comet formation in collapsing pebble-clouds.Methods.We used Monte Carlo simulations to study the growth of aggregates through coagulation locally in the comet-forming region at 30 au. We used a collision model that can accommodate sticking, bouncing, fragmentation, and porosity of dust- and ice-mixed aggregates. We compared our results to measurements of pebbles on comet 67P/Churyumov-Gerasimenko.Results.We find that aggregate growth becomes limited by radial drift towards the Sun for 1μm sized monomers and by bouncing collisions for 0.1μm sized monomers before the aggregates reach a Stokes number that would trigger the streaming instability (Stmin). We argue that in a bouncing-dominated system, aggregates can reach Stminthrough compression in bouncing collisions if compression is faster than radial drift. In the comet-forming region (~30 au), aggregates with Stminhave volume-filling factors of ~10−2and radii of a few millimetres. These sizes are comparable to the sizes of pebbles found on comet 67P/Churyumov-Gerasimenko. The porosity of the aggregates formed in the solar nebula would imply that comets formed in pebble-clouds with masses equivalent to planetesimals of the order of 100 km in diameter.
Aufbau eines GMP-Radionuklidlabors
Authors: Gildehaus Franz 
Published: December 2017

ZusammenfassungMit der Änderung des Arzneimittelgesetzes 2009 erfolgte eine Neubewertung der Herstellung von Radiopharmaka. Seitdem unterliegt ihre Herstellung grundsätzlich dem Arzneimittelgesetz, wobei dies nicht nur für nicht-zugelassene Radiopharmaka gilt, sondern ebenso für die Herstellung von Tc-Kits aus zugelassenen Mo/Tc-Generatoren mithilfe von zugelassenen Markierungskits. Die für die Herstellung verantwortliche Person muss laut § 13 (1) entweder eine sachkundige Person sein, oder nach § 13 (2b) ein Arzt, der auch persönlich die Anwendung bei einem bestimmten Patienten vornimmt. Die Herstellung und Qualitätskontrolle von Arzneimitteln selbst unterliegt einer Reihe von Gesetzen, Verordnungen, Leitlinien und EU-Richtlinien, die aber oft nicht eindeutig oder nur eingeschränkt auf Radiopharmaka anwendbar sind. Leider erfolgt die Auslegung dieser Regelungen durch die lokalen Überwachungsbehörden innerhalb Deutschlands sehr uneinheitlich. Einer der Gründe dafür ist sicherlich die unterschiedliche Ausstattung der einzelnen Kliniken und Praxen in den verschiedenen Bundesländern. Aus Gründen einer flächendeckenden Patientenversorgung werden noch viele veraltete Einrichtungen geduldet, aber meist zieht eine Modernisierung der Räumlichkeiten auch die Anpassung der Arbeitsweise, Dokumentation und Qualitätssicherungsmaßnahmen an die bestehenden rechtlichen Rahmenbedingungen nach sich. Hierzu müssen sich die Betreiber mit den heute gültigen GMP-Anforderungen auseinandersetzen, die mit ihren vielfältigen Themen wie der baulichen Konzeption, einer personellen Weiterentwicklung, den Bedingungen einer aseptischen Arbeitsweise, der Prozessvalidierung und den Freigabekriterien für Parenteralia hohe Anforderungen stellt. Alle diese Punkte sollten dabei schon im Vorfeld mit den Fachleuten der zuständigen Überwachungsbehörde diskutiert werden, um risikobasiert die notwendigen Maßnahmen abzuschätzen. Dennoch muss eine weitgehende nationale Harmonisierung der Radiopharmaka-Herstellung und die Spezifizierung der gesetzlichen Anforderungen ein vorrangiges Ziel sein, da z. B. PET-Radiopharmaka heute zum Repertoire der modernen Nuklearmedizin gehören, auch wenn der Zugang zu innovativen Tracern für den niedergelassenen Nuklearmediziner in mehrfacher Hinsicht außerordentlich eingeschränkt ist. Die Verfügbarkeit wurde mit dem Inkrafttreten der 15. Novelle des AMG neu geregelt. Durch den Wegfall des ehemaligen § 4a Satz 1 Nr. 3 fallen Herstellung und Anwendung dieser Präparationen nun unter den Geltungsbereich des AMG und die damit verbundenen Tätigkeiten sind nach § 67 Abs. 2 bei der zuständigen Genehmigungsbehörde anzeigepflichtig. Aus der geschilderten Situation ergibt sich die Notwendigkeit, über Möglichkeiten der Eigenherstellung von Radiopharmaka unter GMP-Bedingungen auch in kleineren klinischen Einrichtungen nachzudenken.
„Ich bin hier nur der Fotograf, oder?“ – Untersuchungsbefunde in der Nuklearmedizin richtig kommunizieren
Authors: Karger André , Stoevesandt Dietrich 
Published: December 2017

ZusammenfassungDas Überbringen schlechter Nachrichten zählt zu den häufigsten und herausforderndsten Gesprächssituationen für Arzt und Patient. Erfolgt die Mitteilung schlechter Nachrichten im Rahmen eines Behandlungsverhältnisses, sollten die Erwartungen und Befürchtungen des Patienten berücksichtigt, notwendige Informationen einfach und kurz mitgeteilt werden und die emotionalen Reaktionen der Patienten empathisch beantwortet werden. Orientierung für diese unterschiedlichen kommunikativen Fertigkeiten bietet das SPIKES-Modell. Besteht kein primäres Behandlungsverhältnis, sondern werden Befunde zu rein diagnostischen Zwecken im Auftrag eines zuweisenden Arztes erhoben, gilt es, mit dem Patienten zu Beginn zu besprechen, wie mit der Befundmitteilung umzugehen ist. Grundsätzlich sollte der Patient die Möglichkeit zu einem Befundgespräch mit dem diagnostisch tätigen Arzt haben. Allerdings ist es oft zum Wohle des Patienten am sinnvollsten, wenn die Befundmitteilung durch den primär behandelnden Arzt erfolgt. Hierfür sollten klare Absprachen bestehen.
Health-Related Quality of Life and Mental Health in Primary Aldosteronism: A Systematic Review
Authors: Velema Marieke , de Nooijer Aline , Burgers Vivian , Hermus Ad. , Timmers Henri , Lenders Jacques , Husson Olga , Deinum Jaap 
Published: December 2017

AbstractThe aim of this review was to determine the impact of primary aldosteronism on health-related quality of life (HRQoL) and mental health. We performed a systematic literature search up to July 2017 in six electronic databases. First, we screened the articles derived from this search based on title and abstract. Second, the selected studies were systematically reviewed and checked for our predefined inclusion criteria. The search yielded 753 articles, of which 15 studies met our inclusion criteria. Untreated patients with primary aldosteronism showed an impaired physical and mental HRQoL as compared to the general population. Multiple domains of HRQoL were affected. This applied to patients with both an aldosterone-producing adenoma and bilateral adrenal hyperplasia. Adrenalectomy improves HRQoL. Conflicting results have been reported on the extent of this improvement, the improvement after initiation of medical treatment, and whether there is a difference in HRQoL after both treatments. Similarly, psychopathological symptoms of anxiety, demoralization, stress, depression and nervousness were more frequently reported in untreated patients with primary aldosteronism than in the general population and patients with hypertension. Also an impaired sleep quality has been reported. Improvement of these symptoms was observed after treatment with both adrenalectomy and mineralocorticoid receptor antagonists. This review shows that HRQoL is impaired and psychopathology is more frequently reported in patients with primary aldosteronism. This seems to be at least partly reversible after treatment but the extent of improvement remains unknown. To assess HRQoL in these patients more precisely a primary aldosteronism-specific HRQoL questionnaire is required.
Glycyrrhetic Acid Derivative TY501 Protects Against Lithocholic Acid–Induced Cholestasis
Authors: Zheng Xuemin , Zhu Shichao , Zhou Zhixing , Liu Wei , Xu Weiren 
Published: December 2017

AbstractThe aim of the study is to investigate the protective effects of TY501 against LCA-induced cholestasis in mice and to explore the potential mechanisms. It was demonstrated that TY501(5, 15 or 45 mg/kg, i.g.) can markedly reduced the level of ALT, AST and ALP which increased by LCA treatment. Meanwhile, TY501 also lowered total bile acids, total bilirubin and total cholesterol levels in serum. Furthermore, TY501 can protect HepG2 cell cultures from LCA-induced cytotoxicity. RT-PCR and Western Blot analysis showed that TY501 recovered the expression of BSEP, MRP2 and NTCP which were down-regulated by LCA. Moreover, mRNA and protein of FXR was also observed in TY501 treated mice significantly accumulation in nucleus. Taken together, It can be concluded that TY501 exerted beneficial effects on LCA-induced cholestasis, possibly via activation of FXR mediated upregulation of BSEP, MRP2 and NTCP.
Disordered CYP11B2 Expression in Primary Aldosteronism
Authors: Gomez-Sanchez Celso , Kuppusamy Maniselvan , Reincke Martin , Williams Tracy 
Published: December 2017

AbstractPrimary aldosteronism is the most common type of secondary hypertension affecting 6–10% of patients with primary hypertension. PA is mainly caused by unilateral hyperaldosteronism due to an aldosterone-producing adenoma, unilateral hyperplasia with or without micronodules or bilateral zona glomerulosa hyperplasias with or without macro or micronodules. The development of antibodies against the terminal enzyme of aldosterone biosynthesis (CYP11B2) has permitted the further characterization of normal adrenals and resected adrenals from patients with primary aldosteronism. Normal adrenals exhibit two different patterns of cellular expression of CYP11B2: young individuals display a relatively uniform expression of the enzyme throughout the zona glomerulosa while the adrenals of older individuals have dispersed CYP11B2-expressing cells but have more groups of cells called aldosterone-producing cell clusters (APCC). APAs exhibit different patterns of CYP11B2 staining that vary from uniform to homogeneous. There are also a proportion of cells within the APA that co-express different enzymes that are not normally co-expressed in normal individuals. Approximately 30% of patients with unilateral hyperaldosteronism do not have an APA, but either have an increased number of CYP11B2 expressing micronodules or hyperplasia of the zona glomerulosa. In summary, the studies reported in this review are shedding new light on the pathophysiology of primary aldosteronism. The wide variation in histopathological features of the adenomas and concurrent presence of APCCs raises the possibility that most cases of unilateral production of aldosterone actually might represent bilateral asymmetric hyperplasia with nodules frequently due to the development of somatic aldosterone-driving mutations.
Aldosterone-Producing Cell Clusters in Normal and Pathological States
Authors: Omata Kei , Tomlins Scott , Rainey William 
Published: December 2017

AbstractPrimary aldosteronism (PA) significantly increases the risk of cardiovascular complications, and early diagnosis and targeted treatment based on its pathophysiology is warranted. Next-generation sequencing (NGS) has revealed recurrent somatic mutations in aldosterone-driving genes in aldosterone-producing adenoma (APA). By applying CYP11B2 (aldosterone synthase) immunohistochemistry and NGS to adrenal glands from normal subjects and PA patients, we and others have shown that CYP11B2-positive cells make small clusters, termed aldosterone-producing cell clusters (APCC), beneath the adrenal capsule, and that APCC harbor somatic mutations in genes mutated in APA. We have shown that APCC are increased in CT-negative PA adrenals, while others showed potential progression from APCC to micro APA through mutations. These results suggest that APCC are a key factor for understanding the origin of PA, and further investigation on the relation between APCC and PA is highly needed.