bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innate Immune Functions of Astrocytes are Dependent Upon Tumor Necrosis Factor-Alpha
Authors: Rodgers Kyla R. , Lin Yufan , Langan Thomas J. , Iwakura Yoichiro , Chou Richard C. 
Published: April 2020

AbstractAcute inflammation is a key feature of innate immunity that initiates clearance and repair in infected or damaged tissues. Alternatively, chronic inflammation is implicated in numerous disease processes. The contribution of neuroinflammation to the pathogenesis of neurological conditions, including infection, traumatic brain injury, and neurodegenerative diseases, has become increasingly evident. Potential drivers of such neuroinflammation include toll-like receptors (TLRs). TLRs confer a wide array of functions on different cell types in the central nervous system (CNS). Importantly, how TLR activation affects astrocyte functioning is unclear. In the present study, we examined the role of TLR2/4 signaling on various astrocyte functions (i.e., proliferation, pro-inflammatory mediator production, regulatory mechanisms, etc) by stimulating astrocytes with potent exogenous TLR2/4 agonist, bacterial lipopolysaccharide (LPS). Newborn astrocytes were derived from WT, Tnfα−/−, Il1α−/−/Il1β−/−, and Tlr2−/−/Tlr4−/− mice as well as Sprague Dawley rats for all in vitro studies. LPS activated mRNA expression of different pro-inflammatory cytokines and chemokines in time- and concentration-dependent manners, and upregulated the proliferation of astrocytes based on increased 3H-thymidine update. Following LPS-mediated TLR2/4 activation, TNF-α and IL-1β self-regulated and modulated the expression of pro-inflammatory cytokines and chemokines. Polyclonal antibodies against TNF-α suppressed TLR2/4-mediated upregulation of astrocyte proliferation, supporting an autocrine/paracrine role of TNF-α on astrocyte proliferation. Astrocytes perform classical innate immune functions, which contradict the current paradigm that microglia are the main immune effector cells of the CNS. TNF-α plays a pivotal role in the LPS-upregulated astrocyte activation and proliferation, supporting their critical roles in in CNS pathogenesis.
Non-cell autonomous promotion of astrogenesis at late embryonic stages by constitutive YAP activation
Authors: Han Dasol , Kwon Mookwang , Lee Sun Min , Pleasure Samuel J. , Yoon Keejung 
Published: April 2020

AbstractAlthough astrocytes have gained increased recognition as an important regulator in normal brain function and pathology, the mechanisms underlying their genesis are not well understood. In this study, we show that constitutive YAP activation by in utero introduction of a non-degradable form of the YAP gene (YAP 5SA) causes productive GFAP+ cell generation at late embryonic periods, and this activity is nuclear localization- and TEAD transcription factor-dependent. Moreover, we found that the GFAP+ cells were not YAP 5SA-expressing cells themselves but cells in the vicinity in vivo. Conditioned medium prepared from YAP 5SA-expressing cells induced GFAP+ cell production in vitro, suggesting that a soluble factor(s) was mediating the astrogenic activity of YAP 5SA. Indeed, YAP 5SA expression greatly increased CNTF and BMP4 transcription in neural progenitor cells, and a neutralizing antibody against CNTF reduced the astrogenic effects of YAP 5SA-conditioned medium. Furthermore, the YAP 5SA-expressing cells were identified as FN1+ mesenchymal cells which are responsible for the precocious astrogenesis. These results suggest a novel molecular mechanism by which YAP activation can induce astrogenesis in a non-cell autonomous manner.
Mapping of QTL for Grain Yield Components Based on a DH Population in Maize
Authors: Yang Jiwei , Liu Zonghua , Chen Qiong , Qu Yanzhi , Tang Jihua , Lübberstedt Thomas , Li Haochuan 
Published: April 2020

AbstractThe elite maize hybrid Zhengdan 958 (ZD958), which has high and stable yield and extensive adaptability, is widely grown in China. To elucidate the genetic basis of yield and its related traits in this elite hybrid, a set of doubled haploid (DH) lines derived from ZD958 were evaluated in four different environments at two locations over two years, and a total of 49 quantitative trait loci (QTL) and 24 pairs of epistatic interactions related to yield and yield components were detected. Furthermore, 21 QTL for six investigated phenotypic traits were detected across two different sites. Combining the results of these QTL in each environment and across both sites, three main QTL hotspots were found in chromosomal bins 2.02, 2.05–2.06, and 6.05 between the simple sequence repeat (SSR) markers umc1165-bnlg1017, umc1065-umc1637, and nc012-bnlg345, respectively. The existence of three QTL hotspots associated with various traits across multiple environments could be explained by pleiotropic QTL or multiple tightly linked QTL. These genetic regions could provide targets for genetic improvement, fine mapping, and marker-assisted selection in future studies.
A cyclic dipeptide from the Chilean hazelnut cotyledons (Gevuina avellana Mol., Proteaceae)
Authors: Schmeda-Hirschmann Guillermo , de Andrade Jean Paulo , Jiménez-Aspee Felipe , Mieres-Castro Daniel 
Published: April 2020

AbstractThe Chilean hazelnut (Gevuina avellana Mol., Proteaceae) is a southern South American nut consumed as a snack and included in different preparations of traditional Chilean cuisine. Recently we described the fatty acid profile, oxylipins, phenolic compounds, as well as the antioxidant capacity. The main compounds of the phenolic-enriched extract were only tentatively identified by spectrometric means. In the present work, we describe the isolation and full characterization of a cyclic dipeptide cyclo(Arg-Trp) and other compounds from the phenolic enriched extracts of the G. avellana cotyledons. Compounds were isolated by means of counter-current chromatography and structures were established by spectroscopic and spectrometric methods. This is the first report on small peptides in G. avellana and adds evidence on the possible beneficial effects of this nut in human health.
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Authors: Karadagi Ahmad , Cavedon Alex G. , Zemack Helen , Nowak Greg , Eybye Marianne E. , Zhu Xuling , Guadagnin Eleonora , White Rebecca A. , Rice Lisa M. , Frassetto Andrea L. , Strom Stephen , Jorns Carl , Martini Paolo G. V. , Ellis Ewa 
Published: April 2020

AbstractAlpha 1-antitrypsin (AAT) deficiency arises from an inherited mutation in the SERPINA1 gene. The disease causes damage in the liver where the majority of the AAT protein is produced. Lack of functioning circulating AAT protein also causes uninhibited elastolytic activity in the lungs leading to AAT deficiency-related emphysema. The only therapy apart from liver transplantation is augmentation with human AAT protein pooled from sera, which is only reserved for patients with advanced lung disease caused by severe AAT deficiency. We tested modified mRNA encoding human AAT in primary human hepatocytes in culture, including hepatocytes from AAT deficient patients. Both expression and functional activity were investigated. Secreted AAT protein increased from 1,14 to 3,43 µg/ml in media from primary human hepatocytes following mRNA treatment as investigated by ELISA and western blot. The translated protein showed activity and protease inhibitory function as measured by elastase activity assay. Also, mRNA formulation in lipid nanoparticles was assessed for systemic delivery in both wild type mice and the NSG-PiZ transgenic mouse model of AAT deficiency. Systemic intravenous delivery of modified mRNA led to hepatic uptake and translation into a functioning protein in mice. These data support the use of systemic mRNA therapy as a potential treatment for AAT deficiency.
Robust high-Q filter with complete transmission by conjugated topological photonic crystals
Authors: Lin Yu-Chuan , Chou Shih-Han , Hsueh Wen-Jeng 
Published: April 2020

AbstractHigh quality factor (High-Q) and transmission optical devices are required for various applications in the fields of physics and engineering. Critical for these applications is the realization of a structure with high-Q, complete transmission and small volume. A robust high-Q filter with complete transmission by conjugated topological photonic crystals (CTPC) is presented. The study shows that an ultra-high-Q of more than 108 with complete transmission is obtained by the CTPC with 2 μm long due to the excitation of conjugated topological edge-states (CTES). It is also found that even though the quality factor of resonances increases as the periodic number of multilayers increases, these resonances are still complete transmission. A novel concept of CTES is first proposed in this study and investigated the effect of its topological phenomenon on high quality factor via CTPC. We theoretically realize the robust high-Q and complete transmission in the CTPC, which is different from those in periodic, quasi-periodic, Fabry-Perot photonic crystals and traditional topological photonic crystals (TPC).
Dynamic network interactions among distinct brain rhythms as a hallmark of physiologic state and function
Authors: Lin Aijing , Liu Kang K. L. , Bartsch Ronny P. , Ivanov Plamen Ch. 
Published: April 2020

AbstractBrain rhythms are associated with a range of physiologic states, and thus, studies have traditionally focused on neuronal origin, temporal dynamics and fundamental role of individual brain rhythms, and more recently on specific pair-wise interactions. Here, we aim to understand integrated physiologic function as an emergent phenomenon of dynamic network interactions among brain rhythms. We hypothesize that brain rhythms continuously coordinate their activations to facilitate physiologic states and functions. We analyze healthy subjects during sleep, and we demonstrate the presence of stable interaction patterns among brain rhythms. Probing transient modulations in brain wave activation, we discover three classes of interaction patterns that form an ensemble representative for each sleep stage, indicating an association of each state with a specific network of brain-rhythm communications. The observations are universal across subjects and identify networks of brain-rhythm interactions as a hallmark of physiologic state and function, providing new insights on neurophysiological regulation with broad clinical implications.
Blood microRNA 202-3p associates with the risk of essential hypertension by targeting soluble ST2
Authors: Li Lu , Zhong Danrong , Xie Yudan , Yang Xinlei , Yu Zuozhong , Zhang Dangui , Jiang Xinghua , Wu Yanqing , Wu Fangqin 
Published: April 2020

Abstract
MicroRNA (miR)-202-3p has attracted a great deal of attention in the fields of oncology, gynecology, and metabolic disorders. However, its role in cardiovascular diseases remains to be clarified. We previously found that disruption of miR-202-3p mediated regulation of expression of soluble (s)ST2, a decoy receptor for interleukin (IL)-33, promotes essential hypertension (EH). In the present study, we first measured miR-202-3p expression levels in the blood of 182 EH cases and 159 healthy controls using TaqMan assays. miR-202-3p levels were shown to be significantly higher in EH cases than controls (fold change = 3.58, P&lt;0.001). Logistic regression analysis revealed that higher miR-202-3p expression was associated with an increased occurrence of EH (adjusted odds ratio (OR): 1.57; 95% confidence interval (CI), 1.36–1.82; P&lt;0.001). Addition of miR-202-3p to traditional risk factors showed an additive prediction value for EH. Further functional experiments indicated that miR-202-3p could be induced by angiotensin II (Ang II) and inhibited by Ang II-triggered soluble ST2 (sST2) expression in a negative feedback manner. Moreover, blood miR-202-3p levels were negatively correlated with sST2 expression in vivo. Our study shows that blood miR-202-3p levels were significantly associated with the occurrence of EH. These findings indicate that miR-202-3p exerts a protective role against EH by antagonizing the induction of sST2 by Ang II.
Novel compound variants of the AR and MAP3K1 genes are related to the clinical heterogeneity of androgen insensitivity syndrome
Authors: Cheng Yiping , Sun Yan , Ji Yiming , Jiang Dongqing , Teng Guoxin , Zhou Xiaoming , Zhou Xinli , Li Guimei , Xu Chao 
Published: April 2020

Abstract
Androgen insensitivity syndrome (AIS; OMIM 300068) is the most frequent cause of 46, XY disorders of sex development (DSD). However, the correlation between genotype and phenotype has not been determined. We conducted a systematic analysis of the clinical characteristics, hormone levels, ultrasonography data and histopathology of a 46, XY Chinese patient with AIS. The family was followed up for nearly 8 years. We applied whole-exome sequencing (WES) for genetic analysis of the pedigree and performed bioinformatic analysis of the identified variants. Human embryonic kidney 293T/17 (HEK293T/17) cells were transiently transfected with wild-type or mutant AR and MAP3K1 plasmid. Cell lysates were used to analyze androgen receptor (AR) production. A novel hemizygous AR variant (c.2070C&gt;A, p. His690Glu) and a rare heterozygous MAP3K1 variant (c.778C&gt;T, p. Arg260Cys) were identified by WES in the proband and her mother. Bioinformatic analysis predicted these two variants to be pathogenic. Multiple amino acid sequence alignments showed that p. His690 and p. Arg260 are conserved among various species. His690Glu is a mutation that decreased the AR production, whereas the Arg260Cys mutation increased the AR production. The novel compound variants of the AR and MAP3K1 genes also increased the production of AR protein. Thus, the phenotype of the patient may be caused by defects in both the AR and MAP3K1 signaling pathways. Compound variants of the AR and MAP3K1 genes resulted in a specific phenotype in this patient with AIS. WES might reveal genetic variants that explain the heterogeneity of AIS.
Treg und Th17-Zellen: Verwandtschaft mit Folgen
Authors: Prelog Martina 
Published: April 2020

ZUSAMMENFASSUNGVerschiedene Helfer-T-Zellen (Th) unterscheiden sich in Merkmalen und Funktionen. Th1 werden durch IL-12/IFN-gamma induziert, exprimieren T-bet und produzieren IFN-gamma. IL-17-produzierende Th17 exprimieren RORC, tragen den Chemokinrezeptor CCR6 und werden durch IL-1beta/IL-6/IL-23 stimuliert. Regulatorische T-Zellen (Treg) werden durch IL-2/TGF-beta stimuliert, exprimieren FoxP3 und produzieren IL-10. Th1 sind physiologischerweise an der intrazellulären Erregerabwehr beteiligt, Th2 von Parasiten, Th17 von extrazellulären Bakterien und Pilzen und Treg an der peripheren T-Zell-Homöostase. Eine Dysbalance zwischen Treg/Th1 und Th17 wird mit Autoimmunprozessen in Zusammenhang gebracht. Insbesondere synoviale Th1/Th17-Zellen, die CD161 exprimieren, zeigen enge Korrelationen mit schweren Verläufen der JIA, während IL-17-produzierende Treg/Th17-Zellen pro- und antiinflammatorische Fähigkeiten vereinen können. Alle Th weisen eine hohe Plastizität in unterschiedlichen inflammatorischen Milieus auf. Es gibt Hinweise, dass eine effiziente Hemmung von bestimmten Zytokinen zu einer Rekonstitution der Treg-Funktion beiträgt, was in neuen Therapieansätzen genutzt werden könnte.
Blood Flow Volume Measurement in Cervical and Intracranial Arteries using Quantitative Magnetic Resonance Angiography and Duplex Sonography (Bocaccia) – A Prospective Observational Study
Authors: Fiedler Jiří , Reiser Martin , Košťál Petr , Kubále Jiří , Ostrý Svatopluk , Hrbáč Tomáš , Kešnerová Petra , Fadrná Táňa , Langová Kateřina , Herzig Roman , Školoudík David 
Published: April 2020

Abstract
Purpose Cerebral blood flow volume is an important factor for the accurate diagnosis of neurovascular diseases and treatment indication. This study aims to assess correlations of blood flow volume measurements in cervical and intracranial arteries between duplex sonography and quantitative magnetic resonance angiography (qMRA).
Materials and Methods Consecutive patients with suspicion of cerebral vascular pathology underwent qMRA and duplex sonography of cervical and intracranial arteries with measurement of blood flow volume in bilateral common (CCA), internal (ICA) and external carotid arteries, vertebral and basilar arteries, middle, anterior, posterior cerebral and posterior communicating arteries using 2 different ultrasound machines. Ten patients underwent all examinations twice. Correlations between blood flow volume measurements were evaluated using Spearman’s correlation coefficient and inter-class correlation coefficient (ICC).
Results In total, 21 subjects (15 males, mean age: 56.3 ± 6.2 years) were included in the study. Duplex sonography inter-investigator correlation was excellent (ICC = 0.972, p < 0.0001) as well as intra-investigator correlations of both qMRA and duplex sonography (ICC ˃ 0.990, p < 0.0001). Mostly high correlations were recorded between qMRA and duplex sonography in particular cervical arteries but only low to moderate correlations were obtained for intracranial arteries. The mean differences between blood flow volume measurements were 10.9 ± 8.1 % in the CCA and its branches when using qMRA and 15.0 ± 11.9 % when using duplex sonography, 13.5 ± 11.8 %/35.4 ± 34.2 % in the ICA siphon and its branches when using qMRA/duplex sonography, and 24.1 ± 19.7 %/44.9 ± 44.0 % in both vertebral arteries and the basilar artery when using qMRA/duplex sonography.
Conclusion Duplex sonography as well as qMRA allow for highly reproducible measurement of blood flow volume in cervical and intracranial arteries in routine clinical practice.
Analgetische Strahlentherapie gutartiger Erkrankungen des Skelettsystems
Authors: Niewald Marcus 
Published: April 2020

ZusammenfassungDer entzündungshemmende Effekt kleiner Strahlendosen ist seit Langem bekannt und strahlenbiologisch gut untermauert. Zahlreiche retrospektive Arbeiten und einige randomisierte Studien weisen darauf hin, dass ein gutes Ansprechen bei Enthesiopathien wie der Fasciitis plantaris, der Achillodynie, der Epicondylitis und z. B. der Tendinitis calcarea der Schulter zu erzielen ist (Ansprechraten von 60–80 %). Auch bei Arthrosen weisen retrospektive Daten auf eine gute Wirksamkeit der Strahlentherapie hin, der randomisierte Nachweis wird derzeit diskutiert und ist Studienfrage. Indiziert ist die Strahlentherapie bei Patienten im Alter von > 40 Jahren und einer minimalen Anamnesedauer von 3–6 Monaten. In dieser Zeit sollten die konservativen Therapiemethoden durchgeführt worden sein. Eine Gesamtdosis von 3–6 Gy wird in zweimal wöchentlichen Sitzungen über 3 Wochen appliziert. Während und nach der Strahlentherapie kann es zu einer kurzzeitigen Schmerzzunahme kommen. Das Ansprechen ist frühestens 3 Monate nach Therapie zu beurteilen. Nebenwirkungen wie z. B. Hautreaktionen werden überaus selten gesehen. Ein vielfach diskutiertes Tumorrisiko liegt nach bisherigen Daten im Sub-Promillebereich.
Orthopädisch-unfallchirurgische Begutachtung unter besonderer Berücksichtigung von Schmerz
Authors: Middeldorf Stefan 
Published: April 2020

ZusammenfassungDie Begutachtung unter besonderer Berücksichtigung von Schmerz kann nicht schematisch erfolgen. Sie muss stets auf den Einzelfall ausgerichtet sein und die gesamte biografische Anamnese mit einbeziehen, zum Beispiel auch die tatsächlich durchgeführten Therapiemaßnahmen und deren Ergebnis, Auswirkungen auf Alltagsaktivitäten sind so genau wie möglich zu ermitteln. Weiterhin ist dann eine Beurteilung des Schweregrades zur Störung ebenso durchzuführen wie eine Abgrenzung gegenüber Aggravation und Simulation. Nachvollziehbar und unter Berücksichtigung geeigneter Instrumente ist die Überprüfung der Konsistenz vorzunehmen, die Diagnosen unter Berücksichtigung geltender ICD-Kriterien und Kodierungshilfen als Vollbeweis zu ermitteln. Dabei ist zu berücksichtigen, dass Erkrankungen der Stütz- und Bewegungsorgane sehr häufig mit psychischen Komorbiditäten einhergehen. Diese gilt es zu erfassen. Darüber hinaus sind Erkrankungen der seelischen Gesundheit, die mit Schmerzen einhergehen, ebenfalls von höchster Relevanz für das Fachgebiet der Orthopädie und Unfallchirurgie und deren Begutachtung. Hier sind es vor allen Dingen die somatoformen Störungen und die chronische Schmerzstörung mit somatischen und psychischen Faktoren, die differenzialdiagnostisch abzugrenzen sind.
Entwicklung und Evaluation des Fragebogens zur Erfassung Aversiver und Protektiver Kindheitserfahrungen (APK)
Authors: Ehrenthal Johannes C. , Schauenburg Henning , Wagner Frank E. , Dinger Ulrike , Volz Matthias 
Published: April 2020

Zusammenfassung
Ziel der Studie Erste Evaluation des neu entwickelten Fragebogens zur Erfassung Aversiver und Protektiver Kindheitserfahrungen (APK).
Methodik In einer Stichprobe von 128 Patienten in stationärer oder teilstationärer Psychotherapie wurden die Reliabilität des APK sowie konvergente und Kriteriumsvalidität untersucht.
Ergebnisse Der APK zeigte in seinen Gesamtskalen und in den meisten Subskalen eine hohe bis sehr hohe interne Konsistenz, deutliche Hinweise auf konvergente Validität, sowie Zusammenhänge mit Depressivität und Bindungsunsicherheit. Insbesondere die Skala zu protektiven Kindheitserfahrungen klärte eigenständige Varianz in Bezug auf Validitätsaspekte auf.
Schlussfolgerung Mit dem APK liegt ein erweitertes Instrument zur Traumadiagnostik vor. Neben der Erfassung aversiver Kindheitserfahrungen hat die Möglichkeit des gleichzeitigen Erfassens protektiver Kindheitserfahrungen für Forschung wie Praxis eine besondere Bedeutung.