bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc-finger protein CNBP alters the 3-D structure of lncRNA Braveheart in solution
Authors: Kim Doo Nam , Thiel Bernhard C. , Mrozowich Tyler , Hennelly Scott P. , Hofacker Ivo L. , Patel Trushar R. , Sanbonmatsu Karissa Y. 
Published: January 2020

AbstractLong non-coding RNAs (lncRNAs) constitute a significant fraction of the transcriptome, playing important roles in development and disease. However, our understanding of structure-function relationships for this emerging class of RNAs has been limited to secondary structures. Here, we report the 3-D atomistic structural study of epigenetic lncRNA,Braveheart (Bvht), and its complex with CNBP (Cellular Nucleic acid Binding Protein). Using small angle X-ray scattering (SAXS), we elucidate the ensemble ofBvhtRNA conformations in solution, revealing thatBvhtlncRNA has a well-defined, albeit flexible 3-D structure that is remodeled upon CNBP binding. Our study suggests that CNBP binding requires multiple domains ofBvhtand theRHT/AGILRNA motif. We show that RHT/AGIL, previously shown to interact with CNBP, contains a highly flexible loop surrounded by more ordered helices. As one of the largest RNA-only 3-D studies, the work lays the foundation for future structural studies of lncRNA-protein complexes.
The inducible amphisome isolates viral hemagglutinin and defends against influenza A virus infection
Authors: Omi Jumpei , Watanabe-Takahashi Miho , Igai Katsura , Shimizu Eiko , Tseng Ching-Yi , Miyasaka Tomohiro , Waku Tsuyoshi , Hama Shinichiro , Nakanishi Rieka , Goto Yuki , Nishino Yuri , Miyazawa Atsuo , Natori Yasuhiro , Yamashita Makoto , Nishikawa Kiyotaka 
Published: January 2020

AbstractThe emergence of drug-resistant influenza type A viruses (IAVs) necessitates the development of novel anti-IAV agents. Here, we target the IAV hemagglutinin (HA) protein using multivalent peptide library screens and identify PVF-tet, a peptide-based HA inhibitor. PVF-tet inhibits IAV cytopathicity and propagation in cells by binding to newly synthesized HA, rather than to the HA of the parental virus, thus inducing the accumulation of HA within a unique structure, the inducible amphisome, whose production from the autophagosome is accelerated by PVF-tet. The amphisome is also produced in response to IAV infection in the absence of PVF-tet by cells overexpressing ABC transporter subfamily A3, which plays an essential role in the maturation of multivesicular endosomes into the lamellar body, a lipid-sorting organelle. Our results show that the inducible amphisomes can function as a type of organelle-based anti-viral machinery by sequestering HA. PVF-tet efficiently rescues mice from the lethality of IAV infection.
The nuclear pore complex prevents sister chromatid recombination during replicative senescence
Authors: Aguilera Paula , Whalen Jenna , Minguet Christopher , Churikov Dmitri , Freudenreich Catherine , Simon Marie-Noëlle , Géli Vincent 
Published: January 2020

AbstractThe Nuclear Pore Complex (NPC) has emerged as an important hub for processing various types of DNA damage. Here, we uncover that fusing a DNA binding domain to the NPC basket protein Nup1 reduces telomere relocalization to nuclear pores early after telomerase inactivation. This Nup1 modification also impairs the relocalization to the NPC of expanded CAG/CTG triplet repeats. Strikingly, telomerase negative cells bypass senescence when expressing this Nup1 modification by maintaining a minimal telomere length compatible with proliferation through rampant unequal exchanges between sister chromatids. We further report that a Nup1 mutant lacking 36 C-terminal residues recapitulates the phenotypes of the Nup1-LexA fusion indicating a direct role of Nup1 in the relocation of stalled forks to NPCs and restriction of error-prone recombination between repeated sequences. Our results reveal a new mode of telomere maintenance that could shed light on how 20% of cancer cells are maintained without telomerase or ALT.
Terrestrial land-cover type richness is positively linked to landscape-level functioning
Authors: Oehri Jacqueline , Schmid Bernhard , Schaepman-Strub Gabriela , Niklaus Pascal A. 
Published: January 2020

AbstractBiodiversity–ecosystem functioning (BEF) experiments have shown that local species richness promotes ecosystem functioning and stability. Whether this also applies under real-world conditions is still debated. Here, we focus on larger scales of space, time and ecological organization. We develop a quasi-experimental design in which we relate land-cover type richness as measure of landscape richness to 17-year time series of satellite-sensed functioning in 4974 landscape plots 6.25 or 25 ha in size. We choose plots so that landscape richness is orthogonal to land cover-type composition and environmental conditions across climatic gradients. Landscape-scale productivity and temporal stability increase with landscape richness, irrespective of landscape plot size. Peak season near-infrared surface albedo, which is relevant for surface energy budgets, is higher in mixed than in single land-cover type landscapes. Effect sizes are as large as those reported from BEF-experiments, suggesting that landscape richness promotes landscape functioning at spatial scales relevant for management.
Structure-activity relationship studies of four novel 4-aminopyridine K+ channel blockers
Authors: Rodríguez-Rangel Sofia , Bravin Alyssa D. , Ramos-Torres Karla M. , Brugarolas Pedro , Sánchez-Rodríguez Jorge E. 
Published: January 2020

Abstract4-Aminopyridine (4AP) is a specific blocker of voltage-gated potassium channels (KV1 family) clinically approved for the symptomatic treatment of patients with multiple sclerosis (MS). It has recently been shown that [18F]3F4AP, a radiofluorinated analog of 4AP, also binds to KV1 channels and can be used as a PET tracer for the detection of demyelinated lesions in rodent models of MS. Here, we investigate four novel 4AP derivatives containing methyl (-CH3), methoxy (-OCH3) as well as trifluoromethyl (-CF3) in the 2 and 3 position as potential candidates for PET imaging and/or therapy. We characterized the physicochemical properties of these compounds (basicity and lipophilicity) and analyzed their ability to block Shaker K+ channel under different voltage and pH conditions. Our results demonstrate that three of the four derivatives are able to block voltage-gated potassium channels. Specifically, 3-methyl-4-aminopyridine (3Me4AP) was found to be approximately 7-fold more potent than 4AP and 3F4AP; 3-methoxy- and 3-trifluoromethyl-4-aminopyridine (3MeO4AP and 3CF34AP) were found to be about 3- to 4-fold less potent than 4AP; and 2-trifluoromethyl-4-AP (2CF34AP) was found to be about 60-fold less active. These results suggest that these novel derivatives are potential candidates for therapy and imaging.
Influence of defects on structural colours generated by laser-induced ripples
Authors: Maragkaki Stella , Skaradzinski Christian A. , Nett Ralf , Gurevich Evgeny L. 
Published: January 2020

AbstractThe colourisation of metallic surface which appears due to periodic surface patterns induced by ultrashort laser pulses is studied. Ripples due to the sub-micrometer size of their period act as a diffraction grating, generating structural colours. Carefully chosen strategy of the laser spot scanning allows us to mimic the nanostructures responsible for structural colours of some flowers on the metal substrate. We investigate the correlation between the colourising effects and the artificially-induced defects in the ripples structure and show that these defects can make the colours observable in a larger range of viewing angles. Further we address the influence of the processing parameters on the spectral profile of the reflected light.
The Influence of Cell Culture Density on the Cytotoxicity of Adipose-Derived Stem Cells Induced by L-Ascorbic Acid-2-Phosphate
Authors: Wu Yuan-Kun , Tu Yuan-Kun , Yu Jiashing , Cheng Nai-Chen 
Published: January 2020

AbstractAscorbic acid-2-phosphate (A2-P) is an oxidation-resistant derivative of ascorbic acid that has been widely employed in culturing adipose-derived stem cells (ASCs) for faster expansion and cell sheet formation. While high dose ascorbic acid is known to induce cellular apoptosis via metabolic stress and genotoxic effects, potential cytotoxic effects of A2-P at high concentrations has not been explored. In this study, the relationship between ASC seeding density and A2-P-induced cytotoxicity was investigated. Spheroid-derived ASCs with smaller cellular dimensions were generated to investigate the effect of cell-cell contact on the resistance to A2-P-induced cytotoxicity. Decreased viability of ASC, fibroblast, and spheroid-derived ASC was noted at higher A2-P concentration, and it could be reverted with high seeding density. Compared to control ASCs, spheroid-derived ASCs seeded at the same density exhibited decreased viability in the A2-P-supplemented medium. The expression of antioxidant enzymes (catalase, SOD1, and SOD2) was enhanced in ASCs at higher seeding densities. However, their enhanced expression in spheroid-derived ASCs was less evident. Furthermore, we found that co-administration of catalase or N-acetylcysteine nullified the observed cytotoxicity. Collectively, A2-P can induce ASC cytotoxicity at higher concentrations, which can be prevented by seeding ASCs at high density or co-administration of another antioxidant.
Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages
Authors: Selley Liza , Schuster Linda , Marbach Helene , Forsthuber Theresa , Forbes Ben , Gant Timothy W , Sandström Thomas , Camiña Nuria , Athersuch Toby J , Mudway Ian , Kumar Abhinav 
Published: January 2020

Abstract
Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4–25 μg ml−1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.
2-Methylquinazoline derivative 23BB as a highly selective histone deacetylase 6 inhibitor alleviated cisplatin-induced acute kidney injury
Authors: Hao Yan , Guo Fan , Huang Zhuo , Feng Yuying , Xia Zijing , Liu Jing , Li Lingzhi , Huang Rongshuang , Lin Lin , Ma Liang , Fu Ping 
Published: January 2020

AbstractHistone deacetylases 6 (HDAC6) has been reported to be involved in the pathogenesis of cisplatin-induced acute kidney injury (AKI). Selective inhibition of HDAC6 might be a potential treatment for AKI. In our previous study, a highly selective HDAC6 inhibitor (HDAC6i) 23BB effectively protected against rhabdomyolysis-induced AKI with good safety. However, whether 23BB possessed favorable renoprotection against cisplatin-induced AKI and the involved mechanisms remained unknown. In the study, cisplatin-injected mice developed severe AKI symptom as indicated by acute kidney dysfunction and pathological changes, companied by the overexpression of HDAC6 in tubular epithelial cells. Pharmacological inhibition of HDAC6 by the treatment of 23BB significantly attenuated sCr, BUN and renal tubular damage. Mechanistically, 23BB enhanced the acetylation of histone H3 to reduce the HDAC6 activity. Cisplatin-induced AKI triggered multiple signal mediators of endoplasmic reticulum (ER) stress including PERK, ATF6 and IRE1 pathway, as well as CHOP, GRP78, p-JNK and caspase 12 proteins. Oral administration of our HDAC6i 23BB at a dose of 40 mg/kg/d for 3 days notably improved above-mentioned responses in the injured kidney tissues. HDAC6 inhibition also reduced the number of TUNEL-positive tubular cells and regulated apoptosis-related protein expression. Overall, these data highlighted that HDAC6 inhibitor 23BB modulated apoptosis via the inhibition of ER stress in the tubular epithelial cells of cisplatin-induced AKI.
Alcohol promotes renal fibrosis by activating Nox2/4-mediated DNA methylation of Smad7
Authors: Yang Qin , Chen Hai-Yong , Wang Jia-nan , Han Huai-Qin , Jiang Ling , Wu Wei-Feng , Wei Biao , Gao Li , Ma Qiu-ying , Liu Xue-qi , Chen Qi , Wen Jia-gen , Jin Juan , Huang Yan , Ni Wei-jian , Ma Tao-tao , Li Jun , Meng Xiao-Ming 
Published: January 2020

Abstract
Alcohol consumption causes renal injury and compromises kidney function. The underlying mechanism of the alcoholic kidney disease remains largely unknown. In the present study, an alcoholic renal fibrosis animal model was first employed which mice received liquid diet containing alcohol for 4 to 12 weeks. The Masson’s Trichrome staining analysis showed that kidney fibrosis increased at week 8 and 12 in the animal model that was further confirmed by albumin assay, Western blot, immunostaining and real-time PCR of fibrotic indexes (collagen I and α-SMA). In vitro analysis also confirmed that alcohol significantly induced fibrotic response (collagen I and α-SMA) in HK2 tubular epithelial cells. Importantly, both in vivo and in vitro studies showed alcohol treatments decreased Smad7 and activated Smad3. We further determined how the alcohol affected the balance of Smad7 (inhibitory Smad) and Smad3 (regulatory Smad). Genome-wide methylation sequencing showed an increased DNA methylation of many genes and bisulfite sequencing analysis showed an increased DNA methylation of Smad7 after alcohol ingestion. We also found DNA methylation of Smad7 was mediated by DNMT1 in ethyl alcohol (EtOH)-treated HK2 cells. Knockdown of Nox2 or Nox4 decreased DNMT1 and rebalanced Smad7/Smad3 axis, and thereby relieved EtOH-induced fibrotic response. The inhibition of reactive oxygen species by the intraperitoneal injection of apocynin attenuated renal fibrosis and restored renal function in the alcoholic mice. Collectively, we established novel in vivo and in vitro alcoholic kidney fibrosis models and found that alcohol induces renal fibrosis by activating oxidative stress-induced DNA methylation of Smad7. Suppression of Nox-mediated oxidative stress may be a potential therapy for long-term alcohol abuse-induced kidney fibrosis.
Die operative Entfernung zerebraler Hydatid-Zysten
Authors: Datz Annett , El Damaty Ahmed 
Published: January 2020

ZusammenfassungDie zystische Echinokokkose ist eine seltene und gefährliche parasitäre Erkrankung des Menschen, verursacht durch die Infektion mit Echinococcus granulosus, dem sogenannten Hundebandwurm. Dabei können sich Zysten im Gehirn bilden, die operativ entfernt werden müssen. Eine dieser sehr seltenen Operationen wurde erfolgreich am Universitätsklinikum Heidelberg in der Abteilung für Neurochirurgie zusammen mit den Tropenmedizinern durchgeführt.
Risiko-adaptiertes Vorgehen bei Schilddrüsen-karzinomen
Authors: Allelein Stephanie , Schott Matthias 
Published: January 2020

ZUSAMMENFASSUNGDas therapeutische Vorgehen beim Schilddrüsenkarzinom hängt u. a. von der Größe, der Ausbreitung und dem histologischen Ergebnis ab. Im Regelfall stehen beim differenzierten und entdifferenzierten Schilddrüsenkarzinom die Thyreoidektomie mit Lymphknotendissektion und nachfolgender Radiojodtherapie sowie in Abhängigkeit der Größe und Histologie die TSH-suppressive Therapie im Vordergrund. Bei den metastasierten, entdifferenzierten und medullären Schilddrüsenkarzinomen kommen bei definiertem Tumorprogress Tyrosinkinaseinhibitoren zum Einsatz, die häufig mit einer Verlängerung des progressionsfreien Überlebens und ggf. des Gesamtüberlebens vergesellschaftet sind. Die verschiedenen Aspekte des therapeutischen Vorgehens werden aktuell national und international intensiv diskutiert. Eine nationale S3-Leitlinie für die Behandlung des Schilddrüsenkarzinoms ist in Bearbeitung.
Evaluation of Platelet Activity Markers in Prognostic Value of Children with Crimean-Congo Hemorrhagic Fever
Authors: Güven Ahmet Sami , Duksal Fatma , Metin Akcan Özge , Aygüneş Utku , Oflaz Mehmet Burhan 
Published: January 2020

Abstract
Objective The aim of this study is to investigate the prognostic value of platelet (PLT) activity markers in children with Crimean-Congo hemorrhagic fever (CCHF) and compare results with healthy controls.
Materials and Methods A total of 135 patients with CCHF and 100 healthy children were included in this retrospective study. Mean age was 12.4 ± 3.3 years in CCHF group, and 92 patients were male. We measured PLT count, mean platelet volume (MPV), platelet distribution width (PDW), and mean platelet mass (MPM) as PLT activity markers.
Results A statistically significant decrease in MPM and PLT, and significantly higher levels of PDW and activated partial thromboplastin time (aPTT) and no significant difference in MPV were observed in patients with CCHF compared with controls. Although there were no significant differences between the severe and nonsevere CCHF groups in term of MPV and PDW, the MPM value was significantly decreased in severe patients (p < 0.001). Furthermore, MPM values were inversely correlated with aPTT (r = −0.617, p = 0.015), and positively correlated with PLT (r = 0.703, p < 0.001) which are considered likely to be indicators of disease severity. Multivariate logistic regression analysis revealed MPM as an independent risk factor for severe disease.
Conclusion Our study demonstrated that MPM values were decreased in severe cases compared with nonsevere in children with CCHF. The MPM as an indicator of PLT activation at the time of diagnosis in children with CCHF can be used as a prognostic index for disease severity.
Quadriparesis following a Low-Voltage Electrical Injury in a 4-Year-Old Girl
Authors: Forouzan Arash , Masoumi Kambiz , Bastan Amir Sadegh Iran , Karimi Mohammad 
Published: January 2020

AbstractElectricity injuries are a global health problem, especially in low-income countries. The present case report involves a 4-year-old girl with quadriparesis following a low-voltage electrical injury. She was alert and her vital signs were normal on admission. The results of her examination were normal, except for decreased muscle power of the limbs, which was significantly improved during observation in the emergency ward and the subsequent follow-up. Clinical evidence suggested the diagnosis of transient neurologic effects associated with the electrical injury. Some degrees of neurological impairment are often observed in patients after electrical damage. Given the multiorgan dysfunction observed in many electrical injury patients, it is recommended to perform neurological examinations, if possible, at the first visit and follow-ups.
Effect of Potassium Infusions on Serum Levels in Children during Treatment of Diabetic Ketoacidosis
Authors: Basnet Sangita , Musaitif Rawan , Khanal Aayush , Powell Kimberly , Caprirolo Giovanna , Majcina Ryan , Robbs Randall S. 
Published: January 2020

AbstractA retrospective study was done to determine the effect of potassium (K+) infusions on serum levels in children admitted to the pediatric intensive care unit (PICU) with diabetic ketoacidosis (DKA). Eighty-two percent of 92 cases studied received 40 mEq/L K+ infusion over the treatment period of median 13.0 (interquartile range [IQR]: 7–18) hours. The median K+ value at the end of this period was 3.9 (IQR: 3.4–4.2) mEq/L. There were 31 data points of low K+ values (<3.5 mEq/L) and 4 high values (>5.5 mEq/L) during this treatment period. The K+ infusions of 40 mEq/L may be sufficient to normalize serum K+ when treating DKA.
Contribution of Habitual Activity to Cruciate Ligament Rupture in Labrador Retrievers
Authors: Terhaar Hannah M. , Muir Peter , Baker Lauren A. , Binversie Emily E. , Chi Jacqueline , Sample Susannah J. 
Published: January 2020

Abstract
Objective The aim of this study was to describe the contribution of signalment and habitual activity in the development of cruciate ligament rupture (CR) in Labrador Retrievers.
Study Design Four hundred and twelve client-owned purebred Labrador Retrievers were recruited. Dogs were assigned either as affected with CR or as controls based on signalment, physical examination and radiographic evidence of disease. Clients were asked to complete a questionnaire related to signalment, concurrent disease and a questionnaire pertaining to their dog's activity before development of CR or general activity during the dog's most active years.
Results Habitual activity was not significantly different between dogs affected with CR and controls. There was no significant difference in neuter status or body weight between CR affected dogs and controls. Labrador Retrievers with a yellow coat, and Labradors that did not maintain an optimal body weight in the opinion of their veterinarian were at increased risk of developing CR.
Conclusions Habitual activity level is not a risk factor for development of CR in Labrador Retrievers. Our study did not show neuter status, sex or body weight to be risk factors for CR. However, coat colour and not sustaining optimal body condition are significant risk factors for CR.
Bruns Syndrome Caused by Intraventricular Neurocysticercosis: Literature Review
Authors: Silva Guilherme Gago da , Ferreira Nelson Pires , Britz João Pedro Einsfeld 
Published: January 2020

AbstractBruns syndrome is one of the clinical presentations of intraventricular neurocysticercosis, and it is characterized by episodes of headache, vertigo and vomiting. The intraventricular form of neurocysticercosis occurs in 7% to 20% of the cases, and it is more serious than the intraparenchymal form. The management is primarily surgical, associated with pharmacological therapy with anthelmintic drugs and corticosteroids. We report the case of a patient who presented Bruns syndrome due to neurocysticercosis.