bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium butyrate inhibits high cholesterol-induced neuronal amyloidogenesis by modulating NRF2 stabilization-mediated ROS levels: involvement of NOX2 and SOD1
Authors: Kim Seo Yihl , Chae Chang Woo , Lee Hyun Jik , Jung Young Hyun , Choi Gee Euhn , Kim Jun Sung , Lim Jae Ryong , Lee Joo Eun , Cho Ji Hyeon , Park Hansoo , Park Changho , Han Ho Jae 
Published: June 2020

AbstractThe gut–brain axis is currently being studied as a therapeutic strategy for neurological diseases, especially Alzheimer’s disease (AD). Obesity results in the gut microbiota dysbiosis, which includes butyrate-producing bacteria are reduced. Although sodium butyrate (NaB) has emerged as the potential therapeutic substance in AD, there is a lack of detailed results into what signaling pathways affect amyloidogenesis in AD induced by obesity. Thus, we investigated the regulatory role of NaB on amyloidogenesis in neuronal cells under high cholesterol. In our results, we verified that increased amyloid β peptide (Aβ) accumulation in the brain of obese mice and a reduction in butyrate-producing bacteria due to the gut microbiota dysbiosis induced by obesity. We showed that NaB decreased the expression levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and Aβ accumulation induced by high cholesterol in SK-N-MC cells. We demonstrated that NaB was absorbed in cells through sodium-coupled monocarboxylate transporter 1 (SMCT1) and then inhibited high cholesterol-induced Aβ accumulation. Subsequently, we also observed that reactive oxygen species (ROS) were overproduced because of increased NADPH oxidase 2 (NOX2) expression under high cholesterol. Meanwhile, NaB decreased NOX2 levels through a reduction of NF-κB activity, which ultimately inhibited Aβ accumulation caused by high cholesterol. We demonstrated that NaB increased the expression levels of p21 under high cholesterol, contributing to p21/NRF2 (Nuclear factor erythroid 2-related factor 2) colocalization, which leads to NRF2 stabilization. NRF2 stabilization causes NF-κB inactivation, followed by NOX2 suppression and superoxide dismutase 1 (SOD1) upregulation. Thus, NaB withSOD1silencing under high cholesterol did not eliminate excessive ROS, and eventually resulted in Aβ accumulation. In conclusion, we demonstrated that NaB prevents excessive ROS through NOX2 suppression and SOD1 upregulation by p21/NRF2 pathway, which is critical for inhibiting BACE1-dependent amyloidogenesis in neuronal cells exposed to high cholesterol environment.
Radiation-resistant metal-organic framework enables efficient separation of krypton fission gas from spent nuclear fuel
Authors: Elsaidi Sameh K. , Mohamed Mona H. , Helal Ahmed S. , Galanek Mitchell , Pham Tony , Suepaul Shanelle , Space Brian , Hopkinson David , Thallapally Praveen K. , Li Ju 
Published: June 2020

AbstractCapture and storage of volatile radionuclides that result from processing of used nuclear fuel is a major challenge. Solid adsorbents, in particular ultra-microporous metal-organic frameworks, could be effective in capturing these volatile radionuclides, including 85Kr. However, metal-organic frameworks are found to have higher affinity for xenon than for krypton, and have comparable affinity for Kr and N2. Also, the adsorbent needs to have high radiation stability. To address these challenges, here we evaluate a series of ultra-microporous metal-organic frameworks, SIFSIX-3-M (M = Zn, Cu, Ni, Co, or Fe) for their capability in 85Kr separation and storage using a two-bed breakthrough method. These materials were found to have higher Kr/N2 selectivity than current benchmark materials, which leads to a notable decrease in the nuclear waste volume. The materials were systematically studied for gamma and beta irradiation stability, and SIFSIX-3-Cu is found to be the most radiation resistant.
Genetic breakdown of a Tet-off conditional lethality system for insect population control
Authors: Zhao Yang , Schetelig Marc F. , Handler Alfred M. 
Published: June 2020

AbstractGenetically modified conditional lethal strains have been created to improve the control of insect pest populations damaging to human health and agriculture. However, understanding the potential for the genetic breakdown of lethality systems by rare spontaneous mutations, or selection for inherent suppressors, is critical since field release studies are in progress. This knowledge gap was addressed in a Drosophila tetracycline-suppressible embryonic lethality system by analyzing the frequency and structure of primary-site spontaneous mutations and second-site suppressors resulting in heritable survivors from 1.2 million zygotes. Here we report that F1 survivors due to primary-site deletions and indels occur at a 5.8 × 10−6 frequency, while survival due to second-site maternal-effect suppressors occur at a ~10−5 frequency. Survivors due to inherent lethal effector suppressors could result in a resistant field population, and we suggest that this risk may be mitigated by the use of dual redundant, albeit functionally unrelated, lethality systems.
EEG microstates are a candidate endophenotype for schizophrenia
Authors: da Cruz Janir Ramos , Favrod Ophélie , Roinishvili Maya , Chkonia Eka , Brand Andreas , Mohr Christine , Figueiredo Patrícia , Herzog Michael H. 
Published: June 2020

AbstractElectroencephalogram microstates are recurrent scalp potential configurations that remain stable for around 90 ms. The dynamics of two of the four canonical classes of microstates, commonly labeled as C and D, have been suggested as a potential endophenotype for schizophrenia. For endophenotypes, unaffected relatives of patients must show abnormalities compared to controls. Here, we examined microstate dynamics in resting-state recordings of unaffected siblings of patients with schizophrenia, patients with schizophrenia, healthy controls, and patients with first episodes of psychosis (FEP). Patients with schizophrenia and their siblings showed increased presence of microstate class C and decreased presence of microstate class D compared to controls. No difference was found between FEP and chronic patients. Our findings suggest that the dynamics of microstate classes C and D are a candidate endophenotype for schizophrenia.
Core Binding Factors are essential for ovulation, luteinization, and female fertility in mice
Authors: Lee-Thacker Somang , Jeon Hayce , Choi Yohan , Taniuchi Ichiro , Takarada Takeshi , Yoneda Yukio , Ko CheMyong , Jo Misung 
Published: June 2020

AbstractCore Binding Factors (CBFs) are a small group of heterodimeric transcription factor complexes composed of DNA binding proteins, RUNXs, and a non-DNA binding protein, CBFB. The LH surge increases the expression of Runx1 and Runx2 in ovulatory follicles, while Cbfb is constitutively expressed. To investigate the physiological significance of CBFs, we generated a conditional mutant mouse model in which granulosa cell expression of Runx2 and Cbfb was deleted by the Esr2Cre. Female Cbfbflox/flox;Esr2cre/+;Runx2flox/flox mice were infertile; follicles developed to the preovulatory follicle stage but failed to ovulate. RNA-seq analysis of mutant mouse ovaries collected at 11 h post-hCG unveiled numerous CBFs-downstream genes that are associated with inflammation, matrix remodeling, wnt signaling, and steroid metabolism. Mutant mice also failed to develop corpora lutea, as evident by the lack of luteal marker gene expression, marked reduction of vascularization, and excessive apoptotic staining in unruptured poorly luteinized follicles, consistent with dramatic reduction of progesterone by 24 h after hCG administration. The present study provides in vivo evidence that CBFs act as essential transcriptional regulators of both ovulation and luteinization by regulating the expression of key genes that are involved in inflammation, matrix remodeling, cell differentiation, vascularization, and steroid metabolisms in mice.
Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer
Authors: Ha Dong-Hyeon , Min Ahrum , Kim Seongyeong , Jang Hyemin , Kim So Hyeon , Kim Hee-Jun , Ryu Han Suk , Ku Ja-Lok , Lee Kyung-Hun , Im Seock-Ah 
Published: June 2020

AbstractDue to its regulation of CDK1/2 phosphorylation, WEE1 plays essentially roles in the regulations of G2/M checkpoint and DNA damage response (DDR). WEE1 inhibition can increase genomic instability by inducing replication stress and G2/M checkpoint inactivation, which result in increased cellular sensitivity to DNA damaging agents. We considered an increase in genomic instability induced by WEE1 inhibition might be used to augment the effects of drugs targeting DNA repair protein. Typically, PARP inhibitors are effective in germline BRCA 1/2 mutated breast and ovarian cancer, but their applicabilities in triple-negative breast cancer (TNBC) are limited. This study was conducted to investigate the anti-tumor effects of the WEE1 inhibitor, AZD1775, and the mechanism responsible for its potentiation of sensitivity to olaparib (a PARP inhibitor) via the modulation of DDR in TNBC cells. Our results suggest that AZD1775 could be used to broaden the application range of olaparib in TNBC and provide a rationale for a clinical trial of combined olaparib and AZD1775 therapy.
Improved survival after treatments of patients with nonalcoholic fatty liver disease associated hepatocellular carcinoma
Authors: Benhammou Jihane N. , Aby Elizabeth S. , Shirvanian Gayaneh , Manansala Kohlett , Hussain Shehnaz K. , Tong Myron J. 
Published: June 2020

AbstractWorldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Despite the rise in these disease entities, detailed long-term outcomes of large NAFLD-associated HCC cohorts are lacking. In this report, we compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. Distinguishing features of NAFLD-associated HCC patients in the cirrhosis and non-cirrhosis setting were also identified. We conducted a retrospective study of 125 NAFLD, 170 HBV and 159 HCV HCC patients, utilizing clinical, pathological and radiographic data. Multivariate regression models were used to study the overall and recurrence-free survival. The overall survival rates were significantly higher in the NAFLD-HCC cases compared to HBV-HCC (HR = 0.35, 95% CI 0.15–0.80) and HCV-HCC (HR = 0.37, 95% CI 0.17–0.77) cases. The NAFLD-HCC patients had a trend for higher recurrence-free survival rates compared to HBV and HCV-HCC cases. Within the NAFLD group, 18% did not have cirrhosis or advanced fibrosis; Hispanic ethnicity (OR = 12.34, 95% CI 2.59–58.82) and high BMI (OR = 1.19, 95% CI 1.07–1.33) were significantly associated with having cirrhosis. NAFLD-HCC cases were less likely to exhibit elevated serum AFP (p < 0.0001). After treatments, NAFLD-related HCC patients had longer overall but not recurrence-free survival rates compared to patients with viral-associated HCC. Non-Hispanic ethnicity and normal BMI differentiated non-cirrhosis versus cirrhosis NAFLD HCC. Further studies are warranted to identify additional biomarkers to stratify NAFLD patients without cirrhosis who are at risk for HCC.
Walls offer potential to improve urban biodiversity
Authors: Chen Chundi , Mao Longfei , Qiu Yonggui , Cui Jian , Wang Yuncai 
Published: June 2020

AbstractWithin urban environment with high-rise buildings and structures, walls represent the most common vertical spaces. Conventionally, such spaces are viewed as abiotic areas, where spontaneous flora is neglected. Through investigations in a typical mountainous city Chongqing, this study concerns the spontaneous species diversity on walls and the influences of wall factors and the adjacent environment. A total of 239 vascular plant species belonging to 172 genera and 75 families were found; 90% of the species are indigenous. More fern species inhabit walls, compared with xerophytes that dominate general urban environment. Variation partitioning indicated that wall attributes played a more important role in explaining the total variation in wall vegetation composition and structure than did the adjacent environment. Given that there are limited possibilities to extend more green space in urban land environment, we support a “let Nature take its course” approach to improve urban biodiversity, where vertical urban space with spontaneous flora can act as a valuable complement to biodiversity and ecosystem services in dense urban environment. This study should raise urban designers’ and ecosystem managers’ awareness of the possibilities of this type of informal, unconventional habitat as a “supplement” for urban greening and landscaping.
Backbone Interactions Between Transcriptional Activator ExsA and Anti-Activator ExsD Facilitate Regulation of the Type III Secretion System in Pseudomonas aeruginosa
Authors: Shrestha Manisha , Bernhards Robert C. , Fu Yichen , Ryan Kylie , Schubot Florian D. 
Published: June 2020

AbstractThe type III secretion system (T3SS) is a pivotal virulence mechanism of many Gram-negative bacteria. During infection, the syringe-like T3SS injects cytotoxic proteins directly into the eukaryotic host cell cytoplasm. In Pseudomonas aeruginosa, expression of the T3SS is regulated by a signaling cascade involving the proteins ExsA, ExsC, ExsD, and ExsE. The AraC-type transcription factor ExsA activates transcription of all T3SS-associated genes. Prior to host cell contact, ExsA is inhibited through direct binding of the anti-activator protein ExsD. Host cell contact triggers secretion of ExsE and sequestration of ExsD by ExsC to cause the release of ExsA. ExsA does not bind ExsD through the canonical ligand binding pocket of AraC-type proteins. Using site-directed mutagenesis and a specific in vitro transcription assay, we have now discovered that backbone interactions between the amino terminus of ExsD and the ExsA beta barrel constitute a pivotal part of the ExsD-ExsA interface. Follow-up bacterial two-hybrid experiments suggest additional contacts create an even larger protein–protein interface. The discovered role of the amino terminus of ExsD in ExsA binding explains how ExsC might relieve the ExsD-mediated inhibition of T3SS gene expression, because the same region of ExsD interacts with ExsC following host cell contact.
Evaluation of eye movements and visual performance in patients with cataract
Authors: Wan Yu , Yang Jiarui , Ren Xiaotong , Yu Zitong , Zhang Rong , Li Xuemin 
Published: June 2020

AbstractEye movement is an essential component of visual perception. Eye movement disorders have been observed in many eye disease, and are thought to affect various visual performance in daily life. However, eye movement behaviors of the elderly with cataract are poorly understood, and the impact of cataract surgery on eye movements has not been investigated. In this study, we observed the eye movement behaviors in thirty patients with bilateral age-related cataract while performing three performance-based tasks (visual search, face recognition and reading). Eye movements were automatically recorded by an eye tracker during task performance. We found an overall improved visual performance postoperatively, presented as elevated percentage of correctly identified objects and faces, reduced search time and increased reading speed. Eye movement parameters were found significantly altered after cataract surgery. Fixation count, total fixation duration and total visit duration were markedly increased in the visual search task and face recognition task. The proportion of regressive saccades was obviously decreased in the reading task. These eye movement parameters were found to be correlated with the measures of visual performance. Our findings suggested a potential association between the eye movement disturbance and impaired visual performance, and provided a new insight on the potential usefulness of eye movement as an objective and valid tool to understand visual impairments caused by cataract, as well as evaluate practical outcomes of cataract surgery.
Prediction of slope failure in open-pit mines using a novel hybrid artificial intelligence model based on decision tree and evolution algorithm
Authors: Bui Xuan-Nam , Nguyen Hoang , Choi Yosoon , Nguyen-Thoi Trung , Zhou Jian , Dou Jie 
Published: June 2020

AbstractIn this study, the objective was to develop a new and highly-accurate artificial intelligence model for slope failure prediction in open-pit mines. For this purpose, the M5Rules algorithm was combined with a genetic algorithm (GA) in a novel hybrid technique, named M5Rules–GA model, for slope stability estimation and analysis and 450-slope observations in an open-pit mine in Vietnam were modeled using the Geo-Studio software based on essential parameters. The factor of safety was used as the model outcome. Artificial neural networks (ANN), support vector regression (SVR), and previously introduced models (such as FFA-SVR, ANN-PSO, ANN-ICA, ANN-GA, and ANN-ABC) were also developed for evaluating the proposed M5Rules–GA model. The evaluation of the model performance involved applying and computing the determination coefficient, variance account for, and root mean square error, as well as a general ranking and color scale. The results confirmed that the proposed M5Rules–GA model is a robust tool for analyzing slope stability. The other investigated models yielded less robust performance under the evaluation metrics.
Highly efficient synchronization of sheep skin fibroblasts at G2/M phase and isolation of sheep Y chromosomes by flow cytometric sorting
Authors: Yao Yanzhu , Zhang Yuanyuan , Liu Wansheng , Deng Xuemei 
Published: June 2020

AbstractAt present, based on whole genome sequencing, sequences and genes annotation of the sheep (Ovis aries) Y chromosome are still absent. The isolation of Y chromosomes followed by sequencing has been approved as an effective approach to analyze this complex chromosome in other species. In this study, we established a highly efficient synchronization method for G2/M phase of sheep fibroblasts, which was successfully applied to flow-sorting chromosomes of sheep, with a focus on isolation and sequencing of the ovine Y chromosome. The isolated (~80,000) Y chromosomes were verified by fluorescence quantitative real-time polymerase chain reaction, further confirmed by fluorescence in situ hybridization, and amplified by the MALBAC method before next-generation sequencing. The sequence results indicated that 68.90% of reads were Y chromosome-related sequences as they are homologous to the bovine Y chromosome. The remaining 31.1% of reads were aligned to the sheep reference genome, including 13.57% reads to chromosome X and 6.68% to chromosome 17. Importantly, the paired-end reads that are properly aligned to the bovine Y sequence assembly accounted for 46.49%, indicating the success in the ovine Y chromosome isolation and the high quality of the Y chromosome sequences. This study not only set up a foundation for future sequencing, assembly and annotation of the ovine Y chromosome, but also provide a validated approach to overcoming difficulties in sequencing Y chromosome in other mammalian species.
Experimental device-independent certified randomness generation with an instrumental causal structure
Authors: Agresti Iris , Poderini Davide , Guerini Leonardo , Mancusi Michele , Carvacho Gonzalo , Aolita Leandro , Cavalcanti Daniel , Chaves Rafael , Sciarrino Fabio 
Published: June 2020

AbstractThe intrinsic random nature of quantum physics offers novel tools for the generation of random numbers, a central challenge for a plethora of fields. Bell non-local correlations obtained by measurements on entangled states allow for the generation of bit strings whose randomness is guaranteed in a device-independent manner, i.e. without assumptions on the measurement and state-generation devices. Here, we generate this strong form of certified randomness on a new platform: the so-called instrumental scenario, which is central to the field of causal inference. First, we theoretically show that certified random bits, private against general quantum adversaries, can be extracted exploiting device-independent quantum instrumental-inequality violations. Then, we experimentally implement the corresponding randomness-generation protocol using entangled photons and active feed-forward of information. Moreover, we show that, for low levels of noise, our protocol offers an advantage over the simplest Bell-nonlocality protocol based on the Clauser-Horn-Shimony-Holt inequality.
Frühintervention bei Schizophrenie – ein Update
Authors: Leopold Karolina , Becker Thomas , Förstl Johann , Kiefer Falk , de Millas Walter , Janetzky Wolfgang , Lambert Martin , Pfennig Andrea , Bechdolf Andreas 
Published: June 2020

ZusammenfassungIn Deutschland werden Psychosen immer noch zu spät diagnostiziert. Die Dauer der unbehandelten Psychose (DUP) liegt im Durchschnitt bei einem Jahr. Daher sollte die Frühintervention einen höheren Stellenwert erhalten. Denn je kürzer die Dauer der DUP, desto höher ist die Wahrscheinlichkeit der dauerhaften Recovery sowie einer besseren Langzeitprognose. Aufklärungsarbeit in der Öffentlichkeit und spezialisierte Früherkennungszentren mit niedrigschwelligem Zugang können die Versorgung und damit die Perspektive der meist jungen Patientinnen und Patienten bereits in der Frühphase der Erkrankung verbessern. Notwendig sind dazu neben der antipsychotischen Therapie evidenzbasierte psychotherapeutische Verfahren, Angehörigen- und Peerarbeit sowie begleitende Angebote, durch die Patientinnen und Patienten individuell darin unterstützt werden, wieder im Arbeitsmarkt integriert zu werden oder zu verbleiben („Individual Placement and Support“, IPS). Während die Möglichkeit zur Frühintervention in einigen Ländern, z. B. Dänemark und Australien, bereits einen Teil der Regelversorgung darstellt, ist Deutschland noch nicht über Modellprojekte hinausgekommen. Dies zu ändern muss eines der wesentlichen Ziele der nächsten Jahre sein. Mit dieser Übersichtsarbeit möchten die Autoren daher zum Weiterdenken und Handeln anregen.
Aktuelle Aspekte der Cholesteatomchirurgie – Teil 2: chirurgische Therapie im Wandel der Zeit
Authors: Schulze Anja , Zahnert Thomas 
Published: June 2020

AbstractDue to cholesteatoma's slowly progressive and destructive growth there is a risk of intracranial and potentially life-threatening complications. That's why every cholesteatoma is a basically absolute indication for surgery. Only asymptomatic and small retractions, so-called prae-cholesteatomas, may be under observation. While the first part of this article focused on the basics of pathogenesis and diagnostics, this one provides an overview of current surgical strategies, both proven and new ones.