bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light‐Controlled Cell‐Cycle Arrest and Apoptosis
Authors: Uhl Edgar , Wolff Friederike , Mangal Sriyash , Dube Henry , Zanin Esther 
Published: October 2020

AbstractCell‐cycle interference by small molecules has widely been used to study fundamental biological mechanisms and to treat a great variety of diseases, most notably cancer. However, at present only limited possibilities exist for spatio‐temporal control of the cell cycle. Here we report on a photocaging strategy to reversibly arrest the cell cycle at metaphase or induce apoptosis using blue‐light irradiation. The versatile proteasome inhibitor MG132 is photocaged directly at the reactive aldehyde function effectively masking its biological activity. Upon irradiation reversible cell‐cycle arrest in the metaphase is demonstrated to take place in vivo. Similarly, apoptosis can efficiently be induced by irradiation of human cancer cells. With the developed photopharmacological approach spatio‐temporal control of the cell cycle is thus enabled with very high modulation, as caged MG132 shows no effect on proliferation in the dark. In addition, full compatibility of photo‐controlled uncaging with dynamic microscopy techniques in vivo is demonstrated. This visible‐light responsive tool should be of great value for biological as well as medicinal approaches in need of high‐precision targeting of the proteasome and thereby the cell cycle and apoptosis.
The high biodiversity and vulnerability of two Mediterranean bathyal seamounts support the need for creating offshore protected areas
Authors: Bo Marzia , Coppari Martina , Betti Federico , Enrichetti Francesco , Bertolino Marco , Massa Francesco , Bava Simone , Gay Guido , Cattaneo‐Vietti Riccardo , Bavestrello Giorgio 
Published: October 2020

Abstract

Seamounts host some of the most important deep‐sea ecosystems. The unique environmental characteristics of seamounts sustain rich biological hot spots, which, in recent times, have suffered the effects of intense fishing pressure.
Biodiversity and vulnerability data are extremely scarce for Mediterranean seamounts, and this, in addition to the complex socio‐economic and juridical status of offshore sites, results in difficulty in identifying the best management strategies.
An extensive remotely operated vehicle (ROV) survey was used to characterize the megabenthic assemblages of the summits of two upper bathyal seamounts, Ulisse and Penelope (Ligurian Sea, north‐west Mediterranean Sea). The biogeographic implications of these findings and the possible environmental factors favouring the occurrence of these communities are discussed.
High densities of abandoned, lost, or otherwise discarded fishing gear (mainly longlines) and a reduction in the average size of the fragile and slow‐growing habitat‐forming gorgonian Callogorgia verticillata indicate the occurrence of high levels of anthropogenic impacts on the summit regions, which are fishing grounds for artisanal and recreational fishers.
The recovery of fishing data describing the first catches in the 1970s proved to be useful in inferring the short‐ and long‐term effects of fishing practices in these previously unexploited offshore areas. In particular, the local extinction of demersal top predators, subjected to exceptional catches nearly 50 years ago, highlights the slow recovery rate of such species.
Criteria defining vulnerability are discussed for the two study areas, and specific conservation actions, including the creation of regulated protected areas, are proposed.
Changes in histidine decarboxylase expression influence extramedullary hematopoiesis in postnatal mice
Authors: Otsuka Hirotada , Endo Yasuo , Ohtsu Hiroshi , Inoue Satoshi , Kuraoka Mutsuki , Koh Miki , Yagi Hideki , Nakamura Masanori , Soeta Satoshi 
Published: October 2020

AbstractHistidine decarboxylase (HDC), histamine synthase, is expressed in hematopoietic stem cells and in lineage‐committed progenitors in the bone marrow (BM). However, the role of histamine in hematopoiesis is not well described. To evaluate the role of histamine in hematopoiesis, we analyzed the changes in HDC expression at hematopoietic sites, the BM, spleen, and liver of 2‐, 3‐, and 6‐week‐old wild‐type mice. We also performed morphological analyses of the hematopoietic sites using HDC‐deficient (HDC‐KO) mice. In wild‐type adults, HDC expression in the BM was higher than that in the spleen and liver and showed an age‐dependent increase. Histological analysis showed no significant change in the adult BM and spleen of HDC‐KO mice compared to wild‐type mice. In the liver, HDC expression was temporarily increased at 3 weeks and decreased at 6 weeks of age. Morphological analysis of the liver revealed more numerous hematopoietic colonies and megakaryocytes in HDC‐KO mice compared to wild‐type mice at 2 and 3 weeks of age, whereas no changes were observed in adults. Most of these hematopoietic colonies consisted of B220‐positive B‐lymphocytes and TER119‐positive erythroblasts and were positive for the cell proliferation marker PCNA. Notably, these hematopoietic colonies declined in HDC‐KO mice upon N‐acetyl histamine treatment. A significant increase in the expression of hematopoiesis‐related cytokines, Il3, Il7, Epo, Gcsf, and Cxcl12 mRNA was observed in the liver of 3‐week‐old HDC‐KO mice compared to wild‐type mice. These results suggest that histamine‐deficiency may maintain an microenvironment suitable for hematopoiesis by regulating hematopoiesis‐related cytokine expression in the liver of postnatal mice.
MicroRNA‐34a‐5p Promotes Joint Destruction During Osteoarthritis
Authors: Endisha Helal , Datta Poulami , Sharma Anirudh , Nakamura Sayaka , Rossomacha Evgeny , Younan Carolen , Ali Shabana A. , Tavallaee Ghazaleh , Lively Starlee , Potla Pratibha , Shestopaloff Konstantin , Rockel Jason S. , Krawetz Roman , Mahomed Nizar N. , Jurisica Igor , Gandhi Rajiv , Kapoor Mohit 
Published: October 2020

ObjectiveMicroRNA‐34a‐5p (miR‐34a‐5p) expression is elevated in the synovial fluid of patients with late‐stage knee osteoarthritis (OA); however, its exact role and therapeutic potential in OA remain to be fully elucidated. This study was undertaken to examine the role of miR‐34a‐5p in OA pathogenesis.MethodsExpression of miR‐34a‐5p was determined in joint tissues and human plasma (n = 71). Experiments using miR‐34a‐5p mimic or antisense oligonucleotide (ASO) treatment were performed in human OA chondrocytes, fibroblast‐like synoviocytes (FLS) (n = 7–9), and mouse OA models, including destabilization of the medial meniscus (DMM; n = 22) and the accelerated, more severe model of mice fed a high‐fat diet and subjected to DMM (n = 11). Wild‐type (WT) mice (n = 9) and miR‐34a–knockout (KO) mice (n = 11) were subjected to DMM. Results were expressed as the mean ± SEM and analyzed by t‐test or analysis of variance, with appropriate post hoc tests. P values less than 0.05 were considered significant. RNA sequencing was performed on WT and KO mouse chondrocytes.ResultsExpression of miR‐34a‐5p was significantly increased in the plasma, cartilage, and synovium of patients with late‐stage OA and in the cartilage and synovium of mice subjected to DMM. Plasma miR‐34a‐5p expression was significantly increased in obese patients with late‐stage OA, and in the plasma and knee joints of mice fed a high‐fat diet. In human OA chondrocytes and FLS, miR‐34a‐5p mimic increased key OA pathology markers, while miR‐34a‐5p ASO improved cellular gene expression. Intraarticular miR‐34a‐5p mimic injection induced an OA‐like phenotype. Conversely, miR‐34a‐5p ASO injection imparted cartilage‐protective effects in the DMM and high‐fat diet/DMM models. The miR‐34a–KO mice exhibited protection against DMM‐induced cartilage damage. RNA sequencing of WT and KO chondrocytes revealed a putative miR‐34a‐5p signaling network.ConclusionOur findings provide comprehensive evidence of the role and therapeutic potential of miR‐34a‐5p in OA.
Activatable Off‐on Near‐Infrared QCy7‐based Fluorogenic Probes for Bioimaging
Authors: Chen Xueqian , Bian Yongning , Li Mingrui , Zhang Yong , Gao Xueyun , Su Dongdong 
Published: October 2020

AbstractThe activatable off‐on near‐infrared QCy7‐based fluorogenic probes have emerged as powerful modalities for detecting and monitoring biological analytes and understanding their biological processes in cells and organisms. The use of biomarker‐activated QCy7‐based probes enables simple synthesis, minimum photo‐damage to biological samples, and minimum background interference from biological systems. In this minireview, we aim to provide a rigorous but concise overview of activatable QCy7‐based fluorogenic probes by reporting the significant progress made in recent years. The design strategies and the main applications of accurate detection and imaging of disease‐related biomarkers (including ROS/RSS, enzymes, metal ions, and other related species) were reasonably analyzed and discussed. The potential challenges and prospects of activatable QCy7‐based fluorogenic probes are also emphasized to further advance the development of new methods for biomarker detection and bioimaging.
Continuous Multistep Encapsulation Process for the Generation of Multiple Emulsions
Authors: Luhede Laura , Besser Benjamin , Schumacher Daniel , Wilhelm Michaela , Fritsching Udo 
Published: October 2020

AbstractMultiple emulsions (ME) are of interest as carrier of active ingredients that can be released in a controlled way. ME are thermodynamically unstable with a strong tendency to coalesce or flocculate, resulting in a complex emulsion generation and stabilization process. Typical encapsulation procedures utilize individual batch operation steps for the ME production. In this work, a multistep membrane encapsulation process is proposed to allow the generation of ME in a continuous shear‐sensitive processing through different membrane stages. The stages combine the premix generation, followed by the internal phase production, and the final ME encapsulation step. For each step, a tailored membrane with different surface properties is used and combined into the continuous process.
Extraction of Oxidative Enzymes from Green Tea Leaves and Optimization of Extraction Conditions
Authors: Koohi Saleh , Nasernejad Bahram , Zare Masoud Habibi , Elahifard Maryam , Shirazian Saeed , Ghadiri Mahdi 
Published: October 2020

AbstractOxidative enzymes, polyphenol oxidase (PPO) and peroxidase (POD), were extracted from tea leaves and their activities were assessed. The Taguchi approach was used for the design, optimization, and statistical analysis of PPO and POD extraction. It was found that PPO and POD have the highest activity at an extraction temperature of 50 °C, at pH = 9 and 5 for PPO and POD, respectively, a buffer solution concentration of 0.05 M, a buffer solution/tea leaves ratio of 3, a contact time of 2 min, and in the presence of 6 % polyvinylpyrrolidone and 5 % Tween® 80. The highest activities were 0.380 and 0.022 U mL−1 for PPO and POD, respectively. Furthermore, PPO was completely inactivated after 30 min at 40 and 60 °C. In contrast, POD lost only 40 % of its activity after 30 min at 40 and 60 °C.
Single‐Electron Transfer Reactions Enabled by N‐Heterocyclic Carbene Organocatalysis
Authors: Li Qing‐Zhu , Zeng Rong , Han Bo , Li Jun‐Long 
Published: October 2020

AbstractOver the past decades, N‐heterocyclic carbene (NHC) organocatalysis has undergone a flourish of development on the basis of closed‐shell reaction paths. By contrast, the emerging area of single‐electron transfer (SET) reactions enabled by NHC catalysis still remain underdeveloped, but offer plenty of opportunities to develop new catalytic modes and useful synthetic methods. A number of interesting transformations were triggered by the SET process from the electron‐rich Breslow intermediates to various single‐electron acceptors. In additions, recent studies revealed that the Breslow radical cations could also be generated by single‐electron reduction of the electron‐deficient acyl azolium intermediates. These discoveries open a new avenue for NHC organocatalysis to harness radical reactions. The present review will focus on the exciting advancements in the dynamic area of radical NHC organocatalysis.
Numerical study of mixing of cavitating flows in a Venturi tube
Authors: Shi Hongbo , Liu Qingxia , Nikrityuk Petr 
Published: October 2020

AbstractThis work is devoted to a computational investigation of the cavitation and mixing characteristics of two miscible (Schmidt number Sc = 103) turbulent water flows with different viscosity ratios in a Venturi tube. The 2D axis‐symmetric RANS and 3D LES turbulence models are used for the prediction of flow characteristics. The numerical results reveal that the RANS solutions underpredict the rate of vapour production and overestimate the mixing rate of two miscible fluids in comparison to LES simulations for the inlet Reynolds number of 19 738 (Case‐1) and 19 286 (Case‐2). In particular, there is a larger cavitation zone in the Venturi tube with LES in comparison to RANS calculations.
Population Pharmacokinetic Analysis of BMS‐986166, a Novel Selective Sphingosine‐1‐Phosphate‐1 Receptor Modulator, and Exposure‐Response Assessment of Lymphocyte Counts and Heart Rate in Healthy Participants
Authors: Bihorel Sébastien , Singhal Shalabh , Shevell Diane , Sun Huadong , Xie Jenny , Basdeo Shenita , Liu Ang , Dutta Santanu , Ludwig Elizabeth , Huang Hannah , Lin Kuan‐ju , Fura Aberra , Throup John , Girgis Ihab G. 
Published: October 2020

AbstractSphingosine‐1‐phosphate (S1P) binding to the S1P‐1 receptor (S1P1R) controls the egress of lymphocytes from lymphoid organs and targets modulation of immune responses in autoimmune diseases. Pharmacologic modulation of S1P receptors has been linked to heart rate reduction. BMS‐986166, a prodrug of the active phosphorylated metabolite BMS‐986166‐P, presents an improved cardiac safety profile in preclinical studies compared to other S1P1R modulators. The pharmacokinetics, safety, and pharmacodynamics of BMS‐986166 versus placebo after single (0.75–5.0 mg) and repeated (0.25–1.5 mg/day) oral administration were assessed in healthy participants after a 1‐day lead‐in placebo period. A population model was developed to jointly describe BMS‐986166 and BMS‐986166‐P pharmacokinetics and predict individual exposures. Inhibitory sigmoid models described the relationships between average daily BMS‐986166‐P concentrations and nadir of time‐matched (day –1) placebo‐corrected heart rate on day 1 (nDDHR, where DD represents ∆∆) and nadir of absolute lymphocyte count (nALC). Predicted decreases in nDDHR and nALC were 9 bpm and 20% following placebo, with maximum decreases of 10 bpm in nDDHR due to drug effect, and approximately 80% in nALC due to drug and placebo. A 0.5‐mg/day dose regimen achieves the target 65% reduction in nALC associated with a 2‐bpm decrease in nDDHR over placebo.
Toward a multilevel scalable parallel Zielonka's algorithm for solving parity games
Authors: D'Amore Luisa , Murano Aniello , Sorrentino Loredana , Arcucci Rossella , Laccetti Giuliano 
Published: October 2020

SummaryIn this work, we perform the feasibility analysis of a multi‐grained parallel version of the Zielonka Recursive (ZR) algorithm exploiting the coarse‐ and fine‐ grained concurrency. Coarse‐grained parallelism relies on a suitable splitting of the problem, that is, a graph decomposition based on its Strongly Connected Components (SCC) or a splitting of the formula generating the game, while fine‐grained parallelism is introduced inside the Attractor which is the most intensive computational kernel. This configuration is new and addressed for the first time in this article. Innovation goes from the introduction of properly defined metrics for the strong and weak scaling of the algorithm. These metrics conduct to an analysis of the values of these metrics for the fine grained algorithm, we can infer the expected performance of the multi‐grained parallel algorithm running in a distributed and hybrid computing environment. Results confirm that while a fine‐grained parallelism have a clear performance limitation, the performance gain we can expect to get by employing a multilevel parallelism is significant.
Improved publicly verifiable auditing protocol for cloud storage
Authors: Zhang Jindan , Lin Chuan , Ogiela Urszula , Nedjah Nadia , Sangaiah Arun K. , Wang Xuan 
Published: October 2020

SummaryOutsourcing data to cloud servers is a popular service for data owners, however, how to check the integrity and freshness of the outsourced data is very challenge. Recently, Jin et al. proposed a cloud auditing protocol with full integrity and freshness support for cloud data, unfortunately in this article, we show their proposal is not secure. Concretely, the cloud servers can forge the authentication tag and thus has the ability to forge proof of data possession, which obviously invalidates their cloud auditing protocol. We also give a new cloud auditing protocol and analysis its security and performance. The results show our protocol is more efficient and secure.
Inferences of individual differences in response to tripterysium glycosides across patients with Rheumatoid arthritis using a novel ceRNA regulatory axis
Authors: Zhang Yanqiong , Wang Xiaoyue , Li Weijie , Wang Hailong , Yin Xiaoli , Jiang Funeng , Su Xiaohui , Chen Wenjia , Li Taixian , Mao Xia , Guo Minqun , Jiang Quan , Lin Na 
Published: October 2020

AbstractBackgroundTo identify biomarkers for guiding therapy and predicting clinical response of Tripterysium Glycosides Tablets (TGT) treatment is an urgent task due to individual differences in TGT response across rheumatoid arthritis (RA) patients. Competing endogenous RNA (ceRNA) regulatory system may influence drug response with involvement in diverse biological processes. Herein, we aimed to identify a TGT response‐related ceRNA axis.MethodsA TGT response‐related ceRNA axis was screened according to clinical cohort‐based RNA expression profiling, lncRNA‐mRNA coexpression, and ceRNA network analyses. Its clinical relevance was evaluated by computational modeling. Regulatory mechanisms of ceRNA axis were also experimentally investigated.ResultsThe ceRNA regulatory axis combined with lncRNA ENST00000494760, miR‐654‐5p, and C1QC was identified as a candidate biomarker for RA patients' response to TGT. Both ENST00000494760 and C1QC mRNA expression were significantly lower, while miR‐654‐5p expression was dramatically higher in TGT responders than nonresponders. Its clinical relevance was verified by computational modeling based on both independent clinical validation cohort and collagen‐induced arthritis (CIA) mice. Mechanistically, miR‐654‐5p directly bound to the 3′‐untranslated region of both ENST00000494760 and C1QC mRNA to inhibit their expression. Moreover, miR‐654‐5p suppressed C1QC mRNA expression, but ENST00000494760 bound to miR‐654‐5p and relieved its repression on C1QC mRNA, leading to RA aggressive progression and weak TGT response.ConclusionsLncRNA ENST00000494760 overexpression may sponge miR‐654‐5p to promote C1QC expression in RA patients. This novel ceRNA axis may serve as a biomarker for screening the responsive RA patients to TGT treatment, which will allow improved personalized healthcare.
Predictive ability of a process‐based versus a correlative species distribution model
Authors: Higgins Steven I. , Larcombe Matthew J. , Beeton Nicholas J. , Conradi Timo , Nottebrock Henning 
Published: October 2020

AbstractSpecies distribution modeling is a widely used tool in many branches of ecology and evolution. Evaluations of the transferability of species distribution models—their ability to predict the distribution of species in independent data domains—are, however, rare. In this study, we contrast the transferability of a process‐based and a correlative species distribution model. Our case study uses 664 Australian eucalypt and acacia species. We estimate models for these species using data from their native Australia and then assess whether these models can predict the adventive range of these species. We find that the correlative model—MaxEnt—has a superior ability to describe the data in the training data domain (Australia) and that the process‐based model—TTR‐SDM—has a superior ability to predict the distribution of the study species outside of Australia. The implication of this analysis, that process‐based models may be more appropriate than correlative models when making projections outside of the domain of the training data, needs to be tested in other case studies.
Epithelioid hemangioma of bone harboring FOS and FOSB gene rearrangements: A clinicopathologic and molecular study
Authors: Tsuda Yusuke , Suurmeijer Albert J. H. , Sung Yun‐Shao , Zhang Lei , Healey John H. , Antonescu Cristina R. 
Published: October 2020

AbstractThe diagnosis of epithelioid hemangioma (EH) remains challenging due to its rarity, worrisome histologic features, and locally aggressive clinical and radiographic presentation. Especially in the bone, EH can be misdiagnosed as a malignant vascular neoplasm due its lytic, often destructive or multifocal growth, as well as atypical morphology. The discovery of recurrent FOS and FOSB gene fusions in the pathogenesis of most EH has strengthened its stand‐alone classification, distinct from other malignant epithelioid vascular lesions, such as epithelioid hemangioendothelioma or angiosarcoma. In this study we investigate a group of molecularly confirmed skeletal EH by the presence of FOS or FOSB gene rearrangements to better define its clinical and pathologic characteristics within a homogenous molecular subset. The cohort included 38 patients (25 males, 13 females), with a mean age at diagnosis of 38 years (range, 4‐75). Regional, multifocal presentation was noted in 10 cases. Only six cases were correctly recognized as EH by the referring institutions, while most were misdiagnosed as other vascular tumors. Of the 17 patients with follow‐up data available, five patients (29%) developed local recurrence after marginal en bloc excision (n = 3) or curettage (n = 2). Local recurrence‐free survival rates were 84% at 3 years and 38% at 5 years. No metastasis or disease‐related death was identified. Imaging studies exhibited no specific features, showing cortical bone destruction and soft‐tissue extension in 14 (38%) cases. FOS gene rearrangements were detected in 28 (74%) of cases, while FOSB rearrangements in 10 (26%) cases. Our results highlight the significant challenges encountered in establishing a correct diagnosis exclusive of the molecular testing, mainly due to its overlap to other malignant epithelioid vascular tumors. Skeletal EH emerges as a genetically defined locally aggressive vascular neoplasm, with a high rate of local recurrence, but lacking the propensity for distant spread.