bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescently labeled circular DNA molecules for DNA topology and topoisomerases
Authors: Gu Maxwell , Berrido Andrea , Gonzalez Walter G. , Miksovska Jaroslava , Chambers Jeremy W. , Leng Fenfei 
Published: October 2016

AbstractDNA topology plays essential roles in several fundamental biological processes, such as DNA replication, recombination, and transcription. Typically agarose gel electrophoresis is employed to study DNA topology. Since gel electrophoresis is time-consuming and labor intensive, it is desirable to develop other methods, such as fluorescence-based methods, for such studies. In this paper we report the synthesis of a type of unique fluorescence-labeled DNA molecules that can be used to study DNA topology and topoisomerases by fluorescence resonance energy transfer (FRET). Specifically, we inserted an 82 nt. synthetic DNA oligomer FL905 carrying a 42 nt. AT sequence with fluorescein and dabcyl labels into a gapped DNA molecule to generate relaxed and supercoiled pAB1_FL905. Since the fluorescence intensity of pAB1_FL905 is dependent on its supercoiling status, pAB1_FL905 is a powerful tool to study DNA topology and topoisomerases by FRET. pAB1_FL905 can also be developed into rapid and efficient high-throughput screening assays to identify inhibitors that target various DNA topoisomerases.
Orexin signaling regulates both the hippocampal clock and the circadian oscillation of Alzheimer’s disease-risk genes
Authors: Ma Zhixiong , Jiang Weiliang , Zhang Eric Erquan 
Published: October 2016

AbstractAlzheimer’s disease (AD) is a circadian clock-related disease. However, it is not very clear whether pre-symptomatic AD leads to circadian disruption or whether malfunction of circadian rhythms exerts influence on development of AD. Here, we report a functional clock that exists in the hippocampus. This oscillator both receives input signals and maintains the cycling of the hippocampalPer2gene. One of the potential inputs to the oscillator is orexin signaling, which can shorten the hippocampal clock period and thereby regulate the expression of clock-controlled-genes (CCGs). A 24-h time course qPCR analysis followed by a JTK_CYCLE algorithm analysis indicated that a number of AD-risk genes are potential CCGs in the hippocampus. Specifically, we found thatBace1andBace2, which are related to the production of the amyloid-beta peptide, are CCGs.BACE1is inhibited byE4BP4, a repressor of D-box genes, whileBACE2is activated by CLOCK:BMAL1. Finally, we observed alterations in the rhythmic expression patterns ofBace2andApoEin the hippocampus of agedAPP/PS1dE9mice. Our results therefore indicate that there is a circadian oscillator in the hippocampus whose oscillation could be regulated by orexins. Hence, orexin signaling regulates both the hippocampal clock and the circadian oscillation of AD-risk genes.
Targeting Non-classical Myelin Epitopes to Treat Experimental Autoimmune Encephalomyelitis
Authors: Wang Xiaohua , Zhang Jintao , Baylink David J. , Li Chih-Huang , Watts Douglas M. , Xu Yi , Qin Xuezhong , Walter Michael H. , Tang Xiaolei 
Published: October 2016

AbstractQa-1 epitopes, the peptides that bind to non-classical major histocompatibility complex Ib Qa-1 molecules and are recognized by Qa-1-restricted CD8+ regulatory T (Treg) cells, have been identified in pathogenic autoimmune cells that attack myelin sheath in experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis [MS]). Additionally, immunization with such epitopes ameliorates the EAE. However, identification of such epitopes requires knowledge of the pathogenic autoimmune cells which are largely unknown in MS patients. Hence, we asked whether the CD8+ Treg cells could directly target the myelin sheath to ameliorate EAE. To address this question, we analyzed Qa-1 epitopes in myelin oligodendrocyte glycoprotein (MOG that is a protein in myelin sheath). Here, we report identification of a MOG-specific Qa-1 epitope. Immunization with this epitope suppressed ongoing EAE, which was abrogated by CD8+ T cell depletion. Additionally, the epitope immunization activated the epitope-specific CD8+ T cells which specifically accumulated in the CNS-draining cervical lymph nodes. Finally, CD8+ T cells primed by the epitope immunization transferred EAE suppression. Hence, this study reveals a novel regulatory mechanism mediated by the CD8+ Treg cells. We propose that immunization with myelin-specific HLA-E epitopes (human homologues of Qa-1 epitopes) is a promising therapy for MS.
High-resolution MALDI mass spectrometry imaging of gallotannins and monoterpene glucosides in the root of Paeonia lactiflora
Authors: Li Bin , Bhandari Dhaka Ram , Römpp Andreas , Spengler Bernhard 
Published: October 2016

AbstractHigh-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) at 10 μm pixel size was performed to unravel the spatio-chemical distribution of major secondary metabolites in the root of Paeonia lactiflora. The spatial distributions of two major classes of bioactive components, gallotannins and monoterpene glucosides, were investigated and visualized at the cellular level in tissue sections of P. lactiflora roots. Accordingly, other primary and secondary metabolites were imaged, including amino acids, carbohydrates, lipids and monoterpenes, indicating the capability of untargeted localization of metabolites by using high-resolution MSI platform. The employed AP-SMALDI MSI system provides significant technological advancement in the visualization of individual molecular species at the cellular level. In contrast to previous histochemical studies of tannins using unspecific staining reagents, individual gallotannin species were accurately localized and unequivocally discriminated from other phenolic components in the root tissues. High-quality ion images were obtained, providing significant clues for understanding the biosynthetic pathway of gallotannins and monoterpene glucosides and possibly helping to decipher the role of tannins in xylem cells differentiation and in the defence mechanisms of plants, as well as to investigate the interrelationship between tannins and lignins.
Development and characterization of a microfluidic model of the tumour microenvironment
Authors: Ayuso Jose M. , Virumbrales-Muñoz María , Lacueva Alodia , Lanuza Pilar M. , Checa-Chavarria Elisa , Botella Pablo , Fernández Eduardo , Doblare Manuel , Allison Simon J. , Phillips Roger M. , Pardo Julián , Fernandez Luis J. , Ochoa Ignacio 
Published: October 2016

AbstractThe physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live ‘window’ into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device’s potential to enable more physiological in vitro drug screening.
Lymphadenectomy and risk of reoperation or mortality shortly after surgery for oesophageal cancer
Authors: Lagergren Jesper , Mattsson Fredrik , Davies Andrew , Lindblad Mats , Lagergren Pernilla 
Published: October 2016

AbstractThe prognostic role of lymphadenectomy during surgery for oesophageal cancer is questioned. We aimed to test whether higher lymph node harvest increases the risk of early postoperative reoperation or mortality. A population-based cohort study including almost all patients who underwent resection for oesophageal cancer in Sweden in 1987–2010. Data were collected from medical records and well-established nationwide Swedish registries. The exposures were number of removed lymph nodes (primary) and number of node metastases (secondary). The main study outcome was reoperation/mortality within 30 days of primary surgery. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated using Poisson regression, adjusted for age, sex, co-morbidity, neoadjuvant therapy, tumour stage, tumour histology, surgeon volume, and calendar period. Among 1,820 participants, the risk of reoperation/mortality did not increase with greater lymph node harvest (RR = 0.98, 95%CI 0.96–1.00, discrete variable) or with greater number of removed metastatic nodes (RR = 1.00, 95% CI 0.95–1.05, discrete variable). Similarly, in stratified analyses within pre-defined categories of tumor stage, surgeon volume and calendar period, increased number of removed nodes or node metastases did not increase the risk of reoperation/mortality. Lymphadenectomy during oesophageal cancer surgery is a safe procedure in the short term perspective.
Prognostic significance of miR-1268a expression and its beneficial effects for post-operative adjuvant transarterial chemoembolization in hepatocellular carcinoma
Authors: Lu Yun-Long , Yao Jin-Guang , Huang Xiao-Ying , Wang Chao , Wu Xue-Min , Xia Qiang , Long Xi-Dai 
Published: October 2016

AbstractOur recent investigation has shown that the variables of microRNA-1268a may involve in hepatocellular carcinoma (HCC) tumorigenesis. Here, we attempted to identify the prognostic significance of microRNA-1268a expression in tumor tissues by a retrospective analysis in 411 patients with HCC, and analyze its effects on post-operative adjuvant transarterial chemoembolization (TACE) improving HCC prognosis. All cases received tumor resection or tumor resection plus post-operative adjuvant TACE as an initial treatment. Logistical regression analysis exhibited that microRNA-1268a expression was significantly correlated with tumor stage, tumor grade, tumor size, and microvessel density. Cox regression analysis showed that microRNA-1268a expression was an independent prognostic factor for HCC, and TACE treatment had no effects on prognosis of HCC patients with high microRNA-1268a expression. More intriguingly, TACE improved the prognosis of HCC patients with low microRNA-1268a expression. Functionally, overexpression of microRNA-1268a inhibited while its inhibitor enhanced doxorubicin-induced the death of cancer cells. These results suggest that microRNA-1268a may be an independent prognostic factor for HCC patients, and that decreasing microRNA-1268a expression may be beneficial for post-operative adjuvant TACE treatment in HCC.
A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma
Authors: Radhakrishnan Aneesha , Nanjappa Vishalakshi , Raja Remya , Sathe Gajanan , Puttamallesh Vinuth N. , Jain Ankit P. , Pinto Sneha M. , Balaji Sai A. , Chavan Sandip , Sahasrabuddhe Nandini A. , Mathur Premendu P. , Kumar Mahesh M. , Prasad T. S. Keshava , Santosh Vani , Sukumar Geethanjali , Califano Joseph A. , Rangarajan Annapoorni , Sidransky David , Pandey Akhilesh , Gowda Harsha , Chatterjee Aditi 
Published: October 2016

AbstractDespite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC.
Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy
Authors: Tang Chun-Mei , Liu Fang-zhou , Zhu Jie-Ning , Fu Yong-Heng , Lin Qiu-Xiong , Deng Chun-Yu , Hu Zhi-Qin , Yang Hui , Zheng Xi-Long , Cheng Jian-Ding , Wu Shu-Lin , Shan Zhi-Xin 
Published: October 2016

AbstractThe role of microRNA-214-3p (miR-214-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. In mice with either Ang-II infusion or transverse aortic constriction (TAC) model, miR-214-3p expression was markedly decreased in the hypertrophic myocardium. Down-regulation of miR-214-3p was observed in the myocardium of patients with cardiac hypertrophy. Expression of miR-214-3p was upregulated in Ang-II-induced hypertrophic neonatal mouse ventricular cardiomyocytes. Cardiac hypertrophy was attenuated in Ang-II-infused mice by tail vein injection of miR-214-3p. Moreover, miR-214-3p inhibited the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC) in Ang-II-treated mouse cardiomyocytesin vitro. Myocyte-specific enhancer factor 2C (MEF2C), which was increased in Ang-II-induced hypertrophic mouse myocardium and cardiomyocytes, was identified as a target gene of miR-214-3p. Functionally, miR-214-3p mimic, consistent with MEF2C siRNA, inhibited cell size increase and protein expression of ANP and β-MHC in Ang-II-treated mouse cardiomyocytes. The NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in cardiomyocytes. Taken together, our results revealed that MEF2C is a novel target of miR-214-3p, and attenuation of miR-214-3p expression may contribute to MEF2Cexpressionin cardiac hypertrophy.
Cerebellar theta burst stimulation modulates the neural activity of interconnected parietal and motor areas
Authors: Casula Elias Paolo , Pellicciari Maria Concetta , Ponzo Viviana , Stampanoni Bassi Mario , Veniero Domenica , Caltagirone Carlo , Koch Giacomo 
Published: October 2016

AbstractVoluntary movement control and execution are regulated by the influence of the cerebellar output over different interconnected cortical areas, through dentato-thalamo connections. In the present study we applied transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to directly assess the effects of cerebellar theta-burst stimulation (TBS) over the controlateral primary motor cortex (M1) and posterior parietal cortex (PPC) in a group of healthy volunteers. We found a TBS-dependent bidirectional modulation over TMS-evoked activity; specifically, cTBS increased whereas iTBS decreased activity between 100 and 200 ms after TMS, in a similar manner over both M1 and PPC areas. On the oscillatory domain, TBS induced specific changes over M1 natural frequencies of oscillation: TMS-evoked alpha activity was decreased by cTBS whereas beta activity was enhanced by iTBS. No effects were observed after sham stimulation. Our data provide novel evidence showing that the cerebellum exerts its control on the cortex likely by impinging on specific set of interneurons dependent on GABA-ergic activity. We show that cerebellar TBS modulates cortical excitability of distant interconnected cortical areas by acting through common temporal, spatial and frequency domains.
Glycosylation changes in the globular head of H3N2 influenza hemagglutinin modulate
receptor binding without affecting virus virulence
Authors: Alymova Irina V. , York Ian A. , Air Gillian M. , Cipollo John F. , Gulati Shelly , Baranovich Tatiana , Kumar Amrita , Zeng Hui , Gansebom Shane , McCullers Jonathan A. 
Published: October 2016

AbstractSince the emergence of human H3N2 influenza A viruses in the pandemic of 1968, these
viruses have become established as strains of moderate severity. A decline in
virulence has been accompanied by glycan accumulation on the hemagglutinin globular
head, and hemagglutinin receptor binding has changed from recognition of a broad
spectrum of glycan receptors to a narrower spectrum. The relationship between
increased glycosylation, binding changes, and reduction in H3N2 virulence is not
clear. We evaluated the effect of hemagglutinin glycosylation on receptor binding
and virulence of engineered H3N2 viruses. We demonstrate that low-binding virus is
as virulent as higher binding counterparts, suggesting that H3N2 infection does not
require either recognition of a wide variety of, or high avidity binding to,
receptors. Among the few glycans recognized with low-binding virus, there were two
structures that were bound by the vast majority of H3N2 viruses isolated between
1968 and 2012. We suggest that these two structures support physiologically relevant
binding of H3N2 hemagglutinin and that this physiologically relevant binding has not
changed since the 1968 pandemic. Therefore binding changes did not contribute to
reduced severity of seasonal H3N2 viruses. This work will help direct the search for
factors enhancing influenza virulence.
Abrupt onset of tongue deformation and phase space response of ions in magnetically-confined plasmas
Authors: Ida K. , Kobayashi T. , Itoh K. , Yoshinuma M. , Tokuzawa T. , Akiyama T. , Moon C. , Tsuchiya H. , Inagaki S. , Itoh S.-I. 
Published: October 2016

AbstractAn abrupt onset of the new tongue-shaped deformation of magnetic surface in magnetized plasmas, which was conjectured in since the 1960s but has not been observed, is experimentally identified just before an abrupt onset of a large-scale collapse event. Two novel properties of the event are identified. First, the transition of symmetry of perturbation (rather than a growth of linearly unstable MHD modes) was found to be a key for the onset of abrupt collapse, i.e., the transition of symmetry gives a new route to the collapse from stable state. Second, as a phase-space response of ions, the distortion from Maxwell-Boltzmann distribution of epithermal ions was observed for the first time.
The Association between Impaired Glucose Regulation and Prognosis of Chinese Patients with Intracerebral Hemorrhage
Authors: Sun Shichao , Pan Yuesong , Zhao Xingquan , Liu Liping , Li Hao , He Yan , Guo Li , Wang Yilong , Wang Yongjun 
Published: October 2016

AbstractThis study aimed at observing the influence of impaired glucose regulation (IGR) on 1-year outcomes in patients with intracerebral hemorrhage (ICH). Patients hospitalized for ICH from 2008 to 2009 were recruited consecutively at 35 centres across China. A standard oral glucose tolerance test at day 14 ± 3 after stroke onset or before discharge was performed to identify IGR. The outcomes were death (modified Rankin scale [mRS] score of 6), dependency (mRS score of 2 to 5) and poor outcome (mRS score of 2 to 6) at 1 year. Cox proportion hazard model for death and logistic regression model for dependency and poor outcome were performed to investigate the influence of IGR on 1-year outcomes. A total of 288 non-diabetic ICH patients were included in this analysis, among which 150 (52.1%) were IGR. IGR was associated with 1-year dependency (adjusted odds ratio [OR] 2.18, 95% confidence interval [CI], 1.19–3.99; P = 0.01) and poor outcome (adjusted OR 2.17; 95% CI, 1.24–3.80; P = 0.007) of patients with ICH. However, IGR showed no significant association with 1-year death (adjusted hazard ratio 1.49, 95% CI, 0.60–3.67; P = 0.39). IGR was independently associated with 1-year poor outcome of ICH in Chinese patients, with more important influence on dependency than death.
Strontium inhibits titanium particle-induced osteoclast activation and chronic inflammation via suppression of NF-κB pathway
Authors: Zhu Shijun , Hu Xuanyang , Tao Yunxia , Ping Zichuan , Wang Liangliang , Shi Jiawei , Wu Xiexing , Zhang Wen , Yang Huilin , Nie Zhikui , Xu Yaozeng , Wang Zhirong , Geng Dechun 
Published: October 2016

AbstractWear-particle-induced chronic inflammation and osteoclastogenesis have been identified as critical factors of aseptic loosening. Although strontium is known to be involved in osteoclast differentiation, its effect on particle-induced inflammatory osteolysis remains unclear. In this study, we investigate the potential impact and underling mechanism of strontium on particle-induced osteoclast activation and chronic inflammation in vivo and in vitro. As expected, strontium significantly inhibited titanium particle-induced inflammatory infiltration and prevented bone loss in a murine calvarial osteolysis model. Interestingly, the number of mature osteoclasts decreased after treatment with strontium in vivo, suggesting osteoclast formation might be inhibited by strontium. Additionally, low receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor-α, interleukin-1β, interleukin-6 and p65 immunochemistry staining were observed in strontium-treatment groups. In vitro, strontium obviously decreased osteoclast formation, osteoclastogenesis-related gene expression, osteoclastic bone resorption and pro-inflammatory cytokine expression in bone-marrow-derived macrophages in a dose-dependent manner. Furthermore, we demonstrated that strontium impaired osteoclastogenesis by blocking RANKL-induced activation of NF-κB pathway. In conclusion, our study demonstrated that strontium can significantly inhibit particle-induced osteoclast activation and inflammatory bone loss by disturbing the NF-κB pathway, and is an effective therapeutic agent for the treatment of wear particle-induced aseptic loosening.