bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between antipsychotic/antidepressant drug treatments and hospital admissions in schizophrenia assessed using a mental health case register
Authors: Cardinal Rudolf N , Savulich George , Mann Louisa M , Fernández-Egea Emilio 
Published: October 2015

AbstractBackground:The impact of psychotropic drug choice upon admissions for schizophrenia is not well understood.Aims:To examine the association between antipsychotic/antidepressant use and time in hospital for patients with schizophrenia.Methods:We conducted an observational study, using 8 years’ admission records and electronically generated drug histories from an institution providing secondary mental health care in Cambridgeshire, UK, covering the period 2005–2012 inclusive. Patients with a coded ICD-10 diagnosis of schizophrenia were selected. The primary outcome measure was the time spent as an inpatient in a psychiatric unit. Antipsychotic and antidepressant drugs used by at least 5% of patients overall were examined for associations with admissions. Periods before and after drug commencement were compared for patients having pre-drug admissions, in mirror-image analyses correcting for overall admission rates. Drug use in one 6-month calendar period was used to predict admissions in the next period, across all patients, in a regression analysis accounting for the effects of all other drugs studied and for time.Results:In mirror-image analyses, sulpiride, aripiprazole, clozapine, and olanzapine were associated with fewer subsequent admission days. In regression analyses, sulpiride, mirtazapine, venlafaxine, and clozapine–aripiprazole and clozapine–amisulpride combinations were associated with fewer subsequent admission days.Conclusions:Use of these drugs was associated with fewer days in hospital. Causation is not implied and these findings require confirmation by randomized controlled trials.
Selector function of MHC I molecules is determined by protein plasticity
Authors: Bailey Alistair , Dalchau Neil , Carter Rachel , Emmott Stephen , Phillips Andrew , Werner Jörn M. , Elliott Tim 
Published: October 2015

AbstractThe selection of peptides for presentation at the surface of most nucleated cells by major histocompatibility complex class I molecules (MHC I) is crucial to the immune response in vertebrates. However, the mechanisms of the rapid selection of high affinity peptides by MHC I from amongst thousands of mostly low affinity peptides are not well understood. We developed computational systems models encoding distinct mechanistic hypotheses for two molecules, HLA-B*44:02 (B*4402) and HLA-B*44:05 (B*4405), which differ by a single residue yet lie at opposite ends of the spectrum in their intrinsic ability to select high affinity peptides. We used in vivo biochemical data to infer that a conformational intermediate of MHC I is significant for peptide selection. We used molecular dynamics simulations to show that peptide selector function correlates with protein plasticity and confirmed this experimentally by altering the plasticity of MHC I with a single point mutation, which altered in vivo selector function in a predictable way. Finally, we investigated the mechanisms by which the co-factor tapasin influences MHC I plasticity. We propose that tapasin modulates MHC I plasticity by dynamically coupling the peptide binding region and α3 domain of MHC I allosterically, resulting in enhanced peptide selector function.
The non-octarepeat copper binding site of the prion protein is a key regulator of prion conversion
Authors: Giachin Gabriele , Mai Phuong Thao , Tran Thanh Hoa , Salzano Giulia , Benetti Federico , Migliorati Valentina , Arcovito Alessandro , Longa Stefano Della , Mancini Giordano , D’Angelo Paola , Legname Giuseppe 
Published: October 2015

AbstractThe conversion of the prion protein (PrPC) into prions plays a key role in transmissible spongiform encephalopathies. Despite the importance for pathogenesis, the mechanism of prion formation has escaped detailed characterization due to the insoluble nature of prions. PrPC interacts with copper through octarepeat and non-octarepeat binding sites. Copper coordination to the non-octarepeat region has garnered interest due to the possibility that this interaction may impact prion conversion. We used X-ray absorption spectroscopy to study copper coordination at pH 5.5 and 7.0 in human PrPC constructs, either wild-type (WT) or carrying pathological mutations. We show that mutations and pH cause modifications of copper coordination in the non-octarepeat region. In the WT at pH 5.5, copper is anchored to His96 and His111, while at pH 7 it is coordinated by His111. Pathological point mutations alter the copper coordination at acidic conditions where the metal is anchored to His111. By using in vitro approaches, cell-based and computational techniques, we propose a model whereby PrPC coordinating copper with one His in the non-octarepeat region converts to prions at acidic condition. Thus, the non-octarepeat region may act as the long-sought-after prion switch, critical for disease onset and propagation.
Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice
Authors: Shih Yao-Ming , Sun Cheng-Pu , Chou Hui-Hsien , Wu Tzu-Hui , Chen Chun-Chi , Wu Ping-Yi , Enya Chen Yu-Chen , Bissig Karl-Dimiter , Tao Mi-Hua 
Published: October 2015

AbstractSelection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the “PICKY” software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients.
Pretreatment with β-Boswellic Acid Improves Blood Stasis Induced Endothelial Dysfunction: Role of eNOS Activation
Authors: Wang Mingming , Chen Minchun , Ding Yi , Zhu Zhihui , Zhang Yikai , Wei Peifeng , Wang Jingwen , Qiao Yi , Li Liang , Li Yuwen , Wen Aidong 
Published: October 2015

AbstractVascular endothelial cells play an important role in modulating anti-thrombus and maintaining the natural function of vascular by secreting many active substances. β-boswellic acid (β-BA) is an active triterpenoid compound from the extract of boswellia serrate. In this study, it is demonstrated that β-BA ameliorates plasma coagulation parameters, protects endothelium from blood stasis induced injury and prevents blood stasis induced impairment of endothelium-dependent vasodilatation. Moreover, it is found that β-BA significantly increases nitric oxide (NO) and cyclic guanosine 3’, 5’-monophosphate (cGMP) levels in carotid aortas of blood stasis rats. To stimulate blood stasis-like conditions in vitro, human umbilical vein endothelial cells (HUVECs) were exposed to transient oxygen and glucose deprivation (OGD). Treatment of β-BA significantly increased intracellular NO level. Western blot and immunofluorescence as well as immunohistochemistry reveal that β-BA increases phosphorylation of enzyme nitric oxide synthase (eNOS) at Ser1177. In addition, β-BA mediated endothelium-dependent vasodilatation can be markedly blocked by eNOS inhibitor L-NAME in blood stasis rats. In OGD treated HUEVCs, the protective effect of β-BA is attenuated by knockdown of eNOS. In conclusion, the above findings provide convincing evidence for the protective effects of β-BA on blood stasis induced endothelial dysfunction by eNOS signaling pathway.
The N-cadherin cytoplasmic domain confers anchorage-independent growth and the loss of contact inhibition
Authors: Ozawa Masayuki 
Published: October 2015

AbstractTumor growth is characterized by anchorage independence and the loss of contact inhibition. Previously, we showed that either a red fluorescent protein (DsRed)-tagged N-cadherin or E-cadherin cytoplasmic domain (DNCT or DECT) could function as a dominant negative inhibitor by blocking the cell surface localization of endogenous E-cadherin and inducing cell dissociation. Here, we show that expression of DNCT abrogated contact inhibition of proliferation and conferred anchorage-independent growth. DNCT expression induced the relocation of the tumor suppressor Merlin from the cell surface to intracellular compartments. Although DNCT expression induced redistribution of TAZ from the cytoplasm to the nucleus, YAP/TAZ signaling was not activated. An E-cadherin–α-catenin chimera that functions as a β-catenin–independent cell adhesion molecule restored contact inhibition and anchorage-dependency of growth. Addition of the SV40 large T antigen nuclear localization signal reversed the effects of DNCT expression, indicating that DNCT functioned outside of the nucleus.
Pathophysiological analyses of cortical malformation using gyrencephalic mammals
Authors: Masuda Kosuke , Toda Tomohisa , Shinmyo Yohei , Ebisu Haruka , Hoshiba Yoshio , Wakimoto Mayu , Ichikawa Yoshie , Kawasaki Hiroshi 
Published: October 2015

AbstractOne of the most prominent features of the cerebral cortex of higher mammals is the presence of gyri. Because malformations of the cortical gyri are associated with severe disability in brain function, the mechanisms underlying malformations of the cortical gyri have been of great interest. Combining gyrencephalic carnivore ferrets and genetic manipulations using in utero electroporation, here we successfully recapitulated the cortical phenotypes of thanatophoric dysplasia (TD) by expressing fibroblast growth factor 8 in the ferret cerebral cortex. Strikingly, in contrast to TD mice, our TD ferret model showed not only megalencephaly but also polymicrogyria. We further uncovered that outer radial glial cells (oRGs) and intermediate progenitor cells (IPs) were markedly increased. Because it has been proposed that increased oRGs and/or IPs resulted in the appearance of cortical gyri during evolution, it seemed possible that increased oRGs and IPs underlie the pathogenesis of polymicrogyria. Our findings should help shed light on the molecular mechanisms underlying the formation and malformation of cortical gyri in higher mammals.
Interactive Volumetry Of Liver Ablation Zones
Authors: Egger Jan , Busse Harald , Brandmaier Philipp , Seider Daniel , Gawlitza Matthias , Strocka Steffen , Voglreiter Philip , Dokter Mark , Hofmann Michael , Kainz Bernhard , Hann Alexander , Chen Xiaojun , Alhonnoro Tuomas , Pollari Mika , Schmalstieg Dieter , Moche Michael 
Published: October 2015

AbstractPercutaneous radiofrequency ablation (RFA) is a minimally invasive technique that destroys cancer cells by heat. The heat results from focusing energy in the radiofrequency spectrum through a needle. Amongst others, this can enable the treatment of patients who are not eligible for an open surgery. However, the possibility of recurrent liver cancer due to incomplete ablation of the tumor makes post-interventional monitoring via regular follow-up scans mandatory. These scans have to be carefully inspected for any conspicuousness. Within this study, the RF ablation zones from twelve post-interventional CT acquisitions have been segmented semi-automatically to support the visual inspection. An interactive, graph-based contouring approach, which prefers spherically shaped regions, has been applied. For the quantitative and qualitative analysis of the algorithm’s results, manual slice-by-slice segmentations produced by clinical experts have been used as the gold standard (which have also been compared among each other). As evaluation metric for the statistical validation, the Dice Similarity Coefficient (DSC) has been calculated. The results show that the proposed tool provides lesion segmentation with sufficient accuracy much faster than manual segmentation. The visual feedback and interactivity make the proposed tool well suitable for the clinical workflow.
High variability of genomic instability and gene expression profiling in different HeLa clones
Authors: Frattini Annalisa , Fabbri Marco , Valli Roberto , De Paoli Elena , Montalbano Giuseppe , Gribaldo Laura , Pasquali Francesco , Maserati Emanuela 
Published: October 2015

AbstractThe HeLa cell line is one of the most popular cell lines in biomedical research, despite its well-known chromosomal instability. We compared the genomic and transcriptomic profiles of 4 different HeLa batches and showed that the gain and loss of genomic material varies widely between batches, drastically affecting basal gene expression. Moreover, different pathways were activated in response to a hypoxic stimulus. Our study emphasizes the large genomic and transcriptomic variability among different batches, to the point that the same experiment performed with different batches can lead to distinct conclusions and irreproducible results. The HeLa cell line is thought to be a unique cell line but it is clear that substantial differences between the primary tumour and the human genome exist and that an indeterminate number of HeLa cell lines may exist, each with a unique genomic profile.
Caerulomycin A inhibits Th2 cell activity: a possible role in the management of asthma
Authors: Kujur Weshely , Gurram Rama Krishna , Haleem Nazia , Maurya Sudeep K. , Agrewala Javed N. 
Published: October 2015

AbstractWe have recently demonstrated that Caerulomycin A induces regulatory T cells differentiation by suppressing Th1 cells activity. The role of regulatory T cells is well established in suppressing the function of Th2 cells. Th2 cells are known to inflict the induction of the activation of asthma. Consequently, in the present study, we monitored the influence of Caerulomycin A in inhibiting the activity of Th2 cells and its impact in recuperating asthma symptoms. Interestingly, we observed that Caerulomycin A significantly suppressed the differentiation of Th2 cells, as evidenced by downregulation in the GATA-3 expression. Further, decline in the levels of IL-4, IL-5 and IL-13 cytokines and IgE was noted in the animals suffering from asthma. Furthermore, we noticed substantial suppression in the inflammatory response and number of eosinophils in the lungs. In essence, this study signifies an important therapeutic role of Caerulomycin A in asthma.
How to Regenerate and Protect Desert Riparian Populus euphratica Forest in Arid Areas
Authors: Ling Hongbo , Zhang Pei , Xu Hailiang , Zhao Xinfeng 
Published: October 2015

AbstractWe found that the most suitable flooding disturbance model for regenerating Populus euphratica forest was two to three times per year with a duration of 15–20 days and an intensity of 25–30 m3/s. The flooding should take place during the seed emergence to young tree growth stages and should be based on flooding experiments and data from vegetation quadrats and ecological water conveyance. Furthermore, we found that tree-ring width index for P. euphratica declined as the groundwater depth increased and ascertained that the minimum groundwater depths for young trees, near-mature trees, mature trees and over-mature trees were 4.0 m, 5.0–5.4 m, 6.9 m and 7.8 m, respectively. These were derived from a quantitative relationship model between groundwater depth and tree-ring width index. The range for ecological water conveyance volume was 311–320 million m3 in the lower reaches of the Tarim River. This study not only provides a technical basis for sustainable ecological water conveyance in the Tarim River Basin, but also offers a theoretical guide and scientific information that could be used in similar areas to regenerate and protect Populus euphratica around the world.
Endogenous vs Exogenous Allosteric Modulators in GPCRs: A dispute for shuttling CB1 among different membrane microenvironments
Authors: Stornaiuolo Mariano , Bruno Agostino , Botta Lorenzo , Regina Giuseppe La , Cosconati Sandro , Silvestri Romano , Marinelli Luciana , Novellino Ettore 
Published: October 2015

AbstractA Cannabinoid Receptor 1 (CB1) binding site for the selective allosteric modulator ORG27569 is here identified through an integrate approach of consensus pocket prediction, mutagenesis studies and Mass Spectrometry. This unprecedented ORG27569 pocket presents the structural features of a Cholesterol Consensus Motif, a cholesterol interacting region already found in other GPCRs. ORG27569 and cholesterol affects oppositely CB1 affinity for orthosteric ligands. Moreover, the rise in cholesterol intracellular level results in CB1 trafficking to the axonal region of neuronal cells, while, on the contrary, ORG27568 binding induces CB1 enrichment at the soma. This control of receptor migration among functionally different membrane regions of the cell further contributes to downstream signalling and adds a previously unknown mechanism underpinning CB1 modulation by ORG27569 , that goes beyond a mere control of receptor affinity for orthosteric ligands.
Quantum Rabi Model with Trapped Ions
Authors: Pedernales J. S. , Lizuain I. , Felicetti S. , Romero G. , Lamata L. , Solano E. 
Published: October 2015

AbstractWe propose the quantum simulation of the quantum Rabi model in all parameter regimes by means of detuned bichromatic sideband excitations of a single trapped ion. We show that current setups can reproduce, in particular, the ultrastrong and deep strong coupling regimes of such a paradigmatic light-matter interaction. Furthermore, associated with these extreme dipolar regimes, we study the controlled generation and detection of their entangled ground states by means of adiabatic methods. Ion traps have arguably performed the first quantum simulation of the Jaynes-Cummings model, a restricted regime of the quantum Rabi model where the rotating-wave approximation holds. We show that one can go beyond and experimentally investigate the quantum simulation of coupling regimes of the quantum Rabi model that are difficult to achieve with natural dipolar interactions.
DNA binding protein identification by combining pseudo amino acid composition and profile-based protein representation
Authors: Liu Bin , Wang Shanyi , Wang Xiaolong 
Published: October 2015

AbstractDNA-binding proteins play an important role in most cellular processes. Therefore, it is necessary to develop an efficient predictor for identifying DNA-binding proteins only based on the sequence information of proteins. The bottleneck for constructing a useful predictor is to find suitable features capturing the characteristics of DNA binding proteins. We applied PseAAC to DNA binding protein identification and PseAAC was further improved by incorporating the evolutionary information by using profile-based protein representation. Finally, Combined with Support Vector Machines (SVMs), a predictor called iDNAPro-PseAAC was proposed. Experimental results on an updated benchmark dataset showed that iDNAPro-PseAAC outperformed some state-of-the-art approaches and it can achieve stable performance on an independent dataset. By using an ensemble learning approach to incorporate more negative samples (non-DNA binding proteins) in the training process, the performance of iDNAPro-PseAAC was further improved. The web server of iDNAPro-PseAAC is available at http://bioinformatics.hitsz.edu.cn/iDNAPro-PseAAC/.
TYR as a multifunctional reporter gene regulated by the Tet-on system for multimodality imaging: an in vitro study
Authors: Feng Hongyan , Xia Xiaotian , Li Chongjiao , Song Yiling , Qin Chunxia , Zhang Yongxue , Lan Xiaoli 
Published: October 2015

AbstractThe human tyrosinase gene TYR is a multifunctional reporter gene with potential use in photoacoustic imaging (PAI), positron emission tomography (PET) and magnetic resonance imaging (MRI). We sought to establish and evaluate a reporter gene system using TYR under the control of the Tet-on gene expression system (gene expression induced by doxycycline [Dox]) as a multimodality imaging agent. We transfected TYR into human breast cancer cells (MDA-MB-231), naming the resulting cell line 231-TYR. Using non-transfected MDA-MB-231 cells as a control, we verified successful expression of TYR by 231-TYR after incubation with Dox using western blot, cellular tyrosinase activity, Masson-Fontana silver staining and a cell immunofluorescence study, while the control cells and 231-TYR cells without Dox exposure revealed no TYR expression. Detected by its absorbance at 405 nm, increasing concentrations of melanin correlated positively with Dox concentration and incubation time. TYR expression by Dox-induced transfected cells shortened MRI T1 and T2 relaxation times. Photoacoustic signals were easily detected in these cells. 18F-5-fluoro-N-(2-[diethylamino]ethyl)picolinamide (18F-5-FPN), which targets melanin, quickly accumulated in Dox-induced 231-TYR cells. These show that TYR induction of melanin production is regulated by the Tet-on system and TYR-containing indicator cells may have utility in multimodality imaging.
Controlled delay‐through dynamic logic: leakage‐tolerant high‐speed dynamic logic
Authors: Dev A. , Sharma R.K 
Published: October 2015

A new model for dynamic logic is proposed with low power consumption and leakage without the degradation of speed. This logic works perfectly with cascaded and differential style without inverters. Controlled delay‐through dynamic logic (CDTDL) is comparatively faster than other dynamic logics because of the parallel‐type configuration with clock and inputs. CDTDL‐based circuits can perform better in high‐frequency operations due to lower propagation delay and dynamic power consumption at the cost of area. The proposed technique can avoid the chance of leakage current with the help of a control block and a delayed clock mechanism. The simulation results show that the new dynamic logic using 180 nm technology yields a minimum 49.7% improvement in power delay product compared with its predecessors such as conventional domino and current comparison‐based domino for standard circuits.
Emergence of system roles in normative neurodevelopment
Authors: Gu Shi , Satterthwaite Theodore D. , Medaglia John D. , Yang Muzhi , Gur Raquel E. , Gur Ruben C. , Bassett Danielle S. 
Published: October 2015

Significance
The human brain is a complex system displaying intricate, dynamic functions. In a multidisciplinary effort, the recent application of tools from network science to characterize the interconnected nature of the brain has enabled a tremendous advance in our understanding of cognition. Here, we develop and apply an extension of these tools to define and characterize the role of cognitive systems in the larger scale brain network, and to map how these roles change during adolescent development, providing an important context for understanding psychopathology. Our results are also consistent with the hypothesis that individual variation in network configuration implies differential vulnerability to cognitive abilities or deficits.