bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proinflammatory isoforms of IL-32 as novel and robust biomarkers for control failure in HIV-infected slow progressors
Authors: El-Far Mohamed , Kouassi Pascale , Sylla Mohamed , Zhang Yuwei , Fouda Ahmed , Fabre Thomas , Goulet Jean-Philippe , van Grevenynghe Julien , Lee Terry , Singer Joel , Harris Marianne , Baril Jean-Guy , Trottier Benoit , Ancuta Petronela , Routy Jean-Pierre , Bernard Nicole , Tremblay Cécile L. ,   Investigators of the Canadian HIV+ Slow Progressor Cohort, Angel Jonathan , Conway Brian , Côté Pierre , Gill John , Johnston Lynn , Kovacs Colin , Loutfy Mona , Logue Kenneth , Piché Alain , Rachlis Anita , Rouleau Danielle , Thompson Bill , Thomas Réjean , Trottier Sylvie , Walmsley Sharon , Wobeser Wendy 
Published: March 2016

AbstractHIV-infected slow progressors (SP) represent a heterogeneous group of subjects who spontaneously control HIV infection without treatment for several years while showing moderate signs of disease progression. Under conditions that remain poorly understood, a subgroup of these subjects experience failure of spontaneous immunological and virological control. Here we determined the frequency of SP subjects who showed loss of HIV control within our Canadian Cohort of HIV+ Slow Progressors and identified the proinflammatory cytokine IL-32 as a robust biomarker for control failure. Plasmatic levels of the proinflammatory isoforms of IL-32 (mainly β and γ) at earlier clinic visits positively correlated with the decline of CD4 T-cell counts, increased viral load, lower CD4/CD8 ratio and levels of inflammatory markers (sCD14 and IL-6) at later clinic visits. We present here a proof-of-concept for the use of IL-32 as a predictive biomarker for disease progression in SP subjects and identify IL-32 as a potential therapeutic target.
Primary brain calcification in patients undergoing treatment with the biphosphanate alendronate
Authors: Oliveira J. R. M , Oliveira M. F 
Published: March 2016

AbstractBrain calcification might be associated with various metabolic, infectious or vascular conditions. Clinically, brain calcification can include symptons such as migraine, parkinsonism, psychosis or dementia. The term Primary Brain Calcification was recently used for those patients without an obvious cause (formerly idiopathic) while Primary Familial Brain Calcifications was left for the cases with autosomal dominant inheritance. Recent studies found mutations in four genes (SLC20A2, PDGFRB, PDGFB and XPR1). However, these gene represent only 60% of all familial cases suggesting other genes remain to be elucidated. Studies evaluating treatments for such a devastating disease are scattered, usually appearing as single case reports. In the present study, we describe a case series of 7 patients treated with Alendronate, a widely prescribed biphosphanate. We observed good tolerance and evidence of improvements and stability by some patients. No side effects were reported and no specific symptoms related to medication. Younger patients and one individual continuing a prescription (prior to study commencement) appeared to respond more positively with some referred improvements in symptoms. Biphosphanates may represent an excellent prospect for the treatment of brain calcifications due to their being well tolerated and easily available. Conversely, prospective and controlled studies should promptly address weaknesses found in the present analysis.
On Sequence Learning Models: Open-loop Control Not Strictly Guided by Hick’s Law
Authors: Pavão Rodrigo , Savietto Joice P. , Sato João R. , Xavier Gilberto F. , Helene André F. 
Published: March 2016

AbstractAccording to the Hick’s law, reaction times increase linearly with the uncertainty of target stimuli. We tested the generality of this law by measuring reaction times in a human sequence learning protocol involving serial target locations which differed in transition probability and global entropy. Our results showed that sigmoid functions better describe the relationship between reaction times and uncertainty when compared to linear functions. Sequence predictability was estimated by distinct statistical predictors: conditional probability, conditional entropy, joint probability and joint entropy measures. Conditional predictors relate to closed-loop control models describing that performance is guided by on-line access to past sequence structure to predict next location. Differently, joint predictors relate to open-loop control models assuming global access of sequence structure, requiring no constant monitoring. We tested which of these predictors better describe performance on the sequence learning protocol. Results suggest that joint predictors are more accurate than conditional predictors to track performance. In conclusion, sequence learning is better described as an open-loop process which is not precisely predicted by Hick’s law.
Bacterial regulon modeling and prediction based on systematic cis regulatory motif analyses
Authors: Liu Bingqiang , Zhou Chuan , Li Guojun , Zhang Hanyuan , Zeng Erliang , Liu Qi , Ma Qin 
Published: March 2016

AbstractRegulons are the basic units of the response system in a bacterial cell and each consists of a set of transcriptionally co-regulated operons. Regulon elucidation is the basis for studying the bacterial global transcriptional regulation network. In this study, we designed a novel co-regulation score between a pair of operons based on accurate operon identification and cis regulatory motif analyses, which can capture their co-regulation relationship much better than other scores. Taking full advantage of this discovery, we developed a new computational framework and built a novel graph model for regulon prediction. This model integrates the motif comparison and clustering and makes the regulon prediction problem substantially more solvable and accurate. To evaluate our prediction, a regulon coverage score was designed based on the documented regulons and their overlap with our prediction; and a modified Fisher Exact test was implemented to measure how well our predictions match the co-expressed modules derived from E. coli microarray gene-expression datasets collected under 466 conditions. The results indicate that our program consistently performed better than others in terms of the prediction accuracy. This suggests that our algorithms substantially improve the state-of-the-art, leading to a computational capability to reliably predict regulons for any bacteria.
Phonon-assisted nonlinear optical processes in ultrashort-pulse pumped optical parametric amplifiers
Authors: Isaienko Oleksandr , Robel István 
Published: March 2016

AbstractOptically active phonon modes in ferroelectrics such as potassium titanyl phosphate (KTP) and potassium titanyl arsenate (KTA) in the ~7–20 THz range play an important role in applications of these materials in Raman lasing and terahertz wave generation. Previous studies with picosecond pulse excitation demonstrated that the interaction of pump pulses with phonons can lead to efficient stimulated Raman scattering (SRS) accompanying optical parametric oscillation or amplification processes (OPO/OPA) and to efficient polariton-phonon scattering. In this work, we investigate the behavior of infrared OPAs employing KTP or KTA crystals when pumped with ~800-nm ultrashort pulses of duration comparable to the oscillation period of the optical phonons. We demonstrate that under conditions of coherent impulsive Raman excitation of the phonons, when the effective χ(2) nonlinearity cannot be considered instantaneous, the parametrically amplified waves (most notably, signal) undergo significant spectral modulations leading to an overall redshift of the OPA output. The pump intensity dependence of the redshifted OPA output, the temporal evolution of the parametric gain, as well as the pump spectral modulations suggest the presence of coupling between the nonlinear optical polarizations PNL of the impulsively excited phonons and those of parametrically amplified waves.
Frequency and amplitude modulation of ultra-compact terahertz quantum cascade lasers using an integrated avalanche diode oscillator
Authors: Castellano Fabrizio , Li Lianhe , Linfield Edmund H. , Davies A. Giles , Vitiello Miriam S. 
Published: March 2016

AbstractMode-locked comb sources operating at optical frequencies underpin applications ranging from spectroscopy and ultrafast physics, through to absolute frequency measurements and atomic clocks. Extending their operation into the terahertz frequency range would greatly benefit from the availability of compact semiconductor-based sources. However, the development of any compact mode-locked THz laser, which itself is inherently a frequency comb, has yet to be achieved without the use of an external stimulus. High-power, electrically pumped quantum cascade lasers (QCLs) have recently emerged as a promising solution, owing to their octave spanning bandwidths, the ability to achieve group-velocity dispersion compensation and the possibility of obtaining active mode-locking. Here, we propose an unprecedented compact architecture to induce both frequency and amplitude self-modulation in a THz QCL. By engineering a microwave avalanche oscillator into the laser cavity, which provides a 10 GHz self-modulation of the bias current and output power, we demonstrate multimode laser emission centered around 3 THz, with distinct multiple sidebands. The resulting microwave amplitude and frequency self-modulation of THz QCLs opens up intriguing perspectives, for engineering integrated self-mode-locked THz lasers, with impact in fields such as nano- and ultrafast photonics and optical metrology.
Accurate Determination of Conformational Transitions in Oligomeric Membrane Proteins
Authors: Sanz-Hernández Máximo , Vostrikov Vitaly V. , Veglia Gianluigi , De Simone Alfonso 
Published: March 2016

AbstractThe structural dynamics governing collective motions in oligomeric membrane proteins play key roles in vital biomolecular processes at cellular membranes. In this study, we present a structural refinement approach that combines solid-state NMR experiments and molecular simulations to accurately describe concerted conformational transitions identifying the overall structural, dynamical, and topological states of oligomeric membrane proteins. The accuracy of the structural ensembles generated with this method is shown to reach the statistical error limit, and is further demonstrated by correctly reproducing orthogonal NMR data. We demonstrate the accuracy of this approach by characterising the pentameric state of phospholamban, a key player in the regulation of calcium uptake in the sarcoplasmic reticulum, and by probing its dynamical activation upon phosphorylation. Our results underline the importance of using an ensemble approach to characterise the conformational transitions that are often responsible for the biological function of oligomeric membrane protein states.
Growth inhibition and apoptosis in cancer cells induced by polyphenolic compounds of Acacia hydaspica: Involvement of multiple signal transduction pathways
Authors: Afsar Tayyaba , Trembley Janeen H. , Salomon Christine E. , Razak Suhail , Khan Muhammad Rashid , Ahmed Khalil 
Published: March 2016

AbstractAcacia hydaspica R. Parker is known for its medicinal uses in multiple ailments. In this study, we performed bioassay-guided fractionation of cytotoxic compounds from A. hydaspica and investigated their effects on growth and signaling activity in prostate and breast cancer cell lines. Four active polyphenolic compounds were identified as 7-O-galloyl catechin (GC), catechin (C), methyl gallate (MG), and catechin-3-O-gallate (CG). The four compounds inhibited prostate cancer PC-3 cell growth in a dose-dependent manner, whereas CG and MG inhibited breast cancer MDA-MB-231 cell growth. All tested compounds inhibited cell survival and colony growth in both cell lines, and there was evidence of chromatin condensation, cell shrinkage and apoptotic bodies. Further, acridine orange, ethidium bromide, propidium iodide and DAPI staining demonstrated that cell death occurred partly via apoptosis in both PC-3 and MDA-MB-231 cells. In PC-3 cells treatment repressed the expression of anti-apoptotic molecules Bcl-2, Bcl-xL and survivin, coupled with down-regulation of signaling pathways AKT, NFκB, ERK1/2 and JAK/STAT. In MDA-MB-231 cells, treatment induced reduction of CK2α, Bcl-xL, survivin and xIAP protein expression along with suppression of NFκB, JAK/STAT and PI3K pathways. Our findings suggest that certain polyphenolic compounds derived from A. hydaspica may be promising chemopreventive/therapeutic candidates against cancer.
Crystal Field Splitting is Limiting the Stability and Strength of Ultra-incompressible Orthorhombic Transition Metal Tetraborides
Authors: Zhang R. F. , Wen X. D. , Legut D. , Fu Z. H. , Veprek S. , Zurek E. , Mao H. K. 
Published: March 2016

AbstractThe lattice stability and mechanical strengths of the supposedly superhard transition metal tetraborides (TmB4, Tm = Cr, Mn and Fe) evoked recently much attention from the scientific community due to the potential applications of these materials, as well as because of general scientific interests. In the present study, we show that the surprising stabilization of these compounds from a high symmetry to a low symmetry structure is accomplished by an in-plane rotation of the boron network, which maximizes the in-plane hybridization by crystal field splitting between d orbitals of Tm and p orbitals of B. Studies of mechanical and electronic properties of TmB4suggest that these tetraborides cannot be intrinsically superhard. The mechanical instability is facilitated by a unique in-plane or out-of-plane weakening of the three-dimensional covalent bond network of boron along different shear deformation paths. These results shed a novel view on the origin of the stability and strength of orthorhombic TmB4, highlighting the importance of combinational analysis of a variety of parameters related to plastic deformation of the crystalline materials when attempting to design new ultra-incompressible, and potentially strong and hard solids.
Genomic identification of WRKY transcription factors in carrot (Daucus carota) and analysis of evolution and homologous groups for plants
Authors: Li Meng-Yao , Xu Zhi-Sheng , Tian Chang , Huang Ying , Wang Feng , Xiong Ai-Sheng 
Published: March 2016

AbstractWRKY transcription factors belong to one of the largest transcription factor families. These factors possess functions in plant growth and development, signal transduction and stress response. Here, we identified 95 DcWRKY genes in carrot based on the carrot genomic and transcriptomic data and divided them into three groups. Phylogenetic analysis of WRKY proteins from carrot and Arabidopsis divided these proteins into seven subgroups. To elucidate the evolution and distribution of WRKY transcription factors in different species, we constructed a schematic of the phylogenetic tree and compared the WRKY family factors among 22 species, which including plants, slime mold and protozoan. An in-depth study was performed to clarify the homologous factor groups of nine divergent taxa in lower and higher plants. Based on the orthologous factors between carrot and Arabidopsis, 38 DcWRKY proteins were calculated to interact with other proteins in the carrot genome. Yeast two-hybrid assay showed that DcWRKY20 can interact with DcMAPK1 and DcMAPK4. The expression patterns of the selected DcWRKY genes based on transcriptome data and qRT-PCR suggested that those selected DcWRKY genes are involved in root development, biotic and abiotic stress response. This comprehensive analysis provides a basis for investigating the evolution and function of WRKY genes.
Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model
Authors: Shim Aeri , Song Jae-Hyoung , Kwon Bo-Eun , Lee Jeong-Jun , Ahn Jae-Hee , Kim Yeon-Jeong , Rhee Ki-Jong , Chang Sun-Young , Cha Younggil , Lee Yong-Soo , Kweon Mi-Na , Park Kwi Sung , Kim Dong-Eun , Cho Sungchan , Cho Hyun-Jong , Ko Hyun-Jeong 
Published: March 2016

AbstractHuman rhinovirus (HRV) is the most common viral infectious agent in humans and is the predominant cause of the common cold. There is a need for appropriate vaccines or therapeutic agents to treat HRV infection. In this study, we investigated whether itraconazole (ICZ) can protect cells from HRV-induced cytotoxicity. Replication of HRV1B was reduced by ICZ treatment in the lungs of HRV1B- as compared to vehicle-treated mice. The numbers of immune cells, including granulocytes and monocytes, were reduced in bronchoalveolar lavage fluid (BALF) by ICZ administration after HRV1B infection, corresponding to decreased pro-inflammatory cytokine and chemokine levels in BALF. A histological analysis of lung tissue showed that ICZ suppressed inflammation caused by HRV1B infection. Interestingly, pretreatment of mice with ICZ in the form of a nasal spray had potent prophylactic antiviral activity. Cholesterol accumulation in the plasma membrane was observed upon HRV infection; ICZ blocked cholesterol trafficking to the plasma membrane, as well as resulted in its accumulation in subcellular compartments near the nucleus. These findings suggest that ICZ is a potential antiviral agent for the treatment of HRV infection, which can be adopted preventatively as well as therapeutically.
Minicircle DNA Provides Enhanced and Prolonged Transgene Expression Following Airway Gene Transfer
Authors: Munye Mustafa M. , Tagalakis Aristides D. , Barnes Josephine L. , Brown Rachel E. , McAnulty Robin J. , Howe Steven J. , Hart Stephen L. 
Published: March 2016

AbstractGene therapy for cystic fibrosis using non-viral, plasmid-based formulations has been the subject of intensive research for over two decades but a clinically viable product has yet to materialise in large part due to inefficient transgene expression. Minicircle DNA give enhanced and more persistent transgene expression compared to plasmid DNA in a number of organ systems but has not been assessed in the lung. In this study we compared minicircle DNA with plasmid DNA in transfections of airway epithelial cells. In vitro, luciferase gene expression from minicircles was 5–10-fold higher than with plasmid DNA. In eGFP transfections in vitro both the mean fluorescence intensity and percentage of cells transfected was 2–4-fold higher with minicircle DNA. Administration of equimolar amounts of DNA to mouse lungs resulted in a reduced inflammatory response and more persistent transgene expression, with luciferase activity persisting for 2 weeks from minicircle DNA compared to plasmid formulations. Transfection of equal mass amounts of DNA in mouse lungs resulted in a 6-fold increase in transgene expression in addition to more persistent transgene expression. Our findings have clear implications for gene therapy of airway disorders where plasmid DNA transfections have so far proven inefficient in clinical trials.
Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans
Authors: Acerbi Enzo , Viganò Elena , Poidinger Michael , Mortellaro Alessandra , Zelante Teresa , Stella Fabio 
Published: March 2016

AbstractT helper 17 (TH17) cells represent a pivotal adaptive cell subset involved in multiple immune disorders in mammalian species. Deciphering the molecular interactions regulating TH17 cell differentiation is particularly critical for novel drug target discovery designed to control maladaptive inflammatory conditions. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling TH17 differentiation. From the network, we identified the Prdm1 gene encoding the B lymphocyte-induced maturation protein 1 as a crucial negative regulator of human TH17 cell differentiation. The results have been validated by perturbing Prdm1 expression on freshly isolated CD4+ naïve T cells: reduction of Prdm1 expression leads to augmentation of IL-17 release. These data unravel a possible novel target to control TH17 polarization in inflammatory disorders. Furthermore, this study represents the first in vitro validation of continuous time Bayesian networks as gene network reconstruction method and as hypothesis generation tool for wet-lab biological experiments.
Impact of 4-epi-oxytetracycline on the gut microbiota and blood metabolomics of Wistar rats
Authors: Han Hongxing , Xiao Hailong , Zhang Kai , Lu Zhenmei 
Published: March 2016

AbstractThe impact of 4-epi-oxytetracycline (4-EOTC), one of the main oxytetracycline (OTC) metabolites, on the gut microbiota and physiological metabolism of Wistar rats was analyzed to explore the dynamic alterations apparent after repeated oral exposure (0.5, 5.0 or 50.0 mg/kg bw) for 15 days as shown by 16S rRNA pyrosequencing and UPLC-Q-TOF/MS analysis. Both principal component analysis and cluster analysis showed consistently altered patterns with distinct differences in the treated groups versus the control groups. 4-EOTC treatment at 5.0 or 50.0 mg/kg increased the relative abundance of the Actinobacteria, specifically Bifidobacteriaceae and improved the synthesis of lysophosphatidylcholine (LysoPC), as shown by the lipid biomarkers LysoPC(16:0), LysoPC(18:3), LysoPC(20:3) and LysoPC(20:4). The metabolomic analysis of urine samples also identified four other decreased metabolites: diacylglycerol, sphingomyelin, triacylglycerol and phosphatidylglycerol. Notably, the significant changes observed in these biomarkers demonstrated the ongoing disorder induced by 4-EOTC. Blood and urine analysis revealed that residual 4-EOTC accumulated in the rats, even two weeks after oral 4-EOTC administration, ceased. Thus, through thorough analysis, it can be concluded that the alteration of the gut microbiota and disorders in blood metabolomics are correlated with 4-EOTC treatment.
Conservation triage or injurious neglect in endangered species recovery
Authors: Gerber Leah R. 
Published: March 2016

Significance
Although government funding available for species protection and recovery is one of the best predictors of successful recovery, government spending is both insufficient and highly disproportionate among groups of species. Here I demonstrate that expenditures for recovery in excess of the recommended recovery budget would not necessarily translate into better conservation outcomes. More importantly, elimination of the budget surplus for “costly yet futile” recovery plans can provide sufficient funding to offset funding deficits for more than 180 species. Using a return on investment analysis, I show that triage by budget compression provides better funding for a larger sample of species, and that a larger sample of adequately funded recovery plans should produce better outcomes even if by chance.
Multiple First Names in the Netherlands (1760–2014)
Authors: Bloothooft Gerrit , Onland David 
Published: March 2016

Although in Europe the custom to choose more than one name for a child first arose in the early Renaissance in Italy, its popularity reached the Netherlands only in the eighteenth century. On the basis of a high-coverage sample of the birth and name information for 26 million individuals from 1760 until 2014, the preference for multiple first names in the Netherlands has been studied, both annually and geographically. With the exception of recent years, religion has played a dominant role in name choices, including the number of names. Protestants only started to adopt double names in the nineteenth century, while Catholics increasingly chose three names, many including Maria (but only during a period of 50 years in the mid-twentieth century for boys). A tax proposal in 1915 on the number of names not only demonstrates the effect of financial cost on naming, but also the consistency of parents’ name choices concerning their children. Whereas during previous centuries the changes were gradual, preferences varied rapidly over the last 50 years.