bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Evaluation of a Rapid and Sensitive EBOV-RPA Test for Rapid Diagnosis of Ebola Virus Disease
Authors: Yang Mingjuan , Ke Yuehua , Wang Xuesong , Ren Hang , Liu Wei , Lu Huijun , Zhang Wenyi , Liu Shiwei , Chang Guohui , Tian Shuguang , Wang Lihua , Huang Liuyu , Liu Chao , Yang Ruifu , Chen Zeliang 
Published: June 2016

AbstractConfirming Ebola virus disease (EVD), a deadly infectious disease, requires real-time RT-PCR, which takes up to a few hours to yield results. Therefore, a rapid diagnostic assay is imperative for EVD diagnosis. A rapid nucleic acid test based on recombinase polymerase amplification (EBOV-RPA) was developed to specifically detect the 2014 outbreak strains. The EBOV-RPA assay was evaluated by testing samples from suspected EVD patients in parallel with RT-PCR. An EBOV-RPA, which could be completed in 20 min, was successfully developed. Of 271 patients who tested positive for Ebola virus by RT-PCR, 264 (sensitivity: 97%, 95% CI: 95.5–99.3%) were positive by EBOV-RPA; 101 of 104 patients (specificity: 97%, 95% CI: 93.9–100%) who tested negative by RT-PCR were also negative by EBOV-RPA. The sensitivity values for samples with a Ct value of <34, which accounted for 95.59% of the samples, was 100%. Discordant samples positive by RT-PCR but negative by EBOV-RPA had significantly high Ct values. Results of external quality assessment samples with EBOV-RPA were 100%, consistent with those of RT-PCR. The EBOV-RPA assay showed 97% sensitivity and 97% specificity for all EVD samples tested, making it a rapid and sensitive test for EVD diagnosis.
Pharmacological inhibition of MyD88 homodimerization counteracts renal ischemia reperfusion-induced progressive renal injury in vivo and in vitro
Authors: Zhang Li-Min , Liu Jian-Hua , Xue Cheng-Biao , Li Ming-Qiang , Xing Shuai , Zhang Xue , He Wen-Tao , Jiang Feng-Chao , Lu Xia , Zhou Ping 
Published: June 2016

AbstractThe activation of innate immunity via myeloid differentiation factor 88 (MyD88) contributes to ischemia reperfusion (I/R) induced acute kidney injury (AKI) and chronic kidney injury. However, since there have not yet been any effective therapy, the exact pharmacological role of MyD88 in the prevention and treatment of renal ischemia reperfusion injury (IRI) is not known. We designed a small molecular compound, TJ-M2010-2, which inhibited MyD88 homodimerization. We used an established unilateral I/R mouse model. All mice undergoing 80 min ischemia through uninephrectomy died within five days without intervention. However, treatment with TJ-M2010-2 alone significantly improved the survival rate to 58.3%. Co-treatment of TJ-M2010-2 with the CD154 antagonist increased survival rates up to 100%. Twenty-eight days post-I/R of 60 min ischemia without nephrectomy, TJ-M2010-2 markedly attenuated renal interstitial and inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Furthermore, TJ-M2010-2 remarkably inhibited TLR/MyD88 signaling in vivo and in vitro. In conclusion, our findings highlight the promising clinical potential of MyD88 inhibitor in preventing and treating acute or chronic renal I/R injuries, and the therapeutic functionality of dual-system inhibition strategy in IRI-induced AKI. Moreover, MyD88 inhibition ameliorates renal I/R injury-induced tubular interstitial fibrosis by suppressing EMT.
4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions
Authors: Dong Jinhuan , Shi Lou , Pan Ling , Xu Xianxiu , Liu Qun 
Published: June 2016

AbstractIn recent years, numerous methods have emerged for the synthesis of trifluoromethylated arenes based on the late-stage introduction of a trifluoromethyl group onto an aryl ring. In sharp comparison, the synthesis of trifluoromethylated arenes based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon has rarely been addressed. It has been found that 4-trifluoromethyl-p-quinol silyl ethers, the readily available and relatively stable compounds, can act as dielectrophiles to be applied to multi-component reactions for the synthesis of various trifluoromethylated arenes. Catalyzed by In(OTf)3, 4-trifluoromethyl-p-quinol silyl ethers react with C-, N- and S-nucleophiles, respectively, in a regiospecific 1,2-addition manner to generate the corresponding highly reactive electrophilic intermediates. Further reaction of the in-situ generated electrophiles with a C-nucleophile followed by spontaneous aromatization enables the construction of functionalized trifluoromethyl arenes. This three-component, double nucleophilic addition/aromatization reaction based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon provides a divergent strategy for the synthesis of trifluoromethylated arenes under mild reaction conditions in a single operation.
Polyamine transporter in Streptococcus pneumoniae is essential for evading early innate immune responses in pneumococcal pneumonia
Authors: Rai Aswathy N. , Thornton Justin A. , Stokes John , Sunesara Imran , Swiatlo Edwin , Nanduri Bindu 
Published: June 2016

AbstractStreptococcus pneumoniae is the most common bacterial etiology of pneumococcal pneumonia in adults worldwide. Genomic plasticity, antibiotic resistance and extreme capsular antigenic variation complicates the design of effective therapeutic strategies. Polyamines are ubiquitous small cationic molecules necessary for full expression of pneumococcal virulence. Polyamine transport system is an attractive therapeutic target as it is highly conserved across pneumococcal serotypes. In this study, we compared an isogenic deletion strain of S. pneumoniae TIGR4 in polyamine transport operon (ΔpotABCD) with the wild type in a mouse model of pneumococcal pneumonia. Our results show that the wild type persists in mouse lung 24 h post infection while the mutant strain is cleared by host defense mechanisms. We show that intact potABCD is required for survival in the host by providing resistance to neutrophil killing. Comparative proteomics analysis of murine lungs infected with wild type and ΔpotABCD pneumococci identified expression of proteins that could confer protection to wild type strain and help establish infection. We identified ERM complex, PGLYRP1, PTPRC/CD45 and POSTN as new players in the pathogenesis of pneumococcal pneumonia. Additionally, we found that deficiency of polyamine transport leads to up regulation of the polyamine synthesis genes speE and cad in vitro.
Phosphorylation of FEZ1 by Microtubule Affinity Regulating Kinases regulates its function in presynaptic protein trafficking
Authors: Butkevich Eugenia , Härtig Wolfgang , Nikolov Miroslav , Erck Christian , Grosche Jens , Urlaub Henning , Schmidt Christoph F. , Klopfenstein Dieter R. , Chua John Jia En 
Published: June 2016

AbstractAdapters bind motor proteins to cargoes and therefore play essential roles in Kinesin-1 mediated intracellular transport. The regulatory mechanisms governing adapter functions and the spectrum of cargoes recognized by individual adapters remain poorly defined. Here, we show that cargoes transported by the Kinesin-1 adapter FEZ1 are enriched for presynaptic components and identify that specific phosphorylation of FEZ1 at its serine 58 regulatory site is mediated by microtubule affinity-regulating kinases (MARK/PAR-1). Loss of MARK/PAR-1 impairs axonal transport, with adapter and cargo abnormally co-aggregating in neuronal cell bodies and axons. Presynaptic specializations are markedly reduced and distorted in FEZ1 and MARK/PAR-1 mutants. Strikingly, abnormal co-aggregates of unphosphorylated FEZ1, Kinesin-1 and its putative cargoes are present in brains of transgenic mice modelling aspects of Alzheimer’s disease, a neurodegenerative disorder exhibiting impaired axonal transport and altered MARK activity. Our findings suggest that perturbed FEZ1-mediated synaptic delivery of proteins arising from abnormal signalling potentially contributes to the process of neurodegeneration.
Phosphatidylinositol-3-phosphate is light-regulated and essential for survival in retinal rods
Authors: He Feng , Agosto Melina A. , Anastassov Ivan A. , Tse Dennis Y. , Wu Samuel M. , Wensel Theodore G. 
Published: June 2016

AbstractPhosphoinositides play important roles in numerous intracellular membrane pathways. Little is known about the regulation or function of these lipids in rod photoreceptor cells, which have highly active membrane dynamics. Using new assays with femtomole sensitivity, we determined that whereas levels of phosphatidylinositol-3,4-bisphosphate and phosphatidylinositol-3,4,5-trisphosphate were below detection limits, phosphatidylinositol-3-phosphate (PI(3)P) levels in rod inner/outer segments increased more than 30-fold after light exposure. This increase was blocked in a rod-specific knockout of the PI-3 kinase Vps34, resulting in failure of endosomal and autophagy-related membranes to fuse with lysosomes, and accumulation of abnormal membrane structures. At early ages, rods displayed normal morphology, rhodopsin trafficking, and light responses, but underwent progressive neurodegeneration with eventual loss of both rods and cones by twelve weeks. The degeneration is considerably faster than in rod knockouts of autophagy genes, indicating defects in endosome recycling or other PI(3)P-dependent membrane trafficking pathways are also essential for rod survival.
Bound States in the Continuum in double layer structures
Authors: Li LiangSheng , Yin Hongcheng 
Published: June 2016

AbstractWe have theoretically investigated the reflectivity spectrums of single- and double-layer photonic crystal slabs and the dielectric multilayer stack. It is shown that light can be perfectly confined in a single-layer photonic crystal slab at a given incident angle by changing the thickness, permittivity or hole radius of the structure. With a tunable double-layer photonic crystal slab, we demonstrate that the occurrence of tunable bound states in the continuum is dependent on the spacing between two slabs. Moreover, by analytically investigating the Drude lossless multilayer stack model, the spacing dependence of bound states in the continuum is characterized as the phase matching condition that illuminates these states can occur at any nonzero incident angles by adjusting the spacing.
Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses
Authors: Sankhwar Monica , Sankhwar Satya Narayan , Bansal Sandeep Kumar , Gupta Gopal , Rajender Singh 
Published: June 2016

AbstractCompromised activity of the DNA repair enzymes may raise the risk of a number of cancers. We analyzed polymorphisms in the Xeroderma Pigmentosum, Complementation Group C (XPC) gene for their correlation with urinary bladder cancer. Ala499Val and Lys939Gln polymorphisms were genotyped in 234 urinary bladder cancer cases and 258 control samples. A significant association between Ala499Val polymorphism and bladder cancer was observed (OR = 1.78, CI = 1.19–2.66, p = 0.005); however, Lys939Gln was unrelated (OR = 0.97, CI = 0.65–1.45, P = 0.89). Further analysis revealed that Ala499Val was a significant risk factor only in the presence of smoking (OR = 2.23, CI = 1.28–3.87, p < 0.004) or tobacco chewing (OR = 2.40, CI = 1.43–4.04, p = 0.0008). To further appraise the association, we undertook meta-analyses on seven studies (2893 cases and 3056 controls) on Ala499Val polymorphism and eleven studies (5064 cases and 5208 controls) on Lys939Gln polymorphism. Meta-analyses corroborated the above results, showing strong association of Ala499Val (OR = 1.54, CI = 1.21–1.97, p = 0.001) but not that of Lys939Gln (OR = 1.13, CI = 0.95–1.34, p = 0.171) with urinary bladder cancer risk. In conclusion, XPC Ala499Val substitution increases urinary bladder cancer risk, but Lys939Gln appears to be neutral.
ATAC-seq on biobanked specimens defines a unique chromatin accessibility structure in naïve SLE B cells
Authors: Scharer Christopher D. , Blalock Emily L. , Barwick Benjamin G. , Haines Robert R. , Wei Chungwen , Sanz Ignacio , Boss Jeremy M. 
Published: June 2016

AbstractBiobanking is a widespread practice for storing biological samples for future studies ranging from genotyping to RNA analysis. However, methods that probe the status of the epigenome are lacking. Here, the framework for applying the Assay for Transposase Accessible Sequencing (ATAC-seq) to biobanked specimens is described and was used to examine the accessibility landscape of naïve B cells from Systemic Lupus Erythematosus (SLE) patients undergoing disease flares. An SLE specific chromatin accessibility signature was identified. Changes in accessibility occurred at loci surrounding genes involved in B cell activation and contained motifs for transcription factors that regulate B cell activation and differentiation. These data provide evidence for an altered epigenetic programming in SLE B cells and identify loci and transcription factor networks that potentially impact disease. The ability to determine the chromatin accessibility landscape and identify cis-regulatory elements has broad application to studies using biorepositories and offers significant advantages to improve the molecular information obtained from biobanked samples.
Lower bound for the spatial extent of localized modes in photonic-crystal waveguides with small random imperfections
Authors: Faggiani Rémi , Baron Alexandre , Zang Xiaorun , Lalouat Loïc , Schulz Sebastian A. , O’Regan Bryan , Vynck Kevin , Cluzel Benoît , de Fornel Frédérique , Krauss Thomas F. , Lalanne Philippe 
Published: June 2016

AbstractLight localization due to random imperfections in periodic media is paramount in photonics research. The group index is known to be a key parameter for localization near photonic band edges, since small group velocities reinforce light interaction with imperfections. Here, we show that the size of the smallest localized mode that is formed at the band edge of a one-dimensional periodic medium is driven instead by the effective photon mass, i.e. the flatness of the dispersion curve. Our theoretical prediction is supported by numerical simulations, which reveal that photonic-crystal waveguides can exhibit surprisingly small localized modes, much smaller than those observed in Bragg stacks thanks to their larger effective photon mass. This possibility is demonstrated experimentally with a photonic-crystal waveguide fabricated without any intentional disorder, for which near-field measurements allow us to distinctly observe a wavelength-scale localized mode despite the smallness (~1/1000 of a wavelength) of the fabrication imperfections.
Neuronal activity in dorsomedial and dorsolateral striatum under the requirement for temporal credit assignment
Authors: Her Eun Sil , Huh Namjung , Kim Jieun , Jung Min Whan 
Published: June 2016

AbstractTo investigate neural processes underlying temporal credit assignment in the striatum, we recorded neuronal activity in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively) of rats performing a dynamic foraging task in which a choice has to be remembered until its outcome is revealed for correct credit assignment. Choice signals appeared sequentially, initially in the DMS and then in the DLS, and they were combined with action value and reward signals in the DLS when choice outcome was revealed. Unlike in conventional dynamic foraging tasks, neural signals for chosen value were elevated in neither brain structure. These results suggest that dynamics of striatal neural signals related to evaluating choice outcome might differ drastically depending on the requirement for temporal credit assignment. In a behavioral context requiring temporal credit assignment, the DLS, but not the DMS, might be in charge of updating the value of chosen action by integrating choice, action value, and reward signals together.
Crystal structures of the ligand-binding region of uPARAP: effect of calcium ion binding
Authors: Yuan Cai , Jürgensen Henrik J. , Engelholm Lars H. , Li Rui , Liu Min , Jiang Longguang , Luo Zhipu , Behrendt Niels , Huang Mingdong 
Published: June 2016

The proteins of the mannose receptor (MR) family share a common domain organization and have a broad range of biological functions. Urokinase plasminogen activator receptor-associated protein (uPARAP) (or Endo180) is a member of this family and plays an important role in extracellular matrix remodelling through interaction with its ligands, including collagens and urokinase plasminogen activator receptor (uPAR). We report the crystal structures of the first four domains of uPARAP (also named the ligand-binding region, LBR) at pH 7.4 in Ca2+-bound and Ca2+-free forms. The first domain (cysteine-rich or CysR domain) folds into a new and unique conformation different from the β-trefoil fold of typical CysR domains. The so-called long loop regions (LLRs) of the C-type lectin-like domain (CTLD) 1 and 2 (the third and fourth domain) mediate the direct contacts between these domains. These LLRs undergo a Ca2+-dependent conformational change, and this is likely to be the key structural determinant affecting the overall conformation of uPARAP. Our results provide a molecular mechanism to support the structural flexibility of uPARAP, and shed light on the structural flexibility of other members of the MR family.
Controlled bile acid exposure to oesophageal mucosa causes up-regulation of nuclear γ-H2AX possibly via iNOS induction
Authors: Jiang Bo , Zhao Shengqian , Tao Zhen , Wen Jin , Yang Yancheng , Zheng Yin , Yan Hongling , Sheng Ying , Gao Aimin 
Published: June 2016

Using an in vitro model in which flatmounts of oesophagus was periodically exposed to bile acids, we demonstrate, using multiple methods, that the bile acid receptor TGR5, inducible nitric oxide synthase (iNOS) and γ-histone family 2A variant (γ-H2AX) are up-regulated. This indicates that bile acids cause up-regulation of iNOS, which further causes genotoxic stress as evidenced by increase of the highly sensitive marker, phosphorylated histone. In vitro nitric oxide (NO) assays showed increased production of nitric acid in the oesophageal epithelium exposed to the bile acids. This increase was inhibited in the presence of the nonspecific iNOS inhibitor aminoguanidine (AG). Cumulatively, the results of the present study provide suggestion that not only acid reflux, but also non-acid reflux of bile may cause genotoxic stress. These aspects merit to be tested in wide spectrum of Barrett epithelial tissues.
Digital epidemiology reveals global childhood disease seasonality and the effects of immunization
Authors: Bakker Kevin M. , Martinez-Bakker Micaela Elvira , Helm Barbara , Stevenson Tyler J. 
Published: June 2016

Significance
Disease surveillance systems largely focus on infectious diseases with high mortality, whereas less severe diseases often go unreported. Using chicken pox as an example, we demonstrate that Internet queries can be used as a proxy for disease incidence when reporting is lacking. We established that Google Trends accurately reflected clinical cases in countries with surveillance, and thus population-level dynamics of chicken pox. Then, we discovered robust seasonal variation in query behavior, with a striking latitudinal gradient on a global scale. Next, we showed that real-time data-mining of queries could forecast the timing and magnitude of outbreaks. Finally, our analyses revealed that countries with government-mandated vaccination programs have significantly reduced seasonality of queries, indicating vaccination efforts mitigated chicken pox outbreaks.
Knowledge without Observation
Authors: Martin C. B. 
Published: June 2016

In answering the question, “How is the concept of a person possible?”, Strawson (Individuals. London: Methuen, 1959) lays great stress upon a particular class of predicate.He says, “They are predicates, roughly, which involve doing something, which clearly imply intention or a state of mind or at least consciousness in general, and which indicate a characteristic pattern, or range of patterns, of bodily movement, while not indicating at all precisely any very definite sensation or experience … . Such predicates have the interesting characteristic of many P-predicates, that one does not, in general, ascribe them to oneself on the strength of observation, whereas one does ascribe them to others on the strength of observations. But, in the case of these predicates, one feels minimal reluctance to concede that what is ascribed in these two different ways is the same. This is because of the marked dominance of a fairly definite pattern of bodily movement in what they describe, and the marked absence of any distinctive experience.
Reasons for Action
Authors: Rachels James 
Published: June 2016

We can often explain a person's action by citing some fact which prompted him to do what he did. For example:Tom quit his job because he was offered more money elsewhere;Dick took his daughter to the dentist because she had a toothache;Harry rushed out of the theater because it was on fire.In each case there are four elements which fit together in a characteristic pattern. (1) The first is the fact that Tom has been offered more money, that Dick's daughter has a toothache, or that the theater in which Harry is sitting is on fire. If the theater were not on fire, for example, then we would have to give a different sort of explanation of why Harry rushed out: we would have to say that he left because he thought it was on fire, not because it was on fire. I shall have more to say about this point later. (2) The second is their knowledge of these facts. If Dick is unaware of the girl's toothache, he can hardly do anything on account of it; and of course the same goes for the other cases. (3) The third element is the attitude which each agent has toward the existing state-of-affairs. Tom wants to earn more money; Dick loves his daughter and doesn't want her to suffer; and Harry, like the rest of us, doesn't want to be burned. (4) Finally, there is the action which is being explained: Tom quits his job, Dick takes the girl to the dentist, and Harry rushes from the theater.
Predicates and Projectibility
Authors: Kelley Michael H. 
Published: June 2016

Nelson Goodman's new riddle of induction wears many faces. In one of its guises the new riddle of induction appears as the problem of providing a general account of the distinction between projectible and non-projectible predicates. This is the form of the riddle which is supposed to point up a lacuna in the foundations of confirmation theories such as Carnap's which, Goodman charges, work only to the extent that one builds into them just the right (projectible) predicates. As a new riddle of induction, the problem of distinguishing projectible from non-projectible predicates has the virtue that it is in fact new—a virtue not shared by some other forms of the riddle.Philosophers had recognized previously that some predicates are more projectible than others in the sense that, for instance, the prediction that a certain toss of a die will turn up an even face is safer and more likely to be true than the prediction that the same toss will turn up six.