julilili42/papers huggingface dataset:
Expression of the LRRC52 g subunit (g2) may provide Ca 2+ ‐independent activation of BK currents in mouse inner hair cells
2019-07-26

Mammalian inner hair cells (IHCs) transduce sound into depolarization and transmitter release. Big conductance and voltage‐ and Ca 2+ ‐activated K + (BK) channels are responsible for fast membrane repolarization and small time constants of mature IHCs. For unknown reasons, they activate at around ‐75 mV with a voltage of half‐maximum activation ( V half ) of ‐50 mV although being largely insensitive to Ca 2+ influx. Ca 2+ ‐independent activation of BK channels was observed by others in heterologous expression systems if γ subunits leucine‐rich repeat‐containing protein (LRRC)26 (γ1) and LRRC52 (γ2) were coexpressed with the pore‐forming BKα subunit, which shifted V half by ‐140 and ‐100 mV, respectively. Using nested PCR, we consistently detected transcripts for LRRC52 but not for LRRC26 in IHCs of 3‐wk‐old mice. Confocal immunohistochemistry showed synchronous up‐regulation of LRRC52 protein with BKα at the onset of hearing. Colocalization of LRRC52 protein and BKα at the IHC neck within ≤40 nm was specified using an in situ proximity ligation assay. Mice deficient for the voltage‐gated Ca v 1.3 Ca 2+ channel encoded by Cacna1d do not express BKα protein. LRRC52 protein was neither expressed in IHCs of BKα nor in IHCs of Ca v 1.3 knockout mice. Together, LRRC52 is a γ2 subunit of BK channel complexes and is a strong candidate for causing the Ca 2+ ‐independent activation of BK currents at negative membrane potentials in mouse IHCs.—Lang, I., Jung, M., Niemeyer, B. A., Ruth, P., Engel, J. Expression of the LRRC52 γ subunit (γ2) may provide Ca 2+ ‐independent activation of BK currents in mouse inner hair cells. FASEB J. 33, 11721‐11734 (2019). www.fasebj.org
Culture Dependent and Independent Analysis of Potential Probiotic Bacterial Genera and Species Present in the Phyllosphere of Raw Eaten Produce
2019-07-26

The plant phyllosphere is colonized by a complex ecosystem of microorganisms. Leaves of raw eaten vegetables and herbs are habitats for bacteria important not only to the host plant, but also to human health when ingested via meals. The aim of the current study was to determine the presence of putative probiotic bacteria in the phyllosphere of raw eaten produce. Quantification of bifidobacteria showed that leaves of Lepidium sativum L., Cichorium endivia L., and Thymus vulgaris L. harbor between 103 and 106 DNA copies per gram fresh weight. Total cultivable bacteria in the phyllosphere of those three plant species ranged from 105 to 108 CFU per gram fresh weight. Specific enrichment of probiotic lactic acid bacteria from C. endivia, T. vulgaris, Trigonella foenum-graecum L., Coriandrum sativum L., and Petroselinum crispum L. led to the isolation of 155 bacterial strains, which were identified as Pediococcus pentosaceus, Enterococcus faecium, and Bacillus species, based on their intact protein pattern. A comprehensive community analysis of the L. sativum leaves by PhyloChip hybridization revealed the presence of genera Bifidobacterium, Lactobacillus, and Streptococcus. Our results demonstrate that the phyllosphere of raw eaten produce has to be considered as a substantial source of probiotic bacteria and point to the development of vegetables and herbs with added probiotic value.
Religious education for plural societies: the selected works of Robert Jackson (World Library of Educationalists)
2019-07-26

It is quite rare that a religious educator will find a publisher who is willing to edit his or her ‘selected works’. And it is even more unusual that an author from this field is granted the honour...
AtDAT1 is a key enzyme of D-amino acid stimulated ethylene production inArabidopsis thaliana
2019-07-26

Abstract D-enantiomers of proteinogenic amino acids (D-AAs) are found ubiquitously, but the knowledge about their metabolism and functions in plants is scarce. A long forgotten phenomenon in this regard is the D-AA-stimulated ethylene production in plants. As a starting point to investigate this effect the Arabidopsis accession Landsberg erecta (Ler) got into focus as it was found defective in metabolizing D-AAs. Combining genetics and molecular biology of T-DNA lines and natural variants together with biochemical and physiological approaches we could identify AtDAT1 as a major D-AA transaminase in Arabidopsis. Atdat1 loss-of-function mutants and Arabidopsis accessions with defective AtDAT1 alleles were not able to produce D-Ala, D-Glu and L-Met, the metabolites of D-Met, anymore. This result corroborates the biochemical characterization of AtDAT1, which showed highest activity using D-Met as substrate. Germination of seedlings in light and dark led to enhanced growth inhibition of atdat1 mutants on D-Met. Ethylene measurements revealed an enhanced D-AA stimulated ethylene production in these mutants. According to initial working models of this phenomenon D-Met is preferentially malonylated instead of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). This decrease of ACC degradation should then lead to the increase of ethylene production. We could observe in our studies a reciprocal relation of malonylated methionine and ACC upon D-Met application and even significantly more malonyl-methionine in atdat1 mutants. Unexpectedly, the malonyl-ACC levels did not differ between mutants and wild type in these experiments. With AtDAT1, the first central enzyme of plant D-AA metabolism was characterized biochemically and physiologically. The specific effects of D-Met on ACC metabolization, ethylene production and plant development of dat1 mutants unraveled the impact of AtDAT1 on these processes, but they are not in full accordance to previous working models. Instead, our results imply the influence of additional candidate factors or processes on D-AA-stimulated ethylene production which await to be uncovered.
Sorafenib Activity and Disposition in Liver Cancer Does Not Depend on Organic Cation Transporter 1
2019-07-27

Systemic therapy of advanced hepatocellular carcinoma (HCC) with the small‐molecule multikinase inhibitor sorafenib is associated with large interindividual pharmacokinetic variability and unpredictable side effects potentially requiring dose reduction or treatment termination. Organic cation transporter (OCT1; gene SLC22A1 ) has been proposed as a clinical biomarker of HCC response. Because proof is lacking that OCT1 transports sorafenib, we used a combinatorial approach to define how OCT1 contributes to sorafenib transport. Overexpression of functional OCT1 protein in Xenopus laevis oocytes and mammalian cell lines did not facilitate sorafenib transport. Otherwise, sorafenib considerably accumulated in liver cancer cell lines despite negligible OCT1 mRNA and protein levels. Sorafenib pharmacokinetics was independent of OCT1 genotype in mice. Finally, SLC22A1 mRNA expression was significantly reduced by DNA methylation in The Cancer Genome Atlas HCC cohort. These results clearly demonstrate OCT1‐independent cellular sorafenib uptake indicating that OCT1 is apparently not a valid biomarker of sorafenib response in HCC.
Representing torture in Zero Dark Thirty (2012): Popular culture as a site of norm contestation
2019-07-27

The global war on terror (GWOT) is undoubtedly the most recent case where a government authorized ‘enhanced interrogation techniques’, a euphemism for torture. In addition to shocking stories and photographs from Guantánamo, Abu Ghraib and CIA black site prisons, popular culture assists in the production of torture’s public image and indicates a site of norm contestation. Therefore, the aim of this article is threefold. First, the author shows that Zero Dark Thirty (2012, dir. Kathryn Bigelow) is constitutive for the public image of torture and its meaning-in-use. Second, she argues that the film’s representation of torture works as a popular site of contesting the anti-torture norm. Finally, she reflects on the continuum between popular culture and the politics of torture.
Path guiding in production
2019-07-28

Path guiding is a family of adaptive variance reduction techniques in physically-based rendering, which includes methods for sampling both direct and indirect illumination, surfaces and volumes but also for sampling optimal path lengths and making splitting decisions. Since adoption of path tracing as a de facto standard in the VFX industry several years ago, there has been an increased interest in producing high-quality images with low amount of Monte Carlo samples per pixel. Path guiding, which has received attention in the research community in the past few years, has proven to be useful for this task and therefore has been adopted by Weta Digital. Recently, it has also been implemented in the Walt Disney Animation Studios' Hyperion and Pixar's Renderman. The goal of this course is to share our practical experience with path guiding in production and to provide self-contained overview of recently published techniques and to discuss their pros and cons. We also take audience through theoretical background of various path guiding methods which are mostly based on machine learning - used to adapt sampling distributons based on observed samples - and zero-variance random walk theory - used as a framework for combining different sampling decisions in an optimal way. At the end of our course we discuss open problems and invite researchers to further develop path guiding in their future work.
Boosting for Comparison-Based Learning
2019-07-28

We consider the problem of classification in a comparison-based setting: given a set of objects, we only have access to triplet comparisons of the form ``object A is closer to object B than to object C.'' In this paper we introduce TripletBoost, a new method that can learn a classifier just from such triplet comparisons. The main idea is to aggregate the triplets information into weak classifiers, which can subsequently be boosted to a strong classifier. Our method has two main advantages: (i) it is applicable to data from any metric space, and (ii) it can deal with large scale problems using only passively obtained and noisy triplets. We derive theoretical generalization guarantees and a lower bound on the number of necessary triplets, and we empirically show that our method is both competitive with state of the art approaches and resistant to noise.
Fiberoptic endoscopic evaluation of swallowing and videofluoroscopy swallowing assessment in adults in residential care facilities
2019-07-29

A three-step search strategy will be used to explore relevant literature. All citations and articles retrieved during the searches will be imported into a software application for systematic reviews. Once duplicates are removed, two reviewers will screen the titles and abstracts against predefined inclusion criteria. Information will be extracted from literature that meets the selection criteria using a purposefully developed charting form. The search strategy and results will be illustrated through a Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram. Key findings and their relationship to the research questions will be summarized in a chart and discussed in interpretive narrative form.
Anti-consensus: detecting trees that have an evolutionary signal that is lost in consensus
2019-07-29

A bstract In phylogenetics, a set of gene trees is often summarized by a consensus tree, such as the majority consensus, which is based on the set of all splits that are present in more than 50% of the input trees. A “consensus network” is obtained by lowering the threshold and considering all splits that are contained in 10% of the trees, say, and then computing the corresponding splits network. By construction and in practice, a consensus network usually shows the majority tree, extended by a number of rectangles that represent local rearrangements around internal nodes of the consensus tree. This may lead to the false conclusion that the input trees do not differ in a significant way because “even a phylogenetic network” does not display any large discrepancies. To harness the full potential of a phylogenetic network, we introduce the new concept of an anti-consensus network that aims at representing the largest interesting discrepancies found in a set of gene trees. We provide an efficient algorithm for computing an anti-consensus and illustrate its application using a set of gene trees from species and strains in the genus Kosakonia .
Adaptive denoising for chemical exchange saturation transfer MR imaging
2019-07-30

High image signal–to–noise ratio (SNR) is required to reliably detect the inherently small chemical exchange saturation transfer (CEST) effects in vivo. In this study, it was demonstrated that identifying spectral redundancies of CEST data by principal component analysis (PCA) in combination with an appropriate data–driven extraction of relevant information can be used for an effective and robust denoising of CEST spectra. The relationship between the number of relevant principal components and SNR was studied on fitted in vivo Z–spectra with artificially introduced noise. Three different data–driven criteria to automatically determine the optimal number of necessary components were investigated. In addition, these criteria facilitate straightforward assessment of data quality that could provide guidance for CEST MR protocols in terms of SNR. Insights were applied to achieve a robust denoising of highly sampled low power Z–spectra of the human brain at 3 and 7 T. The median criterion provided the best estimation for the optimal number of components consistently for all three investigated artificial noise levels. Application of the denoising technique to in vivo data revealed a considerable increase in image quality for the amide and rNOE contrast with a considerable SNR gain. At 7 T the denoising capability was quantified to be comparable or even superior to an averaging of six measurements. The proposed denoising algorithm enables an efficient and robust denoising of CEST data by combining PCA with appropriate data–driven truncation criteria. With this generally applicable technique at hand, small CEST effects can be reliably detected without the need for repeated measurements.
Ancient RNA from Late Pleistocene permafrost and historical canids shows tissue-specific transcriptome survival
2019-07-30

While sequencing ancient DNA (aDNA) from archaeological material is now commonplace, very few attempts to sequence ancient transcriptomes have been made, even from typically stable deposition environments such as permafrost. This is presumably due to assumptions that RNA completely degrades relatively quickly, particularly when dealing with autolytic, nuclease-rich mammalian tissues. However, given the recent successes in sequencing ancient RNA (aRNA) from various sources including plants and animals, we suspect that these assumptions may be incorrect or exaggerated. To challenge the underlying dogma, we generated shotgun RNA data from sources that might normally be dismissed for such study. Here, we present aRNA data generated from two historical wolf skins, and permafrost-preserved liver tissue of a 14,300-year-old Pleistocene canid. Not only is the latter the oldest RNA ever to be sequenced, but it also shows evidence of biologically relevant tissue specificity and close similarity to equivalent data derived from modern-day control tissue. Other hallmarks of RNA sequencing (RNA-seq) data such as exon-exon junction presence and high endogenous ribosomal RNA (rRNA) content confirms our data's authenticity. By performing independent technical library replicates using two high-throughput sequencing platforms, we show not only that aRNA can survive for extended periods in mammalian tissues but also that it has potential for tissue identification. aRNA also has possible further potential, such as identifying in vivo genome activity and adaptation, when sequenced using this technology.
Trimethylscandium
2019-07-30

The hitherto unknown homoleptic tetramethylaluminate complex [Sc(AlMe<sub>4</sub>)<sub>3</sub>] could be obtained by reacting the ate complex [Li<sub>3</sub>ScMe<sub>6</sub>(thf)<sub>1.2</sub>] with AlMe<sub>3</sub> in the cold. It cocrystallizes with AlMe<sub>3</sub> as [Sc(AlMe<sub>4</sub>)<sub>3</sub>(Al<sub>2</sub>Me<sub>6</sub>)<sub>0.5</sub>] and decomposes at ambient temperature in <i>n</i>-pentane via multiple C-H bond activations to the mixed methyl/methylidene complex [Sc<sub>3</sub>(μ<sub>3</sub>-CH<sub>2</sub>)<sub>2</sub>(μ<sub>2</sub>-CH<sub>3</sub>)<sub>3</sub>(AlMe<sub>4</sub>)<sub>2</sub>(AlMe<sub>3</sub>)<sub>2</sub>]. Donor-induced methylaluminate cleavage of [Sc(AlMe<sub>4</sub>)<sub>3</sub>(Al<sub>2</sub>Me<sub>6</sub>)<sub>0.5</sub>] produced [ScMe<sub>3</sub>]<sub><i>n</i></sub> in good yield, which could be derivatized with trimethyltriazacyclononane (Me<sub>3</sub>TACN) to form the structurally characterizable [(Me<sub>3</sub>TACN)ScMe<sub>3</sub>]. Additionally, half-sandwich complex [Cp*Sc(AlMe<sub>4</sub>)<sub>2</sub>] and sandwich complex [Cp*<sub>2</sub>Sc(AlMe<sub>4</sub>)] were accessible by salt metathesis reactions from [Sc(AlMe<sub>4</sub>)<sub>3</sub>(Al<sub>2</sub>Me<sub>6</sub>)<sub>0.5</sub>] and KCp* (Cp* = C<sub>5</sub>Me<sub>5</sub>). <sup>45</sup>Sc NMR spectroscopy was applied as a significant probe to evidence the existence of [ScMe<sub>3</sub>]<sub><i>n</i></sub>. Compounds [(Me<sub>3</sub>TACN)ScMe<sub>3</sub>] (+624.6 ppm) and [ScMe<sub>3</sub>(thf)<sub><i>x</i></sub>] (+601.7 ppm) gave large <sup>45</sup>Sc NMR shifts, revealing the strong deshielding effect of the σ-bonded alkyl ligands on the scandium nuclei. Ultimately, cationized [Sc(AlMe<sub>4</sub>)<sub>3</sub>(Al<sub>2</sub>Me<sub>6</sub>)<sub>0.5</sub>] was employed in isoprene polymerization, leading to polymers in high yields (>95%) and with high (>90%) <i>cis</i>-1,4-polyisoprene content.
Nanoparticles With a Specific Size and Surface Charge Promote Disruption of the Secondary Structure and Amyloid-Like Fibrillation of Human Insulin Under Physiological Conditions
2019-07-30

Nanoparticles attract much interest as fluorescent labels for diagnostic and therapeutic tools, although their applications are often hindered by size- and shape-dependent cytotoxicity. This cytotoxicity is related not only to the leak of toxic metals from nanoparticles into a biological solution, but also to molecular cytotoxicity effects determined by the formation of a protein corona, appearance of an altered protein conformation leading to exposure of cryptic epitopes and cooperative effects involved in the interaction of proteins and peptides with nanoparticles. In the last case, nanoparticles may serve, depending on their nature, as centers of self-association or fibrillation of proteins and peptides, provoking amyloid-like proteinopathies, or as inhibitors of self-association of proteins, or they can self-assemble on biopolymers as on templates. In this study, human insulin protein was used to analyze nanoparticle-induced proteinopathy in physiological conditions. It is known that human insulin may form amyloid fibers, but only under extreme experimental conditions (very low pH and high temperatures). Here, we have shown that the quantum dots (QDs) may induce amyloid-like fibrillation of human insulin under physiological conditions through a complex process strongly dependent on the size and surface charge of QDs. The insulin molecular structure and fibril morphology have been shown to be modified at different stages of its fibrillation, which has been proved by comparative analysis of the data obtained using circular dichroism, dynamic light scattering, amyloid-specific thioflavin T (ThT) assay, transmission electron microscopy, and high-speed atomic force microscopy. We have found important roles of the QD size and surface charge in the destabilization of the insulin structure and the subsequent fibrillation. Remodeling of the insulin secondary structure accompanied by remarkable increase in the rate of formation of amyloid-like fibrils under physiologically normal conditions was observed when the protein was incubated with QDs of exact specific diameter coated with slightly negative specific polyethylene glycol (PEG) derivatives. Strongly negatively or slightly positively charged PEG-modified QDs of the same specific diameter or QDs of bigger or smaller diameters had no effect on insulin fibrillation. The observed effects pave the way to the control of amyloidosis proteinopathy by varying the nanoparticle size and surface charge.
Early Aβ reduction prevents progression of cerebral amyloid angiopathy
2019-07-30

Objective Clinical trials targeting β‐amyloid peptides (Aβ) for Alzheimer disease (AD) failed for arguable reasons that include selecting the wrong stages of AD pathophysiology or Aβ being the wrong target. Targeting Aβ to prevent cerebral amyloid angiopathy (CAA) has not been rigorously followed, although the causal role of Aβ for CAA and related hemorrhages is undisputed. CAA occurs with normal aging and to various degrees in AD, where its impact and treatment is confounded by the presence of parenchymal Aβ deposition. Methods APPDutch mice develop CAA in the absence of parenchymal amyloid, mimicking hereditary cerebral hemorrhage with amyloidosis Dutch type (HCHWA‐D). Mice were treated with a β‐site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor. We used 3‐dimensional ultramicroscopy and immunoassays for visualizing CAA and assessing Aβ in cerebrospinal fluid (CSF) and brain. Results CAA onset in mice was at 22 to 24 months, first in frontal leptomeningeal and superficial cortical vessels followed by vessels penetrating the cortical layers. CSF Aβ increased with aging followed by a decrease of both Aβ40 and Aβ42 upon CAA onset, supporting the idea that combined reduction of CSF Aβ40 and Aβ42 is a specific biomarker for vascular amyloid. BACE1 inhibitor treatment starting at CAA onset and continuing for 4 months revealed a 90% Aβ reduction in CSF and largely prevented CAA progression and associated pathologies. Interpretation This is the first study showing that Aβ reduction at early disease time points largely prevents CAA in the absence of parenchymal amyloid. Our observation provides a preclinical basis for Aβ‐reducing treatments in patients at risk of CAA and in presymptomatic HCHWA‐D. ANN NEUROL 2019;86:561–571
Wnt Receptor Frizzled-4 as a Marker for Isolation of Enteric Neural Progenitors in Human Children
2019-07-30

Identification and isolation of neural progenitor cells from the human enteric nervous system (ENS) is currently hampered by the lack of reliable, specific markers. Here, we define the Wnt-receptor frizzled-4 as a marker for the isolation of enteric neural progenitor cells derived from paediatric gut samples. We show that the Wnt-receptor frizzled-4 is expressed in the human colon and in Tunica muscularis-derived enterospheres. To obtain a purified culture, we carried out fluorescence-activated cell sorting (FACS) using PE-conjugated frizzled-4 antibodies. Frizzled-4positive cells gave rise to neurosphere-like bodies and ultimately differentiated into neurons as revealed by BrdU-proliferation assays and immunocytochemistry, whereas in frizzled-4negative cultures we did not detect any neuronal and glial cells. By using a patch-clamp approach, we also demonstrated the expression of functional sodium and potassium channels in frizzled-4positive cell cultures after differentiation in vitro.