bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 counteracts an innate restriction by amyloid precursor protein resulting in neurodegeneration
Authors: Chai Qingqing , Jovasevic Vladimir , Malikov Viacheslav , Sabo Yosef , Morham Scott , Walsh Derek , Naghavi Mojgan H. 
Published: November 2017

AbstractWhile beta-amyloid (Aβ), a classic hallmark of Alzheimer’s disease (AD) and dementia, has long been known to be elevated in the human immunodeficiency virus type 1 (HIV-1)-infected brain, why and how Aβ is produced, along with its contribution to HIV-associated neurocognitive disorder (HAND) remains ill-defined. Here, we reveal that the membrane-associated amyloid precursor protein (APP) is highly expressed in macrophages and microglia, and acts as an innate restriction against HIV-1. APP binds the HIV-1 Gag polyprotein, retains it in lipid rafts and blocks HIV-1 virion production and spread. To escape this restriction, Gag promotes secretase-dependent cleavage of APP, resulting in the overproduction of toxic Aβ isoforms. This Gag-mediated Aβ production results in increased degeneration of primary cortical neurons, and can be prevented by γ-secretase inhibitor treatment. Interfering with HIV-1’s evasion of APP-mediated restriction also suppresses HIV-1 spread, offering a potential strategy to both treat infection and prevent HAND.
Reverse stress testing interbank networks
Authors: Grigat Daniel , Caccioli Fabio 
Published: November 2017

AbstractWe reverse engineer dynamics of financial contagion to find the scenario of smallest exogenous shock that, should it occur, would lead to a given final systemic loss. This reverse stress test can be used to identify the potential triggers of systemic events, and it removes the arbitrariness in the selection of shock scenarios in stress testing. We consider in particular the case of distress propagation in an interbank market, and we study a network of 44 European banks, which we reconstruct using data collected from banks statements. By looking at the distribution across banks of the size of smallest exogenous shocks we rank banks in terms of their systemic importance, and we show the effectiveness of a policy with capital requirements based on this ranking. We also study the properties of smallest exogenous shocks as a function of the parameters that determine the endogenous amplification of shocks. We find that the size of smallest exogenous shocks reduces and that the distribution across banks becomes more localized as the system becomes more unstable.
Using a quantitative quadruple immunofluorescent assay to diagnose isolated mitochondrial Complex I deficiency
Authors: Ahmed Syeda T. , Alston Charlotte L. , Hopton Sila , He Langping , Hargreaves Iain P. , Falkous Gavin , Oláhová Monika , McFarland Robert , Turnbull Doug M. , Rocha Mariana C. , Taylor Robert W. 
Published: November 2017

AbstractIsolated Complex I (CI) deficiency is the most commonly observed mitochondrial respiratory chain biochemical defect, affecting the largest OXPHOS component. CI is genetically heterogeneous; pathogenic variants affect one of 38 nuclear-encoded subunits, 7 mitochondrial DNA (mtDNA)-encoded subunits or 14 known CI assembly factors. The laboratory diagnosis relies on the spectrophotometric assay of enzyme activity in mitochondrially-enriched tissue homogenates, requiring at least 50 mg skeletal muscle, as there is no reliable histochemical method for assessing CI activity directly in tissue cryosections. We have assessed a validated quadruple immunofluorescent OXPHOS (IHC) assay to detect CI deficiency in the diagnostic setting, using 10 µm transverse muscle sections from 25 patients with genetically-proven pathogenic CI variants. We observed loss of NDUFB8 immunoreactivity in all patients with mutations affecting nuclear-encoding structural subunits and assembly factors, whilst only 3 of the 10 patients with mutations affecting mtDNA-encoded structural subunits showed loss of NDUFB8, confirmed by BN-PAGE analysis of CI assembly and IHC using an alternative, commercially-available CI (NDUFS3) antibody. The IHC assay has clear diagnostic potential to identify patients with a CI defect of Mendelian origins, whilst highlighting the necessity of complete mitochondrial genome sequencing in the diagnostic work-up of patients with suspected mitochondrial disease.
Evaluation of Critical Flicker-Fusion Frequency Measurement Methods for the Investigation of Visual Temporal Resolution
Authors: Eisen-Enosh Auria , Farah Nairouz , Burgansky-Eliash Zvia , Polat Uri , Mandel Yossi 
Published: November 2017

AbstractRecent studies highlight the importance of the temporal domain in visual processing. Critical Flicker-Fusion Frequency (CFF), the frequency at which a flickering light is perceived as continuous, is widely used for evaluating visual temporal processing. However, substantial variability in the psychophysical paradigms, used for measuring CFF, leads to substantial variability in the reported results. Here, we report on a comprehensive comparison of CFF measurements through three different psychophysical paradigms: methods of limits; method of constant stimuli, and staircase method. Our results demonstrate that the CFF can be reliably measured with high repeatability by all three psychophysics methods. However, correlations (r = 0.92, p≪0.001) and agreement (Bland Altman test indicated 95% confidence limit variation of ±3.6 Hz), were highest between the staircase and the constant stimuli methods. The time required to complete the test was significantly longer for the constant stimuli method as compared to other methods (p < 0.001). Our results highlight the suitability of the adaptive paradigm for efficiently measuring temporal resolution in the visual system.
Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity
Authors: Mehrpouya-Bahrami Pegah , Chitrala Kumaraswamy Naidu , Ganewatta Mitra S. , Tang Chuanbing , Murphy E. Angela , Enos Reilly T. , Velazquez Kandy T. , McCellan Jamie , Nagarkatti Mitzi , Nagarkatti Prakash 
Published: November 2017

AbstractObesity is characterized by chronic low-grade, systemic inflammation, altered gut microbiota, and gut barrier disruption. Additionally, obesity is associated with increased activity of endocannabinoid system (eCB). However, the clear connection between gut microbiota and the eCB system in the regulation of energy homeostasis and adipose tissue inflammation and metabolism, remains to be established. We investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment that blocks endocannabinoid activity can induce changes in gut microbiota and anti-inflammatory state in adipose tissue. Blockade of CB1 attenuated DIO, inflammatory cytokines and trafficking of M1 macrophages into adipose tissue. Decreased inflammatory tone was associated with a lower intestinal permeability and decreased metabolic endotoxemia as evidenced by reduced plasma LPS level, and improved hyperglycemia and insulin resistance. 16S rRNA metagenomics sequencing revealed that CB1 blockade dramatically increased relative abundance of Akkermansia muciniphila and decreased Lanchnospiraceae and Erysipelotrichaceae in the gut. Together, the current study suggests that blocking of CB1 ameliorates Diet-Induced Obesity and metabolic disorder by modulating macrophage inflammatory mediators, and that this effect is associated with alterations in gut microbiota and their metabolites.
SensorFRET: A Standardless Approach to Measuring Pixel-based Spectral Bleed-through and FRET Efficiency using Spectral Imaging
Authors: Arsenovic Paul T. , Mayer Carl R. , Conway Daniel E. 
Published: November 2017

AbstractFluorescence microscopy of FRET-based biosensors allow nanoscale interactions to be probed in living cells. This paper describes a novel approach to spectrally resolved fluorescence microscopy, termed sensorFRET, that enables quantitative measurement of FRET efficiency. This approach is an improvement on existing methods (FLIM, sRET, luxFRET, pFRET), as it does not require single fluorophore standards to be measured with every experiment and the acquisition is intensity independent, allowing the laser power to be optimized for varying levels of fluorophore expression. Additionally, it was found that all spectral based methods, including sensorFRET, fail at specific fluorophore-excitation wavelength combinations. These combinations can be determined a priori using sensorFRET, whereas other methods would give no indication of inaccuracies. This method was thoroughly validated and compared to existing methods using simulated spectra, Fluorescein and TAMRA dye mixtures as a zero FRET control, and Cerulean-Venus FRET standards as positive FRET controls. Simulations also provided a means of quantifying the uncertainty in each measurement by relating the fit residual of noisy spectra to the standard deviation of the measured FRET efficiency. As an example application, Teal-Venus force sensitive biosensors integrated into E-cadherin were used to resolve piconewton scale forces along different parts of an individual cell junction.
Proteotoxicity in cardiac amyloidosis: amyloidogenic light chains affect the levels of intracellular proteins in human heart cells
Authors: Imperlini Esther , Gnecchi Massimiliano , Rognoni Paola , Sabidò Eduard , Ciuffreda Maria Chiara , Palladini Giovanni , Espadas Guadalupe , Mancuso Francesco Mattia , Bozzola Margherita , Malpasso Giuseppe , Valentini Veronica , Palladini Giuseppina , Orrù Stefania , Ferraro Giovanni , Milani Paolo , Perlini Stefano , Salvatore Francesco , Merlini Giampaolo , Lavatelli Francesca 
Published: November 2017

AbstractAL amyloidosis is characterized by widespread deposition of immunoglobulin light chains (LCs) as amyloid fibrils. Cardiac involvement is frequent and leads to life-threatening cardiomyopathy. Besides the tissue alteration caused by fibrils, clinical and experimental evidence indicates that cardiac damage is also caused by proteotoxicity of prefibrillar amyloidogenic species. As in other amyloidoses, the damage mechanisms at cellular level are complex and largely undefined. We have characterized the molecular changes in primary human cardiac fibroblasts (hCFs) exposedin vitroto soluble amyloidogenic cardiotoxic LCs from AL cardiomyopathy patients. To evaluate proteome alterations caused by a representative cardiotropic LC, we combined gel-based with label-free shotgun analysis and performed bioinformatics and data validation studies. To assess the generalizability of our results we explored the effects of multiple LCs on hCF viability and on levels of a subset of cellular proteins. Our results indicate that exposure of hCFs to cardiotropic LCs translates into proteome remodeling, associated with apoptosis activation and oxidative stress. The proteome alterations affect proteins involved in cytoskeletal organization, protein synthesis and quality control, mitochondrial activity and metabolism, signal transduction and molecular trafficking. These results support and expand the concept that soluble amyloidogenic cardiotropic LCs exert toxic effects on cardiac cells.
NF-κB Protects NKT Cells from Tumor Necrosis Factor Receptor 1-induced Death
Authors: Kumar Amrendra , Gordy Laura E. , Bezbradica Jelena S. , Stanic Aleksandar K. , Hill Timothy M. , Boothby Mark R. , Van Kaer Luc , Joyce Sebastian 
Published: November 2017

AbstractSemi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-xL-codingBcl2l1transgene into NF-κB signalling-deficientIκBΔNtransgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas. Surprisingly, the single and combined deficiency in PKC-θ or CARMA-1—the two signal transducers at the NKT TCR proximal signalling node—only partially recapitulated the NKT cell deficiency observed inIκBΔNtgmouse. Accordingly, introgression of theBcl2l1transgene into PKC-θ null mouse failed to rescue NKT cell development. Instead, TNFR1-deficiency, but not the Fas-deficiency, rescued NKT cell development inIκBΔNtgmice. Consistent with this finding, treatment of thymocytes with an antagonist of the inhibitor of κB kinase —which blocks downstream NF-κB activation— sensitized NKT cells to TNF-α-induced cell deathin vitro. Hence, we conclude that signal integration by NF-κB protects developing NKT cells from death signals emanating from TNFR1, but not from the NKT TCR or Fas.
Selective Blocking Property of Microporous Polymer Membranes Fabricated by Chemical Vapor Deposition
Authors: Shii Takeshi , Hatori Masaru , Yokota Kazuma , Hattori Yoshiyuki , Kimura Mutsumi 
Published: November 2017

AbstractPoly-p-xylylene films have been utilized as protective and barrier layers for gases and solvents on electronic and implantable devices. Here we report a new approach to create highly permeable and selective nanofiltration membranes coated with microporous poly-p-xylylene nanofilms fabricated through a dry chemical vapor deposition process by using [2.2]paracyclophanes derivatives on ultrafiltration membranes. The introduction of crosslinking points into rigid poly-p-xylylenes enhanced microporosity and mechanical strength due to insufficient packing and depression of structural relaxation among polymer chains in three-dimensional networks. Crosslinked nanofilms with thicknesses down to 50 nm showed outstanding permeability for water and alcohols at a pressure difference of 0.5 MPa and exhibited higher rejection ratios for water-soluble organic dyes than non-crosslinked nanofilms. Poly-p-xylylene nanofilms also showed an excellent blocking property for non-polar organic solvent permeation through specific interaction of hydrophilic pores with organic solvents.
Sedentary behavior and altered metabolic activity by AgNPs ingestion in Drosophila melanogaster
Authors: Raj Akanksha , Shah Prasanna , Agrawal Namita 
Published: November 2017

AbstractAmong several nanoparticles, silver nanoparticles (AgNPs) are extensively used in a wide variety of consumer products due to its unique antimicrobial property. However, dosage effect of AgNPs on behavior and metabolic activity in an in vivo condition is not well studied. Therefore, to elucidate the impact of AgNPs on behavior and metabolism, systematic and detailed dosages study of AgNPs was performed by rearing Drosophila melanogaster on food without and with AgNPs. We found that dietary intake of AgNPs at early larval stage leads to behavioral abnormalities such as poor crawling and climbing ability of larvae and adults respectively. Interestingly, intake of higher dosage of AgNPs at larval stage significantly altered metabolic activity that includes lipid, carbohydrate and protein levels in adult flies. Further, detailed analysis revealed that AgNPs causes remarkable reduction in the number of lipid droplets (LDs) which are lipid storage organelles in Drosophila. We also observed an increased production of reactive oxygen species (ROS) in AgNPs ingested larval tissues. These results strongly imply that higher dosage of AgNPs ingestion from early larval stage of Drosophila is inimical and thereby draws concern towards the usage of AgNPs in consumer goods.
Population genetic structure of the land snail Camaena cicatricosa (Stylommatophora, Camaenidae) in China inferred from mitochondrial genes and ITS2 sequences
Authors: Zhou Weichuan , Yang Haifang , Ding Hongli , Yang Shanping , Lin Junhong , Wang Pei 
Published: November 2017

AbstractThe phylogeographic structure of the land snailCamaena cicatricosawas analyzed in this study based on mitochondrial gene (COIand16srRNA, mt DNA) and internal transcribed spacer (ITS2) sequences in 347 individuals. This snail is the vector of the zoonotic food-borne parasiteAngiostrongylus cantonensisand one of the main harmful snails distributed exclusively in China. The results revealed significant fixation indices of genetic differentiation and high gene flow between most populations except several populations. An isolation-by-distance test showed no significant correlation between genetic distance and geographical distance amongC. cicatricosapopulations, which suggested that gene flow was not restricted by distance. The levels of haplotype and nucleotide diversity ofC. cicatricosawere generally high, except those in some special populations, according to the mt DNA and ITS2 data. Furthermore, the phylogenetic trees and asteroid networks of haplotypes indicated nonobvious genetic structure, the same as results got based on the synonymous and non synonymous sites of 347 sequences of theCOIgene. All lines of evidence indicated that climatic changes and geographical and human barriers do not substantially affect the current population structure and distribution of the investigated snails.
A mobile device-based imaging spectrometer for environmental monitoring by attaching a lightweight small module to a commercial digital camera
Authors: Cai Fuhong , Lu Wen , Shi Wuxiong , He Sailing 
Published: November 2017

AbstractSpatially-explicit data are essential for remote sensing of ecological phenomena. Lately, recent innovations in mobile device platforms have led to an upsurge in on-site rapid detection. For instance, CMOS chips in smart phones and digital cameras serve as excellent sensors for scientific research. In this paper, a mobile device-based imaging spectrometer module (weighing about 99 g) is developed and equipped on a Single Lens Reflex camera. Utilizing this lightweight module, as well as commonly used photographic equipment, we demonstrate its utility through a series of on-site multispectral imaging, including ocean (or lake) water-color sensing and plant reflectance measurement. Based on the experiments we obtain 3D spectral image cubes, which can be further analyzed for environmental monitoring. Moreover, our system can be applied to many kinds of cameras, e.g., aerial camera and underwater camera. Therefore, any camera can be upgraded to an imaging spectrometer with the help of our miniaturized module. We believe it has the potential to become a versatile tool for on-site investigation into many applications.
5-Aminolevulinic Acid Guided Sampling of Glioblastoma Microenvironments Identifies Pro-Survival Signaling at Infiltrative Margins
Authors: Ross James L. , Cooper Lee A. D. , Kong Jun , Gutman David , Williams Merete , Tucker-Burden Carol , McCrary Myles R. , Bouras Alexandros , Kaluzova Milota , Dunn William D. , Duong Duc , Hadjipanayis Constantinos G. , Brat Daniel J. 
Published: November 2017

AbstractGlioblastoma (GBM) contains diverse microenvironments with uneven distributions of oncogenic alterations and signaling networks. The diffusely infiltrative properties of GBM result in residual tumor at neurosurgical resection margins, representing the source of relapse in nearly all cases and suggesting that therapeutic efforts should be focused there. To identify signaling networks and potential druggable targets across tumor microenvironments (TMEs), we utilized 5-ALA fluorescence-guided neurosurgical resection and sampling, followed by proteomic analysis of specific TMEs. Reverse phase protein array (RPPA) was performed on 205 proteins isolated from the tumor margin, tumor bulk, and perinecrotic regions of 13 previously untreated, clinically-annotated and genetically-defined high grade gliomas. Differential protein and pathway signatures were established and then validated using western blotting, immunohistochemistry, and comparable TCGA RPPA datasets. We identified 37 proteins differentially expressed across high-grade glioma TMEs. We demonstrate that tumor margins were characterized by pro-survival and anti-apoptotic proteins, whereas perinecrotic regions were enriched for pro-coagulant and DNA damage response proteins. In both our patient cohort and TCGA cases, the data suggest that TMEs possess distinct protein expression profiles that are biologically and therapeutically relevant.
A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure
Authors: Komiya Yuko , Bai Zhiyong , Cai Na , Lou Liping , Al-Saadi Namariq , Mezzacappa Courtney , Habas Raymond , Runnels Loren W. 
Published: November 2017

AbstractIn humans, germline mutations in Trpm6 cause autosomal dominant hypomagnesemia with secondary hypocalcemia disorder. Loss of Trpm6 in mice also perturbs cellular magnesium homeostasis but additionally results in early embryonic lethality and neural tube closure defects. To define the mechanisms by which TRPM6 influences neural tube closure, we functionally characterized the role of TRPM6 during early embryogenesis in Xenopus laevis. The expression of Xenopus TRPM6 (XTRPM6) is elevated at the onset of gastrulation and is concentrated in the lateral mesoderm and ectoderm at the neurula stage. Loss of XTRPM6 produced gastrulation and neural tube closure defects. Unlike XTRPM6′s close homologue XTRPM7, whose loss interferes with mediolateral intercalation, depletion of XTRPM6 but not XTRPM7 disrupted radial intercalation cell movements. A zinc-influx assay demonstrated that TRPM6 has the potential to constitute functional channels in the absence of TRPM7. The results of our study indicate that XTRPM6 regulates radial intercalation with little or no contribution from XTRPM7 in the region lateral to the neural plate, whereas XTRPM7 is mainly involved in regulating mediolateral intercalation in the medial region of the neural plate. We conclude that both TRPM6 and TRPM7 channels function cooperatively but have distinct and essential roles during neural tube closure.
The effects of artocarpin on wound healing: in vitro and in vivo studies
Authors: Yeh Chung-Ju , Chen Chin-Chuan , Leu Yann-Lii , Lin Ming-Wei , Chiu Mei-Miao , Wang Shu-Huei 
Published: November 2017

AbstractThe skin protects the body against harmful substances and microorganisms. When the skin is damaged, wound healing must be finely regulated to restore the normal function of skin tissue. Artocarpin (ARTO), a prenylated flavonoid purified from the plant Artocarpus communis, has been reported to have anti-inflammatory and anti-cancer properties. The aim of the present study was to evaluate the wound healing potential and therapeutic mechanism of ARTO. Immunohistochemical staining of neutrophils and macrophages and mouse cytokine array analysis demonstrated that ARTO accelerates inflammatory progression and subsequently decreases persistent inflammation. ARTO increases collagen production and increases human fibroblast proliferation and migration by activating the P38 and JNK pathways. Moreover, ARTO increases the proliferation and migration of human keratinocytes through the ERK and P38 pathways and augments human endothelial cell proliferation and tube formation through the Akt and P38 pathways. Together, our data suggested that ARTO enhances skin wound healing, possibly by accelerating the inflammatory phase and by increasing myofibroblast differentiation, proliferation and migration of fibroblasts and keratinocytes, collagen synthesis and maturation, re-epithelialization, and angiogenesis. These findings indicate that ARTO has potential as a potent therapeutic agent for the treatment of skin wounds.