bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression
Authors: Corciulo Carmen , Lendhey Matin , Wilder Tuere , Schoen Hanna , Cornelissen Alexander Samuel , Chang Gregory , Kennedy Oran D. , Cronstein Bruce N. 
Published: May 2017

AbstractOsteoarthritis (OA) is characterized by cartilage destruction and chondrocytes have a central role in this process. With age and inflammation chondrocytes have reduced capacity to synthesize and maintain ATP, a molecule important for cartilage homeostasis. Here we show that concentrations of ATP and adenosine, its metabolite, fall after treatment of mouse chondrocytes and rat tibia explants with IL-1β, an inflammatory mediator thought to participate in OA pathogenesis. Mice lacking A2A adenosine receptor (A2AR) or ecto-5′nucleotidase (an enzyme that converts extracellular AMP to adenosine) develop spontaneous OA and chondrocytes lacking A2AR develop an ‘OA phenotype’ with increased expression ofMmp13andCol10a1. Adenosine replacement by intra-articular injection of liposomal suspensions containing adenosine prevents development of OA in rats. These results support the hypothesis that maintaining extracellular adenosine levels is an important homeostatic mechanism, loss of which contributes to the development of OA; targeting adenosine A2A receptors might treat or prevent OA.
Unconventional double-bended saturation of carrier occupation in optically excited graphene due to many-particle interactions
Authors: Winzer Torben , Mittendorff Martin , Winnerl Stephan , Mittenzwey Henry , Jago Roland , Helm Manfred , Malic Ermin , Knorr Andreas 
Published: May 2017

AbstractSaturation of carrier occupation in optically excited materials is a well-established phenomenon. However, so far, the observed saturation effects have always occurred in the strong-excitation regime and have been explained by Pauli blocking of the optically filled quantum states. On the basis of microscopic theory combined with ultrafast pump-probe experiments, we reveal a new low-intensity saturation regime in graphene that is purely based on many-particle scattering and not Pauli blocking. This results in an unconventional double-bended saturation behaviour: both bendings separately follow the standard saturation model exhibiting two saturation fluences; however, the corresponding fluences differ by three orders of magnitude and have different physical origin. Our results demonstrate that this new and unexpected behaviour can be ascribed to an interplay between time-dependent many-particle scattering and phase-space filling effects.
Identification of mouse cochlear progenitors that develop hair and supporting cells in the organ of Corti
Authors: Xu Jinshu , Ueno Hiroo , Xu Chelsea Y. , Chen Binglai , Weissman Irving L. , Xu Pin-Xian 
Published: May 2017

AbstractThe adult mammalian cochlear sensory epithelium houses two major types of cells, mechanosensory hair cells and underlying supporting cells, and lacks regenerative capacity. Recent evidence indicates that a subset of supporting cells can spontaneously regenerate hair cells after ablation only within the first week postparturition. Here in vivo clonal analysis of mouse inner ear cells during development demonstrates clonal relationship between hair and supporting cells in sensory organs. We report the identification in mouse of a previously unknown population of multipotent stem/progenitor cells that are capable of not only contributing to the hair and supporting cells but also to other cell types, including glia, in cochlea undergoing development, maturation and repair in response to damage. These multipotent progenitors originate from Eya1-expressing otic progenitors. Our findings also provide evidence for detectable regenerative potential in the postnatal cochlea beyond 1 week of age.
Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice
Authors: Walsh Ryan M. , Shen Erica Y. , Bagot Rosemary C. , Anselmo Anthony , Jiang Yan , Javidfar Behnam , Wojtkiewicz Gregory J. , Cloutier Jennifer , Chen John W. , Sadreyev Ruslan , Nestler Eric J. , Akbarian Schahram , Hochedlinger Konrad 
Published: May 2017

AbstractPHF8 is a histone demethylase with specificity for repressive modifications. While mutations of PHF8 have been associated with cognitive defects and cleft lip/palate, its role in mammalian development and physiology remains unexplored. Here, we have generated a Phf8 knockout allele in mice to examine the consequences of Phf8 loss for development and behaviour. Phf8 deficient mice neither display obvious developmental defects nor signs of cognitive impairment. However, we report a striking resiliency to stress-induced anxiety- and depression-like behaviour on loss of Phf8. We further observe misregulation of serotonin signalling within the prefrontal cortex of Phf8 deficient mice and identify the serotonin receptors Htr1a and Htr2a as direct targets of PHF8. Our results clarify the functional role of Phf8 in mammalian development and behaviour and establish a direct link between Phf8 expression and serotonin signalling, identifying this histone demethylase as a potential target for the treatment of anxiety and depression.
The digestive and defensive basis of carcass utilization by the burying beetle and its microbiota
Authors: Vogel Heiko , Shukla Shantanu P. , Engl Tobias , Weiss Benjamin , Fischer Rainer , Steiger Sandra , Heckel David G. , Kaltenpoth Martin , Vilcinskas Andreas 
Published: May 2017

AbstractInsects that use ephemeral resources must rapidly digest nutrients and simultaneously protect them from competitors. Here we use burying beetles (Nicrophorus vespilloides), which feed their offspring on vertebrate carrion, to investigate the digestive and defensive basis of carrion utilization. We characterize gene expression and microbiota composition in the gut, anal secretions, and on carcasses used by the beetles. We find a strict functional compartmentalization of the gut involving differential expression of immune effectors (antimicrobial peptides and lysozymes), as well as digestive and detoxifying enzymes. A distinct microbial community composed of Firmicutes, Proteobacteria and a clade of ascomycetous yeasts (genus Yarrowia) is present in larval and adult guts, and is transmitted to the carcass via anal secretions, where the yeasts express extracellular digestive enzymes and produce antimicrobial compounds. Our results provide evidence of potential metabolic cooperation between the host and its microbiota for digestion, detoxification and defence that extends from the beetle’s gut to its nutritional resource.
Proline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells
Authors: Elia Ilaria , Broekaert Dorien , Christen Stefan , Boon Ruben , Radaelli Enrico , Orth Martin F. , Verfaillie Catherine , Grünewald Thomas G. P. , Fendt Sarah-Maria 
Published: May 2017

AbstractMetastases are the leading cause of mortality in patients with cancer. Metastasis formation requires cancer cells to adapt their cellular phenotype. However, how metabolism supports this adaptation of cancer cells is poorly defined. We use 2D versus 3D cultivation to induce a shift in the cellular phenotype of breast cancer cells. We discover that proline catabolism via proline dehydrogenase (Prodh) supports growth of breast cancer cells in 3D culture. Subsequently, we link proline catabolism to in vivo metastasis formation. In particular, we find that PRODH expression and proline catabolism is increased in metastases compared to primary breast cancers of patients and mice. Moreover, inhibiting Prodh is sufficient to impair formation of lung metastases in the orthotopic 4T1 and EMT6.5 mouse models, without adverse effects on healthy tissue and organ function. In conclusion, we discover that Prodh is a potential drug target for inhibiting metastasis formation.
Regulation of cardiomyocyte behavior in zebrafish trabeculation by Neuregulin 2a signaling
Authors: Rasouli S. Javad , Stainier Didier Y. R. 
Published: May 2017

AbstractTrabeculation is crucial for cardiac muscle growth in vertebrates. This process requires the Erbb2/4 ligand Neuregulin (Nrg), secreted by the endocardium, as well as blood flow/cardiac contractility. Here, we address two fundamental, yet unresolved, questions about cardiac trabeculation: why does it initially occur in the ventricle and not the atrium, and how is it modulated by blood flow/contractility. Using loss-of-function approaches, we first show that zebrafish Nrg2a is required for trabeculation, and using a protein-trap line, find that it is expressed in both cardiac chambers albeit with different spatiotemporal patterns. Through gain-of-function experiments, we show that atrial cardiomyocytes can also respond to Nrg2a signalling, suggesting that the cardiac jelly, which remains prominent in the atrium, represents a barrier to Erbb2/4 activation. Furthermore, we find that blood flow/contractility is required for Nrg2a expression, and that while non-contractile hearts fail to trabeculate, non-contractile cardiomyocytes are also competent to respond to Nrg2a/Erbb2 signalling.
Construction of genotyping-by-sequencing based high-density genetic maps and QTL mapping for fusarium wilt resistance in pigeonpea
Authors: Saxena Rachit K. , Singh Vikas K. , Kale Sandip M. , Tathineni Revathi , Parupalli Swathi , Kumar Vinay , Garg Vanika , Das Roma R. , Sharma Mamta , Yamini K. N. , Muniswamy S. , Ghanta Anuradha , Rathore Abhishek , Kumar C. V. Sameer , Saxena K. B. , Kishor P. B. Kavi , Varshney Rajeev K. 
Published: May 2017

AbstractFusarium wilt (FW) is one of the most important biotic stresses causing yield losses in pigeonpea. Genetic improvement of pigeonpea through genomics-assisted breeding (GAB) is an economically feasible option for the development of high yielding FW resistant genotypes. In this context, two recombinant inbred lines (RILs) (ICPB 2049 × ICPL 99050 designated as PRIL_A and ICPL 20096 × ICPL 332 designated as PRIL_B) and one F2 (ICPL 85063 × ICPL 87119) populations were used for the development of high density genetic maps. Genotyping-by-sequencing (GBS) approach was used to identify and genotype SNPs in three mapping populations. As a result, three high density genetic maps with 964, 1101 and 557 SNPs with an average marker distance of 1.16, 0.84 and 2.60 cM were developed in PRIL_A, PRIL_B and F2, respectively. Based on the multi-location and multi-year phenotypic data of FW resistance a total of 14 quantitative trait loci (QTLs) including six major QTLs explaining >10% phenotypic variance explained (PVE) were identified. Comparative analysis across the populations has revealed three important QTLs (qFW11.1, qFW11.2 and qFW11.3) with upto 56.45% PVE for FW resistance. This is the first report of QTL mapping for FW resistance in pigeonpea and identified genomic region could be utilized in GAB.
Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance are exacerbated by TRAIL deletion in mice
Authors: Cartland Siân P. , Harith Hanis H. , Genner Scott W. , Dang Lei , Cogger Victoria C. , Vellozzi Melissa , Di Bartolo Belinda A. , Thomas Shane R. , Adams Leon A. , Kavurma Mary M. 
Published: May 2017

AbstractNon-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail−/− mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride content, inflammation and fibrosis were increased with TRAIL-deletion, with elevated expression of genes regulating lipogenesis and gluconeogenesis. Moreover, Trail−/− mice exhibited reduced aortic vasorelaxation, impaired insulin signaling, and >20-fold increased mRNA expression for IL-1β, IL-6, and TNF-α. In vitro, palmitate treatment of hepatocytes increased lipid accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced. TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake. Finally, patients with NASH had significantly reduced plasma TRAIL compared to control, simple steatosis or obese individuals. These findings suggest that TRAIL protects against insulin resistance, NAFLD and vascular inflammation. Increasing TRAIL levels may be an attractive therapeutic strategy, to reduce features of diabetes, as well as liver and vascular injury, so commonly observed in individuals with NAFLD.
Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of endometrial epithelial cell receptivity for blastocyst implantation
Authors: Kumar Vijay , Soni Upendra Kumar , Maurya Vineet Kumar , Singh Kiran , Jha Rajesh Kumar 
Published: May 2017

AbstractIntegrin beta8 (ITGB8) is involved in the endometrial receptivity. The blastocyst first interacts with the luminal endometrial epithelial cells during its implantation; therefore, we have investigated the signaling of ITGB8 via FAK and VAV-RAC1 in the endometrial epithelial cells. Integrin beta8 was found elevated in epithelial cells at late-pre-receptive (day4, 1600 h) and receptive (day5, 0500 h) stages of endometrial receptivity period in the mouse. Integrins downstream molecule FAK has demonstrated an increased expression and phosphorylation (Y397) in the endometrium as well as in the isolated endometrial epithelial cells during receptive and post-receptive stages. Integrin beta8 can functionally interact with FAK, VAV and RAC1 as the levels of phosphorylated-FAK, and VAV along with the RAC-GTP form was reduced after ITGB8 knockdown in the endometrial epithelial cells and uterus. Further, VAV and RAC1 were seen poorly active in the absence of FAK activity, suggesting a crosstalk of ITGB8 and FAK for VAV and RAC1 activation in the endometrial epithelial cells. Silencing of ITGB8 expression and inhibition of FAK activity in the Ishikawa cells rendered poor attachment of JAr spheroids. In conclusion, ITGB8 activates VAV-RAC1 signaling axis via FAK to facilitate the endometrial epithelial cell receptivity for the attachment of blastocyst.
Exploring optoelectronic properties and mechanisms of layered ferroelectric K4Nb6O17 nanocrystalline films and nanolaminas
Authors: Deng Qinglin , Li Mengjiao , Wang Junyong , Zhang Peng , Jiang Kai , Zhang Jinzhong , Hu Zhigao , Chu Junhao 
Published: May 2017

AbstractTwo-dimensional layered K4Nb6O17 (KN) was easily formed as a secondary phase caused by the volatilization of alkali metal ions, when preparing ferroelectric K
x
Na1−x
NbO3 based ceramics and films. In this work, it was believed that KN film is with weak ferroelectricity and has a little effect on the ferroelectric properties of K
x
Na1−x
NbO3 based films. Moreover, temperature dependent (77–500 K) dielectric functions of KN film have been firstly extracted by fitting ellipsometric spectra with the Adachi dielectric function model and a four-phase layered model. The high-frequency dielectric constant linearly increases and optical band gap slightly decreases with increasing the temperature. We also research its photoelectrochemical properties and its application in high-efficient light-induced H2 evolution. In addition, X-ray photoelectron spectroscopy, Raman scattering, temperature dependent transmittance and infrared reflectance spectra, and first-principles calculation were conjointly performed to further reveal the intrinsic optoelectronic features and relevant mechanisms of KN.
Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestine
Authors: Selby-Pham Sophie N. B. , Miller Rosalind B. , Howell Kate , Dunshea Frank , Bennett Louise E. 
Published: May 2017

AbstractA diet high in phytochemical-rich plant foods is associated with reducing the risk of chronic diseases such as cardiovascular and neurodegenerative diseases, obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the common component underlying these chronic diseases. Whilst the positive health effects of phytochemicals and their metabolites have been demonstrated to regulate OSI, the timing and absorption for best effect is not well understood. We developed a model to predict the time to achieve maximal plasma concentration (Tmax) of phytochemicals in fruits and vegetables. We used a training dataset containing 67 dietary phytochemicals from 31 clinical studies to develop the model and validated the model using three independent datasets comprising a total of 108 dietary phytochemicals and 98 pharmaceutical compounds. The developed model based on dietary intake forms and the physicochemical properties lipophilicity and molecular mass accurately predicts Tmaxof dietary phytochemicals and pharmaceutical compounds over a broad range of chemical classes. This is the first direct model to predict Tmaxof dietary phytochemicals in the human body. The model informs the clinical dosing frequency for optimising uptake and sustained presence of dietary phytochemicals in circulation, to maximise their bio-efficacy for positively affect human health and managing OSI in chronic diseases.
Multivariate EEG analyses support high-resolution tracking of feature-based attentional selection
Authors: Fahrenfort Johannes Jacobus , Grubert Anna , Olivers Christian N. L. , Eimer Martin 
Published: May 2017

AbstractThe primary electrophysiological marker of feature-based selection is the N2pc, a lateralized posterior negativity emerging around 180–200 ms. As it relies on hemispheric differences, its ability to discriminate the locus of focal attention is severely limited. Here we demonstrate that multivariate analyses of raw EEG data provide a much more fine-grained spatial profile of feature-based target selection. When training a pattern classifier to determine target position from EEG, we were able to decode target positions on the vertical midline, which cannot be achieved using standard N2pc methodology. Next, we used a forward encoding model to construct a channel tuning function that describes the continuous relationship between target position and multivariate EEG in an eight-position display. This model can spatially discriminate individual target positions in these displays and is fully invertible, enabling us to construct hypothetical topographic activation maps for target positions that were never used. When tested against the real pattern of neural activity obtained from a different group of subjects, the constructed maps from the forward model turned out statistically indistinguishable, thus providing independent validation of our model. Our findings demonstrate the power of multivariate EEG analysis to track feature-based target selection with high spatial and temporal precision.
PICK1 Genetic Variation and Cognitive Function in Patients with Schizophrenia
Authors: Chen Yi-Ting , Lin Chieh-Hsin , Huang Chiung-Hsien , Liang Wen-Miin , Lane Hsien-Yuan 
Published: May 2017

AbstractThe gene of protein interacting with C kinase 1 alpha (PICK1) has been implicated in schizophrenia, nevertheless, conflicting results existed. However, its role in cognitive function remains unclear. Besides, cognitive deficits impair the long-term outcome. We explored whether the polymorphisms of PICK1 (rs2076369, rs3952) affected cognitive functions in schizophrenic patients. We analyzed 302 patients and tested the differences of cognitive functions, clinical symptoms between genetic groups. We also used general linear model to analyze the effect of PICK1 genetic polymorphisms on cognitive functions. After adjustment for gender, age, education, the patients with rs2076369 G/T genotype showed better performance than T/T homozygotes in the summary score, global composite score, neurocognitive composite score, category fluency subtest, WAIS-III-Digit Symbol Coding subtest, working memory, WMS-III-Spatial Span (backward) subtest, MSCEIT-managing emotions branch (p = 0.038, 0.025, 0.046, 0.036, 0.025, 0.027, 0.035, 0.028, respectively). G/G homozygotes performed better than T/T in category fluency subtest (p = 0.049). A/A homozygotes of rs3952 performed better than G/G in trail making A subtest (p = 0.048). To our knowledge, this is the first study to indicate that PICK1 polymorphisms may associate with cognitive functions in schizophrenic patients. Further replication studies in healthy controls or other ethnic groups are warranted.
Overcoming thermal noise in non-volatile spin wave logic
Authors: Dutta Sourav , Nikonov Dmitri E. , Manipatruni Sasikanth , Young Ian A. , Naeemi Azad 
Published: May 2017

AbstractSpin waves are propagating disturbances in magnetically ordered materials, analogous to lattice waves in solid systems and are often described from a quasiparticle point of view as magnons. The attractive advantages of Joule-heat-free transmission of information, utilization of the phase of the wave as an additional degree of freedom and lower footprint area compared to conventional charge-based devices have made spin waves or magnon spintronics a promising candidate for beyond-CMOS wave-based computation. However, any practical realization of an all-magnon based computing system must undergo the essential steps of a careful selection of materials and demonstrate robustness with respect to thermal noise or variability. Here, we aim at identifying suitable materials and theoretically demonstrate the possibility of achieving error-free clocked non-volatile spin wave logic device, even in the presence of thermal noise and clock jitter or clock skew.
Rapid susceptibility profiling of carbapenem-resistant Klebsiella pneumoniae
Authors: Mulroney K. T. , Hall J. M. , Huang X. , Turnbull E. , Bzdyl N. M. , Chakera A. , Naseer U. , Corea E. M. , Ellington M. J. , Hopkins K. L. , Wester A. L. , Ekelund O. , Woodford N. , Inglis T. J. J. 
Published: May 2017

AbstractThe expanding global distribution of multi-resistant Klebsiella pneumoniae demands faster antimicrobial susceptibility testing (AST) to guide antibiotic treatment. Current ASTs rely on time-consuming differentiation of resistance and susceptibility after initial isolation of bacteria from a clinical specimen. Here we describe a flow cytometry workflow to determine carbapenem susceptibility from bacterial cell characteristics in an international K. pneumoniae isolate collection (n = 48), with a range of carbapenemases. Our flow cytometry-assisted susceptibility test (FAST) method combines rapid qualitative susceptible/non-susceptible classification and quantitative MIC measurement in a single process completed shortly after receipt of a primary isolate (54 and 158 minutes respectively). The qualitative FAST results and FAST-derived MIC (MICFAST) correspond closely with broth microdilution MIC (MICBMD, Matthew’s correlation coefficient 0.887), align with the international AST standard (ISO 200776-1; 2006) and could be used for rapid determination of antimicrobial susceptibility in a wider range of Gram negative and Gram positive bacteria.