bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytotoxic Rocaglate Derivatives from Leaves of Aglaia perviridis
Authors: An Fa-Liang , Wang Xiao-Bing , Wang Hui , Li Zhong-Rui , Yang Ming-Hua , Luo Jun , Kong Ling-Yi 
Published: January 2016

AbstractRocaglates are a series of structurally complex secondary metabolites with considerable cytotoxicity that have been isolated from plants of the Aglaia genus (Meliaceae). A new rocaglate (aglapervirisin A, 1) and its eight new biosynthetic precursors of rocaglate (aglapervirisins B-J, 2–9) together with five known compounds, were isolated from the leaves of Aglaia perviridis. Their structures were elucidated based on a joint effort of spectroscopic methods [IR, UV, MS, ECD, 1D- and 2D-NMR, HRESIMS], chemical conversion and single-crystal X-ray diffraction. Among these isolates, three (1, 10–11) were silvestrols, a rare subtype rocaglates, exhibiting notable cytotoxicity against four human tumor cell lines, with IC50 values between 8.0 and 15.0 nM. Aglapervirisin A (1) induces cell cycle arrest at the G2/M-phase boundary at concentration 10 nM accompanied by reductions in the expression levels of Cdc2 and Cdc25C in HepG2 cells after 72h co-incubation and further induces the apoptosis of HepG2 cells at concentrations over 160 nM.
Length Distribution of Ancestral Tracks under a General Admixture Model and Its Applications in Population History Inference
Authors: Ni Xumin , Yang Xiong , Guo Wei , Yuan Kai , Zhou Ying , Ma Zhiming , Xu Shuhua 
Published: January 2016

AbstractThe length of ancestral tracks decays with the passing of generations which can be used to infer population admixture histories. Previous studies have shown the power in recovering the histories of admixed populations via the length distributions of ancestral tracks even under simple models. We believe that the deduction of length distributions under a general model will greatly elevate the power. Here we first deduced the length distributions under a general model and proposed general principles in parameter estimation and model selection with the deduced length distributions. Next, we focused on studying the length distributions and its applications under three typical special cases. Extensive simulations showed that the length distributions of ancestral tracks were well predicted by our theoretical framework. We further developed a new method, AdmixInfer, based on the length distributions and good performance was observed when it was applied to infer population histories under the three typical models. Notably, our method was insensitive to demographic history, sample size and threshold to discard short tracks. Finally, good performance was also observed when applied to some real datasets of African Americans, Mexicans and South Asian populations from the HapMap project and the Human Genome Diversity Project.
CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients
Authors: Su Shu , Hu Bian , Shao Jie , Shen Bin , Du Juan , Du Yinan , Zhou Jiankui , Yu Lixia , Zhang Lianru , Chen Fangjun , Sha Huizi , Cheng Lei , Meng Fanyan , Zou Zhengyun , Huang Xingxu , Liu Baorui 
Published: January 2016

AbstractStrategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1. We showed that the gene knockout of PD-1 by electroporation of plasmids encoding sgRNA and Cas9 was technically feasible. The disruption of inhibitory checkpoint gene PD-1 resulted in significant reduction of PD-1 expression but didn’t affect the viability of primary human T cells during the prolongedin vitroculture. Cellular immune response of the gene modified T cells was characterized by up-regulated IFN-γ production and enhanced cytotoxicity. These results suggest that we have demonstrated an approach for efficient checkpoint inhibitor disruption in T cells, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies.
Topical imiquimod yields systemic effects due to unintended oral uptake
Authors: Grine Lynda , Steeland Sophie , Van Ryckeghem Sara , Ballegeer Marlies , Lienenklaus Stefan , Weiss Siegfried , Sanders Niek N. , Vandenbroucke Roosmarijn E. , Libert Claude 
Published: January 2016

AbstractRepetitive application of topical imiquimod is used as an experimental model for the induction of psoriasiform skin lesions in mice. The model is characterized by several inflammatory processes, including cytokine production both locally and systemically, cellular infiltration and splenomegaly. To investigate the production of type I interferons in response to imiquimod-containing Aldara cream, IFNβ-luciferase reporter mice were imaged in vivo and ex vivo. Type I interferons were found to be produced in the skin, but also in the intestinal system caused by unintended ingestion of imiquimod by the mice. Through the use of Elizabethan collars to prevent ingestion, these effects, including psoriasiform lesions were nearly completely prevented. Our findings reveal that topical treatment with Aldara induces a psoriasiform skin inflammation, but that its mode of action depends on ingestion of the chemical, which leads to systemic responses and affects local inflammation. Therefore, potential ingestion of topical treatments during experimental procedures should be taken into account during assessment of cutaneous inflammatory parameters in skin disease models.
Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice
Authors: Okubo Hirofumi , Kushiyama Akifumi , Sakoda Hideyuki , Nakatsu Yusuke , Iizuka Masaki , Taki Naoyuki , Fujishiro Midori , Fukushima Toshiaki , Kamata Hideaki , Nagamachi Akiko , Inaba Toshiya , Nishimura Fusanori , Katagiri Hideki , Asahara Takashi , Yoshida Yasuto , Chonan Osamu , Encinas Jeffery , Asano Tomoichiro 
Published: January 2016

AbstractResistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH.
Bilayered photoanode consisting of zinc oxide hollow spheres and urchin-like titanium dioxide microspheres enables fast electron transport and efficient light-harvesting for improved-performance dye-sensitized solar cells
Authors: Zhao Peilu , Wang Le , Yu Zhangduo , Liu Fengmin , Sun Peng , Gao Yuan , Lu Geyu 
Published: January 2016

Derived from ZnO hollow spheres (ZHSs) as the underlayer and urchin-like TiO2 spheres (UTSs) as the light scattering overlayer, a new bilayered photoanode (ZHS + UTS) is fabricated for use in dye-sensitized solar cells (DSSCs).
Environmental Politics: A Very Short Introduction
Authors: Dobson Andrew 
Published: January 2016

Abstract
Environmental Politics: A Very Short Introduction considers the many facets of environmental politics and shows how it operates at multiple scales: it preoccupies individuals as well as governments; drives local agreements as well as international treaties; results in minor business changes as well as wholesale business decisions; and fluctuates between a politics of protest and one of accommodation. Looking towards the future, this VSI asks whether environmental politics will be comfortably accommodated by mainstream politics, or whether the advent of the Anthropocene will herald a break with the politics of growth that has dominated social life since the beginning of the Industrial Revolution.
Deep-scattering layer, gas-bladder density, and size estimates using a two-frequency acoustic and optical probe
Authors: Kloser Rudy J. , Ryan Tim E. , Keith Gordon , Gershwin Lisa 
Published: January 2016

Abstract
Estimating the biomass of gas-bladdered organisms in the mesopelagic ocean is a simple first step to understanding ecosystem structure. An existing two-frequency (38 and 120 kHz) acoustic and optical probe was lowered to 950 m to estimate the number and size of gas-bladders. In situ target strengths from 38 and 120 kHz and their difference were compared with those of a gas-bladder resonance-scattering model. Predicted mean equivalent spherical radius gas-bladder size varied with depth, ranging from 2.1 mm (shallow) to 0.6 mm (deep). Density of night-time organisms varied throughout the water column and were highest (0.019 m−3) in the 200–300 m depth range. Predictions of 38 kHz volume-backscattering strength (Sv) from the density of gas-bladdered organisms could explain 88% of the vessel's 38 kHz Sv at this location (S 40.9, E 166.7). Catch retained by trawls highlighted the presence of gas-bladdered fish of a similar size range but different densities while optical measurements highlighted the depth distribution and biomass of gas-inclusion siphonophores. Organism behaviour and gear selectivity limits the validation of acoustic estimates. Simultaneous optical verification of multifrequency or broadband acoustic targets at depth are required to verify the species, their size and biomass.
The Baltic Sea scale inventory of benthic faunal communities
Authors: Gogina Mayya , Nygård Henrik , Blomqvist Mats , Daunys Darius , Josefson Alf B. , Kotta Jonne , Maximov Alexey , Warzocha Jan , Yermakov Vadim , Gräwe Ulf , Zettler Michael L. 
Published: January 2016

AbstractThis study provides an inventory of the recent benthic macrofaunal communities in the entire Baltic Sea. The analyses of soft-bottom benthic invertebrate community data based on over 7000 locations in the Baltic Sea suggested the existence of 10 major communities based on species abundances and 17 communities based on species biomasses, respectively. The low-saline northern Baltic, characterized by silty sediments, is dominated by Monoporeia affinis, Marenzelleria spp., and Macoma balthica. Hydrobiidae, Pygospio elegans, and Cerastoderma glaucum dominate the community in sandy habitats off the Estonian west coast and in the southeastern and southern Baltic Sea. Deep parts of the Gulf of Finland and central Baltic Sea often experience hypoxia, and when oxygen levels in these regions recover, Bylgides sarsi was the first species to colonize. The southwestern Baltic Sea, with high salinity, has higher macrofaunal diversity compared with the northern parts. To spatially interpolate the distribution of the major communities, we used the Random Forest method. Substrate data, bathymetric maps, and modelled hydrographical fields were used as predictors. Model predictions were in good agreement with observations, quantified by Cohen's κ of 0.90 for the abundance and 0.89 in the wet weight-based model. Misclassifications were mainly associated with uncommon classes in regions with high spatial variability. Our analysis provides a detailed baseline map of the distribution of benthic communities in the Baltic Sea to be used both in science and management.
Establishing an Ambulatory Medicine Quality and Safety Oversight Structure: Leveraging the Fractal Model
Authors: Kravet Steven J. , Bailey Jennifer , Demski Renee , Pronovost Peter 
Published: January 2016

Problem
Academic health systems face challenges in the governance and oversight of quality and safety efforts across their organizations. Ambulatory practices, which are growing in number, size, and complexity, face particular challenges in these areas.

Approach
In February 2014, leaders at Johns Hopkins Medicine (JHM) implemented a governance, oversight, and accountability structure for quality and safety efforts across JHM ambulatory practices. This model was based on the fractal approach, which balances independence and interdependence and provides horizontal and vertical support. It set expectations of accountability at all levels from the Board of Trustees to frontline staff and featured a cascading structure that reached all units and ambulatory practices. This model leveraged an Ambulatory Quality Council led by a physician and nurse dyad to provide the infrastructure to share best practices, continuously improve, and define accountable local leaders.

Outcomes
This model was incorporated into the quality and safety infrastructure across JHM. Improved outcomes in the domains of patient safety/risk reduction, externally reported quality measures, patient care/experience, and value have been demonstrated. An additional benefit was an improvement in Medicaid value-based purchasing metrics, which are linked to several million dollars of revenue.

Next Steps
As this model matures, it will serve as a mechanism to align quality standards and programs across regional, national, and international partners and to provide a clear quality structure as new practices join the health system. Future efforts will link this model to JHM’s academic mission, enhancing education to address Accreditation Council for Graduate Medical Education core competencies.
Versatility of an Extended Posterior Approach for the Treatment of Acetabular Fractures With Reference to the Superior Gluteal Neurovascular Bundle
Authors: Studer Patrick , Kosuge Dennis , Rickman Mark , Solomon Lucian B. 
Published: January 2016

Summary:
The superior gluteal neurovascular bundle is at risk of injury in certain types of acetabular fractures and the associated surgery. This article describes the versatility of an extended posterior approach, previously described for complex revision total hip replacement (the Adelaide approach) and for the treatment of acetabular fractures that allows a wide exposure of the ilium through identification, protection, and mobilization of the superior gluteal neurovascular bundle.
ESPGHAN Committee on Nutrition Position Paper. Intravenous Lipid Emulsions and Risk of Hepatotoxicity in Infants and Children
Authors: Hojsak Iva , Colomb Virginie , Braegger Christian , Bronsky Jiri , Campoy Cristina , Domellöf Magnus , Embleton Nicholas , Fidler Mis Nataša , Hulst Jessie M. , Indrio Flavia , Lapillonne Alexandre , Mihatsch Walter , Molgaard Christian , van Goudoever Johannes , Fewtrell Mary ,   ESPGHAN Committee on Nutrition
Published: January 2016

ABSTRACTThe aim of the present article was to perform a systematic review with meta‐analysis of available scientific evidence regarding the role of different intravenous lipid emulsions (ILE) in the pathogenesis of cholestasis and parenteral nutrition–associated liver disease. A systematic review of the literature (up to March 2015) identified 23 randomized controlled trials (RCTs). Of these, 17 were performed in preterm infants or critically ill neonates with a short duration of intervention, 2 in older children with short‐term use (following surgery or bone marrow transplantation), 1 in neonates with long‐term use, and 3 in infants and children receiving long‐term parenteral nutrition (PN). Meta‐analysis showed no differences in the rate of cholestasis or bilirubin levels associated with short‐term use of different ILEs. Because of high heterogeneity of the long‐term studies no meta‐analysis could be performed. Available studies found that the use of multicomponent fish oil (FO)‐containing ILE compared with pure soya bean oil (SO), ILE‐reduced liver enzymes, and bilirubin levels in noncholestatic children on long‐term PN and one other RCT found that FO‐based ILE‐reversed cholestasis in a proportion of patients. The ESPGHAN Committee on Nutrition concludes that there is no evidence of a difference in rates of cholestasis or bilirubin levels between different ILE for short‐term use in neonates. The use of multicomponent FO‐containing ILE may contribute to a decrease in total bilirubin levels in children with IF on prolonged PN. Well‐designed RCTs are, however, lacking and long‐term effects have not been determined.
Intact Regulatory T‐Cell Function but Defective Generation of IL–17A‐Producing CD4+ T Cells in XIAP Deficiency
Authors: Gurram Bhaskar , Hammelev Erin , Syverson Grant , Haribhai Dipica , Yan Key , Simpson Pippa , Salzman Nita , Verbsky James W. 
Published: January 2016

ABSTRACTObjective:X‐linked inhibitor of apoptosis (xIAP) deficiency is a primary immune deficiency disorder associated with hemophagocytic lymphohistiocytosis. About 17% of xIAP‐deficient patients present with very early onset severe colitis with high mortality. We hypothesized that xIAP deficiency leads to defective generation and/or survival of T regulatory cells (Treg) through its involvement in transforming growth factor‐β signaling.Methods and Results:We used a T‐cell transfer model of chronic colitis and observed a mild increase in colitis severity induced by naïve CD4+ T cells from xIAP0/− mice compared with colitis induced by naïve CD4+ T cells from WT mice. We did not observe any significant difference in the induction of Treg cells in these studies. We next tested whether xIAP is required for Treg cell function by co‐transferring xIAP−/0 or WT Treg cells with naïve WT CD4 cells in this model. We demonstrate that XIAP‐deficient Treg cells were able to prevent disease similarly to WT Treg cells. In these experiments we, however, found a significantly decreased percentage of IL–17A‐producing CD4+ T cells in mice receiving Tregs from xIAP0/− mice.Conclusions:xIAP appears dispensable for the generation of induced Treg cells as well as function of natural Treg cells. There appeared to be a role of xIAP in generation of IL–17‐producing cells from either naïve CD4+ T cells or Treg cells. Further research is needed to explore the role of xIAP in generation of IL–17‐producing cells.
Clinical Characteristics and Prognosis in Children and Adolescents With Autoimmune Hepatitis and Overlap Syndrome
Authors: Rodrigues Adriana T. , Liu Priscila M.F. , Fagundes Eleonora D.T. , Queiroz Thaís C.N. , de Souza Haueisen Barbosa Pamela , Silva Soraya L.C. , Simões e Silva Ana C. , Miranda Débora M. , Ferreira Alexandre R. , Alberti Luiz R. 
Published: January 2016

ABSTRACTObjectives:This is a cohort study of 134 children and adolescents with a known diagnosis of autoimmune hepatitis (AIH). During follow‐up, some of them developed autoimmune sclerosing cholangitis (ASC). This study describes the characteristics of the patients upon diagnosis, and their response to treatment and any complications, and compares the patients who developed ASC during follow‐up (ASC group) with those who did not (AIH group).Methods:A total of 73.1% of the patients were girls with a median age upon diagnosis of 10.41 (7.41–12.53) years.Results:Of 134 patients, 28 (20.9%) developed cholestatic manifestations, with features of ASC. A few differences were observed between the AIH and ASC groups when they were analyzed by χ2 test, such as the smaller predominance of girls in ASC group (P = 0.04), and more common asymptomatic presentation in the ASC group (P = 0.01). Cirrhosis was observed in 68% of biopsies, with no significant difference between groups (P = 0.43). Of 16 deaths, 15 were in the AIH group and 1 in the ASC group (P = 0.22). Of 11 transplants, 10 were in the AIH group and one in the ASC group (P = 0.53). The presence of cirrhosis at baseline was associated with a smaller survival probability (P = 0.015). The survival rate by Kaplan‐Meier method was 94% at 5 years and 80% at 10 years, and was similar in both the groups (P = 0.08).Conclusions:No statistically significant difference was observed between the groups in relation to prognosis and response to treatment.
Atypical Leber Hereditary Optic Neuropathy: 18 Year Interval Between Eyes
Authors: Ohden Kaitlyn L. , Tang Peter H. , Lilley Chrystia C. , Lee Michael S. 
Published: January 2016

Abstract:
A 5-year-old boy developed profound loss of vision in his right eye and was found to have a 11778 mitochondrial point mutation consistent with Leber hereditary optic neuropathy (LHON). He maintained 20/20 vision in the left eye for 18 years until age 23, when he experienced loss of vision in that eye. This 18 year interval between eye involvement in LHON is the longest reported to date and reinforces the variability in presentation and progression seen in this disease.
Nuclear and mitochondrial phylogeny ofRossella(Hexactinellida: Lyssacinosida, Rossellidae): a species and a species flock in the Southern Ocean
Authors: Vargas Sergio , Dohrmann Martin , Göecke Christian , Janussen Dorte , Wöerheide Gert 
Published: January 2016

AbstractHexactinellida (glass sponges) are abundant and important components of Antarctic benthic communities. However, the relationships and systematics within the common genusRossellaCarter, 1872 (Lyssacinosida: Rossellidae) are unclear and in need of revision. The species content of this genus has changed dramatically over the years depending on the criteria used by the taxonomic authority consulted.Rossellawas formerly regarded as a putatively monophyletic group distributed in the Southern Ocean and the North Atlantic. However, molecular phylogenetic analyses have shown thatRossellais restricted to the Southern Ocean, where it shows a circum-Antarctic and subantarctic distribution. Herein, we provide a molecular phylogenetic analysis of the genusRossella, based on mitochondrial (16S rDNA and COI) and nuclear (28S rDNA) markers. We corroborate the monophyly ofRossellaand provide evidence supporting the existence of one species, namelyRossella antarcticaCarter, 1872 and a species flock including specimens determined asRossella racovitzaeTopsent, 1901,Rossella nudaTopsent, 1901,Rossella fibulataSchulze & Kirkpatrick, 1910, andRossella levis(Kirkpatrick, 1907).
A Genetically Encoded Reporter for Diffusion Weighted Magnetic Resonance Imaging
Authors: Mukherjee Arnab , Wu Di , Davis Hunter C. , Shapiro Mikhail G. 
Published: January 2016

ABSTRACTThe ability to monitor gene expression in intact, optically opaque animals is important for a multitude of applications including longitudinal imaging of transgene expression and long term tracking of cell based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatial and temporal resolution. However, existing MRI reporter genes, based primarily on metal-binding proteins or chemical exchange saturation transfer probes, are limited by their reliance on metal ions or relatively low sensitivity. In this work, we introduce a new class of genetically encoded reporters for MRI that work by altering water diffusivity. We show that overexpression of the human water channel aquaporin 1 (AQP1) produces robust contrast in diffusion weighted MRI by increasing effective water diffusivity in tissues by over 100% without affecting cell viability or morphology. Low levels of AQP1 expression (˜1 μM), or mixed populations comprising as few as 10% AQP1-expressing cells, produce sufficient contrast to be observed by MRI. We demonstrate the utility of AQP1in vivoby imaging gene expression in intracranial tumor xenografts. Overall, our results establish AQP1 as a new, metal-free, nontoxic and sensitive genetically encoded reporter for diffusion weighted MRI.