bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming the dichotomy between open and isolated populations using genomic data from a large European dataset
Authors: Anagnostou Paolo , Dominici Valentina , Battaggia Cinzia , Pagani Luca , Vilar Miguel , Wells R. Spencer , Pettener Davide , Sarno Stefania , Boattini Alessio , Francalacci Paolo , Colonna Vincenza , Vona Giuseppe , Calò Carla , Destro Bisol Giovanni , Tofanelli Sergio 
Published: February 2017

AbstractHuman populations are often dichotomized into “isolated” and “open” categories using cultural and/or geographical barriers to gene flow as differential criteria. Although widespread, the use of these alternative categories could obscure further heterogeneity due to inter-population differences in effective size, growth rate, and timing or amount of gene flow. We compared intra and inter-population variation measures combining novel and literature data relative to 87,818 autosomal SNPs in 14 open populations and 10 geographic and/or linguistic European isolates. Patterns of intra-population diversity were found to vary considerably more among isolates, probably due to differential levels of drift and inbreeding. The relatively large effective size estimated for some population isolates challenges the generalized view that they originate from small founding groups. Principal component scores based on measures of intra-population variation of isolated and open populations were found to be distributed along a continuum, with an area of intersection between the two groups. Patterns of inter-population diversity were even closer, as we were able to detect some differences between population groups only for a few multidimensional scaling dimensions. Therefore, different lines of evidence suggest that dichotomizing human populations into open and isolated groups fails to capture the actual relations among their genomic features.
Muscle-specific overexpression of AdipoR1 or AdipoR2 gives rise to common and discrete local effects whilst AdipoR2 promotes additional systemic effects
Authors: Keshvari Sahar , Henstridge Darren C. , Ng Choaping , Febbraio Mark A. , Whitehead Jonathan P. 
Published: February 2017

AbstractHypoadiponectinemia and adiponectin resistance are implicated in the aetiology of obesity-related cardiometabolic disorders, hence represent a potential therapeutic axis. Here we characterised the effects of in vivo electrotransfer-mediated overexpression of the adiponectin receptors, AdipoR1 or AdipoR2, into tibialis anterior muscle (TAM) of lean or obese mice. In lean mice, TAM-specific overexpression of AdipoR1 (TAMR1) or AdipoR2 (TAMR2) increased phosphorylation of AMPK, AKT and ERK and expression of the insulin responsive glucose transporter glut4. In contrast, only TAMR2 increased pparα and a target gene acox1. These effects were decreased in obese mice despite no reduction in circulating adiponectin levels. TAMR2 also increased expression of adipoQ in TAM of lean and obese mice. Furthermore, in obese mice TAMR2 promoted systemic effects including; decreased weight gain; reduced epididymal fat mass and inflammation; increased epididymal adipoQ expression; increased circulating adiponectin. Collectively, these results demonstrate that AdipoR1 and AdipoR2 exhibit overlapping and distinct effects in skeletal muscle consistent with enhanced adiponectin sensitivity but these appear insufficient to ameliorate established obesity-induced adiponectin resistance. We also identify systemic effects upon TAMR2 in obese mice and postulate these are mediated by altered myokine production. Further studies are warranted to investigate this possibility which may reveal novel therapeutic approaches.
Membrane engineering of S. cerevisiae targeting sphingolipid metabolism
Authors: Lindahl Lina , Santos Aline X. S. , Olsson Helén , Olsson Lisbeth , Bettiga Maurizio 
Published: February 2017

AbstractThe sustainable production of fuels and chemicals using microbial cell factories is now well established. However, many microbial production processes are still limited in scale due to inhibition from compounds that are present in the feedstock or are produced during fermentation. Some of these inhibitors interfere with cellular membranes and change the physicochemical properties of the membranes. Another group of molecules is dependent on their permeation rate through the membrane for their inhibition. We have investigated the use of membrane engineering to counteract the negative effects of inhibitors on the microorganism with focus on modulating the abundance of complex sphingolipids in the cell membrane ofSaccharomyces cerevisiae. Overexpression ofELO3, involved in fatty acid elongation, andAUR1, which catalyses the formation of complex sphingolipids, had no effect on the membrane lipid profile or on cellular physiology. Deletion of the genesORM1andORM2, encoding negative regulators of sphingolipid biosynthesis, decreased cell viability and considerably reduced phosphatidylinositol and complex sphingolipids. Additionally, combiningELO3andAUR1overexpression withorm1/2Δimproved cell viability and increased fatty acyl chain length compared with onlyorm1/2Δ. These findings can be used to further study the sphingolipid metabolism, as well as giving guidance in membrane engineering.
Angptl4 does not control hyperglucagonemia or α-cell hyperplasia following glucagon receptor inhibition
Authors: Okamoto Haruka , Cavino Katie , Na Erqian , Krumm Elizabeth , Kim Steven , Stevis Panayiotis E. , Harp Joyce , Murphy Andrew J. , Yancopoulos George D. , Gromada Jesper 
Published: February 2017

Significance
Glucagon supports glucose homeostasis by stimulating hepatic glucose output. Inhibition of glucagon signaling has drawn much attention because of potential implications for diabetes treatment. It is well established that inhibition of glucagon signaling effectively lowers blood glucose but results in compensatory glucagon hypersecretion and expansion of pancreatic α-cell mass. It was recently proposed that Angptl4, an inhibitor of lipoprotein lipase-mediated plasma triglyceride clearance, links glucagon receptor inhibition to α-cell proliferation. Here we confirm that Angptl4 is a powerful regulator of plasma triglycerides, but not of hyperglucagonemia or α-cell hyperplasia. We observed an increase in plasma amino acids in humans following administration of a glucagon receptor-blocking antibody, confirming preclinical findings indicate that amino acids mediate the compensatory α-cell response.
Trophic Interactions and Consumption Rates of Subyearling Chinook Salmon and Nonnative Juvenile American Shad in Columbia River Reservoirs
Authors: Haskell Craig A. , Beauchamp David A. , Bollens Stephen M. 
Published: February 2017

AbstractWe used a large lampara seine coupled with nonlethal gastric lavage to examine the diets and estimate consumption rates of subyearling Chinook Salmon Oncorhynchus tshawytscha during July and August 2013. During August we also examined the diet and consumption rates of juvenile American Shad Alosa sapidissima, a potential competitor of subyearling Chinook Salmon. Subyearling Chinook Salmon consumed Daphnia in July but switched to feeding on smaller juvenile American Shad in August. We captured no juvenile American Shad in July, but in August juvenile American Shad consumed cyclopoid and calanoid copepods. Stomach evacuation rates for subyearling Chinook Salmon were high during both sample periods (0.58 h−1 in July, 0.51 h−1 in August), and daily ration estimates were slightly higher than values reported in the literature for other subyearlings. By switching from planktivory to piscivory, subyearling Chinook Salmon gained greater growth opportunity. While past studies have shown that juvenile American Shad reduce zooplankton availability for Chinook Salmon subyearlings, our work indicates that they also become important prey after Daphnia abundance declines. The diet and consumption data here can be used in future bioenergetics modeling to estimate the growth of subyearling Chinook Salmon in lower Columbia River reservoirs.Received July 27, 2016; accepted November 22, 2016 Published online February 1, 2017
Citizens in appropriate numbers: evaluating five claims about justice and population size
Authors: Meijers Tim 
Published: February 2017

AbstractWhile different worries about population size are present in public debates, political philosophers often take population size as given. This paper is an attempt to formulate a Rawlsian liberal egalitarian approach to population size: does it make sense to speak of ‘too few’ or ‘too many’ people from the point of view of justice? It argues that, drawing on key features of liberal egalitarian theory, several clear constraints on demographic developments – to the extent that they are under our control – can be formulated. Based on these claims, we can clarify both the grounds and content of our obligations to future generations.
Residual urinary extracellular vesicles in ultracentrifugation supernatants after hydrostatic filtration dialysis enrichment
Authors: Musante Luca , Tataruch‐Weinert Dorota , Kerjaschki Dontscho , Henry Michael , Meleady Paula , Holthofer Harry 
Published: February 2017

ABSTRACTUrinary extracellular vesicles (UEVs) appear an ideal source of biomarkers for kidney and urogenital diseases. The majority of protocols designed for their isolation are based on differential centrifugation steps. However, little is still known of the type and amount of vesicles left in the supernatant. Here we used an isolation protocol for UEVs which uses hydrostatic filtration dialysis as first pre‐enrichment step, followed by differential centrifugation. Transmission electron microscopy (TEM), mass spectrometry (MS), western blot, ELISA assays and tuneable resistive pulse sensing (TRPS) were used to characterise and quantify UEVs in the ultracentrifugation supernatant. TEM showed the presence of a variety of small size vesicles in the supernatant while protein identification by MS matched accurately with the protein list available in Vesiclepedia. Screening and relative quantification for specific vesicle markers showed that the supernatant was preferentially positive for CD9 and TSG101. ELISA tests for quantification of exosome revealed that 14%, was left in the supernatant with a particle diameter of 110 nm and concentration of 1.54 × 1010/ml. Here we show a comprehensive characterisation of exosomes and other small size urinary vesicles which the conventional differential centrifugation protocol may lose.
Ribonucleic artefacts: are some extracellular RNA discoveries driven by cell culture medium components?
Authors: Tosar Juan Pablo , Cayota Alfonso , Eitan Erez , Halushka Marc K. , Witwer Kenneth W. 
Published: February 2017

ABSTRACTIn a recently published study, Anna Krichevsky and colleagues raise the important question of whether results of in vitro extracellular RNA (exRNA) studies, including extracellular vesicle (EV) investigations, are confounded by the presence of RNA in cell culture medium components such as foetal bovine serum (FBS). The answer, according to their data, is a resounding “yes”. Even after lengthy ultracentrifugation to remove bovine EVs from FBS, the majority of exRNA in FBS remained. Although technical factors may affect the degree of depletion, residual EVs and exRNA in FBS could influence the conclusions of in vitro studies: certainly, for secreted RNA, and possibly also for cell‐associated RNA. In this commentary, we critically examine some of the literature in this field, including a recent study from some of the authors of this piece, in light of the Wei et al. study and explore how cell culture‐derived RNAs may affect what we think we know about EV RNAs. These findings hold particular consequence as the field moves towards a deeper understanding of EV–RNA associations and potential functions.
TRAIL delivery by MSC‐derived extracellular vesicles is an effective anticancer therapy
Authors: Yuan ZhengQiang , Kolluri Krishna K. , Gowers Kate H. C. , Janes Sam M. 
Published: February 2017

ABSTRACTExtracellular vesicles (EVs) are lipid membrane‐enclosed nanoparticles released by cells. They mediate intercellular communication by transferring biological molecules and therefore have potential as innovative drug delivery vehicles. TNF‐related apoptosis‐inducing ligand (TRAIL) selectively induces apoptosis of cancer cells. Unfortunately, the clinical application of recombinant rTRAIL has been hampered by its low bioavailability and resistance of cancer cells. EV‐mediated TRAIL delivery may circumvent these problems. Mesenchymal stromal cells (MSCs) produce EVs and could be a good source for therapeutic EV production. We investigated if TRAIL could be expressed in MSC‐derived EVs and examined their cancer cell‐killing efficacy. EVs were isolated by ultracentrifugation and were membranous particles of 50–70 nm in diameter. Both MSC‐ and TRAIL‐expressing MSC (MSCT)‐derived EVs express CD63, CD9 and CD81, but only MSCT‐EVs express surface TRAIL. MSCT‐EVs induced apoptosis in 11 cancer cell lines in a dose‐dependent manner but showed no cytotoxicity in primary human bronchial epithelial cells. Caspase activity inhibition or TRAIL neutralisation blocked the cytotoxicity of TRAIL‐positive EVs. MSCT‐EVs induced pronounced apoptosis in TRAIL‐resistant cancer cells and this effect could be further enhanced using a CDK9 inhibitor. These data indicate that TRAIL delivery by MSC‐derived EVs is an effective anticancer therapy.
Pharmacokinetics of anti-TB drugs in Malawian children: reconsidering the role of ethambutol
Authors: Mlotha R. , Waterhouse D. , Dzinjalamala F. , Ardrey A. , Molyneux E. , Davies G. R. , Ward S. 
Published: February 2017

Abstract

Background
Current guidelines for dosing of anti-TB drugs in children advocate higher doses for rifampicin and isoniazid despite limited availability of paediatric data on the pharmacokinetics of these drugs, especially from Africa, where the burden of childhood disease remains high.

Methods
Thirty children aged 6 months to 15 years underwent intensive pharmacokinetic sampling for first-line anti-TB drugs at Queen Elizabeth Central Hospital, Blantyre, Malawi. Rifampicin, isoniazid, pyrazinamide and ethambutol were dosed at 10, 5, 25 and 20 mg/kg, respectively. Plasma drug concentrations were determined using sensitive, validated bioanalytical methods and summary pharmacokinetic parameters were estimated using non-compartmental analysis.

Results
The median (IQR) Cmax was 2.90 (2.08–3.43), 3.37 (2.55–4.59), 34.60 (32.30–40.90) and 1.20 (0.85–1.68) mg/L while the median (IQR) AUC0–∞ was 16.92 (11.10–22.74), 11.48 (7.35–18.93), 333.50 (279.50–487.2) and 8.65 (5.96–11.47) mg·h/L for rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. For all drugs, pharmacokinetic parameters relating to drug absorption and exposure were lower than those published for adults, though similar to existing paediatric data from sub-Saharan Africa. Weight and/or dose predicted at least one measure of exposure for all drugs. Age-related decreases in CL/F for rifampicin and pyrazinamide and a biphasic elimination pattern of isoniazid were observed. Predicted AUC0–∞ for rifampicin dosed at 15 mg/kg was comparable to that of adults while the dose required to achieve ethambutol exposure similar to that in adults was 55 mg/kg or higher.

Conclusions
These data support recently revised WHO recommendations for dosing of anti-TB drugs in children, but dosing of ethambutol in children also appears inadequate by comparison with adult pharmacokinetic data.
The impact of enhanced iron opacity on massive star pulsations: updated instability strips
Authors: Moravveji Ehsan 
Published: February 2017

Abstract
Recently, Bailey et al. made a direct measurement of the iron opacity at the physical conditions of the solar tachocline. They found that the wavelength-integrated iron opacity is roughly 75 per cent higher than what the Opacity Project (OP) and OPAL models predict. Here, we compute new opacity tables with enhanced iron and nickel contributions to the Rosseland mean opacity by 75 per cent each, and compute three dense mesa grids of evolutionary models for Galactic O- and B-type stars covering from 2.5 to 25 M⊙ from zero-age main sequence (ZAMS) until Teff = 10 000 K after the core hydrogen exhaustion. We carry out non-adiabatic mode stability analysis with gyre, and update the extension of the instability strips of heat-driven p- and g-mode pulsators, and the hybrid slowly pulsating B (SPB) - β Cep stars. We compare the position of two confirmed late O-type β Cep and eight confirmed hybrid B-type pulsators with the new instability domains, and justify that ∼75 per cent enhancement, only in iron opacity, is sufficient to consistently reproduce the observed position of these stars on the log Teff versus log g plane. We propose that this improvement in opacities be incorporated in the input physics of new stellar models.
Bayesian redshift-space distortions correction from galaxy redshift surveys
Authors: Kitaura Francisco-Shu , Ata Metin , Angulo Raul E. , Chuang Chia-Hsun , Rodríguez-Torres Sergio , Monteagudo Carlos Hernández , Prada Francisco , Yepes Gustavo 
Published: February 2017

AbstractWe present a Bayesian reconstruction method which maps a galaxy distribution from redshift- to real-space inferring the distances of the individual galaxies. The method is based on sampling density fields assuming a lognormal prior with a likelihood modelling non-linear stochastic bias. Coherent redshift-space distortions are corrected in a Gibbs-sampling procedure by moving the galaxies from redshift- to real-space according to the peculiar motions derived from the recovered density field using linear theory. The virialized distortions are corrected by sampling candidate real-space positions along the line of sight, which are compatible with the bulk flow corrected redshift-space position adding a random dispersion term in high-density collapsed regions (defined by the eigenvalues of the Hessian). This approach presents an alternative method to estimate the distances to galaxies using the three-dimensional spatial information, and assuming isotropy. Hence the number of applications is very broad. In this work, we show the potential of this method to constrain the growth rate up to k ∼ 0.3 h Mpc−1. Furthermore it could be useful to correct for photometric redshift errors, and to obtain improved baryon acoustic oscillations (BAO) reconstructions.
β-1,2-Mannosyltransferases 1 and 3 Participate in Yeast and Hyphae O- and N-Linked Mannosylation and Alter Candida albicans Fitness During Infection
Authors: Courjol Flavie , Jouault Thierry , Mille Céline , Hall Rebecca , Maes Emmanuel , Sendid Boualem , Mallet Jean Maurice , Guerardel Yann , Gow Neil A. R. , Poulain Daniel , Fradin Chantal 
Published: February 2017

Abstractβ-1,2-mannosylation of Candida albicans glycoconjugates has been investigated through the identification of enzymes involved in the addition of β-1,2-oligomannosides (β-Mans) to phosphopeptidomannan and phospholipomannan. β-1,2-oligomannosides are supposed to have virulence properties that they confer to these glycoconjugates. In a previous study, we showed that cell wall mannoproteins (CWMPs) harbor β-Mans in their O-mannosides; therefore, we analyzed their biosynthesis and impact on virulence. In this study, we demonstrate that O-mannans are heterogeneous and that α-mannosylated O-mannosides, which are biosynthesized by Mnt1 and Mnt2 α-1,2-mannosyltransferases, can be modified with β-Mans but only at the nonreducing end of α-1,2-mannotriose. β-1,2-mannosylation of this O-mannotriose depends on growth conditions, and it involves 2 β-1,2-mannosyltransferases, Bmt1 and Bmt3. These Bmts are essential for β-1,2-mannosylation of CWMPs and expression of β-Mans on germ tubes. A bmt1Δ mutant and a mutant expressing no β-Mans unexpectedly disseminated more in BALB/c mice, whereas they had neither attenuated nor enhanced virulence in C57BL/6 mice. In galectin (Gal)3 knockout mice, the reference strain was more virulent than in C57BL/6 mice, suggesting that the β-Mans innate receptor Gal3 is involved in C. albicans fitness during infection.
Inheritance of resistance to peanut mottle virus in Phaseolus vulgaris
Authors: Provvidenti R. , Chirco E. M. 
Published: February 2017

Abstract
One-hundred-and-eleven bean (Phaseolus vulgaris) cultivars of domestic and foreign origin reacted identically to the N and the M strains of peanut mottle virus (PMV). Seventy-eight cultivars (70 percent) developed chlorotic or necrotlc local lesions, without systemic infection (resistant). Thirty cultivars (27 percent) were infected with local chlorotic or necrotic lesions followed by systemic necrosis and death (susceptible). Three cultivars (3 percent) yielded resistant and susceptible plants (heterogeneous populations). In F1, F2, and reciprocal backcross populations derived from crosses between PMV-resistant and -susceptible selections of the cultivar Royalty Purple Pod, resistance to the N strain was conferred by a single, but incompletely dominant gene, designated Pmv. No seed transmission of PMV could be demonstrated in progenies of susceptible cultivars because of premature death. The virus was not transmitted in seed of F2 Intermediate resistant plants.
T-DNA integration is rapid and influenced by the chromatin state of the host genome
Authors: Shilo Shay , Tripathi Pooja , Melamed-Bessudo Cathy , Tzfadia Oren , Muth Theodore R. , Levy Avraham A. 
Published: February 2017

AbstractAgrobacterium tumefaciensmediated T-DNA integration is a common tool for plant genome manipulation. However, there is controversy regarding whether T-DNA integration is biased towards genes or randomly distributed throughout the genome. In order to address this question, we performed high-throughput mapping of T-DNA-genome junctions obtained in the absence of selection at several time points after infection. T-DNA-genome junctions were detected as early as 6 hours post-infection. T-DNA distribution was apparently uniform throughout the chromosomes, yet local biases toward AT-rich motifs and T-DNA border sequence micro-homology were detected. Analysis of the epigenetic landscape of integration showed that selected events reported on previously were associated with extremely low methylation and nucleosome occupancy. Conversely, non-selected events from this study showed chromatin marks, such as high nucleosome occupancy and high H3K27me3 that correspond to 3D-interacting heterochromatin islands embedded within euchromatin. Such structures might play a role in capturing and silencing invading T-DNA.