bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid metabolic perturbation is an early-onset phenotype in adultspinmutants: aDrosophilamodel for lysosomal storage disorders
Authors: Hebbar Sarita , Khandelwal Avinash , Jayashree R , Hindle Samantha J. , Chiang Yin Ning , Yew Joanne Y. , Sweeney Sean T. , Schwudke Dominik 
Published: September 2016

AbstractIntracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases including lysosomal storage disorders (LSD). A detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. In this study, we systematically analyzed lipid perturbations inspinster (spin)mutants, aDrosophilamodel of neurodegeneration associated with LSD. Our results highlight an imbalance in brain ceramide and sphingosine as a crucial phenotype in the early stages of neurodegeneration. This perturbation in ceramide metabolism precedes the accumulation of endomembranous structures, manifestation of altered behavior and buildup of lipofuscin (the ageing pigment). Manipulating levels ofceramidase, and, consequently further altering these lipids inspinmutants have allowed us to conclude that ceramide/sphingosine homeostasis is the driving force in disease progression and is integral tospinfunction in the adult nervous system. Furthermore, we have identified 29 novel and direct interaction partners of Spin. We specifically focused on the lipid carrier protein, Lipophorin (Lpp), and demonstrate its localization with Spin in the adult nervous system and in organs specialized for lipid metabolism including fat bodies and oenocytes. Our observations inspinmutants of altered Lpp immunostaining, and of increased levels of lipid metabolites produced by oenocytes, allude to a functional relevance of the Spin-Lpp interaction.Overall, these results detailing the kinetics of ceramide perturbations in the context of lipofuscin accumulation, as well as the proteomics experiment, represent a valuable resource to further unravel the mechanistic link between systemic changes in lipid metabolism and lysosomal storage disorders.Summary StatementElevations in specific brain lipids and connections to relevant metabolic genes are identified in a fly model for lysosomal storage disorders. This enables a better understanding of disease progression.
The species problem from the modeler’s point of view
Authors: Manceau Marc , Lambert Amaury 
Published: September 2016

AbstractHow to define a partition of individuals into species is a long-standing question called thespecies problemin systematics. Here, we focus on this problem in the thought experiment where individuals reproduce clonally and both the differentiation process and the population genealogies are explicitly known. We point out three desirable properties of species partitions: (A) Heterotypy between species, (B) Homotypy within species and (M) Monophyly of each species. We then ask: How and when is it possible to delineate species in a way satisfying these properties?We point out that the three desirable properties cannot in general be satisfied simultaneously, but that any two of them can. We mathematically prove the existence of the finest partition satisfying (A) and (M) and the coarsest partition satisfying (B) and (M). For each of them, we propose a simple algorithm to build the associated phylogeny out of the genealogy.The ways we propose to phrase the species problem shed new light on the interaction between the genealogical and phylogenetic scales in modeling work. The two definitions centered on the monophyly property can readily be used at a higher taxonomic level as well, e.g. to cluster species into monophyletic genera.
Evapotranspiration is resilient in the face of land cover and climate change in a humid temperate catchment
Authors: Hamilton S. K. , Hussain M. Z. , Lowrie C. , Basso B. , Robertson G. P. 
Published: September 2016

AbstractIn temperate humid catchments, evapotranspiration returns more than half of the annual precipitation to the atmosphere, thereby determining the balance available to recharge groundwaters and support stream flow and lake levels. Changes in evapotranspiration rates and therefore catchment hydrology could be driven by changes in land use or climate. Here we examine the catchment water balance over the past 50 y for a catchment in southwest Michigan covered by cropland, grassland, forest, and wetlands. Over the study period about 27% of the catchment has been abandoned from row-crop agriculture to perennial vegetation and about 20% of the catchment has reverted to deciduous forest, and the climate has warmed by 1.14°C. Despite these changes in land use, precipitation and stream discharge, and by inference catchment-scale evapotranspiration, have been stable over the study period. The remarkably stable rates of evapotranspirative water loss from the catchment across a period of significant land cover change suggest that rainfed annual crops and perennial vegetation do not differ greatly in evapotranspiration rates, and this is supported by measurements of evapotranspiration from various vegetation types based on soil water monitoring in the same catchment. Compensating changes in the other meteorological drivers of evaporative water demand besides air temperature—wind speed, atmospheric humidity, and net radiation—are also possible, but cannot be evaluated due to insufficient local data across the 50-y period. Regardless of the explanation, this study shows that the water balance of this landscape has been resilient in the face of both land cover and climate change over the past 50 y.
Better together: a transboundary approach to brown bear monitoring in the Pyrenees
Authors: Piédallu Blaise , Quenette Pierre-Yves , Jordana Ivan Afonso , Bombillon Nicolas , Gastineau Adrienne , Jato Ramón , Miquel Christian , Muñoz Pablo , Palazón Santiago , Solà de la Torre Jordi , Gimenez Olivier 
Published: September 2016

AbstractHuman administrative borders have no effect on wild animals, and the vast home ranges of large carnivores often cause them to live simultaneously on the territory of two or more countries or jurisdictions with different management policies. Here, we investigate the importance of transboundary population monitoring using as a case study the Pyrenean brown bear population (Ursus arctos) that lives in France, Andorra and Spain. Using capture-recapture models and the Pollock’s robust design, we estimated abundance and demographic parameters using data collected separately in France and Spain and a dataset gathered from joint monitoring on both sides of the border. As expected, the abundance estimates from French (from 11 bears in 2008 to 13 in 2014) or Spanish (from 4 bears in 2008 to 9 in 2014) data only were lower than abundance obtained from both sides of the border (from 11 in 2008 to 18 in 2014). The joint monitoring dataset also highlighted the importance of individual detection heterogeneity that, if ignored, would lead to underestimation. Our results reinforce the importance of transboundary cooperation when dealing with animal populations with territory spanning two or more administrative jurisdictions for collecting reliable scientific data and providing relevant abundance estimation to take sound management decisions.
Insertional mutagenesis in PLNR9Ctransgenic mouse: a case report and a review of the literature on cardiac-specific transgenic expression
Authors: Kraev Alexander 
Published: September 2016

AbstractA mouse line with heterozygous transgenic expression of phospholamban carrying a substitution of cysteine for arginine 9 (PLNR9C) under the control of α-myosin heavy chain (αMHC) promoter features dilated cardiomyopathy, heart failure and premature death. In this line the transgenic array of 13 PLNR9Cexpression cassettes, arranged in a head-to-tail tandem orientation, has integrated into the homologous genomic site, the bi-directional promoter of the αMHC (Myh6) gene and the gene for the regulatory non-coding RNA Myheart (Mhrt), both of which are involved in the execution of the α/β MHC switch during cardiac development and pathology. PLNR9Coverexpression is evident at the age of 1 month but declines dramatically along with a less pronounced concomitant decline of the resident PLN expression, until the animals die. Expression of the non-coding RNA Mhrt in PLNR9Cmice also exhibits a profound deregulation, despite the presence of the second, intact allele. Hence the mouse strain does not faithfully model a human PLNR9Cheterozygote, wherein both the mutant and the wildtype PLN alleles have, in all likelihood, the same temporal expression profile. The intricate regulatory circuit of the α/β MHC switch, involving the non-coding RNA Mhrt, was described in detail only recently, and since publications about αMHC-driven transgenes rarely contain the definition of the transgene integration site or temporal expression profile, it is suggested that some of the pathological phenomena attributed to expression of αMHC-driven transgenes may have an alternative explanation.
Thermographic measurements of the commercial laser powder bed fusion process at NIST
Authors: Lane Brandon , Moylan Shawn , Whitenton Eric P. , Ma Li 
Published: September 2016

Purpose
Quantitative understanding of the temperatures, gradients and heating/cooling rates in and around the melt pool in laser powder bed fusion (L-PBF) is essential for simulation, monitoring and controls development. The research presented here aims to detail experiment design and preliminary results of high speed, high magnification, in-situ thermographic monitoring setup on a commercial L-PBF system designed to capture temperatures and dynamic process phenomena.

Design/methodology/approach
A custom door with angled viewport was designed for a commercial L-PBF system which allows close access of an infrared camera. Preliminary finite element simulations provided size, speed and scale requirements to design camera and optics setup to capture melt pool region temperatures at high magnification and frame rate speed. A custom thermal calibration allowed maximum measurable temperature range of 500°C to 1,025°C. Raw thermographic image data were converted to temperature assuming an emissivity of 0.5. Quantitative temperature results are provided with qualitative observations with discussion regarding the inherent challenges to future thermographic measurements and process monitoring.

Findings
Isotherms around the melt pool change in size depending on the relative location of the laser spot with respect to the stripe edges. Locations near the edges of a stripe are cooled to lower temperatures than the center of a stripe. Temperature gradients are highly localized because of rough or powdery surface. At a specific location, temperatures rise from below the measurable temperature range to above (<550°C to >1100°C) within two frames (<1.11 m/s). Particle ejection is a notable phenomenon with measured ejection speeds >11.7 m/s.

Originality/value
Several works are detailed in the Introduction of this paper that detail high-speed visible imaging (not thermal imaging) of custom or commercial LBPF processes, and lower-speed thermographic measurements for defect detection. However, no work could be found that provides calibrated, high-speed temperature data from a melt-pool monitoring configuration on a commercial L-PBF system. In addition, the paper elucidates several sources of measurement uncertainty (e.g. calibration, emissivity and time and spatial resolution), describes inherent measurement challenges based on observations of the thermal images and discusses on the implications to model validation and process monitoring and control.
Constructions, reconstructions and deconstructions of ‘family’ amongst people who live apart together (LATs)
Authors: Stoilova Mariya , Roseneil Sasha , Carter Julia , Duncan Simon , Phillips Miranda 
Published: September 2016

AbstractThis article explores how people who live apart from their partners in Britain describe and understand ‘family’. It investigates whether, and how far, non‐cohabiting partners, friends, ‘blood’ and legal ties are seen as ‘family’, and how practices of care and support, and feelings of closeness are related to these constructions. It suggests that people in LAT relationships creatively draw and re‐draw the boundaries of family belonging in ways that involve emotionally subjective understandings of family life, and that also refer to normative constructions of what ‘family’ ought to be, as well as to practical recognitions of lived family ‘realities’. This often involves handling uncertainties about what constitutes ‘family’.
The Predictive Value of Preendoscopic Risk Scores to Predict Adverse Outcomes in Emergency Department Patients With Upper Gastrointestinal Bleeding: A Systematic Review
Authors: Ramaekers Rosa , Mukarram Muhammad , Smith Christine A. M. , Thiruganasambandamoorthy Venkatesh 
Published: September 2016

AbstractObjectivesRisk stratification of emergency department (ED) patients with upper gastrointestinal bleeding (UGIB) using preendoscopic risk scores can aid ED physicians in disposition decision‐making. We conducted a systematic review to assess the predictive value of preendoscopic risk scores for 30‐day serious adverse events.MethodsWe searched MEDLINE, PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to March 2015. We included studies involving adult ED UGIB patients evaluating preendoscopic risk scores and excluded reviews, case reports, and animal studies. The composite outcome included 30‐day mortality, recurrent bleeding, and need for intervention. In two phases (screening and full review), two reviewers independently screened articles for inclusion and extracted patient‐level data. The consensus data were used for analysis. We reported sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios with 95% confidence intervals.ResultsWe identified 3,173 articles, of which 16 were included: three studied Glasgow Blatchford score (GBS); one studied clinical Rockall score (cRockall); two studied AIMS65; six compared GBS and cRockall; three compared GBS, a modification of the GBS, and cRockall; and one compared the GBS and AIMS65. Overall, the sensitivity and specificity of the GBS were 0.98 and 0.16, respectively; for the cRockall they were 0.93 and 0.24, respectively; and for the AIMS65 they were 0.79 and 0.61, respectively. The GBS with a cutoff point of 0 had a sensitivity of 0.99 and a specificity of 0.08.ConclusionThe GBS with a cutoff point of 0 was superior over other cutoff points and risk scores for identifying low‐risk patients but had a very low specificity. None of the risk scores identified by our systematic review were robust and, hence, cannot be recommended for use in clinical practice. Future prospective studies are needed to develop robust new scores for use in ED patients with UGIB.
The perfect storm: Weed invasion and intense storms in tropical forests
Authors: Murphy Helen T. , Metcalfe Daniel J. 
Published: September 2016

AbstractClimate change scientists predict an increased intensity of storms (cyclones, hurricanes and typhoons) in the future. Intense storms facilitate plant invasion by increasing resource availability, reducing competition and increasing opportunities for propagule dispersal. We document here the state of current understanding about the response of invasive plant species to intense storms and suggest that the structure and function of forests in storm‐prone regions may be much altered in the future as a result of weed invasion. Intense storms provide a large spatial and temporal window of opportunity for invasion and empirical research demonstrates growth and recruitment rates of invasive species increase following such events, and they spread readily. In particular, lianas and woody invasive species that are shade tolerant and recruit from the seedling layer may constitute the greatest threat to tropical forests following storm events. Forests persisting in fragmented landscapes will be exposed to some of the most severe consequences of intense storms and subsequent weed invasion. In storm‐prone regions, forests of the future are likely to experience a decrease in diversity of native species and homogenization of communities at landscape and regional scales, slower rates of forest succession, increasing degradation of forest fragments and ultimately a decrease in ecosystem function.
Medical and social egg freezing: internet‐based survey of knowledge and attitudes among women in Denmark and the UK
Authors: Lallemant Camille , Vassard Ditte , Nyboe Andersen Anders , Schmidt Lone , Macklon Nick 
Published: September 2016

AbstractIntroductionUntil recently, limited options for preserving fertility in order to delay childbearing were available. Although egg freezing and successful thawing is now possible, it remains unclear to what extent women are aware of the availability of this technique, their attitudes towards its use, or the circumstances under which this technique may be considered.Material and methodsAn online cross‐sectional survey was designed to investigate knowledge and attitudes of women in Denmark and the UK on egg freezing and their potential intentions regarding the procedure.ResultsData was collected from September 2012 to September 2013 and the responses of 973 women were analyzed. In total, 83% of women reported having heard of egg freezing, and nearly all considered it acceptable for medical indications, whilst 89% considered it acceptable for social reasons. Overall, 19% expressed active interest in the procedure, and 27% expressed possible interest. Key factors found to positively influence attitudes to accepting the procedure were reassurance that it would not affect future fertility and greater than 50% chance of achieving a live birth. Characteristics significantly associated with intention to freeze eggs were being single, age under 35 years, childlessness, and a history of infertility. In this group, risk and cost were less important considerations.ConclusionsThis study indicates that there is widespread awareness and support of the availability of eggs freezing for reproductive planning. Reassurance regarding its efficacy appears more important than its potential adverse effects on their health or that of future children, or the costs of the procedure.
Serum fatty acids in infants, reflecting family fish consumption, were inversely associated with allergy development but not related to farm residence
Authors: Jonsson Karin , Barman Malin , Moberg Sara , Sjöberg Agneta , Brekke Hilde K. , Hesselmar Bill , Sandberg Ann‐Sofie , Wold Agnes E. 
Published: September 2016

AbstractAimIn this study, differences in serum fatty acid patterns between farm and nonfarm infants were investigated and related to subsequent allergy development. We also related allergy‐related serum fatty acids to maternal diet and breast milk fatty acids.MethodsThe FARMFLORA birth cohort included 28 farm and 37 nonfarm infants. Serum was obtained from 21 farm infants and 29 controls at four months post‐partum and analysed for phospholipid fatty acids. Allergy was diagnosed by paediatricians at three years of age.ResultsSerum fatty acid patterns were similar in farm and control infants, although farm infants had lower 18:1 omega‐7 proportions. Serum proportions of eicosapentaenoic acid (EPA) were unrelated to farming status, but lower in children who subsequently developed allergy, with an odds ratio of 0.47 and 95% confidence interval of 0.27–0.83 (p = 0.01) for every 0.1% EPA increase. The infants’ serum EPA proportions correlated with breast milk EPA proportions, which, in turn, correlated with maternal oily fish intake during lactation.ConclusionThe allergy‐protective effect of farming was not linked to infant serum fatty acid composition. However, healthy infants had higher proportions of EPA in their sera, probably reflecting a family diet rich in fish, compared to subsequently allergic children.
Quantitative Assessment of Food Effect on the Pharmacokinetics of Nano‐Crystallized Megestrol Acetate
Authors: Guk Jinju , Son Hankil , Chae Dong Woo , Park Kyungsoo 
Published: September 2016

AbstractMegestrol acetate, an appetite stimulant with low bioavailability, shows increased bioavailability when taken together with food. However, the pharmacokinetic characteristics of megestrol acetate and its relation with food are not well understood. This study aimed to investigate the food effect on the pharmacokinetics (PK) of the recently developed nano‐crystallized megestrol acetate (NCMA), using a model‐based approach. Data were obtained from an NCMA PK study consisting of a single dose in fasting (39 individuals) and fed conditions (40 individuals). Plasma concentrations were measured up to 120 hr after dosing. With the incorporation of body‐weight via allometry, NONMEM 7.3 was used to develop a PK model, which was then used to simulate an optimal fasting dose yielding an area under concentration (AUC) and maximum concentration (Cmax) of NCMA close to those obtained with the fed dose. NCMA concentrations were best characterized by a two‐compartment model with first‐order absorption linked to a recycling compartment to account for the multiple concentration peaks observed. Food increased bioavailability 2.2 times and decreased the absorption rate constant 0.58 times. Recycling event times were estimated to be 3.56, 7.99 and 24.0 hr. The optimal fast dose was 2.0 times higher than the fed dose, and the resulting difference in drug exposure between the fasting and fed dose was 7.5%. This work suggests that the PK model developed can be applied to an optimal dosage regimen design for NCMA treatment.
Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases
Authors: Kunnumakkara Ajaikumar B , Bordoloi Devivasha , Padmavathi Ganesan , Monisha Javadi , Roy Nand Kishor , Prasad Sahdeo , Aggarwal Bharat B 
Published: September 2016

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti‐inflammatory activity through the suppression of numerous cell signalling pathways including NF‐κB, STAT3, Nrf2, ROS and COX‐2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials.Linked ArticlesThis article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc