bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the potential for undesired genomic effects of the piggyBac transposon system in human cells
Authors: Saha Sunandan , Woodard Lauren E. , Charron Elizabeth M. , Welch Richard C. , Rooney Cliona M. , Wilson Matthew H. 
Published: January 2015

Abstract
Non-viral transposons have been used successfully for genetic modification of clinically relevant cells including embryonic stem, induced pluripotent stem, hematopoietic stem and primary human T cell types. However, there has been limited evaluation of undesired genomic effects when using transposons for human genome modification. The prevalence of piggyBac(PB)-like terminal repeat (TR) elements in the human genome raises concerns. We evaluated if there were undesired genomic effects of the PB transposon system to modify human cells. Expression of the transposase alone revealed no mobilization of endogenous PB-like sequences in the human genome and no increase in DNA double-strand breaks. The use of PB in a plasmid containing both transposase and transposon greatly increased the probability of transposase integration; however, using transposon and transposase from separate vectors circumvented this. Placing a eGFP transgene within transposon vector backbone allowed isolation of cells free from vector backbone DNA. We confirmed observable directional promoter activity within the 5′TR element of PB but found no significant enhancer effects from the transposon DNA sequence. Long-term culture of primary human cells modified with eGFP-transposons revealed no selective growth advantage of transposon-harboring cells. PB represents a promising vector system for genetic modification of human cells with limited undesired genomic effects.
Discovery of a Novel General Anesthetic Chemotype Using High-throughput Screening
Authors: McKinstry-Wu Andrew R. , Bu Weiming , Rai Ganesha , Lea Wendy A. , Weiser Brian P. , Liang David F. , Simeonov Anton , Jadhav Ajit , Maloney David J. , Eckenhoff Roderic G. 
Published: January 2015

AbstractAbstract
A high-throughput assay based on competitive binding to a soluble protein model was used to screen a library of more than 350,000 compounds for anesthetic-like binding activity. A novel chemotype, the 6-phenylpyridazin-3(2H)-ones, exhibited general anesthetic activity in secondary assays and ultimately in mice.
Supplemental Digital Content is available in the text.

Background:
The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures.

Methods:
Using a novel high-throughput screen employing the fluorescent anesthetic 1-aminoanthracene and apoferritin as a surrogate for on-pathway anesthetic protein target(s), we screened a 350,000 compound library for competition with 1-aminoanthracene–apoferritin binding. Hit compounds meeting structural criteria had their binding affinities for apoferritin quantified with isothermal titration calorimetry and were tested for γ-aminobutyric acid type A receptor binding using a flunitrazepam binding assay. Chemotypes with a strong presence in the top 700 and exhibiting activity via isothermal titration calorimetry were selected for medicinal chemistry optimization including testing for anesthetic potency and toxicity in an in vivo Xenopus laevis tadpole assay. Compounds with low toxicity and high potency were tested for anesthetic potency in mice.

Results:
From an initial chemical library of more than 350,000 compounds, we identified 2,600 compounds that potently inhibited 1-aminoanthracene binding to apoferritin. A subset of compounds chosen by structural criteria (700) was successfully reconfirmed using the initial assay. Based on a strong presence in both the initial and secondary screens the 6-phenylpyridazin-3(2H)-one chemotype was assessed for anesthetic activity in tadpoles. Medicinal chemistry efforts identified four compounds with high potency and low toxicity in tadpoles, two were found to be effective novel anesthetics in mice.

Conclusion:
The authors demonstrate the first use of a high-throughput screen to successfully identify a novel anesthetic chemotype and show mammalian anesthetic activity for members of that chemotype.
Hybrid origins and the earliest stages of diploidization in the highly successful recent polyploidCapsella bursa-pastoris
Authors: Douglas Gavin M. , Gos Gesseca , Steige Kim A. , Salcedo Adriana , Holm Karl , Josephs Emily B. , Arunkumar Ramesh , Ågren J. Arvid , Hazzouri Khaled M. , Wang Wei , Platts Adrian E. , Williamson Robert J. , Neuffer Barbara , Lascoux Martin , Slotte Tanja , Wright Stephen I. 
Published: January 2015

AbstractWhole genome duplication events have occurred repeatedly during flowering plant evolution, and there is growing evidence for predictable patterns of gene retention and loss following polyploidization. Despite these important insights, the rate and processes governing the earliest stages of diploidization remain poorly understood, and the relative importance of genetic drift, positive selection and relaxed purifying selection in the process of gene degeneration and loss is unclear. Here, we conduct whole genome resequencing inCapsella bursa-pastoris, a recently formed tetraploid with one of the most widespread species distributions of any angiosperm. Whole genome data provide strong support for recent hybrid origins of the tetraploid species within the last 100-300,000 years from two diploid progenitors in theCapsellagenus. Major-effect inactivating mutations are frequent, but many were inherited from the parental species and show no evidence of being fixed by positive selection. Despite a lack of large-scale gene loss, we observe a decrease in the efficacy of natural selection genome-wide, due to the combined effects of demography, selfing and genome redundancy from whole genome duplication. Our results suggest that the earliest stages of diploidization are associated with quantitative genome-wide decreases in the strength and efficacy of selection rather than rapid gene loss, and that non-functionalization can receive a 'head start' through a legacy of deleterious variants and differential expression originating in parental diploid populations.
PDMQ-Protein Digestion Multi Query software tool to performin silicodigestion of protein/peptide sequences
Authors: Haraszi Reka , Tasi Csongor , Juhasz Angela , Makai Szabolcs 
Published: January 2015

AbstractMotivationIn silicoenzymatic digestion tools mostly can be used for digestion of single sequence query, which means a significant limitation in their utility when a number of sequences need to be processed. The other limitation of these applications is the selection options of restriction enzymes that are usually allow only simultaneous digestion. Non-conventional proteins such as cereal prolamins require multi-enzyme multi step digestion, and for cereal proteomics experts this type of application is missing.ResultsPDMQ, Protein Digestion Multi Queryapplication was developed having multi query and multi enzyme options and that way can be customized for any digestion protocol.Availability and implementationPDMQ is implemented in C# using the .NET framework and can be downloaded fromhttp://www.agrar.mta.hu/_user/browser/File/bioinformatics/ProteinDigestion_v0_0_0_15.rar
Once upon a time at work: discovering the stories in workplace training
Authors: Stroud Katie 
Published: January 2015

Purpose
– The importance of using stories to impact memory is highly explored and documented; however, little guidance exists for how to develop stories in the context of instructional design. The purpose of this paper is to offer a template for conforming workplace training material into stories. With specific examples and reasoning, the author offers a new way to develop training materials based on the framework of a story.

Design/methodology/approach
– Exploring basic storytelling elements learned in grade school, the author combines past experience with general observations on how stories affect the learner. Applying these concepts, she walks the reader through an experience that reveals how the brain interprets stories. She uses her own story with specific examples and reasoning along the way to help you find the stories that already exist in your everyday world.

Findings
– This paper shows, anecdotally, how to build stories around workplace problems for use in training. It suggests that modeling training around the framework of a story helps the audience to process the information as an experience and therefore retain the information longer.

Originality/value
– This paper was designed to help anyone who is responsible for developing instructional content and has been looking for a structured way to frame that content into a story.
Heterologous expression and characterization of endocellulase from the Japanese pine sawyer Monochamus saltuarius (MsGHF5)
Authors: Ko Hyunjun , Kwon Hyuk‐Min , Ko Hyun‐Jin , Ryu Ji‐Hyeon , Song Hwi‐Seung , Park Yong Chul 
Published: January 2015

AbstractIn this study, the endocellulase gene from Monochamus saltuarius (MsGHF5) was transformed into Escherichia coli (RosettaBlue(DE3)pLysS strain), and induced by IPTG. The molecular weight of recombinant MsGHF5 (rMsGHF5) was 78 kDa and was expressed as a fusion protein with maltose binding protein in pMAL‐c2 expression vector. Native‐PAGE was conducted with 0.1% carboxymethyl cellulose as a substrate, and the zymogenic bands were observed. The Michaelis constant and maximum velocity of rMsGHF5 were 0.199 mg/mL and 0.034 μmol/min/mL, respectively. The optimal condition for rMsGHF5 occurred at pH 5 and 30°C. Fe2+ and Mn2+ stimulated the activity of rMsGHF5 by 167 and 114% respectively, whereas Cu2+, Hg2+ and Zn2+ inhibited its activity.
Covariation in abscission force and terminal velocity of windborne sibling seeds alters long‐distance dispersal projections
Authors: Teller Brittany J. , Marden James H. , Shea Katriona 
Published: January 2015

Summary

Despite the fact that seeds are unlikely to be identical – even among siblings within a maternal individual – dispersal models typically use one mean trait value to represent the ability of an entire species to disperse. Previous work has shown that the environmental conditions under which individuals leave the maternal site strongly affect how far seeds will travel. However, less is known about how trait variation within individuals contributes to dispersal or how such variation might interact with abiotic factors.

Here, we develop the use of an ergometer in a novel application to investigate variation in seed traits, specifically the force required for seed abscission and seed terminal velocity, exhibited by seeds from different locations within maternal capitula of the invasive species Carduus nutans (Asteraceae).

We find that seeds from the centre of capitula are significantly easier to liberate and have slower falling velocities than siblings found near the edge of capitula. When abscission force is positively correlated with terminal velocity, slowly falling, easily abscised, central seeds are projected to travel much further than edge seeds on slow winds.

Our experimental and theoretical results, which together show that within‐individual variation can strongly affect model projections of species dispersal, have important implications for our broader understanding of population spread rates, the spatial structure of populations, metapopulation connectivity and gene flow in the landscape.
A high‐resolution panorama camera system for monitoring colony‐wide seabird nesting behaviour
Authors: Lynch Tim P. , Alderman Rachael , Hobday Alistair J. 
Published: January 2015

Summary

Obtaining accurate and representative demographic metrics for animal populations is critical to many aspects of wildlife monitoring and management. However, at remote animal colonies, metrics derived from sequential counts or other continuous monitoring are often subject to logistical, weather and disturbance challenges. The development of remote camera technologies has assisted monitoring, but limitations in spatial and temporal resolution and sample sizes remain.

Here, we describe the application of a robotic camera system (Gigapan) which takes a tiled sequence of photographs that are automatically stitched together to form high‐resolution panoramas. We demonstrate the application of the Gigapan using data collected during field testing at a shy albatross colony on Albatross Island in northwest Tasmania.

We took daily panoramas over 5 days to estimate mean incubation shift duration, an indirect measure for foraging trip duration, in an existing study area. Similar numbers of occupied nests could be observed at a distance of approximately 100 m in the Gigapan panoramas compared to ground‐based counts (115 and 117, respectively). Of these, birds on 90% of nests visible in the panoramas could be unambiguously identified as marked or unmarked with a small daub of paint throughout the study period and thus a shift change reliably recorded. Gigapan‐based shift duration was estimated using a novel instantaneous statistical method and were longer than estimates earlier in the egg brooding period, potentially revealing a new pattern in shift duration.

This example field application provides proof of concept and demonstration that the relatively low‐cost Gigapan system provides the spatial advantages of aerial photos with the detail and temporal replication of land‐based camera systems. The Gigapan system can extend or enhance traditional data collection methods, particularly for simultaneous observations at distance, of the behaviour of surface nesting colonial seabirds.
On the existence of maximum likelihood estimates for presence‐only data
Authors: Hefley Trevor J. , Hooten Mevin B. 
Published: January 2015

Summary

Presence‐only data can be used to determine resource selection and estimate a species’ distribution. Maximum likelihood is a common parameter estimation method used for species distribution models. Maximum likelihood estimates, however, do not always exist for a commonly used species distribution model – the Poisson point process.

We demonstrate the issue with conventional maximum likelihood mathematically, using a data example, and a simulation experiment and show alternative estimation methods.

We found that when habitat preferences are strong or the number of presence‐only locations is small, by chance, maximum likelihood coefficient estimates for the Poisson point process model may not exist. We found that several alternative estimation methods can produce reliable estimates, but results will depend on the chosen method.

It is important to identify conditions for which maximum likelihood estimates are unlikely to be identifiable from presence‐only data. In data sets where the maximum likelihood estimates do not exist, penalized likelihood and Bayesian methods will produce coefficient estimates, but these are sensitive to the choice of estimation procedure and prior or penalty term. When sample size is small or it is thought that habitat preferences are strong, we propose a suite of estimation procedures researchers can consider using.
Troubleshooting the potential pitfalls of cross‐fostering
Authors: Winney Isabel , Nakagawa Shinichi , Hsu Yu‐Hsun , Burke Terry , Schroeder Julia 
Published: January 2015

Summary

Cross‐fostering is the transfer of offspring between their natal environment and a new social environment. This method allows researchers to disentangle the genetic and interacting environmental effects that influence phenotypes, and is popular in both wild and laboratory studies. Here, we discuss three factors that might bias cross‐fostering and influence ecological and evolutionary conclusions if not accommodated.

First, cross‐fostering tends to be spatially and temporally non‐random because heterogeneous breeding conditions can result in clustered breeding attempts. Secondly, cross‐fostering will often change the brood composition because the exchanged broods are unlikely to be precisely matched in age, size and composition. Thirdly, some methods can introduce bias by using a systematically structured subset of the population, leading to a systematically structured data set.

We use a 12‐year case study of wild house sparrows Passer domesticus to demonstrate how to identify these biases with statistical modelling and how to adjust the cross‐fostering protocol according to the identified biases.

In our data set, cross‐fostered nestlings were more likely to survive than non‐cross‐fostered nestlings, but postfledging and overall survival were not affected. Survival differed between cross‐fostering treatments, partially due to temporally nonrandom breeding conditions and nonrandom offspring selection, demonstrating two of the three forms of bias in data from a wild population.

In all cases, we suggest using statistical models to examine whether cross‐fostering opportunities and offspring fitness are affected by nonrandom breeding, changes to the brood composition and biased methodology. We provide guidelines for optimising a cross‐fostering design and reducing inherent bias.
Adverse event reporting in studies of penetrating acupuncture during pregnancy: a systematic review
Authors: Clarkson Carl E. , O'mahony Deborah , Jones Diana E. 
Published: January 2015

AbstractBackgroundAcupuncture within pregnancy has frequently been investigated, often finding this to be more effective than standard care. However, the adverse event severity, types and occurrence are unclear.ObjectiveTo investigate the quality of reporting adverse events and to attempt to identify occurrence, type and severity of adverse events in acupuncture and non‐acupuncture groups.Data sourcesMEDLINE, CINAHL, Allied and Complementary Medicine Database, and Physiotherapy Evidence Database (PEDro) were searched for relevant studies between 2000 and 2014.Study selectionSeventeen studies using penetrating acupuncture and making comment on adverse events experienced were included. Quality appraisal of the selected publications was performed using either the PEDro scale or the Downs and Black checklist. Quality of reporting was evaluated against STRICTA and CONSORT guidelines, with data on adverse events extracted in accordance with CONSORT and Good Clinical Practice adverse event guidelines.ResultsOverall quality of reporting of adverse events was poor, with information describing the adverse events often lacking in detail. A number of trends were noted: adverse events occurring within a treatment session was 3–17% in the acupuncture groups and 4–25% in the non‐acupuncture groups. The percentage of women affected by an adverse event was between 14 and 17% in the acupuncture groups and between 15 and 19% in non‐acupuncture groups.ConclusionsAdverse event reporting within acupuncture trials is generally poor. The trends noted were that adverse events do occur, but would appear to be largely minor and comparable to non‐acupuncture‐related interventions.
Ovarian preservation in young women with endometrial cancer of endometrioid histology
Authors: Kinjyo Yoshino , Kudaka Wataru , Ooyama Takuma , Inamine Morihiko , Nagai Yutaka , Aoki Yoichi 
Published: January 2015

AbstractObjectiveTo clarify the frequency and risk factors of ovarian metastasis in women with endometrial cancer of endometrioid histology.DesignRetrospective observational study.SettingUniversity of the Ryukyus Japan 1990–2011.PopulationEighty‐eight women ≤45 years of age with endometrial cancer of only endometrioid histology.MethodsClinicopathological factors from the medical records were used. Fisher's exact test and logistic regression analysis were used to analyze predictive factors for ovarian metastasis.Main outcome measuresRisk factors of ovarian malignancy.ResultsAll women underwent total abdominal hysterectomy, bilateral salpingo‐oophorectomy and lymph node dissection. The median age was 39 years, and FIGO stage distributions were: stage I, 63 (71.6%) women; stage II, 14 (15.9%) women; and stage III, 11 (12.5%) women. Pathologically, ovarian metastasis was observed in four (4.5%) women. Only lymph node metastasis was a significant predictive factor for ovarian metastasis (p = 0.0038), and deep myometrial invasion was the only significant factor (p = 0.0085) for the prediction of lymph node metastasis. No ovarian malignancy was found in 72 women with invasion ≤50% myometrial depth and no enlargement of the ovaries. We observed ovarian metastasis in two (14.3%) of 14 women with deep myometrial invasion without ovarian tumor.ConclusionOvarian preservation surgery might be considered in endometrial cancer of endometrioid histology with ≤50% myometrial depth invasion with no ovarian mass after taking into account family history.
Diagnosis and treatment of severe hemolytic disease of the fetus and newborn: a 10‐year nationwide retrospective study
Authors: Sainio Susanna , Nupponen Irmeli , Kuosmanen Malla , Aitokallio‐Tallberg Ansa , Ekholm Eeva , Halmesmäki Erja , Orden Maija‐Riitta , Palo Pertti , Raudaskoski Tytti , Tekay Aydin , Tuimala Jarno , Uotila Jukka , Stefanovic Vedran 
Published: January 2015

AbstractObjectiveOutcome after intrauterine transfusions due to severe hemolytic disease of the fetus and newborn.DesignNationwide population‐based retrospective cohort study.SettingAll women treated with intrauterine transfusions for hemolytic disease of the fetus and newborn in Finland in 2003–2012.Population339 intrauterine transfusions, performed in 104 pregnancies of 84 women.MethodsInformation on antenatal screening of red cell antibodies and red cell units issued for intrauterine transfusion was obtained from the Finnish Red Cross Blood Service database, and obstetric and neonatal data from hospital records.Main outcome measuresProcedure‐related complications, perinatal mortality, neonatal morbidity.ResultsOverall survival was 94.2% (95% confidence interval 89.7–98.7). There were four fetal and two neonatal deaths. Procedure‐related fetal loss rate was 1.2% (95% confidence interval 0.04–2.4) per procedure and 3.8% (95% confidence interval 0.1–7.5) per pregnancy. Of the four procedure‐related losses, three were due to technically difficult intrauterine transfusions causing infection and preterm birth. Of the live born infants, 19% (95% confidence interval 11.3–26.7) were born before 32 weeks' gestation. The incidence of severe neonatal morbidity (respiratory distress syndrome, severe cerebral injury, sepsis) was 22.2% (95% confidence interval 13.4–30.2). Poor outcome (death, severe neonatal morbidity) was negatively associated with gestational age at first transfusion (p = 0.001) and at birth (p = 0.00006). Follow‐up of the infants was too incomplete to assess the neurodevelopmental outcome.ConclusionsAlthough overall survival is comparable with previous studies, our concern is procedure‐related infections and preterm births. Close collaboration between the university hospitals is needed to ensure timely treatment, operator skills and systematic follow‐up of the children.