bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment Patterns and Survival of Elderly Patients With Breast Cancer Brain Metastases
Authors: Leone José P. , Haraldsson Bjarni , Mott Sarah L. , McDowell Bradley D. , Chrischilles Elizabeth A. 
Published: July 2018

Objectives:
The main objective of this study was to analyze treatment patterns of elderly patients with breast cancer brain metastases (BCBM), evaluate characteristics associated with treatment selection, and to analyze trends in overall survival (OS) over time.

Materials and Methods:
We included women with BCBM reported to the Surveillance, Epidemiology, and End Results Medicare Program from 1992 to 2012. Treatments were recorded from Medicare claims from the date of brain metastases diagnosis until 60 days after. Treatments included resection, radiation, and chemotherapy. Cochran-Armitage tests were used for analysis of treatment patterns. Multinomial logistic regression was applied to determine factors associated with treatment selection. Cox regression modelled OS trends within each treatment modality across time.

Results:
Among 5969 patients included, treatment rates increased from 50% in 1992 to 64.1% in 2012 (P<0.01). Therapy combining radiation, resection, and/or chemotherapy also increased from 8.8% to 18% over the same period (P<0.01). Combined therapy was significantly more likely among patients with extracranial metastases, those with estrogen-negative tumors, younger age at diagnosis, no comorbidities and more recently diagnosed brain metastases. OS improved over time for patients who received a combination of ≥2 treatments (hazard ratio, 0.89 per every 5 more recent diagnosis years; P<0.05). Older patients, those with extracranial metastases, or estrogen/progesterone-negative tumors showed significantly shorter OS.

Conclusions:
We observed substantial changes in treatment patterns and OS over time in patients with BCBM. We identified several factors associated with specific treatment use. Patients who underwent a combination of ≥2 treatments experienced a significant improvement in OS over time.
Visualizing aggregate movement in cities
Authors: Batty Michael 
Published: July 2018

We argue here that despite the focus in cities on location and place, it is increasingly clear that a requisite understanding of how cities evolve and change depends on a thorough understanding of human movements at aggregate scales where we can observe emergent patterns in networks and flow systems. We argue that the location of activities must be understood as summations or syntheses of movements or flows, with a much clearer link between flows, activities and the networks that carry and support them. To this end, we introduce a generic class of models that enable aggregated flows of many different kinds of social and economic activity, ranging from the journey to work to email traffic, to be predicted using ideas from discrete choice theory in economics which has analogies to gravitation. We also argue that visualization is an essential construct in making sense of flows but that there are important limitations to illustrating pictorially systems with millions of component parts. To demonstrate these, we introduce a class of generic spatial interaction models and present two illustrations. Our first application is based on transit flows within the high-frequency city over very short time periods of minutes and hours for data from the London Underground. Our second application scales up these models from districts and cities to the nation, and we demonstrate how flows of people from home to work and vice versa define cities and related settlements at much coarser scales. We contrast this approach with more disaggregate, individual studies of flow systems in cities that we consider an essential complement to the ideas presented here.
This article is part of the theme issue ‘Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour’.
Can we identify general architectural principles that impact the collective behaviour of both human and animal systems?
Authors: Penn Alan , Turner J. Scott 
Published: July 2018

The search for general common principles that unify disciplines is a longstanding challenge for interdisciplinary research. Architecture has always been an interdisciplinary pursuit, combining engineering, art and culture. The rise of biomimetic architecture adds to the interdisciplinary span. We discuss the similarities and differences among human and animal societies in how architecture influences their collective behaviour. We argue that the emergence of a fully biomimetic architecture involves breaking down what we call ‘pernicious dualities’ that have permeated our discourse for decades, artificial divisions between species, between organism and environment, between genotype and phenotype, and in the case of architecture, the supposed duality between the built environment and its builders. We suggest that niche construction theory may serve as a starting point for unifying our thinking across disciplines, taxa and spatial scales.This article is part of the theme issue ‘Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour’.
Teachers’ approaches to genetics teaching mirror their choice of content and avoidance of sensitive issues
Authors: Aivelo Tuomas , Uitto Anna 
Published: July 2018

AbstractThe skills required to understand genetic phenomena and transfer knowledge to real world situations are an important part of 21st century scientific literacy. While socio-scientific issues (SSI) are increasingly emphasised in science curricula, teachers have low interest in adopting SSI in teaching. Little is known about how teachers choose content for their teaching, although this process translates curricula to teaching practice. We explored how teachers choose content and contexts for biology courses on cells, heredity, and biotechnology by interviewing ten Finnish upper-secondary school teachers. We studied how the teachers described teaching on genetically modified organisms, hereditary disorders, and human traits. Teachers’ perceptions on genetics teaching were classified to Developmental, Structural and Hereditary approaches. The approaches were connected not only to the teachers’ perceptions of the more important content, but also teacher inclinations towards teaching genetics in the human context and perceptions of students’ interest in different topics. Teachers’ justified their choices by national, local school, and teacher’s personal-level factors. While teachers mentioned that SSI are important, they were never mentioned among the important contexts. Nevertheless, some teachers embraced teaching genetics in the human context while others avoided them. Teachers justified their avoidance for personal and pedagogical factors, such as their competence in dealing with these contexts. Experience played a part in the approach that teachers had, and contrary to the results of previous research, the less experienced teachers were more open to discussing human genetics. We conclude that curriculum development is important to encourage teachers to adopt more SSI-oriented teaching.Disclosure statementTuomas Aivelo has participated in writing biology textbooks for upper-secondary school biology for eOppi Oy. None of the teachers involved in this study used biology textbooks from eOppi Oy.
Hydra Bcl-2 and TMBIMP family proteins display anti-apoptotic functions
Authors: Motamedi Mina , Lindenthal Laura , Wagner Anita , Kemper Margherita , Moneer Jasmin , Steichele Mona , Klimovich Alexander , Wittlieb Jörg , Jenewein Marcell , Böttger Angelika 
Published: July 2018

AbstractBackgroundMechanisms of programmed cell death differ considerably between animals, plants and fungi. In animals they depend on caspases and Bcl-2 family proteins and this kind of cell death is called apoptosis. Most gene families encoding proteins involved in apoptosis are found in multicellular animals already in the eldest phyla but their functional conservation is still being studied. Much older protein families have cytoprotective functions across all kingdoms of life. This includes the TMBIMP-family, the presence and function of which in early metazoans has not been investigated yet.MethodsWe quantified apoptosis in transgenic Hydra overexpressing HyBcl-2-like 4. Moreover, we investigated putative TMBIMP-family members in Hydra by sequence comparison. By overexpression of TMBIMP-family members in Hydra and human HEK cells we analysed their subcellular localisation and in one case their capacity to protect cells from camptothecin induced apoptosis.ResultsHyBcl-2-like 4, as previously shown in a heterologous system, was localised to mitochondria and able to protect Hydra epithelial cells from apoptosis. The TMBIMP-family in Hydra includes HyBax-Inhibitor-1, HyLifeguard-1a and -1b and HyLifeguard 4 proteins. HyBax-inhibitor-1 protein was found localised to ER-membranes, HyLifeguard-family members were found at the plasma membrane and in Golgi-vesicles. Moreover, HyBax-inhibitor-1 protected human cells from apoptosis.ConclusionThis work provides the first functional study to support an anti-apoptotic function of Bcl-2 like proteins in pre-bilaterians within a physiological context. Furthermore it illustrates that genes that were “inherited” from non-animal ancestors, like the TMBIMP-family, were recruited to carry out cell protective anti-apoptotic functions already in early metazoans.
Lack of signal for the impact of venom gene diversity on speciation rates in cone snails
Authors: Phuong Mark A , Alfaro Michael E , Mahardika Gusti N , Marwoto Ristiyanti M , Prabowo Romanus Edy , von Rintelen Thomas , Vogt Philipp WH , Hendricks Jonathan R , Puillandre Nicolas 
Published: July 2018

AbstractUnderstanding why some groups of organisms are more diverse than others is a central goal in macroevolution. Evolvability, or lineages’ intrinsic capacity for evolutionary change, is thought to influence disparities in species diversity across taxa. Over macroevolutionary time scales, clades that exhibit high evolvability are expected to have higher speciation rates. Cone snails (family: Conidae, >900 spp.) provide a unique opportunity to test this prediction because their venom genes can be used to characterize differences in evolvability between clades. Cone snails are carnivorous, use prey-specific venom (conotoxins) to capture prey, and the genes that encode venom are known and diversify through gene duplication. Theory predicts that higher gene diversity confers a greater potential to generate novel phenotypes for specialization and adaptation. Therefore, if conotoxin gene diversity gives rise to varying levels of evolvability, conotoxin gene diversity should be coupled with macroevolutionary speciation rates. We applied exon capture techniques to recover phylogenetic markers and conotoxin loci across 314 species, the largest venom discovery effort in a single study. We paired a reconstructed timetree using 12 fossil calibrations with species-specific estimates of conotoxin gene diversity and used trait-dependent diversification methods to test the impact of evolvability on diversification patterns. Surprisingly, did not detect any signal for the relationship between conotoxin gene diversity and speciation rates, suggesting that venom evolution may not be the rate-limiting factor controlling diversification dynamics in Conidae. Comparative analyses showed some signal for the impact of diet and larval dispersal strategy on diversification patterns, though whether or not we detected a signal depended on the dataset and the method. If our results remain true with increased sampling in future studies, they suggest that the rapid evolution of Conidae venom may cause other factors to become more critical to diversification, such as ecological opportunity or traits that promote isolation among lineages.
A total synthetic approach to CRISPR/Cas9 genome editing and homology directed repair
Authors: DiNapoli Sara E. , Martinez-McFaline Raul , Gribbin Caitlin K. , Wrighton Paul , Balgobin Courtney A. , Nelson Isabel , Leonard Abigail , Maskin Carolyn R. , Shwartz Arkadi , Quenzer Eleanor D. , Mailhiot Darya , Kao Clara , McConnell Sean C. , de Jong Jill L.O. , Goessling Wolfram , Houvras Yariv 
Published: July 2018

ABSTRACTCRISPR/Cas9 has become a powerful tool for genome editing in zebrafish that permits the rapid generation of loss of function mutations and the knock-in of specific alleles using DNA templates and homology directed repair (HDR). We compared synthetic, chemically modified sgRNAs to in vitro transcribed sgRNAs and demonstrate the increased activity of synthetic sgRNAs in combination with recombinant Cas9 protein. We developed an in vivo genetic assay to measure HDR efficiency and we utilized this assay to optimize the design of synthetic DNA templates to promote HDR. Utilizing these principles, we successfully performed knock-in of fluorophores at multiple genomic loci and demonstrate transmission through the germline at high efficiency. We demonstrate that synthetic HDR templates can be used to knock-in bacterial nitroreductase (ntr) to facilitate lineage ablation of specific cell types. Collectively, our data demonstrate the utility of combining synthetic sgRNAs and dsDNA templates to perform homology directed repair and genome editing in vivo.
Low genomic divergence and high gene flow between locally adapted populations of the swamp sparrow
Authors: Deane-Coe P. , Greenberg R. , Lovette I. J. , Harrison R. G. 
Published: July 2018

AbstractPopulations that have recently diverged across sharp environmental gradients provide an opportunity to study the mechanisms by which natural selection drives adaptive divergence. Inland and coastal populations of the North American swamp sparrow have become an emerging model system for studies of natural selection because they are morphologically and behaviourally distinct despite a very recent divergence time (<15,000 years), yet common garden experiments have demonstrated a genetic basis for their phenotypic differences. We characterized genomic patterns of variation within and between inland and coastal swamp sparrows via reduced representation sequencing in order to reconstruct the contributions of demography, gene flow and selection to this case of recent adaptive divergence. Compared to inland swamp sparrows, coastal swamp sparrows exhibited fewer polymorphic sites and reduced nucleotide diversity at those sites, indicating that a bottleneck and/or recent selective sweeps occurred in that population during coastal colonization and local adaptation. Estimates of genome-wide differentiation (FST=0.02) and sequence divergence (ΦST=0.05) between inland and coastal populations were very low, consistent with postglacial divergence. A small number of SNPs were strongly differentiated (max FST=0.8) suggesting selection at linked sites. Swamp sparrows sampled from breeding sites at the habitat transition between freshwater and brackish marshes exhibited high levels of genetic admixture. Such evidence of active contemporary gene flow makes the evolution and maintenance of local adaptation in these two populations even more notable. We summarize several features of the swamp sparrow system that may facilitate the maintenance of adaptive diversity despite gene flow, including the presence of a magic trait.
LEAFYmaintains apical stem cell activity during shoot development in the fernCeratopteris richardii
Authors: Plackett Andrew R.G. , Conway Stephanie J. , Hewett Hazelton Kristen D. , Rabbinowitsch Ester H. , Langdale Jane. A. , Di Stilio Verónica S. 
Published: July 2018

ABSTRACTDuring land plant evolution, determinate spore-bearing axes (retained in extant bryophytes such as mosses) were progressively transformed into indeterminate branching shoots with specialized reproductive axes that form flowers. The LEAFY transcription factor, which is required for the first zygotic cell division in mosses and primarily for floral meristem identity in flowering plants, may have facilitated developmental innovations during these transitions. Mapping the LEAFY evolutionary trajectory has been challenging, however, because there is no functional overlap between mosses and flowering plants, and no functional data from intervening lineages. Here, we report a transgenic analysis in the fernCeratopteris richardiithat reveals a role for LEAFY in maintaining cell divisions in the apical stem cells of both haploid and diploid phases of the lifecycle. These results support an evolutionary trajectory in which an ancestral LEAFY module that promotes cell proliferation was progressively co-opted, adapted and specialized as novel shoot developmental contexts emerged.
Atypical septate junctions maintain the somatic enclosure around maturing spermatids and prevent premature sperm release inDrosophilatestis
Authors: Dubey Pankaj , Kapoor Tushna , Gupta Samir , Shirolikar Seema , Ray Krishanu 
Published: July 2018

AbstractTight junctions prevent the paracellular flow and maintain cell polarity in an epithelium. These are also essential for maintaining the blood-testis-barrier involved in regulating sperm differentiation. Septate junctions are orthologous to the tight junctions in insects. InDrosophilatestis, major septate junction components co-localize at the interface of germline and somatic cells initially and then condense between the two somatic cells in a cyst after germline meiosis. Their localization is extensively remodeled in subsequent stages. We find that characteristic septate junctions are formed between the somatic cyst cells at the elongated spermatid stage. Consistent with the previous reports, knockdown of essential junctional components, Discs-large-1 and Neurexin-IV, in the somatic cyst cells, during the early stages, disrupted sperm differentiation beyond the spermatocyte stage. Somatic knockdown of these proteins during the final stages of spermatid maturation caused premature release of spermatids inside the testes, resulting in partial loss of male fertility. These results indicate the importance of maintaining mechanical integrity of the somatic enclosure during spermatid coiling and release inDrosophilatestis. It also highlights the functional similarity with the tight junction proteins during spermatogenesis in mammalian testes.Summary statementDubey et al., showed that septate junctions stitch the somatic enclosure around maturing spermatids inDrosophilatestis. Maintaining the integrity of this junction is essential for proper release of spermatids.
PBHoover and CigarRoller: a method for confident haploid variant calling on Pacific Biosciences data and its application to heterogeneous population analysis
Authors: Ramirez-Busby Sarah , Elghraoui Afif , Kim Yeon Bin , Kim Kellie , Valafar Faramarz 
Published: July 2018

AbstractMotivationSingle Molecule Real-Time (SMRT) sequencing has important and underutilized advantages that amplification-based platforms lack. Lack of systematic error (e.g. GC-bias), completede novoassembly (including large repetitive regions) without scaffolding, can be mentioned. SMRT sequencing, however suffers from high random error rate and low sequencing depth (older chemistries). Here, we introduce PBHoover, software that uses a heuristic calling algorithm in order to make base calls with high certainty in low coverage regions. This software is also capable of mixed population detection with high sensitivity. PBHoover’s CigarRoller attachment improves sequencing depth in low-coverage regions through CIGAR-string correction.ResultsWe tested both modules on 348M.tuberculosisclinical isolates sequenced on C1 or C2 chemistries. On average, CigarRoller improved percentage of usable read count from 68.9% to 99.98% in C1 runs and from 50% to 99% in C2 runs. Using the greater depth provided by CigarRoller, PBHoover was able to make base and variant calls 99.95% concordant with Sanger calls (QV33). PBHoover also detected antibiotic-resistant subpopulations that went undetected by Sanger. Using C1 chemistry, subpopulations as small as 9% of the total colony can be detected by PBHoover. This provides the most sensitive amplification-free molecular method for heterogeneity analysis and is in line with phenotypic methods’ sensitivity. This sensitivity significantly improves with the greater depth and lower error rate of the newer chemistries.Availability and ImplementationExecutables are freely available under GNU GPL v3+ athttp://www.gitlab.com/LPCDRP/pbhooverandhttp://www.gitlab.com/LPCDRP/CigarRoller. PBHoover is also available on bioconda:https://anaconda.org/bioconda/pbhoover.Contactfaramarz@sdsu.edu
Systems biology reveals NR2F6 and TGFB1 as key regulators of feed efficiency in beef cattle
Authors: Alexandre Pâmela A. , Naval-Sanchez Marina , Porto-Neto Laercio R. , Ferraz José Bento S. , Reverter Antonio , Fukumasu Heidge 
Published: July 2018

AbstractSystems biology approaches are used as strategy to uncover tissue-specific perturbations and regulatory genes related to complex phenotypes. We applied this approach to study feed efficiency (FE) in beef cattle, an important trait both economically and environmentally. Poly-A selected RNA of five tissues (adrenal gland, hypothalamus, liver, skeletal muscle and pituitary) of eighteen young bulls, selected for high and low FE, were sequenced (100bp, pared-end). From the 17,354 expressed genes, 1,317 were prioritized by five selection categories (differentially expressed, harbouring SNPs associated with FE, tissue-specific, secreted in plasma and key regulators) and used for network construction. NR2F6 and TGFB were identified and validated by motif discovery as key regulators of hepatic inflammatory response and muscle tissue development, respectively, two biological processes demonstrated to be associated to FE. Moreover, we indicated potential biomarkers of FE which are related to hormonal control of metabolism and sexual maturity. By using robust methodologies and validation strategies, we confirmed main biological processes related to FE in Bos indicus and indicated candidate genes as regulators or biomarkers of superior animals.
Systematic assessment of GFP tag position on protein localization and growth fitness in yeast
Authors: Davidi Dan , Weill Uri , Krieger Gat , Avihou Zohar , Milo Ron , Schuldiner Maya 
Published: July 2018

AbstractWhile protein tags are ubiquitously utilized in molecular biology, they harbor the potential to interfere with functional traits of their fusion counterparts. Systematic evaluation of the effect of protein tags on localization and function would promote accurate use of tags in experimental setups. Here we examine the effect of Green Fluorescent Protein (GFP) tagging at either the N or C terminus of budding yeast proteins on localization and functionality. We use a competition-based approach to decipher the relative fitness of two strains tagged on the same protein but on opposite termini and from that infer the correct, physiological localization for each protein and the optimal position for tagging. Our study provides a first of a kind systematic assessment of the effect of tags on the functionality of proteins and provides step towards broad investigation of protein fusion libraries.HighlightsProtein tags are widely used in molecular biology although they may interfere with protein function.The subcellular localization of hundreds of proteins in yeast is different when tagged at the N or the C terminus.A competition based assay enables systematic deciphering of correct tagging terminus for essential proteins.The presented approach can be used to derive physiologically relevant tagged libraries.