Comparison of bibliographic data sources Implications for the robustness of university rankings, bioRxiv, 2019-09-01

AbstractUniversities are increasingly evaluated, both internally and externally on the basis of their outputs. Often these are converted to simple, and frequently contested, rankings based on quantitative analysis of those outputs. These rankings can have substantial implications for student and staff recruitment, research income and perceived prestige of a university. Both internal and external analyses usually rely on a single data source to define the set of outputs assigned to a specific university. Although some differences between such databases are documented, few studies have explored them at the institutional scale and examined the implications of these differences for the metrics and rankings that are derived from them. We address this gap by performing detailed bibliographic comparisons between three key databases Web of Science (WoS), Scopus and, the recently relaunched Microsoft Academic (MSA). We analyse the differences between outputs with DOIs identified from each source for a sample of 155 universities and supplement this with a detailed manual analysis of the differences for fifteen universities. We find significant differences between the sources at the university level. Sources differ in the publication year of specific objects, the completeness of metadata, as well as in their coverage of disciplines, outlets, and publication type. We construct two simple rankings based on citation counts and open access status of the outputs for these universities and show dramatic changes in position based on the choice of bibliographic data sources. Those universities that experience the largest changes are frequently those from non-English speaking countries and those that are outside the top positions in international university rankings. Overall MSA has greater coverage than Scopus or WoS, but has less complete affiliation metadata. We suggest that robust evaluation measures need to consider the effect of choice of data sources and recommend an approach where data from multiple sources is integrated to provide a more robust dataset.

biorxiv scientific-communication-and-education 0-100-users 2019

Interspecies transcriptome analyses identify genes that control the development and evolution of limb skeletal proportion, bioRxiv, 2019-09-01

AbstractDespite the great diversity of vertebrate limb proportion and our deep understanding of the genetic mechanisms that drive skeletal elongation, little is known about how individual bones reach different lengths in any species. Here, we directly compare the transcriptomes of homologous growth cartilages of the mouse (Mus musculus) and bipedal jerboa (Jaculus jaculus), which has extremely long metatarsals of the feet and ‘mouse-like’ arms. When we intersected gene expression differences in metatarsals of the two species with expression differences in forearms, we found that about 10% of all orthologous genes are associated with disproportionate elongation of jerboa feet. Among these, Shox2, has gained expression in jerboa metatarsals where it is not expressed in other vertebrates that have been assessed. This transcription factor is necessary for proximal limb elongation, and we show that it is sufficient to increase mouse distal limb length. Unexpectedly, we also found evidence that jerboa foot elongation occurs in part by releasing latent growth potential that is repressed in mouse feet. In jerboa metatarsals, we observed higher expression of Crabp1, an antagonist of growth inhibitory retinoic acid, lower expression of Gdf10, an inhibitory TGFβ ligand, and lower expression of Mab21L2, a BMP signaling inhibitor that we show is sufficient to reduce limb bone elongation. By intersecting our data with prior expression analyses in other systems, we identify mechanisms that may both establish limb proportion during development and diversify proportion during evolution. The genes we identified here therefore provide a framework to understand the modular genetic control of skeletal growth and the remarkable malleability of vertebrate limb proportion.

biorxiv developmental-biology 0-100-users 2019

Insight into the genomic history of the Near East from whole-genome sequences and genotypes of Yemenis, bioRxiv, 2019-08-29

AbstractWe report high-coverage whole-genome sequencing data from 46 Yemeni individuals as well as genome-wide genotyping data from 169 Yemenis from diverse locations. We use this dataset to define the genetic diversity in Yemen and how it relates to people elsewhere in the Near East. Yemen is a vast region with substantial cultural and geographic diversity, but we found little genetic structure correlating with geography among the Yemenis – probably reflecting continuous movement of people between the regions. African ancestry from admixture in the past 800 years is widespread in Yemen and is the main contributor to the country’s limited genetic structure, with some individuals in Hudayda and Hadramout having up to 20% of their genetic ancestry from Africa. In contrast, individuals from Maarib appear to have been genetically isolated from the African gene flow and thus have genomes likely to reflect Yemen’s ancestry before the admixture. This ancestry was comparable to the ancestry present during the Bronze Age in the distant Northern regions of the Near East. After the Bronze Age, the South and North of the Near East therefore followed different genetic trajectories in the North the Levantines admixed with a Eurasian population carrying steppe ancestry whose impact never reached as far south as the Yemen, where people instead admixed with Africans leading to the genetic structure observed in the Near East today.

biorxiv genomics 0-100-users 2019

Galactose-modified duocarmycin prodrugs as senolytics, bioRxiv, 2019-08-25

SUMMARYSenescence is a stable growth arrest that impairs the replication of damaged, old or preneoplastic cells, therefore contributing to tissue homeostasis. Senescent cells accumulate during ageing and are associated with diseases, such as cancer, fibrosis and many age-related pathologies. Recent evidence suggests that the selective elimination of senescent cells can be effective on the treatment of many of these senescence-associated diseases. A universal characteristic of senescent cells is that they display elevated activity of the lysosomal β-galactosidase this has been exploited as a marker for senescence (senescence-associated β-galactosidase activity). Consequently, we hypothesised that galactose-modified cytotoxic prodrugs will be preferentially processed by senescent cells, resulting in their selective killing. Here, we show that different galactose-modified duocarmycin (GMD) derivatives preferentially kill senescent cells. GMD prodrugs induce selective apoptosis of senescent cells in a lysosomal β-galactosidase (GLB1)-dependent manner. GMD prodrugs can eliminate a broad range of senescent cells in culture, and treatment with a GMD prodrug enhances the elimination of bystander senescent cells that accumulate upon whole body irradiation or doxorubicin treatment of mice. Moreover, taking advantage of a mouse model of human adamantinomatous craniopharyngioma (ACP), we show that treatment with a GMD pro-drug result selectively reduced the number of β-catenin-positive preneoplastic senescent cells, what could have therapeutic implications. In summary, the above results show that galactose-modified duocarmycin prodrugs behave as senolytics, suggesting that they could be used to treat a wide range of senescence-related pathologies.

biorxiv cell-biology 0-100-users 2019

 

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