| 11. |
- Malaker, Stacy A., et al.
(författare)
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The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:(15), s. 7278-7287
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Tidskriftsartikel (refereegranskat)abstract
- Mucin-domain glycoproteins are found in nearly every tissue of the human body, and are important in biological processes ranging from embryogenesis to cancer. Because there are few tools to study mucin domains, their biological functions at the molecular scale remain unclear. Here, we help address a hurdle to the study of mucin-domain glycoproteins by characterizing a bacterial protease with selectivity for mucins. This mucinase selectively removes native mucins from cell surfaces and cuts them into fragments amenable to analysis.Mucin domains are densely O-glycosylated modular protein domains that are found in a wide variety of cell surface and secreted proteins. Mucin-domain glycoproteins are known to be key players in a host of human diseases, especially cancer, wherein mucin expression and glycosylation patterns are altered. Mucin biology has been difficult to study at the molecular level, in part, because methods to manipulate and structurally characterize mucin domains are lacking. Here, we demonstrate that secreted protease of C1 esterase inhibitor (StcE), a bacterial protease from Escherichia coli, cleaves mucin domains by recognizing a discrete peptide- and glycan-based motif. We exploited StcE’s unique properties to improve sequence coverage, glycosite mapping, and glycoform analysis of recombinant human mucins by mass spectrometry. We also found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients with ovarian cancer. Finally, using StcE, we discovered that sialic acid-binding Ig-type lectin-7 (Siglec-7), a glycoimmune checkpoint receptor, selectively binds sialomucins as biological ligands, whereas the related receptor Siglec-9 does not. Mucin-selective proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of mucin domain structure and function.
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| 12. |
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| 13. |
- Schweinsberg, Martin, et al.
(författare)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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| 14. |
- Amemiya, Chris T., et al.
(författare)
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The African coelacanth genome provides insights into tetrapod evolution
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7445, s. 311-316
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
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| 15. |
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| 16. |
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| 17. |
- Braasch, Ingo, et al.
(författare)
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The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:4, s. 427-437
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Tidskriftsartikel (refereegranskat)abstract
- To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.
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| 18. |
- Djurfeldt, Göran, et al.
(författare)
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Agrarian Change and Social Mobility in Tamil Nadu
- 2008
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This is a study of social mobility over 25 years in six villages in the former Tiruchy District in Tamil Nadu. The two most important external drivers are local industrialization and social policy in a broad sense. In a mainly descriptive analysis, it is shown that the overall effect seems to be a centripetal tendency in agrarian structure, with tendencies towards a strengthened position for family farming and for both the topdogs and the underdogs in the old agrarian society to leave agriculture altogether, seeking improved life chances in the non-agrarian economy, both inside the villages and in the wider economy. The descriptive analysis in this article is followed up with a modelling exercise in an accompanying article.
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| 19. |
- Doddapaneni, Venkatesh, et al.
(författare)
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Engineered PMMA-ZnO nanocomposites for improving the electric arc interruption capability in electrical switching applications : Unprecedented experimental insights
- 2017
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Ingår i: Composites Science And Technology. - : Elsevier. - 0266-3538 .- 1879-1050. ; 141, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- Polymer inorganic nanocomposites (PINCs) have been engineered for controlling the electrical arc and to improve the arc interruption capability of the electrical switching applications, like circuit breakers. Several PINCs are fabricated by formation of ZnO quantum dots (QDs) in a poly (methyl methacrylate) (PMMA) matrix via in-situ polymerization method to avoid agglomeration of QDs, leading to a good spatial distribution of QDs in the polymer matrix. These PINCs have been characterized in detail for the morphology of QDs, interaction between QDs and polymer matrix, and ultraviolet (UV) radiation absorption. ZnO QDs have been assessed to have particle diameter of 3.5 nm, and their presence in the PMMA is revealed by the unique luminescence characteristics of the QDs under UV light. The presence of ZnO QDs broadened the range of UV radiation absorption of PMMA and the absorption edge is gradually shifted from 270 nm to 338 nm with step-wise loading of ZnO QDs. The PINCs are tested to determine their reproducibility and impact on the electrical arcs of current 1.6 kA generated using a specially designed test-setup. Interaction of PINCs with the electrical arcs generates ablation of chemical species towards core of the electrical arc, resulting in increase of voltage leading to cool-down the arc temperature. This experimental study demonstrates for the first time that these PINCs are reproducible, reliable and provides superior arc interruption capability.
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| 20. |
- Doddapaneni, Venkatesh, et al.
(författare)
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Improving Uv Radiation Absorption by Copper Oxide NPs/PMMA Nanocomposites for Electrical Switching Applications
- 2015
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Ingår i: Powder metallurgy and metal ceramics. - : Springer. - 1068-1302 .- 1573-9066. ; 54:7-8, s. 397-401
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Tidskriftsartikel (refereegranskat)abstract
- Nanocomposites based on the radiation absorbing polymer (PNCs) are of interest for a variety of applications including circuit breakers, UV-shielding windows, contact lenses, and glasses among others. Such PNCs can be made by incorporating suitable radiation absorbing nanoparticles into a polymeric matrix by in situ polymerization. In this study, spherical nanoparticles (5-6 nm) of oleic acid (OA) surface modified cupric oxide (CuO) are synthesized and used to improve the ultra-violet (UV) radiation absorption property of a polymer matrix, i.e., polymethylmethacrylate (PMMA). The synthesis of spherical CuO nanoparticles, surface modification using OA, dispersion of CuO nanoparticles with different concentrations in PMMA, and UV radiation absorption property of the resultant PNC are investigated. Two different PNCs are produced using OA modified CuO nanoparticles with different concentrations. As synthesized CuO nanoparticles and OA modified CuO nanoparticles are examined by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR) techniques. The UV absorption edges are evaluated from the UV-Vis absorption spectra by using UV-Visible absorption spectroscopy. The results show that the UV radiation absorption of the PNC with higher concentration of CuO nanoparticles is improved compared with PMMA and the absorption edge moved towards longer wavelengths i.e., from 271 to 281 nm. These PNCs are successful in arc interruption process by absorbing a broad range of radiation emitted from high-energy copper arcs produced in the circuit breakers.
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