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- Gopalakrishnan, R., et al.
(author)
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Bio-distribution of pharmacologically administered recombinant factor VIIa (rFVIIa)
- 2010
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In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 8:2, s. 301-310
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Journal article (peer-reviewed)abstract
- Background: Recent clinical studies suggest that the prophylactic use of recombinant factor VIIa (rFVIIa) markedly reduces the number of bleeding episodes in hemophilic patients with inhibitors. Given the short biological half-life of rFVIIa, it is unclear how rFVIIa could be effective in prophylactic treatment. Objectives: To examine the extravascular distribution of pharmacologically administered rFVIIa to obtain clues on how rFVIIa could work in prophylaxis. Methods: Recombinant mouse FVIIa tagged with AF488 fluorophore (AF488-FVIIa) was administered into mice via the tail vein. At different time intervals following the administration, mice were exsanguinated and various tissues were collected. The tissue sections were processed for immunohistochemistry to evaluate distribution of rFVIIa. Results: rFVIIa, immediately following the administration, associated with the endothelium lining of large blood vessels. Within 1 h, rFVIIa bound to endothelial cells was transferred to the perivascular tissue surrounding the blood vessels and thereafter diffused throughout the tissue. In the liver, rFVIIa was localized to sinusoidal capillaries and accumulated in hepatocytes. In bone, rFVIIa was accumulated in the zone of calcified cartilage and some of it was retained there for a week. The common finding of the present study is that rFVIIa in extravascular spaces was mostly localized to regions that contain TF expressing cells. Conclusions: The present study demonstrates that pharmacologically administered rFVIIa readily associates with the vascular endothelium and subsequently enters into extravascular spaces where it is likely to bind to TF and is retained for extended time periods. This may explain the prolonged pharmacological effect of rFVIIa.
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| 4. |
- Bergström, Anders, et al.
(author)
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Grey wolf genomic history reveals a dual ancestry of dogs
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 607:7918, s. 313-320
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Journal article (peer-reviewed)abstract
- The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.
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| 7. |
- Lin, Audrey T., et al.
(author)
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The history of Coast Salish "woolly dogs" revealed by ancient genomics and Indigenous Knowledge
- 2023
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In: Science. - 0036-8075 .- 1095-9203. ; 382:6676, s. 1303-1308
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Journal article (peer-reviewed)abstract
- Ancestral Coast Salish societies in the Pacific Northwest kept long-haired woolly dogs that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from "Mutton", collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance.
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| 8. |
- Liu, Shanlin, et al.
(author)
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Ancient and modem genomes unravel the evolutionary history of the rhinoceros family
- 2021
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In: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 184:19, s. 4874-4885.e16
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Journal article (peer-reviewed)abstract
- Only five species of the once-diverse Rhinocerotidae remain, making the reconstruction of their evolutionary history a challenge to biologists since Darwin. We sequenced genomes from five rhinoceros species (three extinct and two living), which we compared to existing data from the remaining three living species and a range of outgroups. We identify an early divergence between extant African and Eurasian lineages, resolving a key debate regarding the phylogeny of extant rhinoceroses. This early Miocene (similar to 16 million years ago [mya]) split post-dates the land bridge formation between the Afro-Arabian and Eurasian landmasses. Our analyses also show that while rhinoceros genomes in general exhibit low levels of genome-wide diversity, heterozygosity is lowest and inbreeding is highest in the modern species. These results suggest that while low genetic diversity is a long-term feature of the family, it has been particularly exacerbated recently, likely reflecting recent anthropogenic-driven population declines.
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| 9. |
- Sabarathinam, C., et al.
(author)
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SARS-CoV-2 phase I transmission and mutability linked to the interplay of climatic variables : a global observation on the pandemic spread
- 2022
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In: Environmental Science and Pollution Research. - : Springer Nature. - 0944-1344 .- 1614-7499. ; 29:48, s. 72366-72383
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Journal article (peer-reviewed)abstract
- The study aims to determine the impact of global meteorological parameters on SARS-COV-2, including population density and initiation of lockdown in twelve different countries. The daily trend of these parameters and COVID-19 variables from February 15th to April 25th, 2020, were considered. Asian countries show an increasing trend between infection rate and population density. A direct relationship between the time-lapse of the first infected case and the period of suspension of movement controls the transmissivity of COVID-19 in Asian countries. The increase in temperature has led to an increase in COVID-19 spread, while the decrease in humidity is consistent with the trend in daily deaths during the peak of the pandemic in European countries. Countries with 65°F temperature and 5 mm rainfall have a negative impact on COVID-19 spread. Lower oxygen availability in the atmosphere, fine droplets of submicron size together with infectious aerosols, and low wind speed have contributed to the increase in total cases and mortality in Germany and France. The onset of the D614G mutation and subsequent changes to D614 before March, later G614 in mid-March, and S943P, A831V, D839/Y/N/E in April were observed in Asian and European countries. The results of the correlation and factor analysis show that the COVID-19 cases and the climatic factors are significantly correlated with each other. The optimum meteorological conditions for the prevalence of G614 were identified. It was observed that the complex interaction of global meteorological factors and changes in the mutational form of CoV-2 phase I influenced the daily mortality rate along with other comorbid factors. The results of this study could help the public and policymakers to create awareness of the COVID-19 pandemic.
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| 10. |
- Abanin, D. A., et al.
(author)
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Distinguishing localization from chaos : Challenges in finite-size systems
- 2021
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In: Annals of Physics. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0003-4916 .- 1096-035X. ; 427
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Journal article (peer-reviewed)abstract
- We re-examine attempts to study the many-body localization transition using measures that are physically natural on the ergodic/quantum chaotic regime of the phase diagram. Using simple scaling arguments and an analysis of various models for which rigorous results are available, we find that these measures can be particularly adversely affected by the strong finite-size effects observed in nearly all numerical studies of many-body localization. This severely impacts their utility in probing the transition and the localized phase. In light of this analysis, we discuss a recent study (?untajs et al., 2020) of the behaviour of the Thouless energy and level repulsion in disordered spin
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