| 1. |
- Librado, P., et al.
(författare)
-
The origins and spread of domestic horses from the Western Eurasian steppes
- 2021
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
-
Tidskriftsartikel (refereegranskat)abstract
- Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
|
|
| 2. |
- Fages, A., et al.
(författare)
-
Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
- 2019
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 177:6
-
Tidskriftsartikel (refereegranskat)abstract
- Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (>= 1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modem legacy of past equestrian civilisations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modem breeding impacted genetic diversity more dramatically than the previous millennia of human management.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Costa, H., et al.
(författare)
-
Human cytomegalovirus may promote tumour progression by upregulating arginase-2
- 2016
-
Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:30, s. 47221-47231
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression. Results: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA. Methods: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2- overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA). Conclusions: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.
|
|
| 7. |
- Davoudi-Kiakalayeh, A., et al.
(författare)
-
Costs related to drowning and near drowning in northern Iran (Guilan province)
- 2011
-
Ingår i: Ocean and Coastal Management. - Oxon, UK : Elsevier BV. - 0964-5691 .- 1873-524X. ; 54:3, s. 250-255
-
Tidskriftsartikel (refereegranskat)abstract
- In Iran and many other low- and middle-income countries, few studies have been carried out in order to assess which cost analysis methods should be undertaken at the household and community level in relation to incidences of drowning. In this study, we have attempted to develop a model for estimating the impact of the economic burden that drowning and near drowning events incur for victims’ families in the Guilan province in the north of Iran by using an incidence approach. During the financial year of March 2007 to 2008, the following cost-related aspects of drowning episodes were evaluated: (note: main cost elements were income adjusted by family and years) medical costs, productivity loss costs and death costs. A total of 137 drowning fatalities and 104 near drowning incidents were recorded. Males in the age span of 10-29 years constitute a majority of the epidemiology and economy data. When the number of variables included in cost analysis was expanded, the estimated burden of economic duress increased dramatically; however, drowning cost for one drowned victim was equivalent to 17 times the country’s gross domestic product(GDP) per capital. Identification of injured person-based costs in this study will enable development of more effective prevention programs and provide indicators of other costs related to drowning episodes such as property damage and the impact of these accidents on community services and the public health care system. © 2010.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Gustafsson, RKL, et al.
(författare)
-
Direct infection of primary endothelial cells with human cytomegalovirus prevents angiogenesis and migration
- 2015
-
Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 96:12, s. 3598-3612
-
Tidskriftsartikel (refereegranskat)abstract
- Human cytomegalovirus (hCMV) is a beta herpesvirus that establishes lifelong infection. Although the virus does not usually cause overt clinical symptoms in immunocompetent individuals it can have deleterious effects in immunocompromised patients, such as those on post-transplant medication or with HIV infection. hCMV is the most common congenital infection and can lead to serious fetal sequelae. Endothelial cells (ECs) are natural hosts for hCMVin vivo, therefore, investigations of how this cell type is modulated by infection are key to understanding hCMV pathogenesis. Previous studies have examined the effect of secretomes from hCMV-infected cells on EC angiogenesis, whereas the effect of direct infection on this process has not been so well investigated. Here, we show that placental ECs are viral targets during congenital infection and that vessels in infected tissue appear morphologically abnormal. We demonstrate that the clinical hCMV strain VR1814 impaired EC tube assembly inin vitroangiogenesis assays and inhibited wound healing ability in scratch assays. Secretomes from infected cultures did not impair angiogenesis of uninfected ECs, suggesting that cell-intrinsic changes, as opposed to secreted factors, were responsible. We observed viral gene transcription dependent downregulation of the expression of angiogenesis-associated genes, including angiopoietin-2, TEK receptor and vascular endothelial growth factor receptors. An alternative clinical hCMV stain, TB40E showed similar effects on EC angiogenesis. Together, our data indicate that direct infection with hCMV can induce an anti-migratory and anti-angiogenic EC phenotype, which could have a detrimental effect on the vasculature development in infected tissues.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Pollack, Charles V., Jr., et al.
(författare)
-
Relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non-ST-segment elevation acute coronary syndrome in the PLATO trial
- 2017
-
Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 40:6, s. 390-398
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines suggest that "upstream" P2Y(12) receptor antagonists should be considered in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS).Hypothesis: Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency.Methods: In the PLATO trial, 6792 NSTE-ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of "early" (<3h) vs "late" (>= 3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes.Results: Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs >= 3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, P-int = 0.002). Patterns were similar at 30 days and 1 year.Conclusions: The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
