| 1. |
- Librado, P., et al.
(author)
-
The origins and spread of domestic horses from the Western Eurasian steppes
- 2021
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
-
Journal article (peer-reviewed)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.
(author)
-
Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
- 2019
-
In: Cell. - : Elsevier BV. - 0092-8674. ; 177:6
-
Journal article (peer-reviewed)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. |
- Costa, H., et al.
(author)
-
Human cytomegalovirus may promote tumour progression by upregulating arginase-2
- 2016
-
In: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:30, s. 47221-47231
-
Journal article (peer-reviewed)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.
|
|
| 4. |
|
|
| 5. |
- Scirica, Benjamin M., et al.
(author)
-
Safety of ticagrelor in patients with baseline conduction abnormalities : A PLATO (Study of Platelet Inhibition and Patient Outcomes) analysis
- 2018
-
In: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 202, s. 54-60
-
Journal article (peer-reviewed)abstract
- Background: Although bradyarrhythmias have been observed with ticagrelor and its use with advanced atrioventricular block is not recommended, questions arise regarding its use in patients with mild conduction abnormalities. The objectives were to compare rates of clinically relevant arrhythmias in relation to any mild baseline conduction abnormality in patients with acute coronary syndrome randomized to ticagrelor versus clopidogrel. Methods: We included all subjects in the electrocardiographic (ECG) substudy of the Platelet Inhibition and Patient Outcomes trial, excluding those with missing baseline ECG or with a pacemaker at baseline (N = 15,460). Conduction abnormality was defined as sinus bradycardia, first-degree atrioventricular block, hemiblock, or bundle-branch block. The primary arrhythmic outcome was the composite of any symptomatic brady-or tachyarrhythmia, permanent pacemaker placement, or cardiac arrest through 12 months. Results: Patients with baseline conduction abnormalities (n = 4,256, 27.5%) were older and more likely to experience the primary arrhythmic outcome. There were no differences by ticagrelor versus clopidogrel in the composite arrhythmic end point in those with baseline conduction disease (1-year cumulative incidence rate: 17% for both study arms; hazard ratio: 0.99 [0.86-1.15]) or without baseline conduction disease (1-year cumulative incidence rate: clopidogrel 12.8% vs ticagrelor 12.4%; hazard ratio: 0.98 (0.88-1.09). There were also no statistically significant differences between ticagrelor and clopidogrel in the rates of bradycardic (or any individual arrhythmic) events in patients with baseline conduction abnormalities. Conclusions: Ticagrelor compared to clopidogrel did not increase arrhythmic events even in subjects with acute coronary syndrome who present with mild conduction abnormalities on their baseline ECG. (C) 2018 Published by Elsevier Inc.
|
|
| 6. |
- Broushaki, Farnaz, et al.
(author)
-
Early Neolithic genomes from the eastern Fertile Crescent.
- 2016
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 353:6298
-
Journal article (peer-reviewed)abstract
- We sequenced Early Neolithic genomes from the Zagros region of Iran (eastern Fertile Crescent), where some of the earliest evidence for farming is found, and identify a previously uncharacterized population that is neither ancestral to the first European farmers nor has contributed substantially to the ancestry of modern Europeans. These people are estimated to have separated from Early Neolithic farmers in Anatolia some 46,000 to 77,000 years ago and show affinities to modern-day Pakistani and Afghan populations, but particularly to Iranian Zoroastrians. We conclude that multiple, genetically differentiated hunter-gatherer populations adopted farming in southwestern Asia, that components of pre-Neolithic population structure were preserved as farming spread into neighboring regions, and that the Zagros region was the cradle of eastward expansion.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Gustafsson, RKL, et al.
(author)
-
Direct infection of primary endothelial cells with human cytomegalovirus prevents angiogenesis and migration
- 2015
-
In: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 96:12, s. 3598-3612
-
Journal article (peer-reviewed)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.
|
|
| 12. |
- Malekkhaiat Häffner, Sara, et al.
(author)
-
Membrane interactions and antimicrobial effects of layered double hydroxide nanoparticles
- 2017
-
In: Physical Chemistry, Chemical Physics - PCCP. - : ROYAL SOC CHEMISTRY. - 1463-9076 .- 1463-9084. ; 19:35, s. 23832-23842
-
Journal article (peer-reviewed)abstract
- Membrane interactions are critical for the successful use of inorganic nanoparticles as antimicrobial agents and as carriers of, or co-actives with, antimicrobial peptides (AMPs). In order to contribute to an increased understanding of these, we here investigate effects of particle size (42-208 nm) on layered double hydroxide (LDH) interactions with both bacteria-mimicking and mammalian-mimicking lipid membranes. LDH binding to bacteria-mimicking membranes, extraction of anionic lipids, as well as resulting membrane destabilization, was found to increase with decreasing particle size, also translating into size-dependent synergistic effects with the antimicrobial peptide LL-37. Due to strong interactions with anionic lipopolysaccharide and peptidoglycan layers, direct membrane disruption of both Gram-negative and Gram-positive bacteria is suppressed. However, LDH nanoparticles cause size-dependent charge reversal and resulting flocculation of both liposomes and bacteria, which may provide a mechanism for bacterial confinement or clearance. Taken together, these findings demonstrate a set of previously unknown behaviors, including synergistic membrane destabilization and dual confinement/killing of bacteria through combined LDH/AMP exposure, of potential therapeutic interest.
|
|
| 13. |
- Panahi, Mahdi, et al.
(author)
-
Large-scale dynamic flood monitoring in an arid-zone floodplain using SAR data and hybrid machine-learning models
- 2022
-
In: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 611, s. 128001-
-
Journal article (peer-reviewed)abstract
- Although the growing number of synthetic aperture radar (SAR) satellites has increased their application in flood-extent mapping, predictive models for the analysis of flood dynamics that are independent of sensor characteristics must be developed to fully extract information from SAR images for flood mitigation. This study aimed to develop hybrid machine-learning models for flood mapping in the Ahvaz region, Iran, based on SAR data. Each hybrid model consists of a support vector machine (SVM) algorithm coupled with one of the following metaheuristic optimization procedures: grey wolf optimization (GWO), differential evolution, and the imperialist competitive algorithm. Sentinel-1 acquired SAR images before and during flooding between 20 March and 26 May of 2019. The goodness-of-fit level and predictive capability of each model were scrutinized using overall accuracy, producer accuracy, and user accuracy. The SVM-GWO approach yielded the highest accuracy with overall accuracies of 96.07% and 93.39% in the training and validation steps, respectively. Furthermore, this hybrid model provided the most accurate classification of water-inundation class based on producer accuracy (96.67%) and user accuracy (95.05%). The results highlight that wetland is the last land-use/land-cover type to return to normal conditions due to the many previously dry oxbow lakes that could trap water for a long time. Furthermore, the nine most suitable sites for flood-protection structures (e.g., embankments and levees) were identified based on floodwater distribution analysis. This work describes a robust, data-parsimonious approach that will benefit flood mitigation studies seeking to identify the most suitable locations for embankments based on spatio-temporal flood dynamics.
|
|
| 14. |
- Werthen, M, et al.
(author)
-
Pseudomonas aeruginosa-induced infection and degradation of human wound fluid and skin proteins ex vivo are eradicated by a synthetic cationic polymer
- 2004
-
In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 54:4, s. 772-779
-
Journal article (peer-reviewed)abstract
- Objectives: Antimicrobial peptides are important effectors of innate immunity. Bacteria display multiple defence mechanisms against these peptides. For example, Pseudomonas aeruginosa releases potent proteinases that inactivate the human cathelicidin LL-37. Hence, in conditions characterized by persistent bacterial colonization, such as in P. aeruginosa-infected skin wounds, there is a need for efficient means of reducing bacterial load. Here, the effect of the cationic molecule polyhexamethylenebiguanide (PHMB) was evaluated. Methods: Infection models in human wound fluid and human skin were established. Radial diffusion methods, bacterial growth and bactericidal assays were used for determination of effects of PHMB on bacteria in the presence of plasma, wound fluid or human skin. At the protein and tissue levels, SDS-PAGE, light microscopy and scanning electron microscopy were used to study the effects of P. aeruginosa infection before and after addition of PHMB. Results: PHMB killed common ulcer-derived bacteria in the presence of human wound fluid. Furthermore, elastase-expressing P. aeruginosa completely degraded wound fluid proteins as well as human skin during infection ex vivo. The infection, and consequent protein degradation, was reversed by PHMB. Conclusions: The ex vivo infection models presented here should be helpful in the screening of novel antimicrobials and constitute a prerequisite for future clinical studies.
|
|
