The COVID-19 pandemic has kept the world in suspense for the past year. In most federal countries such as Germany, locally varying conditions demand for state- or county-level decisions to adapt to the disease dynamics. However, this requires a deep understanding of the mesoscale outbreak dynamics between microscale agent models and macroscale global models. Here, we use a reparameterized SIQRD network model that accounts for local political decisions to predict the spatiotemporal evolution of the pandemic in Germany at county resolution. Our optimized model reproduces state-wise cumulative infections and deaths as reported by the Robert Koch Institute and predicts the development for individual counties at convincing accuracy during both waves in spring and fall of 2020. We demonstrate the dominating effect of local infection seeds and identify effective measures to attenuate the rapid spread. Our model has great potential to support decision makers on a state and community politics level to individually strategize their best way forward during the months to come.
Since its outbreak in 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) keeps surprising the medical community by evolving diverse immune escape mutations in a rapid and effective manner. To gain deeper insight into mutation frequency and dynamics, we isolated ten ancestral strains of SARS-CoV-2 and performed consecutive serial incubation in ten replications in a suitable and common cell line and subsequently analysed them using RT-qPCR and whole genome sequencing. Along those lines we hoped to gain fundamental insights into the evolutionary capacity of SARS-CoV-2 in vitro. Our results identified a series of adaptive genetic changes, ranging from unique convergent substitutional mutations and hitherto undescribed insertions. The region coding for spike proved to be a mutational hotspot, evolving a number of mutational changes including the already known substitutions at positions S:484 and S:501. We discussed the evolution of all specific adaptations as well as possible reasons for the seemingly inhomogeneous potential of SARS-CoV-2 in the adaptation to cell culture. The combination of serial passage in vitro with whole genome sequencing uncovers the immense mutational potential of some SARS-CoV-2 strains. The observed genetic changes of SARS-CoV-2 in vitro could not be explained solely by selectively neutral mutations but possibly resulted from the action of directional selection accumulating favourable genetic changes in the evolving variants, along the path of increasing potency of the strain. Competition among a high number of quasi-species in the SARS-CoV-2 in vitro population gene pool may reinforce directional selection and boost the speed of evolutionary change. 相似文献
Ferredoxins, iron-sulfur (Fe-S) cluster proteins, play a key role in oxidoreduction reactions. To date, evolutionary analysis of these proteins across the domains of life have been confined to observing the abundance of Fe-S cluster types (2Fe-2S, 3Fe-4S, 4Fe-4S, 7Fe-8S (3Fe-4s and 4Fe-4S) and 2[4Fe-4S]) and the diversity of ferredoxins within these cluster types was not studied. To address this research gap, here we propose a subtype classification and nomenclature for ferredoxins based on the characteristic spacing between the cysteine amino acids of the Fe-S binding motif as a subtype signature to assess the diversity of ferredoxins across the living organisms. To test this hypothesis, comparative analysis of ferredoxins between bacterial groups, Alphaproteobacteria and Firmicutes and ferredoxins collected from species of different domains of life that are reported in the literature has been carried out. Ferredoxins were found to be highly diverse within their types. Large numbers of alphaproteobacterial species ferredoxin subtypes were found in Firmicutes species and the same ferredoxin subtypes across the species of Bacteria, Archaea, and Eukarya, suggesting shared common ancestral origin of ferredoxins between Archaea and Bacteria and lateral gene transfer of ferredoxins from prokaryotes (Archaea/Bacteria) to eukaryotes. This study opened new vistas for further analysis of diversity of ferredoxins in living organisms. 相似文献
Population size has long been considered an important driver of cultural diversity and complexity. Results from population genetics, however, demonstrate that in populations with complex demographic structure or mode of inheritance, it is not the census population size, N, but the effective size of a population, Ne, that determines important evolutionary parameters. Here, we examine the concept of effective population size for traits that evolve culturally, through processes of innovation and social learning. We use mathematical and computational modeling approaches to investigate how cultural Ne and levels of diversity depend on (1) the way traits are learned, (2) population connectedness, and (3) social network structure. We show that one-to-many and frequency-dependent transmission can temporally or permanently lower effective population size compared to census numbers. We caution that migration and cultural exchange can have counter-intuitive effects on Ne. Network density in random networks leaves Ne unchanged, scale-free networks tend to decrease and small-world networks tend to increase Ne compared to census numbers. For one-to-many transmission and different network structures, larger effective sizes are closely associated with higher cultural diversity. For connectedness, however, even small amounts of migration and cultural exchange result in high diversity independently of Ne. Extending previous work, our results highlight the importance of carefully defining effective population size for cultural systems and show that inferring Ne requires detailed knowledge about underlying cultural and demographic processes. 相似文献
Previous in vitro studies indicated that hepatic stellate cells (HSC) and rat liver myofibroblasts (rMF) have to be regarded
as different cell populations of the myofibroblastic lineage with fibrogenic potential. Employing the discrimination features
defined by these studies the localization of HSC and rMF was analyzed in diseased livers. Normal and acutely as well as chronically
carbon tetrachloride-injured livers were analyzed by immunohistochemistry and by in situ hybridization. In normal livers HSC
[desmin/glial fibrillary acid protein (GFAP)-positive cells] were distributed in the hepatic parenchyma, while rMF (desmin/smooth
muscle alpha actin-positive, GFAP-negative cells colocalized with fibulin-2) were located in the portal field, the walls of
central veins, and only occasionally in the parenchyma. Acute liver injury was characterized almost exclusively by an increase
in the number of HSC, while the amount of rMF was nearly unchanged. In early stages of fibrosis, HSC and rMF were detected
within the developing scars. In advanced stages of fibrosis, HSC were mainly present at the scar–parenchymal interface, while
rMF accounted for the majority of the cells located within the scar. At every stage of fibrogenesis, rMF, in contrast to HSC,
were only occasionally detected in the hepatic parenchyma. HSC and rMF are present in normal and diseased livers in distinct
compartments and respond differentially to tissue injury. Acute liver injury is followed by an almost exclusive increase in
the number of HSC, while in chronically injured livers not only HSC but also rMF are involved in scar formation.
Accepted: 16 September 1999 相似文献
Heterologous complementation in yeast has been a successful tool for cloning and characterisation of genes from various organisms. Therefore we constructed conditionally lethal Saccharomyces cerevisiae strains by replacing the endogenous promoter from the genes of interest (glycosyltransferases) by the stringently regulated GAL1-promoter, by a technique called chromosomal promoter replacement. Such yeast strains were constructed for the genes Alg 1, Alg7, Sec59, Wbp1 involved in N-Glycosylation, the genes Gpi2, Gpi3/Spt14, Gaal, Pis1, involved in GPI-anchor biosynthesis and Dpm involved in both pathways. All strains show the expected conditionally lethal phenotype on glucose-containing medium when expression of the respective gene is turned off. 相似文献
Motivated by a biomedical database set up by our group, we aimed to develop a generic database front-end with embedded knowledge
discovery and analysis features. A major focus was the human-oriented representation of the data and the enabling of a closed
circle of data query, exploration, visualization and analysis. 相似文献