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| 2. |
- Wu, Jing, et al.
(författare)
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Interleukin-33 is a Novel Immunosuppressor that Protects Cancer Cells from TIL Killing by a Macrophage-Mediated Shedding Mechanism
- 2021
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 8:21
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Tidskriftsartikel (refereegranskat)abstract
- Recognition of specific antigens expressed in cancer cells is the initial process of cytolytic T cell-mediated cancer killing. However, this process can be affected by other non-cancerous cellular components in the tumor microenvironment. Here, it is shown that interleukin-33 (IL-33)-activated macrophages protect melanoma cells from tumor-infiltrating lymphocyte-mediated killing. Mechanistically, IL-33 markedly upregulates metalloprotease 9 (MMP-9) expression in macrophages, which acts as a sheddase to trim NKG2D, an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, subsets of CD4+ T cells, iNKT cells, and gamma delta T cells. Further, MMP-9 also cleaves the MHC class I molecule, cell surface antigen-presenting complex molecules, expressed in melanoma cells. Consequently, IL-33-induced macrophage MMP-9 robustly mitigates the tumor killing-effect by T cells. Genetic and pharmacological loss-of-function of MMP-9 sheddase restore T cell-mediated cancer killing. Together, these data provide compelling in vitro and in vivo evidence showing novel mechanisms underlying the IL-33-macrophage-MMP-9 axis-mediated immune tolerance against cancer cells. Targeting each of these signaling components, including IL-33 and MMP-9 provides a new therapeutic paradigm for improving anticancer efficacy by immune therapy.
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| 3. |
- Aguileta, Gabriela, et al.
(författare)
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Proposed standard nomenclature for the alpha- and beta-globin gene families
- 2006
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Ingår i: Genes & Genetic Systems. - : Genetics Society of Japan. - 1341-7568 .- 1880-5779. ; 81:5, s. 367-371
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Tidskriftsartikel (refereegranskat)abstract
- The globin family of genes and proteins has been a recurrent object of study for many decades. This interest has generated a vast amount of knowledge. However it has also created an inconsistent and confusing nomenclature, due to the lack of a systematic approach to naming genes and failure to reflect the phylogenetic relationships among genes of the gene family. To alleviate the problems with the existing system, here we propose a standardized nomenclature for the alpha and beta globin family of genes, based on a phylogenetic analysis of vertebrate alpha and beta globins, and following the Guidelines for Human Gene Nomenclature.
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| 4. |
- Beaumont, Mark A, et al.
(författare)
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In defence of model-based inference in phylogeography.
- 2010
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Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 19:3, s. 436-446
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Tidskriftsartikel (refereegranskat)abstract
- Recent papers have promoted the view that model-based methods in general, and those based on Approximate Bayesian Computation (ABC) in particular, are flawed in a number of ways, and are therefore inappropriate for the analysis of phylogeographic data. These papers further argue that Nested Clade Phylogeographic Analysis (NCPA) offers the best approach in statistical phylogeography. In order to remove the confusion and misconceptions introduced by these papers, we justify and explain the reasoning behind model-based inference. We argue that ABC is a statistically valid approach, alongside other computational statistical techniques that have been successfully used to infer parameters and compare models in population genetics. We also examine the NCPA method and highlight numerous deficiencies, either when used with single or multiple loci. We further show that the ages of clades are carelessly used to infer ages of demographic events, that these ages are estimated under a simple model of panmixia and population stationarity but are then used under different and unspecified models to test hypotheses, a usage the invalidates these testing procedures. We conclude by encouraging researchers to study and use model-based inference in population genetics.
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| 5. |
- Höhna, Sebastian, 1983-
(författare)
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Bayesian Phylogenetic Inference : Estimating Diversification Rates from Reconstructed Phylogenies
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Phylogenetics is the study of the evolutionary relationship between species. Inference of phylogeny relies heavily on statistical models that have been extended and refined tremendously over the past years into very complex hierarchical models. Paper I introduces probabilistic graphical models to statistical phylogenetics and elaborates on the potential advantages a unified graphical model representation could have for the community, e.g., by facilitating communication and improving reproducibility of statistical analyses of phylogeny and evolution.Once the phylogeny is reconstructed it is possible to infer the rates of diversification (speciation and extinction). In this thesis I extend the birth-death process model, so that it can be applied to incompletely sampled phylogenies, that is, phylogenies of only a subsample of the presently living species from one group. Previous work only considered the case when every species had the same probability to be included and here I examine two alternative sampling schemes: diversified taxon sampling and cluster sampling. Paper II introduces these sampling schemes under a constant rate birth-death process and gives the probability density for reconstructed phylogenies. These models are extended in Paper IV to time-dependent diversification rates, again, under different sampling schemes and applied to empirical phylogenies. Paper III focuses on fast and unbiased simulations of reconstructed phylogenies. The efficiency is achieved by deriving the analytical distribution and density function of the speciation times in the reconstructed phylogeny.
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| 6. |
- Mugal, Carina Farah, 1981-
(författare)
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Nucleotide Substitution Patterns in Vertebrate Genomes
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The rates and patterns at which nucleotide substitutions occur vary significantly across the genome sequence of vertebrates. A prominent example is the difference in the rate of evolution of functional sequences versus nonfunctional (neutrally evolving) sequences, which is explained by the influence of natural selection on functional sequences. However, even within neutrally evolving sequences there is striking variation in the rates and patterns of nucleotide substitutions. Unraveling the underlying processes that induce this variation is necessary to understand the basic principles of variation in neutral substitution profiles, which in turn is crucial for the identification of regions in the genome where natural selection acts. This research question builds the main focus of the present thesis. I have studied the causes and consequences of variation in different patterns of nucleotide substitutions. In particular, I have investigated substitutional strand asymmetries in mammalian genes and could show that they result from the asymmetric nature of DNA replication and transcription. Comparative analysis of substitutional asymmetries then suggested that the organization of DNA replication and the level of transcription are conserved among mammals. Further, I have examined the variation in CpG mutation rate among human genes and could show that beside DNA methylation also GC content plays a decisive role in CpG mutability. In addition, I have studied the signatures of GC-biased gene conversion and its impact on the evolution of the GC isochore structure in chicken. By comparison of the results in chicken to previous results in human I found evidence that karyotype stability is critical for the evolution of GC isochores. Finally, beside the empirical studies, I have performed theoretical investigations of substitution rates in functional sequences. More precisely, I have explored the temporal dynamics of estimates of the ratio of non-synonymous to synonymous substitution rates dN/dS in a phylogentic-population genetic framework.
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| 7. |
- Tang, Rao, et al.
(författare)
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Wideband Array Antenna with Hybrid SIGW and RGW Feeding Network
- 2021
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Ingår i: 2021 International Conference on Microwave and Millimeter Wave Technology, ICMMT 2021 - Proceedings.
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Konferensbidrag (refereegranskat)abstract
- In this paper, a 4×4-element linearly-polarized wideband array antenna with a feeding network made of a combination of substrate integrated gap waveguide (SIGW) and ridge gap waveguide (RGW) technologies is proposed. The bowtie dipoles are employed as the radiation elements for the array antenna, and the bandwidth is broadened by using the concept of the tightly coupled array. By employing the hybrid feeding network combining the SIGW with the RGW, a high efficiency can be achieved with a low profile. Based on the simulations by using CST Microwave Studio, the proposed 4×4 array antenna exhibits a relative impedance bandwidth of 34% from 22.7 to 32 GHz, with a maximum gain of 18 dBi.
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| 8. |
- Yin, Chunhua, et al.
(författare)
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Role of Host-Guest Charge Transfer in Cyclodextrin Complexation : A Computational Study
- 2019
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Ingår i: The Journal of Physical Chemistry C. - : AMER CHEMICAL SOC. - 1932-7447 .- 1932-7455. ; 123:29, s. 17745-17756
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Tidskriftsartikel (refereegranskat)abstract
- Charge transfer (CT) was proposed to play a role in the cyclodextrin (CD) complexation with guest molecules. To elucidate the importance of CT interactions, here we used computational methods of quantum mechanics, docking, and molecular dynamics (MD) to investigate alpha-CD complexes with aromatic guest molecules of nitrobenzene, carboxybenzene, benzoate, 4-nitrophenol, and 4-nitrophenolate. Considering host guest CT in the docking has more of a chance to search reasonable guest orientations relative to alpha-CD matching the experiment, compared to that without CT. The CT interaction enlarges the difference in binding affinities of varied guests, as evidenced from potential of mean force (PMF) MD calculations. Energy decomposition of the total enthalpy and entropy shows the CT influence on the binding reactions in detail and indicates that there are considerable compensating effects of individual contributions from the binding partners and surrounding water. Charge transfer reduces the total dipole of alpha-CD by 9% on average and alters its dipole direction thereby affecting guest association. Gas-phase zeroth-order symmetry-adapted perturbation theory calculations show host guest CT amounts to approximately 6% of the total binding energy. The continuum solvation model based on the quantum mechanical charge density predicts binding energies comparable with the well depth of PMF profiles in explicit water. The abnormal binding strength of alpha-CD with the similar guests can be rationalized in terms of hydrogen bonding, extent of host guest CT, and dipole arrangement of guest relative to host.
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| 9. |
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| 10. |
- Zhang, Chi, et al.
(författare)
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Evaluation of a Bayesian coalescent method of species delimitation
- 2011
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Ingår i: Systematic Biology. - : Oxford University Press (OUP). - 1063-5157 .- 1076-836X. ; 60:6, s. 747-761
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Tidskriftsartikel (refereegranskat)abstract
- A Bayesian coalescent-based method has recently been proposed to delimit species using multilocus genetic sequence data. Posterior probabilities of different species delimitation models are calculated using reversible-jump Markov chain Monte Carlo algorithms. The method accounts for species phylogenies and coalescent events in both extant and extinct species and accommodates lineage sorting and uncertainties in the gene trees. Although the method is theoretically appealing, its utility in practical data analysis is yet to be rigorously examined. In particular, the analysis may be sensitive to priors on ancestral population sizes and on species divergence times and to gene flow between species. Here we conduct a computer simulation to evaluate the statistical performance of the method, such as the false negatives (the error of lumping multiple species into one) and false positives (the error of splitting one species into several). We found that the correct species model was inferred with high posterior probability with only one or two loci when 5 or 10 sequences were sampled from each population, or with 50 loci when only one sequence was sampled. We also simulated data allowing migration under a two-species model, a mainland-island model and a stepping-stone model to assess the impact of gene flow (hybridization or introgression). The behavior of the method was diametrically different depending on the migration rate. Low rates at < 0.1 migrants per generation had virtually no effect, so that the method, while assuming no hybridization between species, identified distinct species despite small amounts of gene flow. This behavior appears to be consistent with biologists' practice. In contrast, higher migration rates at ≥ 10 migrants per generation caused the method to infer one species. At intermediate levels of migration, the method is indecisive. Our results suggest that Bayesian analysis under the multispecies coalescent model may provide important insights into population divergences, and may be useful for generating hypotheses of species delimitation, to be assessed with independent information from anatomical, behavioral, and ecological data.
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