12 research outputs found
Constructive approach to limiting periodic orbits with exponential and power law dynamics
In dynamical systems limit cycles arise as a result of a Hopf bifurcation,
after a control parameter has crossed its critical value. In this study we
present a constructive method to produce dissipative dynamics which lead to
stable periodic orbits as time grows, with predesigned transient dynamics.
Depending on the construction method a) the limiting orbit can be a regular
circle, an ellipse or a more complex closed orbit and b) the approach to the
limiting orbit can follow an exponential law or a power law. This technique
allows to design nonlinear models of dynamical systems with desired
(exponential or power law) relaxation properties.Comment: 17 pages, 6 figure
AID/APOBEC-network reconstruction identifies pathways associated with survival in ovarian cancer
Background Building up of pathway-/disease-relevant signatures provides a
persuasive tool for understanding the functional relevance of gene alterations
and gene network associations in multifactorial human diseases. Ovarian cancer
is a highly complex heterogeneous malignancy in respect of tumor anatomy,
tumor microenvironment including pro-/antitumor immunity and inflammation;
still, it is generally treated as single disease. Thus, further approaches to
investigate novel aspects of ovarian cancer pathogenesis aiming to provide a
personalized strategy to clinical decision making are of high priority. Herein
we assessed the contribution of the AID/APOBEC family and their associated
genes given the remarkable ability of AID and APOBECs to edit DNA/RNA, and as
such, providing tools for genetic and epigenetic alterations potentially
leading to reprogramming of tumor cells, stroma and immune cells. Results We
structured the study by three consecutive analytical modules, which include
the multigene-based expression profiling in a cohort of patients with primary
serous ovarian cancer using a self-created AID/APOBEC-associated gene
signature, building up of multivariable survival models with high predictive
accuracy and nomination of top-ranked candidate/target genes according to
their prognostic impact, and systems biology-based reconstruction of the AID
/APOBEC-driven disease-relevant mechanisms using transcriptomics data from
ovarian cancer samples. We demonstrated that inclusion of the AID/APOBEC
signature-based variables significantly improves the clinicopathological
variables-based survival prognostication allowing significant patient
stratification. Furthermore, several of the profiling-derived variables such
as ID3, PTPRC/CD45, AID, APOBEC3G, and ID2 exceed the prognostic impact of
some clinicopathological variables. We next extended the signature-/modeling-
based knowledge by extracting top genes co-regulated with target molecules in
ovarian cancer tissues and dissected potential networks/pathways/regulators
contributing to pathomechanisms. We thereby revealed that the AID/APOBEC-
related network in ovarian cancer is particularly associated with
remodeling/fibrotic pathways, altered immune response, and autoimmune
disorders with inflammatory background. Conclusions The herein study is, to
our knowledge, the first one linking expression of entire AID/APOBECs and
interacting genes with clinical outcome with respect to survival of cancer
patients. Overall, data propose a novel AID/APOBEC-derived survival model for
patient risk assessment and reconstitute mapping to molecular pathways. The
established study algorithm can be applied further for any biologically
relevant signature and any type of diseased tissue
AID/APOBEC-network reconstruction identifies pathways associated with survival in ovarian cancer
Entwicklung von Online-Self-Assessments fĂŒr StudiengĂ€nge der Ingenieurwissenschaften an der TU Dresden
Ein Online-Self-Assessment (OSA) fĂŒr Studieninteressierte ist ein webbasierter SelbsteinschĂ€tzungstest, der kĂŒnftigen Studierenden eine realistische SelbsteinschĂ€tzung und eine darauf aufbauende, fundierte Studienwahl ermöglichen soll. Solch ein Test umfasst Aufgaben und Fragen (sogenannte Items), die von den Studieninteressierten selbststĂ€ndig bearbeitet werden. Das Feedback auf den bearbeiteten Test unterstĂŒtzt die Studieninteressierten bei ihrer Studienwahl, indem sie eine EinschĂ€tzung zu ihren orhandenen Kompetenzen, FĂ€higkeiten, Interessen und Erwartungen bezogen auf die tatsĂ€chlichen Anforderungen, Inhalte und Rahmenbedingungen des favorisierten Studiengangs erhalten. Das OSA wirkt unterstĂŒtzend in der Studienorientierungsphase und fördert frĂŒhzeitig eine bewusste Studienwahlentscheidung. [Aus der Einleitung
AID/APOBEC-network reconstruction identifies pathways associated with survival in ovarian cancer
Building up of pathway-/disease-relevant signatures provides a persuasive tool for understanding the functional relevance of gene alterations and gene network associations in multifactorial human diseases. Ovarian cancer is a highly complex heterogeneous malignancy in respect of tumor anatomy, tumor microenvironment including pro-/antitumor immunity and inflammation; still, it is generally treated as single disease. Thus, further approaches to investigate novel aspects of ovarian cancer pathogenesis aiming to provide a personalized strategy to clinical decision making are of high priority. Herein we assessed the contribution of the AID/APOBEC family and their associated genes given the remarkable ability of AID and APOBECs to edit DNA/RNA, and as such, providing tools for genetic and epigenetic alterations potentially leading to reprogramming of tumor cells, stroma and immune cells.status: publishe
Human Neutrophils Produce Antifungal Extracellular Vesicles against Aspergillus fumigatus
Invasive fungal infections caused by the mold Aspergillus fumigatus are a growing concern in the clinic due to the increasing use of immunosuppressive therapies and increasing antifungal drug resistance. These infections result in high rates of mortality, as treatment and diagnostic options remain limited. In healthy individuals, neutrophilic granulocytes are critical for elimination of A. fumigatus from the host; however, the exact extracellular mechanism of neutrophil-mediated antifungal activity remains unresolved. Here, we present a mode of antifungal defense employed by human neutrophils against A. fumigatus not previously described. We found that extracellular vesicles produced by neutrophils in response to A. fumigatus infection are able to associate with the fungus, limit growth, and elicit cell damage by delivering antifungal cargo. In the end, antifungal extracellular vesicle biology provides a significant step forward in our understanding of A. fumigatus host pathogenesis and opens up novel diagnostic and therapeutic possibilities.Polymorphonuclear granulocytes (PMNs) are indispensable for controlling life-threatening fungal infections. In addition to various effector mechanisms, PMNs also produce extracellular vesicles (EVs). Their contribution to antifungal defense has remained unexplored. We reveal that the clinically important human-pathogenic fungus Aspergillus fumigatus triggers PMNs to release a distinct set of antifungal EVs (afEVs). Proteome analyses indicated that afEVs are enriched in antimicrobial proteins. The cargo and the release kinetics of EVs are modulated by the fungal strain confronted. Tracking of afEVs indicated that they associated with fungal cells and even entered fungal hyphae, resulting in alterations in the morphology of the fungal cell wall and dose-dependent antifungal effects. To assess as a proof of concept whether the antimicrobial proteins found in afEVs might contribute to growth inhibition of hyphae when present in the fungal cytoplasm, two human proteins enriched in afEVs, cathepsin G and azurocidin, were heterologously expressed in fungal hyphae. This led to reduced fungal growth relative to that of a control strain producing the human retinol binding protein 7. In conclusion, extracellular vesicles produced by neutrophils in response to A. fumigatus infection are able to associate with the fungus, limit growth, and elicit cell damage by delivering antifungal cargo. This finding offers an intriguing, previously overlooked mechanism of antifungal defense against A. fumigatus
Additional file 1: of AID/APOBEC-network reconstruction identifies pathways associated with survival in ovarian cancer
The following additional data are available with the online version of this paper. Figure S1. Graphical view of the expression range of target genes used in GENEVESTIGATOR-based analysis. Figure S2. Correlation analysis of reference HKGs expression values in microarray data sets. Figure S3. Figure shows the impact of individual variables on survival prediction of the multivariable model (LASSO) for OS if predictors are changed by +1 SD. Figure S4. Figure shows LASSO-based Kaplan/Meier estimates for OS and PFS. Figure S5. Figure shows expression profiles of the AID/APOBEC-based multigene signature in ovarian cancer cell lines. Figure S6. Figure shows the extended analysis of expression profiles of the AID/APOBEC signature genes in a wide range of ovarian cancer cell lines (nâ=â55). Figure S7. Shown is the result of hierarchical clustering for individual genes composing the AID/APOBEC signature across arrays/samples of 55 ovarian cancer cell lines. Figure S8. The heat maps show the distribution of the Canonical Pathways/Functional Annotations/Upstream Regulators between corresponding target genes. Figure S9. The pie charts indicate the overlap of Canonical Pathways/Functional Annotations/Upstream Regulators between output_mixed and output_individual. Table S1. Real-time PCR primer sequences. Table S2. Real-time PCR primers. Table S3. Genes composing the AID/APOBEC multigene signature. Table S4. Univariate Cox regression analysis of clinicopathological variables and gene profiling-derived data sets for OS and PFS. Table S5. Correlation analysis for the AID/APOBEC multigene-derived variables. Table S6. Multivariable models (ridge) for PFS. Table S7. Comparative analysis of multivariable models (LASSO) for prognostication of OS and PFS. Table S8. Multivariable models (LASSO) for OS. Table S9. Multivariable models (LASSO) for PFS. Table S10. Top 50 Affymetrix probe sets co-regulated with APOBEC3G. Table S11. Top 50 Affymetrix probe sets co-regulated with ESR1. Table S12. Top 50 Affymetrix probe sets co-regulated with ID2. Table S13. Top 50 Affymetrix probe sets co-regulated with ID3. Table S14. Top 50 Affymetrix probe sets co-regulated with PTPRC/CD45. Table S15. 10-top-AID/APOBEC signature-linked Canonical Pathways. Table S16. Top-AID/APOBEC signature-linked Upstream Regulators. Table S17. 10-top-AID/APOBEC signature-linked Upstream Regulators. (PDF 4761Â kb