| 1. |
|
|
| 2. |
|
|
| 3. |
- Bekkhus, T., et al.
(author)
-
Automated detection of vascular remodeling in tumor-draining lymph nodes by the deep-learning tool HEV-finder
- 2022
-
In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 258:1, s. 4-11
-
Journal article (peer-reviewed)abstract
- Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker. (c) 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
|
|
| 4. |
|
|
| 5. |
- Khani, Sajjad, et al.
(author)
-
Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function
- 2024
-
In: Nature Metabolism. - 2522-5812.
-
Journal article (peer-reviewed)abstract
- Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5′ truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Cho, Won Sang, et al.
(author)
-
Mass measurement in boosted decay systems at hadron colliders
- 2011
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 84:3, s. 035018-
-
Journal article (peer-reviewed)abstract
- We report a new possibility of using the MCT2 (Constransverse mass) variable for mass measurement in single step decay chains involving missing particles with moderate transverse momentum. We show that its experimental feasibility is enhanced compared to the corresponding MT2-kink method. We apply this method to reconstruct a pair of chargino decay chains.
|
|
| 9. |
- Cojoc, Gheorghe, et al.
(author)
-
Paired arrangement of kinetochores together with microtubule pivoting and dynamics drive kinetochore capture in meiosis I.
- 2016
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- Kinetochores are protein complexes on the chromosomes, whose function as linkers between spindle microtubules and chromosomes is crucial for proper cell division. The mechanisms that facilitate kinetochore capture by microtubules are still unclear. In the present study, we combine experiments and theory to explore the mechanisms of kinetochore capture at the onset of meiosis I in fission yeast. We show that kinetochores on homologous chromosomes move together, microtubules are dynamic and pivot around the spindle pole, and the average capture time is 3-4 minutes. Our theory describes paired kinetochores on homologous chromosomes as a single object, as well as angular movement of microtubules and their dynamics. For the experimentally measured parameters, the model reproduces the measured capture kinetics and shows that the paired configuration of kinetochores accelerates capture, whereas microtubule pivoting and dynamics have a smaller contribution. Kinetochore pairing may be a general feature that increases capture efficiency in meiotic cells.
|
|
| 10. |
- Connell, H., et al.
(author)
-
Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract
- 1996
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 93:18, s. 9827-9832
-
Journal article (peer-reviewed)abstract
- Type 1 fimbriae are adhesion organelles expressed by many Gram-negative bacteria. They facilitate adherence to mucosal surfaces and inflammatory cells in vitro, but their contribution to virulence has not been defined. This study presents evidence that type 1 fimbriae increase the virulence of Escherichia coli for the urinary tract by promoting bacterial persistence and enhancing the inflammatory response to infection. In a clinical study, we observed that disease severity was greater in children infected with E. coli O1:K1:H7 isolates expressing type 1 fimbriae than in those infected with type 1 negative isolates of the same serotype. The E. coli O1:K1:H7 isolates had the same electrophoretic type, were hemolysin-negative, expressed P fimbriae, and carried the fim DNA sequences. When tested in a mouse urinary tract infection model, the type 1-positive E. coli O1:K1:H7 isolates survived in higher numbers, and induced a greater neutrophil influx into the urine, than O1:K1:H7 type 1-negative isolates. To confirm a role of type 1 fimbriae, a fimH null mutant (CNI016) was constructed from an O1:K1:H7 type 1-positive parent. E. coli CNI016 had reduced survival and inflammatogenicity in the mouse urinary tract infection model. E. coli CNI016 reconstituted with type 1 fimbriae (E. coli CN1018) had restored virulence similar to that of the wild- type parent strain. These results show that type 1 fimbriae in the genetic background of a uropathogenic strain contribute to the pathogenesis of E. coli in the urinary tract.
|
|
