Results 51 to 60 of about 147,360 (213)

Evolution in random fitness landscapes: the infinite sites model

, 2007
We consider the evolution of an asexually reproducing population in an uncorrelated random fitness landscape in the limit of infinite genome size, which implies that each mutation generates a new fitness value drawn from a probability distribution $g(w)$.
Arnold B C, Bovier A, Bürger R, David H, Davidsen J Grassberger P Paczuski M, Devroye L, Feller W, Fisher R A, Franz S, Franz S, Gardiner C W, Gavrilets S, Gillespie J H, Jain K, Jain K, Joachim Krug, Kauffman S, Kauffman S A, Kimura M, Lässig M, Ohta T, Orr H A, Sire C, Stein D L, Su-Chan Park, Tachida H, Weinrich D M, Wright S   +27 more
core   +3 more sources

Developmental programmes drive cellular plasticity, disease progression and therapy resistance in lung adenocarcinoma

Molecular Oncology, EarlyView.
This study shows that lung adenocarcinomas exploit developmental branching morphogenesis to acquire a therapy resistant basal‐like tumour cell state. This process was found to be regulated by combined TP53 loss‐of‐function and type‐I interferon signalling, identifying a novel axis for biomarker and therapeutic target discovery.
Kamila J Bienkowska, Stephany Gallardo, Nur S. Zainal, Leena Arora, Matthew Ellis, Maria‐Antoinette Lopez, Judith Austine, Sai Pittla, Serena J Chee, Aiman Alzetani, Emily C Shaw, Christian H Ottensmeier, Gareth J Thomas, Christopher J Hanley   +13 more
wiley   +1 more source

Cascade of Complexity in Evolving Predator-Prey Dynamics

, 2007
We simulate an individual-based model that represents both the phenotype and genome of digital organisms with predator-prey interactions. We show how open-ended growth of complexity arises from the invariance of genetic evolution operators with respect ...
A. N. Kolmogorov, C. Adami, C. Adami, H. Orr, L. Richardson, M. Kimura, M. Maron, Nicholas Guttenberg, Nigel Goldenfeld, R. K. Standish, S. Gavrilets, S. Wright, S. Wright, T. S. Ray   +13 more
core   +1 more source

Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in Egfr‐mutated lung cancer

Molecular Oncology, EarlyView.
Combining osimertinib with the STING agonist ADU‐S100 activates innate and adaptive immunity to overcome the non‐inflamed microenvironment of Egfr‐mutant lung cancer. This combination increases NK and CD8+ T‐cell infiltration, associated with activation of the STING‐IRF3 pathway and local immunogenic cell death.
Jun Nishimura, Tadahiro Kuribayashi, Johannes Brägelmann, Sachi Okawa, Masataka Taoka, Shunta Mori, Tomoka Nishimura, Takaaki Tanaka, Go Makimoto, Kiichiro Ninomiya, Kammei Rai, Eiki Ichihara, Ryohei Katayama, Katsuyuki Hotta, Masahiro Tabata, Yosuke Togashi, Yoshinobu Maeda, Martin L. Sos, Katsuyuki Kiura, Kadoaki Ohashi   +19 more
wiley   +1 more source

Finding novel vulnerabilities of hypomorphic BRCA1 alleles

Molecular Oncology, EarlyView.
Synthetic lethality screens performed to identify novel vulnerabilities often model complete gene loss, thereby overlooking patient‐derived hypomorphic mutations. In this study, we have performed genome‐wide CRISPR screens on BRCA1 hypomorphic mutations, showing BRCA1I26A behaves like wild‐type, while BRCA1R1699Q mimics deficiency. Furthermore, we have
Anne Schreuder, Klaas de Lint, Hồ Mỹ Phúc Võ, Mariana M. Góis, Rosalie A. Kampen, Marta San Martin Alonso, Ilse Nootenboom, Veronica Garzero, Tiemen J. Wendel, Rob M. F. Wolthuis, Sylvie M. Noordermeer   +10 more
wiley   +1 more source

Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization

Molecular Oncology, EarlyView.
In the current study, we demonstrate that the oncogene DMTF1β regulates ULK1 stability by reducing its proteasomal degradation in cancer cells. This stabilization enables ULK1 to induce autophagy, which in turn facilitates cancer cell migration. Consequently, reduced DMTF1β levels lead to decreased autophagy and impaired cancer cell migration.
Jun Xu, Nicolas J. Niklaus, Anna M. Schläfli, Igor Tokarchuk, Magali Humbert, Federico La Manna, Bich Vu, David Maul, Ramin Radpour, Marianna Kruithof‐de Julio, Inti Zlobec, Jörn Dengjel, Bruce E. Torbett, Mario P. Tschan   +13 more
wiley   +1 more source

Applicability of mitotic figure counting by deep learning: a development and pan‐cancer validation study

FEBS Open Bio, EarlyView.
In this study, we developed a deep learning method for mitotic figure counting in H&E‐stained whole‐slide images and evaluated its prognostic impact in 13 external validation cohorts from seven different cancer types. Patients with more mitotic figures per mm2 had significantly worse patient outcome in all the studied cancer types except colorectal ...
Joakim Kalsnes, Maria X. Isaksen, Frida Julbø, Manohar Pradhan, Andreas Kleppe, Sepp De Raedt, Ole‐Johan Skrede, Turid Torheim, John Arne Nesheim, Hans Martin Mohn, Hanne A. Askautrud, Karolina Cyll, Wanja Kildal, Emma Rewcastle, Melinda Lillesand, Vebjørn Kvikstad, Emiel Janssen, Robert Jones, Odd Terje Brustugun, Bjørn Brennhovd, Erik Skaaheim Haug, Lill‐Tove Rasmussen Busund, Elin Richardsen, Sigve Andersen, Tom Dønnem, Kristina Lindemann, Gunnar Kristensen, Neil A. Shepherd, Marco Novelli, Knut Liestøl, David Kerr, Håvard E. Danielsen, Tarjei S. Hveem   +32 more
wiley   +1 more source

Exon 7 splicing of ERα predicts poor prognosis and increases phenotypic heterogeneity in luminal a subtype breast cancer

FEBS Open Bio, EarlyView.
ERα splice variant ERα∆7 lacks the C‐terminus, and its expression may change phenotypes of breast cancers. Our results showed that ERα∆7 is found in the luminal A subtype, and elevated ERα∆7 levels are linked to improved cell survival with lower proliferation and migration.
Long Wai Tsui, Taobo Hu, Thomson Christian Husein, Wai Hei Shek, Bingrong Chen, Depeng Wang, Shu Wang, Weichuan Yu, Xiaodan Fan, Mengping Long, Toyotaka Ishibashi   +10 more
wiley   +1 more source

Matrix metalloproteinase‐9 regulates cell adhesion and membrane protrusive activity of ovarian cancer cells

FEBS Open Bio, EarlyView.
Matrix metalloproteinase‐9 (MMP9) drives ovarian cancer progression. Using MMP9‐null cells (M9‐KO) created from ovarian cancer cells, we found MMP9 loss did not block Epidermal Growth Factor (EGF)‐driven E‐cadherin dissolution or EMT but delayed and reduced EGF‐driven membrane protrusions. Transient MMP9 re‐expression drove membrane protrusion.
Claire Strauel, Sam Bennett, Natalie Ehlinger, Nelson Cook, Katelyn Marvin, Caleb L. Lines, Sam Reyes, Brooke Kirby, Shawn M. Ellerbroek   +8 more
wiley   +1 more source

Large‐scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation

FEBS Open Bio, EarlyView.
Activation of the mitochondrial protein OXR1 increases pSyn129 αSynuclein aggregation by lowering ATP levels and altering mitochondrial membrane potential, particularly in response to MSA‐derived fibrils. In contrast, ablation of the ER protein EMC4 enhances autophagic flux and lysosomal clearance, broadly reducing α‐synuclein aggregates.
Sandesh Neupane, Lea Nikolić, Lorenzo Maraio, Thomas Goiran, Nathan Karpilovsky, Stefano Sellitto, Vangelis Bouris, Jiang‐An Yin, Ronald Melki, Edward A Fon, Adriano Aguzzi, Elena De Cecco   +11 more
wiley   +1 more source