Nature Search

FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence

Evidence for mitotic decline in aged cells and for aneuploidy-driven progression into full senescence is limited. Here, the authors find that in aged cells, mitotic gene repression leads to increased chromosome mis-segregation and aneuploidy that triggers permanent cell cycle arrest and full senescence.

Joana Catarina Macedo
Sara Vaz
Elsa Logarinho
ResearchOpen Access19 Jul 2018
Nature Communications

Volume: 9, P: 1-17
The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.

Deborah R. Caswell
Philippe Gui
Charles Swanton
ResearchOpen Access04 Dec 2023
Nature Genetics

Volume: 56, P: 60-73
Lung adenocarcinoma promotion by air pollutants

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

William Hill
Emilia L. Lim
Charles Swanton
Research05 Apr 2023
Nature

Volume: 616, P: 159-167
Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Sebastijan Hobor
Maise Al Bakir
Charles Swanton
ResearchOpen Access13 Jun 2024
Nature Communications

Volume: 15, P: 1-21
Nuclear chromosome locations dictate segregation error frequencies

Using single-cell DNA sequencing after an error-prone mitosis in untransformed, diploid cell lines and organoids, chromosomes are shown to have different segregation error frequencies that result in non-random aneuploidy landscapes.

Sjoerd J. Klaasen
My Anh Truong
Geert J. P. L. Kops
ResearchOpen Access13 Jul 2022
Nature

Volume: 607, P: 604-609
A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity

High-grade serous ovarian carcinoma is often associated with TP53 mutation and chromosomal instability (CIN). Here, the authors generate ex vivo cultures from biopsies and ascites of patients and perform characterization to evaluate CIN mechanisms and compare drug sensitivity with patient responses.

Louisa Nelson
Anthony Tighe
Stephen S. Taylor
ResearchOpen Access13 Feb 2020
Nature Communications

Volume: 11, P: 1-18
Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids

The authors use three-dimensional live-cell imaging of colorectal carcinoma organoids to show that chromosomal instability is widespread. Single-cell sequencing identifies heterogeneity of copy number alterations and shows clonal evolution.

Ana C. F. Bolhaqueiro
Bas Ponsioen
Geert J. P. L. Kops
Research29 Apr 2019
Nature Genetics

Volume: 51, P: 824-834
A systems study reveals concurrent activation of AMPK and mTOR by amino acids

mTORC1 is known to mediate the signalling activity of amino acids. Here, the authors combine modelling with experiments and find that amino acids acutely stimulate mTORC2, IRS/PI3K and AMPK, independently of mTORC1. AMPK activation through CaMKKβ sustains autophagy under non-starvation conditions.

Piero Dalle Pezze
Stefanie Ruf
Kathrin Thedieck
ResearchOpen Access21 Nov 2016
Nature Communications

Volume: 7, P: 1-19
Esr1⁺ hypothalamic-habenula neurons shape aversive states

The authors find a surprising diversity in hypothalamic neurons projecting to habenula, and using patch-sequencing (Patch-seq), identify an estrogen receptor-expressing neuron type that signals aversion and is linked to stress in female mice.

Daniela Calvigioni
Janos Fuzik
Konstantinos Meletis
ResearchOpen Access22 Jun 2023
Nature Neuroscience

Volume: 26, P: 1245-1255
A functional variant in the CFI gene confers a high risk of age-related macular degeneration

Johannes van de Ven and colleagues report a rare missense mutation in CFI encoding a p.Gly119Arg substitution that confers a high risk of AMD. Sera from AMD cases carrying the p.Gly119Arg variant mediate the degradation of C3b at a significantly lower level than sera from AMD cases without the CFI variant.

Johannes P H van de Ven
Sara C Nilsson
Anneke I den Hollander
Research19 May 2013
Nature Genetics

Volume: 45, P: 813-817
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

Sekar Kathiresan
Olle Melander
Marju Orho-Melander
Research13 Jan 2008
Nature Genetics

Volume: 40, P: 189-197
Methylglyoxal down-regulates the expression of cell cycle associated genes and activates the p53 pathway in human umbilical vein endothelial cells

Jana D. Braun
Diego O. Pastene
Thomas Albrecht
ResearchOpen Access04 Feb 2019
Scientific Reports

Volume: 9, P: 1-14

Search

FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescence

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

Lung adenocarcinoma promotion by air pollutants

Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling

Nuclear chromosome locations dictate segregation error frequencies

A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity

Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids

A systems study reveals concurrent activation of AMPK and mTOR by amino acids

Esr1⁺ hypothalamic-habenula neurons shape aversive states

A functional variant in the CFI gene confers a high risk of age-related macular degeneration

Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

Methylglyoxal down-regulates the expression of cell cycle associated genes and activates the p53 pathway in human umbilical vein endothelial cells

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