Clinical characterization of long-term multiple sclerosis (COLuMbus) patients in Argentina: A cross-sectional non-interventional study.

Background: Most Multiple Sclerosis (MS) clinical trials fail to assess the long-term effects of disease-modifying therapies (DMT) or disability.

Methods: COLuMbus was a single-visit, cross-sectional study in Argentina in adult patients with ≥10 years of MS since first diagnosis. The primary endpoint was to determine patient disability using the Expanded Disability Status Scale (EDSS).

Correction: Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.

[This corrects the article DOI: 10.1371/journal.pgen.

Unscheduled MRE11 activity triggers cell death but not chromosome instability in polymerase eta-depleted cells subjected to UV irradiation.

The elimination of DNA polymerase eta (pol η) causes discontinuous DNA elongation and fork stalling in UV-irradiated cells. Such alterations in DNA replication are followed by S-phase arrest, DNA double-strand break (DSB) accumulation, and cell death. However, their molecular triggers and the relative timing of these events have not been fully elucidated.

Polo-like Kinase 1 Inhibition as a Therapeutic Approach to Selectively Target BRCA1-Deficient Cancer Cells by Synthetic Lethality Induction.

Purpose: BRCA1 and BRCA2 deficiencies are widespread drivers of human cancers that await the development of targeted therapies. We aimed to identify novel synthetic lethal relationships with therapeutic potential using BRCA-deficient isogenic backgrounds.

Experimental Design: We developed a phenotypic screening technology to simultaneously search for synthetic lethal (SL) interactions in BRCA1- and BRCA2-deficient contexts.

Beyond interstrand crosslinks repair: contribution of FANCD2 and other Fanconi Anemia proteins to the replication of DNA.

Biallelic mutations of FANCD2 and other components of the Fanconi Anemia (FA) pathway cause a disease characterized by bone marrow failure, cancer predisposition and a striking sensitivity to agents that induce crosslinks between the two complementary DNA strands (inter-strand crosslinks-ICL). Such genotoxins were used to characterize the contribution of the FA pathway to the genomic stability of cells, thus unravelling the biological relevance of ICL repair in the context of the disease. Notwithstanding this, whether the defect in ICL repair as the sole trigger for the multiple physiological alterations observed in FA patients is still under investigation.

ACCIDENTAL DUPLICATION: Beyond interstrand crosslinks repair: Contribution of FANCD2 and other Fanconi Anemia proteins to the replication of DNA.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/ 10.

Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.

Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown.

Kinase-independent function of checkpoint kinase 1 (Chk1) in the replication of damaged DNA.

The checkpoint kinases Chk1 and ATR are broadly known for their role in the response to the accumulation of damaged DNA. Because Chk1 activation requires its phosphorylation by ATR, it is expected that ATR or Chk1 down-regulation should cause similar alterations in the signals triggered by DNA lesions. Intriguingly, we found that Chk1, but not ATR, promotes the progression of replication forks after UV irradiation.

A device to measure oxygen consumption during the hypothermic perfusion of the liver.

This work deals with the construction and performance of a device designed to measure the oxygen consumption by the liver during hypothermic perfusion in the rat model. Due to its simple design and the utilization of standard materials, it could serve to determine the role of oxygenation during hypothermic perfusion of the liver. The system consists of a reservoir containing the preservation solution, a peristaltic pump and an internal oxygenator made of silicone tube.