Tissue-Specific DNA Repair Activity of ERCC-1/XPF-1

Sabatella et al. image the DNA repair endonuclease ERCC-1/XPF-1 in C. elegans to show that nucleotide excision repair exhibits tissue-specific activity. DNA lesions are very rapidly removed from the entire genome in oocytes but only from transcribed genes in somatic cells. Neurons are more sensitive to DNA damage than muscle cells.Hereditary DNA repair defects affect tissues differently, suggesting that in vivo cells respond differently to DNA damage. Knowledge of the DNA damage response, however, is largely based on in vitro and cell culture studies, and it is currently unclear whether DNA repair changes depending on the cell type. Here, we use in vivo imaging of the nucleotide excision repair (NER) endonuclease ERCC-1/XPF-1 in C. elegans to demonstrate tissue-specific NER activit

Report of the 12th Liaison Meeting

The 12th Liaison meeting was held in Brussels on 8th and 9th October 2015 to address the following Terms of Reference: TOR 1. Discussion on possible follow-­‐‑up to the main outputs/recommendations of: • The 2015 RCMs -­‐‑ specific recommendations addressed to the Liaison Meeting • PGECON, PGDATA, PGMed – outcomes and recommendations from their 2015 meeting • STECF EWG and STECF Plenary -­‐‑ outcomes and recommendations from their 2015 meetings • Data end users (ICES, STECF, RFMOs – GFCM, IATTC, ICCAT, IOTC, WCPFC, NAFO, SPRFMO, CECAF, WECAFC) TOR2. End user feedback on data transmission and related issues • Discuss feedback received from data end-­‐‑users on data transmission: main issues and possible harmonization of end user feedback to the Commission • JRC data transmission IT platform: experience gained and future steps • Discuss best practices on automatization of data upload by MS: data validation tools used by end users • Discussion on new set-­‐‑up for STECF evaluation of AR2014 & data transmission 2014 used in 2015 – continue like this next year? • Harmonisation and dissemination of DCF metadata: codelists, metiers, nomenclatures, best practices, standards • RCM data calls – overview of how MS responded TOR 3. Regional cooperation • Call for proposals MARE/2014/19 'ʹStrengthening Regional Cooperation in the area of fisheries data collection– state of play'ʹ. Presentation by a representative of the two RCG grants and discussions by LM thereafter. What should be the way forward? • Regional databases • Overview of use of the Regional Databases for RCMs in 2015 and problems identified • Other developments (RDB trainings in 2015, RDB Med&BS development) • Changes for the future – any recommendations from the LM? • Future role of RCMs and DCF-­‐‑related meetings: best practices, coordination, cohesion and common structure in line with emerging needs of DCF TOR 4. EU MAP • Discuss recommendations/ output of RCMs: List of proposed stocks, landing obligation, metiers • Discuss design-­‐‑based sampling in relation to DCF: does it fulfil DCF requirements? TOR 5. Availability of data • Overview of latest developments (DCF Database Feasibility Study and plans for a follow-­‐‑up study to this) TOR 6. AOB • Agree on a list of recommendations relating to DCF (that MS will need to report on in their AR2015) – COM will provide a compilation of proposed recommendations from LM & STECF Plenaries in 2014 as input • Prepare a list of recommended meetings for 2016 as guidance for MS • Review and prioritize DCF-­‐‑related study proposals from RCMs, PGECON, EGs etc • ICES update on workshop on concurrent sampling and plans to re-­‐‑evaluate survey

Base and nucleotide excision repair facilitate resolution of platinum drugs-induced transcription blockage

Sensitivity and resistance of cells to platinum drug chemotherapy are to a large extent determined by activity of the DNA damage response (DDR). Combining chemotherapy with inhibition of specific DDR pathways could therefore improve treatment efficacy. Multiple DDR pathways have been implicated in removal of platinum-DNA lesions, but it is unclear which exact pathways are most important to cellular platinum drug resistance. Here, we used CRISPR/Cas9 screening to identify DDR proteins that protect colorectal cancer cells against the clinically applied platinum drug oxaliplatin. We find that besides the expected homologous recombination, Fanconi anemia and translesion synthesis pathways, in particular also transcription-coupled nucleotide excision repair (TC-NER) and base excision repair (BER) protect against platinum-induced cytotoxicity. Both repair pathways are required to overcome oxaliplatin- and cisplatin-induced transcription arrest. In addition to the generation of DNA crosslinks, exposure to platinum drugs leads to reactive oxygen species production that induces oxidative DNA lesions, explaining the requirement for BER. Our findings highlight the importance of transcriptional integrity in cells exposed to platinum drugs and suggest that both TC-NER and BER should be considered as targets for novel combinatorial treatment strategies

Repair protein persistence at DNA lesions characterizes XPF defect with Cockayne syndrome features

The structure-specific ERCC1-XPF endonuclease plays a key role in DNA damage excision by nucleotide excision repair (NER) and interstrand crosslink repair. Mutations in this complex can either cause xeroderma pigmentosum (XP) or XP combined with Cockayne syndrome (XPCS-complex) or Fanconi anemia. However, most patients carry compound heterozygous mutations, which confounds the dissection of the phenotypic consequences for each of the identified XPF alleles. Here, we analyzed the functional impact of individual pathogenic XPF alleles on NER. We show that XP-causing mutations diminish XPF recruitment to DNA damage and only mildly affect global genome NER. In contrast, an XPCS-complex-specific mutation causes persistent recruitment of XPF and the upstream core NER machinery to DNA damage and severely impairs both global genome and transcription-coupled NER. Remarkably, persistence of NER factors at DNA damage appears to be a common feature of XPCS-complex cells, suggesting that this could be a determining factor contributing to the development of additional developmental and/or neurodegenerative features in XP patients

STECF Fisheries Dependent Information – FDI (STECF-19-11)

Commission Decision of 25 February 2016 setting up a Scientific, Technical and Economic Committee for Fisheries, C(2016) 1084, OJ C 74, 26.2.2016, p. 4–10. The Commission may consult the group on any matter relating to marine and fisheries biology, fishing gear technology, fisheries economics, fisheries governance, ecosystem effects of fisheries, aquaculture or similar disciplines. The STECF reviewed the report of the EWG on Fisheries-dependent Information during its winter 2019 plenary meeting

Report of the 12th Liaison Meeting

The 12th Liaison meeting was held in Brussels on 8th and 9th October 2015 to address the following Terms of Reference: TOR 1. Discussion on possible follow-­‐‑up to the main outputs/recommendations of: • The 2015 RCMs -­‐‑ specific recommendations addressed to the Liaison Meeting • PGECON, PGDATA, PGMed – outcomes and recommendations from their 2015 meeting • STECF EWG and STECF Plenary -­‐‑ outcomes and recommendations from their 2015 meetings • Data end users (ICES, STECF, RFMOs – GFCM, IATTC, ICCAT, IOTC, WCPFC, NAFO, SPRFMO, CECAF, WECAFC) TOR2. End user feedback on data transmission and related issues • Discuss feedback received from data end-­‐‑users on data transmission: main issues and possible harmonization of end user feedback to the Commission • JRC data transmission IT platform: experience gained and future steps • Discuss best practices on automatization of data upload by MS: data validation tools used by end users • Discussion on new set-­‐‑up for STECF evaluation of AR2014 & data transmission 2014 used in 2015 – continue like this next year? • Harmonisation and dissemination of DCF metadata: codelists, metiers, nomenclatures, best practices, standards • RCM data calls – overview of how MS responded TOR 3. Regional cooperation • Call for proposals MARE/2014/19 'ʹStrengthening Regional Cooperation in the area of fisheries data collection– state of play'ʹ. Presentation by a representative of the two RCG grants and discussions by LM thereafter. What should be the way forward? • Regional databases • Overview of use of the Regional Databases for RCMs in 2015 and problems identified • Other developments (RDB trainings in 2015, RDB Med&BS development) • Changes for the future – any recommendations from the LM? • Future role of RCMs and DCF-­‐‑related meetings: best practices, coordination, cohesion and common structure in line with emerging needs of DCF TOR 4. EU MAP • Discuss recommendations/ output of RCMs: List of proposed stocks, landing obligation, metiers • Discuss design-­‐‑based sampling in relation to DCF: does it fulfil DCF requirements? TOR 5. Availability of data • Overview of latest developments (DCF Database Feasibility Study and plans for a follow-­‐‑up study to this) TOR 6. AOB • Agree on a list of recommendations relating to DCF (that MS will need to report on in their AR2015) – COM will provide a compilation of proposed recommendations from LM & STECF Plenaries in 2014 as input • Prepare a list of recommended meetings for 2016 as guidance for MS • Review and prioritize DCF-­‐‑related study proposals from RCMs, PGECON, EGs etc • ICES update on workshop on concurrent sampling and plans to re-­‐‑evaluate survey

STECF Fisheries Dependent Information – FDI (STECF-19-11)

Commission Decision of 25 February 2016 setting up a Scientific, Technical and Economic Committee for Fisheries, C(2016) 1084, OJ C 74, 26.2.2016, p. 4–10. The Commission may consult the group on any matter relating to marine and fisheries biology, fishing gear technology, fisheries economics, fisheries governance, ecosystem effects of fisheries, aquaculture or similar disciplines. The STECF reviewed the report of the EWG on Fisheries-dependent Information during its winter 2019 plenary meeting

Long-term safety and efficacy of Eculizumab in Aquaporin-4 IgG-positive NMOSD

Objective During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy. Methods Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. Results Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1–276.9 weeks), for a combined total of 362.3 patient-years (PY). Treatment-related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab-treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6–97.3) of patients remained adjudicated relapse-free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013–0.048) in all eculizumab-treated patients versus 0.350 (95% CI = 0.199–0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use. Interpretation This analysis demonstrates that eculizumab's long-term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long-term eculizumab treatment to reduce relapse risk in patients with AQP4-IgG+ NMOSD. ANN NEUROL 2021;89:1088–109

Towards an Integrated Coastal Zone Management in Campania Region (Italy): A Multidisciplinary Approach to the Analysis of Coastal Fishery Activities and their Socio-Economic Management

AbstractThe paper presents same of the main outcomes of a study concerning the application of the Integrated Coastal Zone Management (ICZM) to Campania region in Italy. The study was focused on the analysis of main uses and activities related to fishery such as the definition of thematic maps describing zones in which fishing activities are prohibited or restricted, areas of distribution of fishing effort, socio economic sustainability of local artisanal fishery, the relevance of fishing tourism and recreational fisheries, an analysis of local fish market. Data provided by official source as the Fishery Data collection, vessel traffic monitoring systems, logbook and legislative sources were successively verified by a field analysis through direct interviews to stakeholders