Short-patch correction of C/C mismatches in human cells

We examined whether the human nucleotide excision repair complex, which is specialized on the removal of bulky DNA adducts, also displays a correcting activity on base mismatches. The cytosine/cytosine (C/C) lesion was used as a model substrate to monitor the correction of base mismatches in human cells. Fibroblasts with different repair capabilities were transfected with shuttle vectors that contain a site-directed C/C mismatch in the replication origin, accompanied by an additional C/C mismatch in one of the flanking sequences that are not essential for replication. Analysis of the vector progeny obtained from these doubly modified substrates revealed that C/C mismatches were eliminated before DNA synthesis not only in the repair-proficient background, but also when the target cells carried a genetic defect in long-patch mismatch repair, in nucleotide excision repair, or when both pathways were deleted. Furthermore, cells deficient for long-patch mismatch repair as well as a cell line that combines mismatch and nucleotide excision repair defects were able to correct multiple C/C mispairs, placed at distances of 21-44 nt, in an independent manner, such that the removal of each lesion led to individual repair patches. These results support the existence of a concurrent short-patch mechanism that rectifies C/C mismatche

Morphology, flow dynamics and evolution of englacial conduits in cold ice

Meltwater routing through ice masses exerts a fundamental control over glacier dynamics and mass balance, and proglacial hydrology. However, despite recent advances in mapping drainage systems in cold, Arctic glaciers, direct observations of englacial channels and their flow conditions remain sparse. Here, using Terrestrial Laser Scanning (TLS) surveys of the main englacial channel of cold-based Austre Brøggerbreen (Svalbard), we map and compare an entrance moulin reach (122 m long) and exit portal reach (273 m long). Analysis of channel planforms, longitudinal profiles, cross-sections and morphological features reveals evidence of spatial variations in water flow conditions and channel incision mechanisms, and the presence of vadose, epiphreatic and phreatic conditions. The entrance reach, located at the base of a perennial moulin, was characterised by vadose, uniform, channel lowering at annual timescales, evidenced by longitudinal grooves, whereas the exit portal reach showed both epiphreatic and vadose conditions, along with upstream knickpoint migration at intra-annual timescales. Fine-scale features, including grooves and scallops, were readily quantified from the TLS point cloud, highlighting the capacity of the technique to inform palaeoflow conditions, and reveal how pulses of meltwater from rainfall events may adjust englacial conduit behaviour. With forecasts of increasing Arctic precipitation in the coming decades, and a progressively greater proportion of glaciers comprising cold ice, augmenting the current knowledge of englacial channel morphology is essential to constrain future glacier hydrological system change

Proglacial icings as indicators of glacier thermal regime : ice thickness changes and icing occurrence in Svalbard

Proglacial icings (also known as naled or aufeis) are frequently observed in the forefields of polar glaciers. Their formation has been ascribed to the refreezing of upwelling groundwater that has originated from subglacial melt, and thus the presence of icings has been used as evidence of polythermal glacier regime. We provide an updated analysis of icing occurrence in Svalbard and test the utility of icings as an indicator of thermal regime by comparing icing presence with: (1) mean glacier thickness, as a proxy for present thermal regime; and (2) evidence of past surge activity, which is an indicator of past thermal regime. A total of 279 icings were identified from TopoSvalbard imagery covering the period 2008-2012, of which 143 corresponded to icings identified by Bukowska-Jania and Szafraniec (2005) from aerial photographs from 1990. Only 46% of icings observed in 2008-2012 were found to occur at glaciers with thicknesses consistent with a polythermal regime, meaning a large proportion were associated with glaciers predicted to be of a cold or transitional thermal regime. As a result, icing presence alone may be an unsuitable indicator of glacier regime. We further found that, of the 279 glaciers with icings, 63% of cold-based glaciers and 64% of transitional glaciers were associated with evidence of surge activity. We therefore suggest that proglacial icing formation in Svalbard may reflect historical (rather than present) thermal regime, and that icings possibly originate from groundwater effusion from subglacial taliks that persist for decades following glacier thinning and associated regime change

Assessment of genetically modified maize MIR604 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA‐GMO‐RX‐013)

Following the submission of application EFSA‐GMO‐RX‐013 under Regulation (EC) No 1829/2003 from Syngenta Crop Protection NV/SA, the EFSA Panel on Genetically Modified Organisms (GMO) was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect‐resistant genetically modified maize MIR604, for food and feed uses, excluding cultivation within the EU. The data received in the context of this renewal application contained post‐market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in maize MIR604 considered for renewal is identical to the corrected sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA‐GMO‐RX‐013 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize MIR604

Assessment of genetically modified maize MON 88017 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA‐GMO‐RX‐014)

Following the submission of application EFSA‐GMO‐RX‐014 under Regulation (EC) No 1829/2003 from Monsanto Company the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect‐resistant and herbicide‐tolerant genetically modified maize MON 88017, for food and feed uses, excluding cultivation within the EU. The data received in the context of this renewal application contained post‐market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in maize MON 88017 considered for renewal is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA‐GMO‐RX‐014 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize MON 88017

Assessment of genetically modified maize MON 89034 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA-GMO-RX-015)

Following the submission of application EFSA-GMO-RX-015 under Regulation (EC) No 1829/2003 from Bayer Agriculture BVBA, the EFSA Panel on Genetically Modified Organisms (GMO Panel) was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect-resistant genetically modified maize MON 89034, for food and feed uses, excluding cultivation within the EU. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in maize MON 89034 considered for renewal is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-015 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize MON 89034

Assessment of genetically modified oilseed rape GT73 for renewal authorisation under Regulation (EC) No 1829/2003 (application EFSA‐GMO‐RX‐002)

Following the submission of application EFSA‐GMO‐RX‐002 under Regulation (EC) No 1829/2003 from Monsanto Company, the Panel on Genetically Modified Organisms of EFSA (GMO) was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide‐tolerant genetically modified oilseed rape GT73. The data received in the context of this renewal application contained post‐market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in oilseed rape GT73 considered for renewal of authorisation is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA‐GMO‐RX‐002 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on oilseed rape GT73

A qualitative study exploring the health-related quality of life and symptomatic experiences of adults and adolescents with ulcerative colitis

Background: Ulcerative colitis (UC) often first presents during adolescence and early adulthood. Primary symptoms of UC are well known, yet similarities and differences of disease experience in adults and adolescents are not well characterized. Methods: To understand the health-related quality of life (HRQoL) and symptomatic experience of UC, in-depth interviews were conducted in the US with 21 adults (20–70 years) and 14 adolescents (12–17 years). Eligibility and medical history were confirmed by clinician report. A previously conducted literature review and resultant conceptual model informed the discussion guide to explore symptoms and HRQoL. Age appropriate creative tasks (“animal” task and collage) were employed to facilitate discussion. Transcripts and collages were subjected to thematic analysis using ATLAS.ti software. Results: Clinician-reported UC severity included 24% mild, 38% moderate, 38% severe among adults; and 64% mild, 29% moderate, 7% severe among adolescents. Among adults, 52% were female, 67% were white. Among adolescents, 50% were female, 71% were white. During analysis it was noted that all participants reported stomach/abdominal pain. Other key symptoms identified were frequent bowel movements, diarrhea, blood in stools, sudden need for bowel movement, stomach cramping, bloating, and feeling gassy/passing gas (?75% of participants). Key impacts identified were embarrassment, dietary limitations, having to plan around UC, worry/fear, anger, low mood/depression, and relationship with others, (?75% of participants). In creative tasks, animals were chosen to represent their UC and content included in the collages reflected the most commonly discussed themes from the interviews. Only adults discussed feeling dehydrated, while only adolescents discussed the impact of UC on school life. Conclusions: Open-ended interviews highlighted the HRQoL and symptomatic experiences of UC from the patient’s perspective, which were similar between adult and adolescent UC patients

Whipple's disease: rare disorder and late diagnosis

Whipple's disease is a rare systemic infectious disorder caused by the bacterium Tropheryma whipplei. We report the case of a 61-year-old male patient who presented to emergency room complaining of asthenia, arthralgia, anorexia, articular complaints intermittent diarrhea, and a 10-kg weight loss in one year. Laboratory tests showed the following results: Hb = 7.5 g/dL, albumin = 2.5 mg/dL, weight = 50.3 kg (BMI 17.4 kg/m²). Upper gastrointestinal endoscopy revealed areas of focal enanthema in the duodenum. An endoscopic biopsy was suggestive of Whipple's disease. Diagnosis was confirmed based on a positive serum polymerase chain reaction. Treatment was initiated with intravenous ceftriaxone followed by oral trimethoprim-sulfamethoxazole. After one year of treatment, the patient was asymptomatic, with Hb = 13.5 g/dL, serum albumin = 5.3 mg/dL, and weight = 70 kg (BMI 24.2 kg/m²). Whipple's disease should be considered a differential diagnosis in patients with prolonged constitutional and/or gastrointestinal symptoms. Appropriate antibiotic treatment improves the quality of life of patients