DNA Repair in Mammalian Cells: Mismatched repair: variations on a theme

Abstract.: Complementary base pairing underlies the genetic template function of the DNA double helix. Therefore, to assure faithful DNA transactions, cells must adhere to a strict application of the Watson-Crick base pairing principle.Yet, mispairing does arise in DNA, most frequently as a result of DNA polymerase errors or base damage. These mismatches need be rectified to avoid mutation. Sometimes, however, mispairing is actively induced to trigger mutagenesis. This happens in activated B-lymphocytes, where the targeted generation and processing of G·U mismatches contributes to somatic hypermutation and antibody diversification. Non-mutagenic mismatches arise in heteroduplex intermediates of homologous recombination, and their processing helps restrict homeologous recombination. Depending on the type of mismatch and the biological context of its occurrence, cells must apply appropriate strategies of repair to properly control mutagenesis. This review will illustrate conceptual and functional challenges of cellular mismatch correction on typical examples of mutagenic base-base mismatches. (Part of a Multi-author Review

European summer climate variability in a heterogeneous multi-model ensemble

Recent results from an enhanced greenhouse-gas scenario over Europe suggest that climate change might not only imply a general mean warming at the surface, but also a pronounced increase in interannual surface temperature variability during the summer season (Schär etal., Nature 427:332-336, 2004). It has been proposed that the underlying physical mechanism is related to land surface-atmosphere interactions. In this study we expand the previous analysis by including results from a heterogeneous ensemble of 11 high-resolution climate models from the PRUDENCE project. All simulations considered comprise 30-year control and enhanced greenhouse-gas scenario periods. While there is considerable spread in the models' ability to represent the observed summer variability, all models show some increase in variability for the scenario period, confirming the main result of the previous study. Averaged over a large-scale Central European domain, the models simulate an increase in the standard deviation of summer mean temperatures between 20 and 80%. The amplification occurs predominantly over land points and is particularly pronounced for surface temperature, but also evident for precipitation. It is also found that the simulated changes in Central European summer conditions are characterized by an emergence of dry and warm years, with early and intensified depletion of root-zone soil moisture. There is thus some evidence that the change in variability may be linked to the dynamics of soil-moisture storage and the associated feedbacks on the surface energy balance and precipitatio

Intraoperative biologische Augmentation an Sehnen und Enthesen

Zusammenfassung: Trotz technischer Weiterentwicklung in der Sehnenrekonstruktionschirurgie besteht postoperativ nach wie vor eine relativ hohe Rerupturrate. Ein Grund dafür ist die Tatsache, dass bei der Sehnenansatz- und Sehnenheilung, bedingt durch eine limitierte Regenerationskapazität, Narbengewebe anstelle von normalem Gewebe gebildet wird. Dieses Narbengewebe ist sowohl in funktioneller als auch struktureller Sicht dem normalen Gewebe unterlegen. Mehrere Strategien zur biologischen Augmentation von Sehnen- und Sehnenansatzläsionen wurden in den letzten Jahren entwickelt und getestet. Dieser Artikel bespricht die klinische Evidenzlage bezüglich der biologischen Augmentation von Sehnen und Enthesen mittels Wachstumsfaktoren in Form von Plättchenkonzentraten, zellbasierten Therapien bzw. biologischen Sehnengraft

Elevation gradients of European climate change in the regional climate model COSMO-CLM

A transient climate scenario experiment of the regional climate model COSMO-CLM is analyzed to assess the elevation dependency of 21st century European climate change. A focus is put on near-surface conditions. Model evaluation reveals that COSMO-CLM is able to approximately reproduce the observed altitudinal variation of 2m temperature and precipitation in most regions and most seasons. The analysis of climate change signals suggests that 21st century climate change might considerably depend on elevation. Over most parts of Europe and in most seasons, near-surface warming significantly increases with elevation. This is consistent with the simulated changes of the free-tropospheric air temperature, but can only be fully explained by taking into account regional-scale processes involving the land surface. In winter and spring, the anomalous high-elevation warming is typically connected to a decrease in the number of snow days and the snow-albedo feedback. Further factors are changes in cloud cover and soil moisture and the proximity of low-elevation regions to the sea. The amplified warming at high elevations becomes apparent during the first half of the 21st century and results in a general decrease of near-surface lapse rates. It does not imply an early detection potential of large-scale temperature changes. For precipitation, only few consistent signals arise. In many regions precipitation changes show a pronounced elevation dependency but the details strongly depend on the season and the region under consideration. There is a tendency towards a larger relative decrease of summer precipitation at low elevations, but there are exceptions to this as wel

Talking about dying and death: Essentials of communicating about approaching death from the perspective of major stakeholders.

OBJECTIVES Although caring for dying patients and their family caregivers (FC) is integral to patient care, training in communication about approaching death is almost inexistent in medical and nursing curricula. Consequently, many health professionals have insufficient knowledge about conducting these conversations. In order to gain a broader insight into essential aspects of this communication from different perspectives, we conducted focus groups with key stakeholders. METHODS Medical specialists, nurses, medical students, bereaved FC and patient representatives participated in five focus groups (n = 30). Following a focus group schedule, we elicited relevant aspects of communication about approaching death, associated emotions, and appropriate communication frameworks. We analyzed data thematically. RESULTS Four main themes were central to conversations about approaching death: (1) embracing care within medical expertise, (2) preparing the conversation while remaining open to the unexpected, (3) recognizing and reflecting on own emotions and reactions, and (4) establishing a meaningful connection with others. SIGNIFICANCE OF RESULTS Communicating about approaching death with dying patients and their FC can be complex and challenging at a professional and personal level. With the recognition of the dying phase, a process is initiated for which health professionals need solid clinical knowledge about but also effective communication skills, constant self-reflection and self-care strategies. Comprehensive training and supervision while dealing with the challenges of communicating approaching death to dying patients and their FC are key, particularly for trainees, less experienced physicians and nurses. The essential components identified in this study can help health professionals to master these conversations

Use of small animal PET-CT imaging for in vivo assessment of tendon-to-bone healing: A pilot study.

BACKGROUND The availability of non-invasive means to evaluate and monitor tendon-bone healing processes in-vivo is limited. Micro Positron-Emission-Tomography (µPET) using 18F-Fluoride is a minimally invasive imaging modality, with which osteoblast activity and bone turnover can be assessed. The aim of this study was to investigate the use of serial in-vivo µPET/CT scans to evaluate bone turnover along the graft-tunnel interface in a rat ACL (anterior cruciate ligament) reconstruction model. METHODS Unilateral autograft ACL reconstruction was performed in six rats. µPET/CT-scans using 18F-Fluoride were performed 7, 14, 21, and 28 days postoperatively. Standard uptake values (SUV) were calculated for three tunnel regions (intraarticular aperture (IAA), mid-tunnel, and extraarticular aperture (EAA)) of the proximal tibia. Animals were sacrificed at 28 days and evaluated with µCT and histological analysis. RESULTS SUVs in both bone tunnels showed an increased 18F-Fluoride uptake at 7 days when compared to 14, 21, and 28 days. SUVs showed a gradient on the tibial side, with most bone turnover in the IAA and least in the EAA. At 7, 14, 21, and 28 days, there were significantly higher SUV values in the IAA compared to the EAA (p = .01, < .01, < .01, < .01). SUVs positively correlated with new bone volumetric density obtained with μCT (r = 0.449, p = .013). Volumetric density of newly formed bone detected on μCT correlated with osteoblast numbers observed along the tunnels in histological sections (r = 0.452, p < .016). CONCLUSIONS Serial in-vivo µPET/CT-scanning has the potential to provide insight into bone turnover and therefore osteoblastic activity during the healing process. As a result, it allows us to directly measure the effect of interventional strategies in tendon-bone healing

Strongyloides stercoralis larvae excretion patterns before and after treatment

The variability of larval excretion impedes the parasitological diagnosis of Strongyloides stercoralis in infected individuals. We assessed the number of larvae excreted per gram (LPG) stool in 219 samples from 38 infected individuals over 7 consecutive days before and in 470 samples from 44 persons for 21 consecutive days after ivermectin treatment (200μgkg−1 BW). The diagnostic sensitivity of a single stool sample was about 75% for individuals with low-intensity infections (⩽1 LPG) and increased to 95% for those with high-intensity infections (⩾10 LPG). Doubling the number of samples examined per person increased sensitivity to more than 95%, even for low-intensity infections. There was no indication of a cyclic excretion of larvae. After treatment, all individuals stopped excreting larvae within 3 days. Larvae were not detected during any of the following 18 days (total 388 Baermann and 388 Koga Agar tests). Two stool samples, collected on consecutive days, are recommended in settings where low or heterogeneous infection intensities are likely. In this way, taking into account the possible biological variability in excretion, the efficacy of ivermectin treatment can be assessed as soon as 4 days after treatmen

Integrative taxonomy reveals cryptic diversity in North American Lasius ants, and an overlooked introduced species

Biological invasions are a grave threat to ecosystems. The black garden ant (Lasius niger) is a pest species in Europe. Current literature states that L. niger occupies a disjunct native distribution in the Holarctic, however, based on recent work, we re-evaluate this distribution. The native range of L. niger is reconsidered based on phylogenetic relationships (nine mitochondrial and nuclear markers, 5670 bp), DNA-barcoding (98 Holarctic specimens), morphometry (88 Holarctic specimens, 19 different measurements) and subjective assessment of phenotype. The potential spread of this species is estimated using ecological niche modeling. Lasius niger is more closely related to other Palearctic species than to the Nearctic ants known under this name. The latter are described as a distinct species, L. ponderosae sp. nov. However, DNA-barcoding discovered established populations of L. niger in metropolitan areas in Canada (Vancouver and Halifax). We describe a morphometrical method to delineate L. ponderosae sp. nov. and L. niger. MtDNA diversity and divergence is high within L. ponderosae sp. nov., but low within L. niger. More than 1,000,000 km 2 are suitable as a habitat for L. niger in North America. This case emphasizes the critical role of integrative taxonomy to detect cryptic species and identify potential biological invasions in their nascent stages