Search

In the 2021 guidelines of the European Resuscitation Council (ERC) on infant CPR, a two-thumb encircling technique (TTET) is advised instead of the former two-finger technique (TFT), even for single rescuers. It is however unclear if this is also feasible and effective in case of dispatcher-assisted CPR by untrained bystanders and was explored in a cross-over infant manikin study including CPR-trained students and lay people. Both groups performed the TTET and the TFT, with dispatcher-assistance (according to Belgian protocol) only being provided to the CPR-untrained group. Results suggest it is feasible to advice single lay rescuers to perform TTET as part of a dispatcher-assisted CPR protocol, although we identified an ongoing risk, regardless of the technique advised, of suboptimal compression depth. Further research should be performed to confirm these preliminary data and explore optimal protocols for dispatcher-assisted infant CPR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

High levels of meat consumption in Belgium may be contributing to increased risk of non-communicable diseases in this population. The objective of this study is to investigate the attitudes and beliefs about vegetarianism and meat consumption among the Belgian population, ultimately to better understand the motivations underlying these dietary behaviours. This cross-sectional study was initiated in March 2011. A total of 2436 individuals from a representative consumer panel from the Flemish and Brussels communities participated. The study sample was evenly distributed by education level and sex (1238 men and 1198 women). An online questionnaire with multiple-choice questions about vegetarianism and meat consumption was completed by all participants. Although representative of the prevalence of vegetarians in the population, the number of vegetarians in the study was low (n = 38); the number of semi-vegetarians (n = 288) and omnivores was high (n = 2031). Vegetarians were more likely than semi-vegetarians to agree that meat production is bad for the environment and that meat consumption is unhealthy. Important reasons for not being vegetarian included lack of interest and awareness, taste, and limited cooking skills. Encouragingly, health and discovering new tastes were seen as the most important motives for considering eating a more vegetarian-based diet. The results of this study highlight the motivations that can be used for encouraging the general public to reduce their meat consumption in favour of a plant-rich diet, and will help to inform more targeted health campaigns for reducing meat consumption in Belgium., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In a previous article, Beschta et al. (Environ Manag 51(2):474-491, 2013) argue that grazing by large ungulates (both native and domestic) should be eliminated or greatly reduced on western public lands to reduce potential climate change impacts. The authors did not present a balanced synthesis of the scientific literature, and their publication is more of an opinion article. Their conclusions do not reflect the complexities associated with herbivore grazing. Because grazing is a complex ecological process, synthesis of the scientific literature can be a challenge. Legacy effects of uncontrolled grazing during the homestead era further complicate analysis of current grazing impacts. Interactions of climate change and grazing will depend on the specific situation. For example, increasing atmospheric CO₂ and temperatures may increase accumulation of fine fuels (primarily grasses) and thus increase wildfire risk. Prescribed grazing by livestock is one of the few management tools available for reducing fine fuel accumulation. While there are certainly points on the landscape where herbivore impacts can be identified, there are also vast grazed areas where impacts are minimal. Broad scale reduction of domestic and wild herbivores to help native plant communities cope with climate change will be unnecessary because over the past 20-50 years land managers have actively sought to bring populations of native and domestic herbivores in balance with the potential of vegetation and soils. To cope with a changing climate, land managers will need access to all available vegetation management tools, including grazing.

Anticancer topoisomerase "poisons" exploit the break-and-rejoining mechanism of topoisomerase II (TOP2) to generate TOP2-linked DNA double-strand breaks (DSBs). This characteristic underlies the clinical efficacy of TOP2 poisons, but is also implicated in chromosomal translocations and genome instability associated with secondary, treatment-related, haematological malignancy. Despite this relevance for cancer therapy, the mechanistic aspects governing repair of TOP2-induced DSBs and the physiological consequences that absent or aberrant repair can have are still poorly understood. To address these deficits, we employed cells and mice lacking tyrosyl DNA phosphodiesterase 2 (TDP2), an enzyme that hydrolyses 5'-phosphotyrosyl bonds at TOP2-associated DSBs, and studied their response to TOP2 poisons. Our results demonstrate that TDP2 functions in non-homologous end-joining (NHEJ) and liberates DSB termini that are competent for ligation. Moreover, we show that the absence of TDP2 in cells impairs not only the capacity to repair TOP2-induced DSBs but also the accuracy of the process, thus compromising genome integrity. Most importantly, we find this TDP2-dependent NHEJ mechanism to be physiologically relevant, as Tdp2-deleted mice are sensitive to TOP2-induced damage, displaying marked lymphoid toxicity, severe intestinal damage, and increased genome instability in the bone marrow. Collectively, our data reveal TDP2-mediated error-free NHEJ as an efficient and accurate mechanism to repair TOP2-induced DSBs. Given the widespread use of TOP2 poisons in cancer chemotherapy, this raises the possibility of TDP2 being an important etiological factor in the response of tumours to this type of agent and in the development of treatment-related malignancy., Competing Interests: The authors have declared that no competing interests exist.

The abortive activity of topoisomerases can result in clastogenic and/or lethal DNA damage in which the topoisomerase is covalently linked to the 3'- or 5'-terminus of a DNA strand break. This type of DNA damage is implicated in chromosome translocations and neurological disease and underlies the clinical efficacy of an important class of anticancer topoisomerase 'poisons'. Tyrosyl DNA phosphodiesterase-1 protects cells from abortive topoisomerase I (Top1) activity by hydrolyzing the 3'-phosphotyrosyl bond that links Top1 to a DNA strand break and is currently the only known human enzyme that displays this activity in cells. Recently, we identified a second tyrosyl DNA phosphodiesterase (TDP2; aka TTRAP/EAPII) that possesses weak 3'-tyrosyl DNA phosphodiesterase (3'-TDP) activity, in vitro. Herein, we have examined whether TDP2 contributes to the repair of Top1-mediated DNA breaks by deleting Tdp1 and Tdp2 separately and together in murine and avian cells. We show that while deletion of Tdp1 in wild-type DT40 cells and mouse embryonic fibroblasts decreases DNA strand break repair rates and cellular survival in response to Top1-induced DNA damage, deletion of Tdp2 does not. However, deletion of both Tdp1 and Tdp2 reduces rates of DNA strand break repair and cell survival below that observed in Tdp1-/- cells, suggesting that Tdp2 contributes to cellular 3'-TDP activity in the absence of Tdp1. Consistent with this idea, over-expression of human TDP2 in Tdp1-/-/Tdp2-/-/- DT40 cells increases DNA strand break repair rates and cell survival above that observed in Tdp1-/- DT40 cells, suggesting that Tdp2 over-expression can partially complement the defect imposed by loss of Tdp1. Finally, mice lacking both Tdp1 and Tdp2 exhibit greater sensitivity to Top1 poisons than do mice lacking Tdp1 alone, further suggesting that Tdp2 contributes to the repair of Top1-mediated DNA damage in the absence of Tdp1. In contrast, we failed to detect a contribution for Tdp1 to repair Top2-mediated damage. Together, our data suggest that Tdp1 and Tdp2 fulfil overlapping roles following Top1-induced DNA damage, but not following Top2-induced DNA damage, in vivo.

Signaling by the many ligands of the TGFβ family strongly converges towards only five receptor-activated, intracellular Smad proteins, which fall into two classes i.e. Smad2/3 and Smad1/5/8, respectively. These Smads bind to a surprisingly high number of Smad-interacting proteins (SIPs), many of which are transcription factors (TFs) that co-operate in Smad-controlled target gene transcription in a cell type and context specific manner. A combination of functional analyses in vivo as well as in cell cultures and biochemical studies has revealed the enormous versatility of the Smad proteins. Smads and their SIPs regulate diverse molecular and cellular processes and are also directly relevant to development and disease. In this survey, we selected appropriate examples on the BMP-Smads, with emphasis on Smad1 and Smad5, and on a number of SIPs, i.e. the CPSF subunit Smicl, Ttrap (Tdp2) and Sip1 (Zeb2, Zfhx1b) from our own research carried out in three different vertebrate models., (Copyright © 2011. Published by Elsevier Ltd.)

Gene trapping in mouse embryonic stem (ES) cells enables near-saturation vector-based insertional mutagenesis across the genome of this model organism. About 135,000 trapped ES cell lines are made available to the scientific community by the International Gene Trap Consortium (IGTC; www.genetrap.org). A search of one of its databases identified an ES cell line (RRS512) with a betaGeo-based gene trap (gt) vector insertion in intron 5 of Ttrap, a gene that encodes an intracellular signalling protein, which is implicated in gastrulation movement and left-right asymmetry in zebrafish embryos. We have determined the exact gt insertion point in the mutant ES cell clone RRS512 and confirmed the production of a chimaeric transcript consisting of the upstream Ttrap exons and the gene trap vector encoded marker/selection fusion sequences. This ES cell line was used to generate heterozygous Ttrap mutant mice, which were further crossed to obtain Ttrap(gt/gt) mice. In contrast to Ttraps documented essential role during nodal and Smad3 controlled zebrafish early embryogenesis, Ttrap(gt/gt) mice were born with a normal Mendelian distribution. However, subsequent analysis of these Ttrap(gt/gt) mice has revealed a duplication of the wild-type Ttrap allele that was already present in the RRS512 cell line. Based on our detailed analysis presented here, we suggest an extensive procedure for the characterization of gene trap ES cell lines prior to generating gene trap mice with these.

During vertebrate development, signaling by the TGFbeta ligand Nodal is critical for mesoderm formation, correct positioning of the anterior-posterior axis, normal anterior and midline patterning, and left-right asymmetric development of the heart and viscera. Stimulation of Alk4/EGF-CFC receptor complexes by Nodal activates Smad2/3, leading to left-sided expression of target genes that promote asymmetric placement of certain internal organs. We identified Ttrap as a novel Alk4- and Smad3-interacting protein that controls gastrulation movements and left-right axis determination in zebrafish. Morpholino-mediated Ttrap knockdown increases Smad3 activity, leading to ectopic expression of snail1a and apparent repression of e-cadherin, thereby perturbing cell movements during convergent extension, epiboly and node formation. Thus, although the role of Smad proteins in mediating Nodal signaling is well-documented, the functional characterization of Ttrap provides insight into a novel Smad partner that plays an essential role in the fine-tuning of this signal transduction cascade.

Smads are intracellular signaling proteins that transduce signals elicited by members of the transforming growth factor (TGF)-beta superfamily. Smad5 and Smad1 are highly homologous, and they mediate primarily bone morphogenetic protein (Bmp) signals. We used the Cre-loxP system and Sm22-Cre and Tie-1-Cre mice to study the function of Smad5 in the developing blood vessel wall. Analysis of embryos demonstrated that deletion of Smad5 in endothelial or smooth muscle cells resulted in a normal organization of embryonic and extra-embryonic vasculature. Angiogenic assays performed in adult mice revealed that mutant mice display a comparable angiogenic and vascular remodeling response to control mice. In Sm22-Cre; Smad5(fl/-) mice, Smad5 is also deleted in cardiomyocytes. Echocardiographic analysis on those 9-month-old female mice demonstrated larger left ventricle internal diameters and decreased fractional shortening compared with control littermates without signs of cardiac hypertrophy. The decreased cardiac contractility was associated with a decreased performance in a treadmill experiment. In isolated cardiomyocytes, fractional shortening was significantly reduced compared with control cells. These data demonstrate that restricted deletion of Smad5 in the blood vessel wall results in viable mice. However, loss of Smad5 in cardiomyocytes leads to a mild heart defect.

Smad5 is a member of the Smad family of intracellular mediators of BMP signals and in endothelial cells of TGF-beta signals. We and others previously showed that loss of Smad5 in the mouse results in embryonic lethality (between E9.5-E11.5) due to multiple embryonic and extraembryonic defects. To circumvent the early embryonic lethality and to allow tissue- and time-specific Smad5 inactivation, we created a conditional Smad5 allele in the mouse. Floxed Smad5 (Smad5(flE2,Neo/flE2,Neo)) mice were generated in which both exon2 and the Neo-cassette were flanked by loxP sites. Here we demonstrate that embryos with ubiquitous Cre-mediated deletion of Smad5 (Smad5(flDeltaE2/flDeltaE2)) phenocopy the conventional Smad5 knockout mice. Smad5(flE2/flE2) mice are now available and will be a valuable tool to analyze the role of Smad5 beyond its crucial early embryonic function throughout development and postnatal life., (Copyright 2003 Wiley-Liss, Inc.)