The First Korean Case of Cutaneous Lung Tissue Heterotopia

Cutaneous lung tissue heterotopia is a very rare disorder where mature lung tissues develop in the skin. This is only the second known report of cutaneous lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn infant had a hemangioma-like, freely movable mass connected to the anterior aspect of the sternal manubrium. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and branchial cleft cyst by histology and the location of the mass. We describe the clinical, radiologic, and pathologic findings of a cutaneous lung tissue heterotopia, the first reported in Korea

Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

PMCID: PMC3566971This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Cancer Genes Hypermethylated in Human Embryonic Stem Cells

Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation

Bone marrow mesenchymal stem cells' secretome exerts neuroprotective effects in a Parkinson's disease rat model

Parkinson's disease (PD) is characterized by a selective loss of dopamine (DA) neurons in the human midbrain causing motor dysfunctions. The exact mechanism behind dopaminergic cell death is still not completely understood and, so far, no cure or neuroprotective treatment for PD is available. Recent studies have brought attention to the variety of bioactive molecules produced by mesenchymal stem cells (MSCs), generally referred to as the secretome. Herein, we evaluated whether human MSCs-bone marrow derived (hBMSCs) secretome would be beneficial in a PD pre-clinical model, when compared directly with cell transplantation of hBMSCs alone. We used a 6-hydroxydpomanie (6-OHDA) rat PD model, and motor behavior was evaluated at different time points after treatments (1, 4, and 7 weeks). The impact of the treatments in the recovery of DA neurons was estimated by determining TH-positive neuronal densities in the substantia nigra and fibers in the striatum, respectively, at the end of the behavioral characterization. Furthermore, we determined the effect of the hBMSCs secretome on the neuronal survival of human neural progenitors in vitro, and characterized the secretome through proteomic-based approaches. This work demonstrates that the injection of hBMSCs secretome led to the rescue of DA neurons, when compared to transplantation of hBMSCs themselves, which can explain the recovery of secretome-injected animals' behavioral performance in the staircase test. Moreover, we observed that hBMSCs secretome induces higher levels of in vitro neuronal differentiation. Finally, the proteomic analysis revealed that hBMSCs secrete important exosome-related molecules, such as those related with the ubiquitin-proteasome and histone systems. Overall, this work provided important insights on the potential use of hBMSCs secretome as a therapeutic tool for PD, and further confirms the importance of the secreted molecules rather than the transplantation of hBMSCs for the observed positive effects. These could be likely through normalization of defective processes in PD, namely proteostasis or altered gene transcription, which lately can lead to neuroprotective effects.Portuguese Foundation for Science and Technology: IF Development Grant (IF/00111/2013) to AS, Post-Doctoral Fellowship to FT (SFRH/BPD/118408/2016) and Doctoral Fellowship to BM-P (SFRH/BD/120124/2016); Canada Research Chair in Biomedical Engineering (LAB). This work was funded by FEDER, through the Competitiveness Internationalization Operational Programme (POCI), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects: POCI-01-0145-FEDER-029751; POCI-01-0145-FEDER-007038; POCI-01-0145-FEDER-032619; POCI-01-0145-FEDER-016428 (ref.: SAICTPAC/0010/2015), POCI-01-0145-FEDER-016795 (ref.: PTDC/NEU-SCC/7051/2014), POCI-01-0145-FEDER-029311 (ref.: PTDC/BTM-TEC/29311/2017), POCI-01-0145-FEDER-30943 (ref.: PTDC/MEC-PSQ/30943/2017) and PTDC/MED-NEU/27946/2017; UID/NEU/04539/2013 and POCI-01-0145-FEDER-007440. This article has also been developed under the scope of the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Co-funded by the Programa Operacional Factores de Competitividade (QREN) and by The National Mass Spectrometry Network under the contract POCI-01-0145-FEDER-402-022125 (ref.: ROTEIRO/0028/2013

Geo‐Hydromorphological Assessment of Europe’s Southernmost Blanket Bogs

Blanket bogs are a globally rare type of ombrotrophic peatland internationally recognised for long‐term terrestrial carbon storage, the potential to serve as carbon sinks, habitat provision and for their palaeoenvironmental archive. This habitat is protected in the European Union under the Habitats Directive (92/43/EEC), but a number of blanket bogs located in the Cantabrian Mountains (northern Spain), representing the southernmost known edge‐of‐range for this habitat in Europe, are currently not recognised and are at increased threat of loss. Using climatic data, topography, aerial photography and peat depth surveys, this study has identified ten new areas of blanket bog located between the administrative regions of Cantabria and Castilla y León. Peat depth data and topography were used to provide a detailed geomorphological description and hydromorphological classification (mesotope units) of these currently unrecognised areas of blanket bog. Maximum peat depth measured across the ten sites ranged from 1.61 m to 3.78 m covering a total area of 18.6 ha of blanket bog (> 40 cm peat depth). The volume of peat accumulated across the sites was determined to be more than 216,000 m3 and is estimated to hold 19.89 ± 3.51kt C. Twenty‐four individual hydrological mesotope units were described indicating a diverse assemblage of blanket bogs in this region. The peatlands identified in this research extend the known limit of blanket bogs in Europe farther south than previously recorded and combined with four other unprotected blanket bogs recently identified in the Cantabrian Mountains, these peatlands represent 10.5% of blanket bog currently recognised and protected in Spain. The range of anthropogenic pressures currently acting on peatlands in the Cantabrian Mountains indicates that without protection these important landforms and carbon stored may be lost. An urgent update of European peatland inventories is thus required to preserve these valuable carbon stores and potential carbon sinks

The biology of inequalities in health: The LIFEPATH project

Socioeconomic differences in health have been consistently observed worldwide. Physical health deteriorates more rapidly with age among men and women with lower socioeconomic status (SES) than among those with higher SES. The biological processes underlying these differences are best understood by adopting a life course approach. In this paper we introduce the pan- European LIFEPATH project which uses multiple cohorts - including biomarker data - to investigate ageing as a phenomenon with two broad stages across life: build-up and decline. The ‘build-up’ stage, from conception and early intra-uterine life to late adolescence or early twenties, is characterised by rapid successions of developmentally and socially sensitive periods. The second stage, starting in early adulthood, is a period of ‘decline’ from maximum attained health to loss of function, overt disease and death. LIFEPATH adopts a study design that integrates social science and public health approaches with biology (including molecular epidemiology), using well-characterised population cohorts and omics measurements (particularly epigenomics). LIFEPATH includes information and biological samples from 17 cohorts, including several with extensive phenotyping and repeat biological samples, and a very large cohort (1 million individuals) without biological samples (WHIP, from Italy). The countries that are covered by the cohorts are France, Italy, Portugal, Ireland, UK, Finland, Switzerland and Australia. These cohorts are only a small proportion of all cohorts available in Europe, but we have chosen them for the combination of good measures of socioeconomic status, risk factors for non-communicable diseases (NCDs) and biomarkers already measured (or availability of blood samples for further testing). The majority of cohorts include ‘hard’ outcomes (diabetes, cancer, Cardiovascular Disease (CVD), total mortality), and the extensively phenotyped cohorts also include several measurements of the functional components of healthy ageing, including frailty, impaired vision, cognitive function, renal and brain function, osteoporosis, sleep disturbances and mental health. All age groups are represented with two birth cohorts, one cohort of adolescents and several cohorts encompassing young adults (age 18 and above). Furthermore, there is a strong representation of elderly subjects in seven cohorts. The specific objectives of the project are: (a) to show that healthy ageing is an achievable goal for society; (b) to improve the understanding of the mechanisms through which healthy ageing pathways diverge by SES, by investigating life course biological pathways using omic technologies; (c) to examine the consequences of the current economic recession on health and the biology of ageing (and the consequent increase in social inequalities); (d) to provide updated, relevant and innovative evidence for healthy ageing policies (particularly ‘health in all policies’) using both observational studies and an experimental approach based on a reanalysis of data from a ‘conditional cash transfer’ randomised experiment in New York and new data collected as part of an earned income tax credit randomised experiment in Atlanta and New York. To achieve these objectives, data are used from three categories of studies: 1. national census-based followup data to obtain mortality by socioeconomic status; 2. cohorts with intense phenotyping and repeat biological samples; 3. large cohorts with biological samples. With these objectives and methodologies, LIFEPATH seeks to provide updated, relevant and innovative evidence to underpin future policies and strategies for the promotion of healthy ageing, targeted disease prevention and clinical interventions that address the issue of social disparities in ageing and the social determinants of health. The present paper describes the design and some initial results of LIFEPATH as an example of the integration of social and biological sciences to provide evidence for public health policies

Bioavailability of iodine in the UK-Peak District environment and its human bioaccessibility: an assessment of the causes of historical goitre in this area

Iodine is an essential micronutrient for human health. Its deficiency causes a number of functional and developmental abnormalities such as goitre. The limestone region of Derbyshire, UK was goitre-endemic until it declined from the 1930s and the reason for this has escaped a conclusive explanation. The present study investigates the cause(s) of goitre in the UK-Peak District area through an assessment of iodine in terms of its environmental mobility, bioavailability, uptake into the food chain and human bioaccessibility. The goitre-endemic limestone area is compared with the background millstone grit area of the UK-Peak District. The findings of this study show that ‘total’ environmental iodine is not linked to goitre in the limestone area, but the governing factors include iodine mobility, bioavailability and bioaccessibility. Compared with the millstone grit area, higher soil pH and calcium content of the limestone area restrict iodine mobility in this area, also soil organic carbon in the limestone area is influential in binding the iodine to the soil. Higher calcium content in the limestone area is an important factor in terms of strongly fixing the iodine to the soil. Higher iodine bioaccessibility in the millstone grit than the limestone area suggests that its oral bioaccessibility is restricted in the limestone area. Iodine taken up by plant roots is transported freely into the aerial plant parts in the millstone grit area unlike the limestone area, thus providing higher iodine into the human food chain in the millstone grit area through grazing animals unlike the goitre-prevalent limestone area

Transcriptomic and biochemical investigations support the role of rootstock-scion interaction in grapevine berry quality

Background In viticulture, rootstock genotype plays a critical role to improve scion physiology, berry quality and to adapt grapevine (Vitis viniferaL.) to different environmental conditions. This study aimed at investigating the effect of two different rootstocks (1103 Paulsen - P - and Mgt 101-14 - M) in comparison with not grafted plants - NGC - on transcriptome (RNA-seq and small RNA-seq) and chemical composition of berry skin inPinot noir, and exploring the influence of rootstock-scion interaction on grape quality. Berry samples, collected at veraison and maturity, were investigated at transcriptional and biochemical levels to depict the impact of rootstock on berry maturation. Results RNA- and miRNA-seq analyses highlighted that, at veraison, the transcriptomes of the berry skin are extremely similar, while variations associated with the different rootstocks become evident at maturity, suggesting a greater diversification at transcriptional level towards the end of the ripening process. In the experimental design, resembling standard agronomic growth conditions, the vines grafted on the two different rootstocks do not show a high degree of diversity. In general, the few genes differentially expressed at veraison were linked to photosynthesis, putatively because of a ripening delay in not grafted vines, while at maturity the differentially expressed genes were mainly involved in the synthesis and transport of phenylpropanoids (e.g. flavonoids), cell wall loosening, and stress response. These results were supported by some differences in berry phenolic composition detected between grafted and not grafted plants, in particular in resveratrol derivatives accumulation. Conclusions Transcriptomic and biochemical data demonstrate a stronger impact of 1103 Paulsen rootstock than Mgt 101-14 or not grafted plants on ripening processes related to the secondary metabolite accumulations in berry skin tissue. Interestingly, theMYB14gene, involved in the feedback regulation of resveratrol biosynthesis was up-regulated in 1103 Paulsen thus supporting a putative greater accumulation of stilbenes in mature berries