Histone deacetylase 1 and 2 drive differentiation and fusion of progenitor cells in human placental trophoblasts

Cell fusion occurs when several cells combine to form a multinuclear aggregate (syncytium). In human placenta, a syncytialized trophoblast (syncytiotrophoblast) layer forms the primary interface between maternal and fetal tissue, facilitates nutrient and gas exchange, and produces hormones vital for pregnancy. Syncytiotrophoblast development occurs by differentiation of underlying progenitor cells called cytotrophoblasts, which then fuse into the syncytiotrophoblast layer. Differentiation is associated with chromatin remodeling and specific changes in gene expression mediated, at least in part, by histone acetylation. However, the epigenetic regulation of human cytotrophoblast differentiation and fusion is poorly understood. In this study, we found that human syncytiotrophoblast development was associated with deacetylation of multiple core histone residues. Chromatin immunoprecipitation sequencing revealed chromosomal regions that exhibit dynamic alterations in histone H3 acetylation during differentiation. These include regions containing genes classically associated with cytotrophoblast differentiation (TEAD4, TP63, OVOL1, CGB), as well as near genes with novel regulatory roles in trophoblast development and function, such as LHX4 and SYDE1. Prevention of histone deacetylation using both pharmacological and genetic approaches inhibited trophoblast fusion, supporting a critical role of this process for trophoblast differentiation. Finally, we identified the histone deacetylases (HDACs) HDAC1 and HDAC2 as the critical mediators driving cytotrophoblast differentiation. Collectively, these findings provide novel insights into the epigenetic mechanisms underlying trophoblast fusion during human placental development

IHE cross-enterprise document sharing for imaging: interoperability testing software

<p>Abstract</p> <p>Background</p> <p>With the deployments of Electronic Health Records (EHR), interoperability testing in healthcare is becoming crucial. EHR enables access to prior diagnostic information in order to assist in health decisions. It is a virtual system that results from the cooperation of several heterogeneous distributed systems. Interoperability between peers is therefore essential. Achieving interoperability requires various types of testing. Implementations need to be tested using software that simulates communication partners, and that provides test data and test plans.</p> <p>Results</p> <p>In this paper we describe a software that is used to test systems that are involved in sharing medical images within the EHR. Our software is used as part of the Integrating the Healthcare Enterprise (IHE) testing process to test the Cross Enterprise Document Sharing for imaging (XDS-I) integration profile. We describe its architecture and functionalities; we also expose the challenges encountered and discuss the elected design solutions.</p> <p>Conclusions</p> <p>EHR is being deployed in several countries. The EHR infrastructure will be continuously evolving to embrace advances in the information technology domain. Our software is built on a web framework to allow for an easy evolution with web technology. The testing software is publicly available; it can be used by system implementers to test their implementations. It can also be used by site integrators to verify and test the interoperability of systems, or by developers to understand specifications ambiguities, or to resolve implementations difficulties.</p

Awareness Tool for Safe and Responsible Driving (OSCAR) : A Potential Educational Intervention for Increasing Interest, Openness and Knowledge About the Abilities Required and Compensatory Strategies Among Older Drivers

Abstract : Objective: This pilot study aimed to verify the impact of the awareness tool for safe and responsible driving (OSCAR) on older adults’ (1) interest, openness, and knowledge about the abilities and compensatory strategies required for safe driving; (2) awareness of changes that have occurred in their own driving abilities; and (3) actual utilization of compensatory strategies. Methods: A preexperimental design, including a pretest (T0) and posttest (T1) 8 to 10 weeks after exposure to the intervention, was used with 48 drivers aged between 67 and 84. The participants had a valid driving license and drove at least once a week. Results: Overall, the results demonstrate that OSCAR increased interest, openness, and knowledge about the abilities and compensatory strategies of older drivers (P < .01). After exposure to OSCAR, the majority of the participants confirmed that changes had occurred in at least one of their abilities. Moreover, half of the older drivers reported having started using 6 or more compensatory strategies. Conclusion: In summary, in addition to increasing older adults’ interest, openness, and knowledge to discussion about driving, OSCAR also improved awareness of the changes that could negatively impact safe driving and enhanced utilization of compensatory strategies. While promoting safe driving and the prevention of crashes and injuries, this intervention could ultimately help older adults maintain or increase their transportation mobility. More studies are needed to further evaluate OSCAR and identify ways to improve its effectiveness

Heteroplasmy:Detection, verification and recurrence in baleen whales

Heteroplasmy is defined as the presence of two or more different mitochondrial DNA (mtDNA) genomes in one individual. Heteroplasmy can arise from insertions or deletions (length heteroplasmy) or single nucleotide substitutions (point heteroplasmy). The phenomenon has been widely studied in humans and model species; however, reports from non-model species are rare, possibly because heteroplasmy was undetected or ignored during sequencing. Among cetaceans, a few studies have reported heteroplasmy and speculated on its possible effects, suggesting that heteroplasmy could be rare or simply ignored. The aim of the present study was to assess and confirm point heteroplasmies, as well as to determine their frequency in five baleen whale species. We analyzed 10,748 mtDNA sequence electropherograms of the mitochondrial control region obtained by Sanger sequencing. A pipeline was developed to detect potential heteroplasmy by analyzing chromatogram peak heights. Potential heteroplasmies were subsequently verified experimentally. A total of 7,882 samples were assessed, among which 326 (4,1%) presented potential point heteroplasmy at more than 35 different nucleotide positions. These results indicated that heteroplasmy is more frequent than previously reported. Several heteroplasmies were tracked across multiple generations, providing insights into the introduction of new mtDNA haplotypes. Ignoring heteroplasmy might bias relatedness analyses as well as estimates of genetic diversity and mtDNA mutation rates. Thus, it is extremely important to develop efficient ways to detect and verify heteroplasmy

Heteroplasmy:Detection, verification and recurrence in baleen whales

Heteroplasmy is defined as the presence of two or more different mitochondrial DNA (mtDNA) genomes in one individual. Heteroplasmy can arise from insertions or deletions (length heteroplasmy) or single nucleotide substitutions (point heteroplasmy). The phenomenon has been widely studied in humans and model species; however, reports from non-model species are rare, possibly because heteroplasmy was undetected or ignored during sequencing. Among cetaceans, a few studies have reported heteroplasmy and speculated on its possible effects, suggesting that heteroplasmy could be rare or simply ignored. The aim of the present study was to assess and confirm point heteroplasmies, as well as to determine their frequency in five baleen whale species. We analyzed 10,748 mtDNA sequence electropherograms of the mitochondrial control region obtained by Sanger sequencing. A pipeline was developed to detect potential heteroplasmy by analyzing chromatogram peak heights. Potential heteroplasmies were subsequently verified experimentally. A total of 7,882 samples were assessed, among which 326 (4,1%) presented potential point heteroplasmy at more than 35 different nucleotide positions. These results indicated that heteroplasmy is more frequent than previously reported. Several heteroplasmies were tracked across multiple generations, providing insights into the introduction of new mtDNA haplotypes. Ignoring heteroplasmy might bias relatedness analyses as well as estimates of genetic diversity and mtDNA mutation rates. Thus, it is extremely important to develop efficient ways to detect and verify heteroplasmy

Heteroplasmy: Detection, verification and recurrence in baleen whales

Heteroplasmy is defined as the presence of two or more different mitochondrial DNA (mtDNA) genomes in one individual. Heteroplasmy can arise from insertions or deletions (length heteroplasmy) or single nucleotide substitutions (point heteroplasmy). The phenomenon has been widely studied in humans and model species; however, reports from non-model species are rare, possibly because heteroplasmy was undetected or ignored during sequencing. Among cetaceans, a few studies have reported heteroplasmy and speculated on its possible effects, suggesting that heteroplasmy could be rare or simply ignored. The aim of the present study was to assess and confirm point heteroplasmies, as well as to determine their frequency in five baleen whale species. We analyzed 10,748 mtDNA sequence electropherograms of the mitochondrial control region obtained by Sanger sequencing. A pipeline was developed to detect potential heteroplasmy by analyzing chromatogram peak heights. Potential heteroplasmies were subsequently verified experimentally. A total of 7,882 samples were assessed, among which 326 (4,1%) presented potential point heteroplasmy at more than 35 different nucleotide positions. These results indicated that heteroplasmy is more frequent than previously reported. Several heteroplasmies were tracked across multiple generations, providing insights into the introduction of new mtDNA haplotypes. Ignoring heteroplasmy might bias relatedness analyses as well as estimates of genetic diversity and mtDNA mutation rates. Thus, it is extremely important to develop efficient ways to detect and verify heteroplasmy