Transcriptome profiling of rabbit parthenogenetic blastocysts developed under in vivo conditions

Parthenogenetic embryos are one attractive alternative as a source of embryonic stem cells, although many aspects related to the biology of parthenogenetic embryos and parthenogenetically derived cell lines still need to be elucidated. The present work was conducted to investigate the gene expression profile of rabbit parthenote embryos cultured under in vivo conditions using microarray analysis. Transcriptomic profiles indicate 2541 differentially expressed genes between parthenotes and normal in vivo fertilised blastocysts, of which 76 genes were upregulated and 16 genes downregulated in in vivo cultured parthenote blastocyst, using 3 fold-changes as a cut-off. While differentially upregulated expressed genes are related to transport and protein metabolic process, downregulated expressed genes are related to DNA and RNA binding. Using microarray data, 6 imprinted genes were identified as conserved among rabbits, humans and mice: GRB10, ATP10A, ZNF215, NDN, IMPACT and SFMBT2. We also found that 26 putative genes have at least one member of that gene family imprinted in other species. These data strengthen the view that a large fraction of genes is differentially expressed between parthenogenetic and normal embryos cultured under the same conditions and offer a new approach to the identification of imprinted genes in rabbit. © 2012 Naturil-Alfonso et al.This work was supported by Generalitat Valenciana research programme (Prometeo 2009/125). Carmen Naturil was supported by Generalitat Valenciana research programme (Prometeo 2009/125). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Naturil Alfonso, C.; Saenz De Juano Ribes, MDLD.; Peñaranda, D.; Vicente Antón, JS.; Marco Jiménez, F. (2012). Transcriptome profiling of rabbit parthenogenetic blastocysts developed under in vivo conditions. PLoS ONE. 7(12):1-11. https://doi.org/10.1371/journal.pone.0051271S111712Harness, J. 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Silencing α-Synuclein Gene Expression Enhances Tyrosine Hydroxylase Activity in MN9D Cells

α-Synuclein has been implicated in the pathogenesis of Parkinson’s disease (PD). Previous studies have shown that α-synuclein is involved in the regulation of dopamine (DA) metabolism, possibly by down-regulating the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in DA biosynthesis. In this study, we constructed α-synuclein stably silenced MN9D/α-SYN− cells by vector mediated RNA interference and examined its effects on DA metabolism. We found that there were no significant differences in TH protein and mRNA levels between MN9D, MN9D/α-SYN− and MN9D/CON cells, suggesting that silencing α-synuclein expression does not affect TH gene expression. However, significant increases in phosphorylated TH, cytosolic 3, 4-dihydroxyphenylalanine (l-DOPA) and DA levels were observed in MN9D/α-SYN− cells. Our data show that TH activity and DA biosynthesis were enhanced by down-regulation of α-synuclein, suggesting that α-synuclein may act as a negative regulator of cytosolic DA. With respect to PD pathology, a loss of functional α-synuclein may result in increased DA levels in neurons that may lead to cell injury or even death

Cardiac Tissue Engineering: Implications for Pediatric Heart Surgery

Children with severe congenital malformations, such as single-ventricle anomalies, have a daunting prognosis. Heart transplantation would be a therapeutic option but is restricted due to a lack of suitable donor organs and, even in case of successful heart transplantation, lifelong immune suppression would frequently be associated with a number of serious side effects. As an alternative to heart transplantation and classical cardiac reconstructive surgery, tissue-engineered myocardium might become available to augment hypomorphic hearts and/or provide new muscle material for complex myocardial reconstruction. These potential applications of tissue engineered myocardium will, however, impose major challenges to cardiac tissue engineers as well as heart surgeons. This review will provide an overview of available cardiac tissue-engineering technologies, discuss limitations, and speculate on a potential application of tissue-engineered heart muscle in pediatric heart surgery

Tissue engineering, stem cells, cloning, and parthenogenesis: new paradigms for therapy

Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs which is worsening yearly due to the aging population. Scientists in the field of tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Both therapeutic cloning (nucleus from a donor cell is transferred into an enucleated oocyte), and parthenogenesis (oocyte is activated and stimulated to divide), permit extraction of pluripotent embryonic stem cells, and offer a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. The present article reviews recent progress in tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure

Human embryonic stem cells: preclinical perspectives

Human embryonic stem cells (hESCs) have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic

A qualitative study of service provision for alcohol related health issues in mid to later life

AIMS:Epidemiological surveys over the last 20 years show a steady increase in the amount of alcohol consumed by older age groups. Physiological changes and an increased likelihood of health problems and medication use make older people more likely than younger age groups to suffer negative consequences of alcohol consumption, often at lower levels. However, health services targeting excessive drinking tend to be aimed at younger age groups. The aim of this study was to gain an in-depth understanding of experiences of, and attitudes towards, support for alcohol related health issues in people aged 50 and over. METHODS:Qualitative interviews (n = 24, 12 male/12 female, ages 51-90 years) and focus groups (n = 27, 6 male/21 female, ages 50-95 years) were carried out with a purposive sample of participants who consumed alcohol or had been dependent. FINDINGS:Participants' alcohol misuse was often covert, isolated and carefully regulated. Participants tended to look first to their General Practitioner for help with alcohol. Detoxification courses had been found effective for dependent participants but only in the short term; rehabilitation facilities were appreciated but seen as difficult to access. Activities, informal groups and drop-in centres were endorsed. It was seen as difficult to secure treatment for alcohol and mental health problems together. Barriers to seeking help included functioning at a high level, concern about losing positive aspects of drinking, perceived stigma, service orientation to younger people, and fatalistic attitudes to help-seeking. Facilitators included concern about risk of fatal illness or pressure from significant people. CONCLUSION:Primary care professionals need training on improving the detection and treatment of alcohol problems among older people. There is also a compelling need to ensure that aftercare is in place to prevent relapse. Strong preferences were expressed for support to be provided by those who had experienced alcohol problems themselves

Student Perceptions of a New Course Using Argumentation in Medical Education

Andrew J Foy,1,2,* Kent E Vrana,3 Paul Haidet,1,2 Bernice L Hausman,2,4 Nancy E Adams,5 Ira Ropson,6 Daniel R Wolpaw,1 David Rabago,2,7 Richard B Mailman,3,8 Xuemei Huang3,8– 10,* 1Penn State Department of Medicine, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 2Penn State Department of Public Health Science, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 3Penn State Department of Pharmacology, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 4Penn State Department of Humanities, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 5Harrel Library Foundational Sciences, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 6Penn State Department of Biochemistry and Molecular Biology, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 7Penn State Department of Family and Community Medicine, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 8Penn State Department of Neurosurgery, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 9Penn State Department of Neurology, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA; 10Penn State Department of Kinesiology, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, PA, USA*These authors contributed equally to this workCorrespondence: Andrew J Foy, Penn State Milton S Hershey Medical Center and College of Medicine, Penn State Heart and Vascular Institute, Division of Cardiology, Hershey, PA, USA, Email [email protected]: Critical thinking and the ability to engage with others of differing views in a civil manner is essential to the practice of medicine. A new format for medical student education (“Argue-to-Learn”) that uses staged debates followed by small group discussions was introduced into the curriculum of first year medical school at the Penn State College of Medicine. The goal was to create a structured environment for spirited, civil discourse, and to encourage students to think critically about clinically controversial topics. This manuscript describes the development of the program, and presents comparative data on student perceptions of the first two mandatory sessions that focused on the treatment of post-menopausal osteoporosis and on COVID-19 vaccine mandates.Methods: Quantitative results were gathered from standardized post-block student surveys for each session and compared to cumulative results of all other courses included in the learning block. Post-block surveys of students include four session-evaluation questions scored on a 5 point Likert scale. Scores were compared using Student’s t-test. Thematic analysis of qualitative data was performed on a single open-ended response from the same survey.Results: Compared to all other courses in the learning block, scores on each of the four questions were either the same or numerically higher for the Argue-to-Learn sessions, but none reached statistical significance. Two important qualitative themes were identified. First, students enjoyed the format, found it interesting and engaging and want more similar sessions. Second, students appreciated hearing opposing viewpoints and presenting their own viewpoints in a safe and supportive environment.Conclusion: These findings support evidence from educational scholarship outside of medicine showing argumentation as a learning tool is well received by students. Further work is needed to determine whether it improves critical thinking skills and enhances learning in medical education.Keywords: argumentation, critical discourse, collaborative learnin