Propuesta de modificaciones a la tecnología para la determinación de problemas y potencialidades / A Proposal of Modifications to the Technology for Determining Problems and Potentialities

Introducción: Para el desarrollo de la investigación científica, la educación médica ha asumido supuestos que conforman la Teoría de la Educación Avanzada, entre los que se encuentran la Tecnología para la determinación de problemas y potencialidades, descrita por reconocidos pedagogos cubanos. Objetivo: Proponer modificaciones a la Tecnología para la determinación de problemas y potencialidades. Métodos: Se utilizaron métodos teóricos: sistematización, histórico-lógico, sistémico estructural, funcional, análisis documental, concreción-abstracción y modelación. Resultados: Los autores realizaron modificaciones a la Tecnología para la determinación de problemas y potencialidades en el primer, quinto, sexto y séptimo pasos, con dos acercamientos al objeto de estudio desde lo genérico y holístico a lo particular, de la aproximación al análisis profundo. Se introdujo en la práctica mediante su utilización en una tesis, defendida en 2021, para optar por el título de Doctor en Ciencias de la Educación Médica. Conclusiones: La Tecnología para la determinación de problemas y potencialidades con modificaciones demuestra la flexibilidad y posibilidad de aplicación de la tecnología inicial en otras ciencias, a partir de modificaciones que pudieran introducirse de acuerdo con sus particularidades y complejidades. Esta innovación tecnológica se propone para el desarrollo de la investigación científica en las ciencias de la educación médica con vista a abordar, con un enfoque holístico, sus objetos de estudio y campos de acción(AU)

Introduction: For the development of scientific research, medical education has taken assumptions that make up the theory of advanced education, among which is the technology for determining problems and potentialities, described by renowned Cuban pedagogues. Objective: To propose modifications to the technology for determining problems and potentialities. Methods: Theoretical methods were used: systematization, historical-logical, structural-systemic, functional, documentary analysis, concretion-abstraction, and modeling. Results: The authors made modifications to the technology for determining problems and potentialities in the first, fifth, sixth and seventh steps, with two approaches to the object of study from the generic and holistic to the particular, from approximation to profound analysis. It was introduced into practice through its use in a thesis, defended in 2021, to opt for the degree of doctor of Medical Education Sciences. Conclusions: The technology for determining problems and potentialities with modifications shows the flexibility and possibility of application of the initial technology into other sciences, from modifications that could be introduced according to their particularities and complexities. This technological innovation is proposed for the development of scientific research in the sciences of medical education, in view of approaching, with a holistic perspective, its objects of study and fields of action(AU)

Role of Histone Modifications and 12/15-lipoxygenase Metabolic Pathway in the Development of Diabetic Kidney Disease / 中山大学学报(医学科学版)

Diabetic kidney disease （DKD） is one of the most common microvascular complications in patients with diabetes. DKD is also the main cause of end-stage renal failure， with very complex pathogenesis. A large number of experiments have confirmed that epigenetic mechanisms， including histone chemical modifications and lipid metabolites 12/15-lipoxygenase （12/15-LO）， are involved in regulating the characteristic pathophysiological process of DKD， based on which， this review further explores the pathogenesis of DKD and provides the new research direction for DKD treatment.

The critical importance of epigenetics in autoimmune-related skin diseases / 医学前沿

Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.

Research progress in the mechanism of anti-atherosclerotic effect of berberine and its derivatives / 国际生物医学工程杂志

Atherosclerosis is usually the underlying cause of cardiovascular diseases. With the change in diet structure and living environment, it has become an increasingly serious global health problem, posing a huge challenge to public health. Berberine, also known as flavonidol, is an isoquinoline-type quaternary alkaloid with purgative and detoxifying effects. Berberine and its derivatives have antibacterial, antiviral, anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, and atherosclerosis prevention effects, etc. Recent research results showed that berberine and its derivatives can play an important role in atherosclerosis prevention through a hypolipidemic effect, anti-oxidative stress and anti-inflammatory activity, improvement of vascular endothelial dysfunction, and regulation of intestinal microbiota. In this review paper, the research progress on the mechanism of action of berberine and its derivatives in the prevention of atherosclerosis was reviewed from the perspectives of a lipid-regulating effect, inhibition of oxidative stress and the inflammatory response, improvement of vascular endothelial dysfunction, and regulation of intestinal microbiota. The aim of this paper is to provide a theoretical basis for reducing the occurrence of atherosclerosis, improving the clinical symptoms of patients, and further developing berberine-based drugs.

Research progress on stimulator of interferon genes (STING) agonists / 中国药科大学学报

@#Stimulator of interferon genes (STING) is an important factor in the auto-immune response of our bodies.Considering the mechanism of activating CD8+ T cells after the activation of STING protein, the combination of STING agonists and immune checkpoint inhibitors for the treatment of tumor immunotherapy has good clinical application prospect.In this paper, the research progress of molecular types, mechanism of action and structural modifications of STING agonists were reviewed.The developing tendency were outlined to provide some references for further investigation.

Antileishmanial metallodrugs and the elucidation of new drug targets linked to post-translational modifications machinery: pitfalls and progress

Despite the increasing number of manuscripts describing potential alternative antileishmanial compounds, little is advancing on translating these knowledges to new products to treat leishmaniasis. This is in part due to the lack of standardisations during pre-clinical drug discovery stage and also depends on the alignment of goals among universities/research centers, government and pharmaceutical industry. Inspired or not by drug repurposing, metal-based antileishmanial drugs represent a class that deserves more attention on its use for leishmaniasis chemotherapy. Together with new chemical entities, progresses have been made on the knowledge of parasite-specific drug targets specially after using CRISPR/Cas system for functional studies. In this regard, Leishmania parasites undergoe post-translational modification as key regulators in several cellular processes, which represents an entire new field for drug target elucidation, once this is poorly explored. This perspective review describes the advances on antileishmanial metallodrugs and the elucidation of drug targets based on post-translational modifications, highlighting the limitations on the drug discovery/development process and suggesting standardisations focused on products addressed to who need it most.

Insights into epigenetic patterns in mammalian early embryos

Mammalian fertilization begins with the fusion of two specialized gametes, followed by major epigenetic remodeling leading to the formation of a totipotent embryo. During the development of the pre-implantation embryo, precise reprogramming progress is a prerequisite for avoiding developmental defects or embryonic lethality, but the underlying molecular mechanisms remain elusive. For the past few years, unprecedented breakthroughs have been made in mapping the regulatory network of dynamic epigenomes during mammalian early embryo development, taking advantage of multiple advances and innovations in low-input genome-wide chromatin analysis technologies. The aim of this review is to highlight the most recent progress in understanding the mechanisms of epigenetic remodeling during early embryogenesis in mammals, including DNA methylation, histone modifications, chromatin accessibility and 3D chromatin organization.

Analysis of hydroxylation and O-glycosylation on lysine sites in deer-hide gelatin / 中国中药杂志

Nano-LC MS/MS was used to analyze trypsin digested deer-hide gelatin(DHG) samples, hydroxylation and O-glycosylation on lysine sites of DHG were comprehensive identified by using PEAKS Studio software. The sites, sorts and amounts of hydroxylation and O-glycosylation on Type Ⅰ collagen α1 chain(COL1 A1) and α2 chain(COL1 A2) of DHG were revealed. As a result, 5 284 peptides were identified from DHG samples, which were mainly from COL1 A1 and COL1 A2. Among these peptides, there were 449 peptides with hydroxylysine, 442 with galactosyl-hydroxylysine, 449 with glucosyl-galactosyl-hydroxylysine. The major modified sites of hydroxylation and O-glycosylation in DHG were shown as follow: α1-9 N and α2-5 N in N-telopeptides, α1-87, α1-174, α1-930, α2-87, α2-174, α2-933 in triple helix domain, and α1-16 C in C-telopeptides. These hydroxylation and O-glycosylation were correlated with the formation and stability of collagen molecules and collagen fibrils. It is feasible for the collagens and peptides dissolving from deer skin collagen fibrils under high temperature and pressure decocting, high temperature and pressure also might destroy inter-molecular covalent cross-linking and help those glycol-peptides formations. The present study provided ideas and strategies for the in-depth investigation on DHG chemical constituents, and showed good theoretical significance and application value.

Evaluation of post-translational modifications in histone proteins: A review on histone modification defects in developmental and neurological disorders

Post-translational modification (PTM) in histone proteins is a covalent modification which mainly consists ofmethylation, phosphorylation, acetylation, ubiquitylation, SUMOylation, glycosylation, and ADP-ribosylation.PTMs have fundamental roles in chromatin structure and function. Histone modifications have also beenknown as epigenetic markers. The PTMs that have taken place in histone proteins can affect gene expressionby altering chromatin structure. Histone modifications act in varied biological processes such as transcriptionalactivation/inactivation, chromosome packaging, mitosis, meiosis, apoptosis, and DNA damage/repair. Defectsin the PTMs pathway have been associated with the occurrence and progression of various human diseases,such as cancer, heart failure, autoimmune diseases, and neurodegenerative disorders such as Parkinson’sdisease, Alzheimer’s disease, and Huntington’s disease. Histone modifications are reversible and used aspotential targets for cancer therapy and prevention. Recent different histone PTMs have key roles in cancercells since it has been shown that histone PTMs markers in cancers are acetylation, methylation, phosphorylation, and ubiquitylation. In this review, we have summarized the six most studied histone modifications andhave examined the role of these modifications in the development of cancer.

Desafíos éticos en investigación genómica y biotecnología. Veinte años de Acta Bioethica / Ethical challenges present in genomic research and biotechnology. Twenty years of Acta Bioethica / Desafios éticos na pesquisa genômica e biotecnológica. Vinte anos de Acta Bioethica

Resumen El presente artículo es una revisión de las reflexiones éticas sobre temas de genética y manipulación genética que se han publicado en 20 años de Acta Bioethica. Se identifican los siguientes temas relevantes en el diálogo bioético: evaluación de riesgos, inequidad, pérdida de la biodiversidad, eugenesia, definir los límites entre natural y artificial, diálogo entre detractores y promotores de la biotecnología, desafíos en el cuidado de la salud, manejo de la información y confidencialidad. Se concluye que la bioética puede actuar como intermediaria entre los diversos interlocutores ante los problemas que se suscitan al aplicar la tecnología a la vida, permitiendo reconocer y llegar a consensos para enfrentar con responsabilidad las diferencias en temas de equidad, autonomía y el balance entre riesgos y beneficios. Las reflexiones en Acta Bioethica sobre genómica son similares a las de otras revistas, solo que el énfasis es en la región latinoamericana. En veinte años de reflexión, los desafíos siguen siendo los mismos, aunque el énfasis está cambiando de la prevención y rechazo en cuanto a los riesgos de la modificación genética, a la regulación de la tecnología de ingeniería genética, que va perfeccionándose cada vez más. En cuanto a los beneficios, la medicina genómica siempre ha generado más expectativas que realidades, sin lograr demostrar eficacia en ensayos clínicos. Con las nuevas técnicas de edición genómica, se amplían aún más las expectativas de mejores intervenciones, pero aumenta la preocupación de que se realicen modificaciones genéticas sin finalidad terapéutica, afectando al equilibrio social y ecológico.

Abstract This article reviews ethical reflections about genetic research and genetic manipulation published in 20 years of Acta Bioethica. The following relevant topics are identified in bioethics dialogue: risks evaluation, inequity, loss of biodiversity, eugenics, definition of limits between artificial and natural, dialogue between detractors and promoters of biotechnology, challenges in health care, information and confidentiality management. Reflections consider that bioethics can act as mediator among diverse stakeholders affronting the problems that arise when applying technology to life, allowing to recognize and to reach consensus for solving differences in equity, autonomy and the balance of risks and benefices. The reflections in Acta Bioethica are similar to those of other journals, but with emphasis in the Latin American region. In twenty years of reflection, the challenges are similar, but the emphasis is changing from preventing to the avoidance of actual risks of genetic modifications, which demands regulation of genetic engineering, taking into account that it is more effective than before. Among the benefits, genomic medicine has always generated more expectations than actual therapy with problems in demonstrating efficacy in clinical trials. With the new technique of genomic edition, there are even more expectations for enhancing therapeutic approaches, but worries increase about using genetic modifications without therapeutic aim and interventions that affect the social and ecological equilibrium.

Resumo O presente artigo é uma revisão das reflexões éticas sobre temas de genética e manipulação genética que foram publicadas em 20 anos de Acta Bioethica. Os seguintes temas de importância para o diálogo bioético foram identificados: avaliação de riscos, inequidade, perda da biodiversidade, eugenia, definir os limites entre natural e artificial, diálogo entre opositores e defensores da biotecnologia, desafios em cuidados à saúde, manejo da informação e confidencialidade. Concluiu-se que a bioética pode atuar como intermediaria entre os diversos interlocutores ante os problemas que aparecem ao aplicar a tecnologia à vida, permitindo reconhecer e alcançar consensos para enfrentar com responsabilidade as diferenças em temas de equidade e autonomia, e o equilíbrio entre riscos e benefícios. As reflexões na Acta Bioethica sobre genômica são similares às de outras revistas, mas com ênfase na região latino-americana. Em vinte anos de reflexão, os desafios seguem sendo os mesmos, ainda que a ênfase esteja mudando da prevenção e repúdio quanto aos riscos da modificação genética, à regulação da tecnologia de engenharia genética, que se aperfeiçoa cada vez mais. Quanto aos benefícios, a medicina genômica sempre gerou mais expectativas que realidades, sem conseguir demonstrar eficácia em ensaios clínicos. Com as novas técnicas de edição genômica, ampliam-se ainda mais as expectativas de melhores intervenções, mas aumenta a preocupação de que se realizem modificações genéticas sem finalidade terapêutica, afetando o equilíbrio social e ecológico.

Elucidation and genetic intervention of CO2 concentration mechanism in Chlamydomonas reinhardtii for increased plant primary productivity

Post-translational modification (PTM) in histone proteins is a covalent modification which mainly consists ofmethylation, phosphorylation, acetylation, ubiquitylation, SUMOylation, glycosylation, and ADP-ribosylation.PTMs have fundamental roles in chromatin structure and function. Histone modifications have also beenknown as epigenetic markers. The PTMs that have taken place in histone proteins can affect gene expressionby altering chromatin structure. Histone modifications act in varied biological processes such as transcriptionalactivation/inactivation, chromosome packaging, mitosis, meiosis, apoptosis, and DNA damage/repair. Defectsin the PTMs pathway have been associated with the occurrence and progression of various human diseases,such as cancer, heart failure, autoimmune diseases, and neurodegenerative disorders such as Parkinson’sdisease, Alzheimer’s disease, and Huntington’s disease. Histone modifications are reversible and used aspotential targets for cancer therapy and prevention. Recent different histone PTMs have key roles in cancercells since it has been shown that histone PTMs markers in cancers are acetylation, methylation, phosphorylation, and ubiquitylation. In this review, we have summarized the six most studied histone modifications andhave examined the role of these modifications in the development of cancer.

Impact Analysis of the National Faculty Development Program for Medical Teachers: A Way Forward

Background: Medical Council of India, New Delhilaunched a National Faculty Development Program(NFDP) across India in 2009. NFDP was neverevaluated in the context of its operational utility,efficiency and effectivity. Aim and Objectives: Presentstudy was undertaken to evaluate the NFDPat one of theMedical Council of India (MCI) Nodal Centre foridentifying the gap with regards to its impact,operational utility and effectivity as envisioned by theregulatory body and to invocate interventionaloperations arising thereof and to calibrate it and tocreate evidences for the same. Material and Methods:The study has been carried out at Jawaharlal NehruMedical College (JNMC), Sawangi (Meghe), Wardha, aNodal Centre recognized by MCI New Delhi for theNFDP. A validated questionnaire was sent to 667stparticipants of the NFDP at JNMC from 1 July 2009 tost31 July 2017 and responses were obtained aboutgenerating evidences in education technology, transferof knowledge at the workplace and contribution in theinstitutional growth. The impact analysis was studied interms of individualization, internalization andinstitutionalization of the participants. Results: 220(52%) of the participants confirmed their involvementin educational research activities in the form of eitheradvance course or a conference or an educationalresearch project. 250 (59%) of the participants couldtransfer their learning to the workplace and broughtchanges in the teaching learning Practices and 28.3% inassessment methods. 255 - 338 (60.32% to 79.90%)participants opined positive impact of NFDP onpersonal/ professional/ Institutional growth.Conclusions: In terms of the observations and findingsthereto, it was proposed that certain modifications(structural, operational and conceptual) are warranted inthe said program. Operational utility of the NFDP isdiscussed under two headings. Its link with CompetencyBased Medical Education and its relation toAccreditation Status of Medical schools in India.

Mitochondrial reactive oxygen species cause major oxidative mitochondrial DNA damages and repair pathways

Mitochondria-derived reactive oxygen species (mROS) are produced at a variety of sites and affect the functionof bio-molecules. The anti-oxidant system from both mitochondria and cytosol tightly coordinate to maintainthe redox balance of cells and reduce damage from mROS. Mitochondrial DNA (mtDNA) are highly susceptible to mROS, and are easily oxidized to accumulate DNA modifications. Frequent oxidative damages inmtDNA have been associated with neurological degeneration, inflammasomes, tumorigenesis, and malignantprogression. Among mitochondrial DNA repair pathways, the base excision repair pathway has been extensively characterized to remove some of oxidative damages in mtDNA as efficiently as the nuclear base excisionrepair. The implications of other pathways remain unclear. This review focuses on: (i) Sources of mROS andthe antioxidant system to balance redox status; (ii) major mtDNA lesions or damages from mROS-mediatedoxidation and the reported repair pathways or repairing factors; (iii) cellular response of oxidized mtDNA andmethods to identify oxidatively generated DNA modifications in pathological conditions. DNA damagescaused by mROS have been increasingly implicated in diseases and aging, and thus we critically discussmethods of the oxidative modifications evaluation and the complexity of non-canonical DNA repair pathwaysin mitochondria.

Da 'volta à natureza' pelo 'milagre das Olimpíadas': narrativas de salvação do Rio de Janeiro no documentário para televisão Naturopolis / 'Back to nature' through 'the miracle of Olympics': narratives on the salvation of Rio de Janeiro in the television documentary Naturopolis / 'Volver a la naturaleza' a través del 'milagro de los Juegos Olímpicos': narraciones de salvación de Río de Janeiro en el documental para televisión Naturopolis

Este artigo busca compreender a produção de significados sobre sustentabilidade no contexto de produção da cidade olímpica. Para tanto, promove uma análise crítica do documentário Naturopolis, relacionando-o com alguns dos documentos oficiais disponibilizados tanto pelo Comitê Olímpico Internacional quanto pelo Comitê Organizador dos Jogos Olímpicos. Busca-se uma leitura polivalente, não dominante, considerando o contexto mais amplo de produção da cidade-mercadoria pela cidade-empresa, por meio de técnicas de city branding. O artigo se concentra na linha narrativa da salvação da cidade em relação à sustentabilidade, por meio dos megaeventos ou, nos termos do documentário, de uma volta à natureza, evocando mudanças necessárias para a construção de um novo país, a partir de uma transformação que pode ser trazida por políticos, pelo milagre das Olimpíadas e pela população em geral.

This article aims to understand the production of meanings about sustainability in the context of the production of the Olympic city. Using as method a critical analysis of the documentary Naturopolis, relating it to some of the official documents made available by both the International Olympic Committee and the Organizing Committee of the Olympic Games. The author seeks a multipurpose, non-dominant reading, considering the broader context of production of the commodity-city by the entrepreneurial city, through city branding techniques. The article focuses on the narrative line that consider mega-events as a catalyst to a possible salvation of the city in relation to sustainability, or, in the terms of the documentary, of a back to nature, evoking necessary changes for the construction of a new country, starting from a transformation that can be brought about by politicians, the miracle of the Olympics and the general population.

Este artículo busca comprender la producción de significados sobre sostenibilidad en el contexto de producción de la ciudad olímpica por medio de un análisis crítico del documental Naturopolis, relacionando la película con algunos de los documentos oficiales puestos a disposición tanto por el Comité Olímpico Internacional como por el Comité Organizador de los Juegos Olímpicos. Se busca una lectura polivalente, no dominante, considerando el contexto más amplio de producción de la ciudad-mercancía por la ciudad empresa, a través de técnicas de city branding. El artículo fija la atención en la línea narrativa de la salvación de la ciudad en relación con la sostenibilidad a través de megaeventos o, en los términos del documental, de un retorno a la naturaleza, evocando los cambios necesarios para la construcción de un nuevo país, a partir de una transformación que puede ser provocada por los políticos, por el milagro de los Juegos Olímpicos y por la población en general.

Male and female meiosis evince differential patterns in chiasma formation: a case study of ornamental plant, Delphinium ajacis L.

Chromosomal behaviour during megasporogenesis and microsporogenesis has been studied in ornamental Delphinium ajacis L. Meiosis in female sex cell initiates later than male. The floral buds which carry egg mother cell (EMC) at diplotene stage has pollen mother cells (PMCs) at tetrad stage of meiosis suggesting protandry. Although the 16 chromosomes formed regular eight bivalents in both the sex cells, they differed in overall chiasma frequency which was 32.95% higher in EMCs and found to be 18.52 ± 2.12 per cell. In PMCs, the average chiasma frequency recorded was 13.93 ± 1.40 per cell. Interestingly, this variation in chiasma frequency was largely confined to the two large bivalents which shared 42.61% chiasma per EMC. The use of Q–Q plot, Box plot and Whisker plot showed departure in the chiasma frequency distributions in EMCs and PMCs from the normal distribution pattern. The difference in chiasma frequency in the two sex cells was significant at all levels as indicated by the low P values of 3.094 9 10-11 obtained from nonparametric test, i.e. Wilcoxon rank-sum test. It is suggested that the two different mechanisms of recombination are operational in the two sex cells, and the sex differences of chiasma frequency could have arisen due to differential epigenetic modifications of the chromatin which pattern the double-strand breaks, and the position and frequency of crossing over visible as chiasmata.

The various metabolic factors involved in stone recurrence: a prospective study

Background: Nephrolithiasis is the most common chronic kidney condition, is globally increasing in both sexes. Five main types of renal stones viz., calcium oxalate stones, calcium phosphate stones, uric acid stones, struvite stones and cystine stones. Purpose of the study is to evaluate various metabolic factors contributing to recurrent renal stone and determining appropriate medical treatment and diet modification to prevent recurrent renal stone disease.Methods: This study was carried out in P.G. Department of Surgery, S.R.N. Hospital associated with M.L.N. Medical College, Allahabad. A total of 120 cases of recurrent renal calculi in and outpatient between August 2017 and July 2019 were included in the study. All patients were stone free at the time of metabolic urine evaluation.Results: Most of the patients in the study were in the age 21 to 50 years. 80% were males and 20% were females. In 24-hour urine analysis most common metabolic abnormality seems to be hyperoxaluria (92.5%) followed by hypercalciuria (82.5%), high pH (67.5%), and least common seems to be hypocitraturia (15%), followed by hyperphosphaturia (20%), hypernatreturia (25%), and low level of potassium (25%).Conclusions: All patient of recurrent stone formation are advised increase fluid intake. In patient with hypercalciuria and hypocitraturia, dietary restriction of protein, oxalate and sodium, treatment includes thiazides supplemented with potassium citrate. In patient with hyperoxaluria dietary restriction of oxalate rich food and in hyperuricosuria dietary restriction of animal protein is advised.

Regulation of epigenetic state by non-histone chromatin proteins and transcription factors: Implications in disease

Besides the fundamental components of the chromatin, DNA and octameric histone, the non-histone chromatinproteins and non-coding RNA play a critical role in the organization of functional chromatin domains. Thenon-histone chromatin proteins therefore regulate the transcriptional outcome in both physiological andpathophysiological state as well. They also help to maintain the epigenetic state of the genome indirectly.Several transcription factors and histone interacting factors also contribute in the maintenance of the epigeneticstates, especially acetylation by the induction of autoacetylation ability of p300/CBP. Alterations of KATactivity have been found to be causally related to disease manifestation, and thus could be potential therapeutictarget.

Role of genomic imprinting in mammalian development

In mammals, DNA methyltransferases transfer a methyl group from S-adenosylmethionine to the 5 position ofcytosine in DNA. The product of this reaction, 5-methylcytosine (5mC), has many roles, particularly insuppressing transposable and repeat elements in DNA. Moreover, in many cellular systems, cell lineagespecification is accompanied by DNA demethylation at the promoters of genes expressed at high levels in thedifferentiated cells. However, since direct cleavage of the C-C bond connecting the methyl group to the 5position of cytosine is thermodynamically disfavoured, the question of whether DNA methylation wasreversible remained unclear for many decades. This puzzle was solved by our discovery of the TET (TenEleven Translocation) family of 5-methylcytosine oxidases, which use reduced iron, molecular oxygen and thetricarboxylic acid cycle metabolite 2-oxoglutarate (also known as a-ketoglutarate) to oxidise the methyl groupof 5mC to 5-hydroxymethylcytosine (5hmC) and beyond. TET-generated oxidised methylcytosines areintermediates in at least two pathways of DNA demethylation, which differ in their dependence on DNAreplication. In the decade since their discovery, TET enzymes have been shown to have important roles inembryonic development, cell lineage specification, neuronal function and cancer. We review these findings anddiscuss their implications here.

TET methylcytosine oxidases: new insights from a decade of research

In primates, males compete for a mate, which is a non-sharable resource. This makes the conditions lessconducive for males to have stable relationships. One such special kind of relationship is a bond where theinteractions are reciprocated, equitable and differentiated. Bonds in macaque societies are based on the degreeof within-group contest competition for mates which is dependent on the synchronization of female fertilephase and reliability of fertility signals. Species of the Fascicularis group, including Nicobar subspecies, showintermediate reliability in the signals with mild peaks, and studies have shown reciprocity but no differentiation. We conducted a study on a group of wild Nicobar long-tailed macaques Macaca fascicularis umbrosusto understand the existing patterns of male-male relationships. We examined whether there is reciprocity inaffiliation among the individuals and whether the rate of affiliation is balanced. We also measured the dominance linearity and steepness in the group to understand the monopolizability of females. We used socialnetwork analysis to understand whether the relations are differentiated based on hierarchical position andwhether the high-ranking individuals are the most central individuals in the distribution of grooming in thegroup. We found that there is reciprocity among the males although that is not equitable. There was no rankrelated differentiation of affiliation among the males of the group. Instead, the identities of individualsinfluenced affiliation patterns. Our results correspond to the existent strong relationships but lack of social bondotherwise found in the Fascicularis group of macaques.

Oxidative Stress Modulates the Expression Pattern of Peroxiredoxin-6 in Peripheral Blood Mononuclear Cells of Asthmatic Patients and Bronchial Epithelial Cells

PURPOSE: Reduction-oxidation reaction homeostasis is vital for regulating inflammatory conditions and its dysregulation may affect the pathogenesis of chronic airway inflammatory diseases such as asthma. Peroxiredoxin-6, an important intracellular anti-oxidant molecule, is reported to be highly expressed in the airways and lungs. The aim of this study was to analyze the expression pattern of peroxiredoxin-6 in the peripheral blood mononuclear cells (PBMCs) of asthmatic patients and in bronchial epithelial cells (BECs).METHODS: The expression levels and modifications of peroxiredoxin-6 were evaluated in PBMCs from 22 asthmatic patients. Phosphorylated and acetylated peroxiredoxin-6 in hydrogen peroxide-treated human BECs was detected using immunoprecipitation analysis. The expression level of peroxiredoxin-6 was also investigated in BECs treated with hydrogen peroxide. Cycloheximide and proteasome inhibitors were used to determine whether peroxiredoxin-6 is degraded by proteasomes.RESULTS: Peroxiredoxin-6 expression was significantly reduced in the PBMCs of asthmatic patients compared to control subjects. Distinct modification patterns for peroxiredoxin-6 were observed in the PBMCs of asthmatic patients using 2-dimensional-electrophoresis. The levels of phosphorylated serine and acetylated lysine in peroxiredoxin-6 were significantly increased in the BECs following hydrogen peroxide treatment. The level of peroxiredoxin-6 expression was reduced in hydrogen peroxide-stimulated BECs, presumably due to proteasomes.CONCLUSIONS: The expression of peroxiredoxin-6, which is down-regulated in the immune cells of asthmatic patients and BECs, can be modified by oxidative stress. This phenomenon may have an effect on asthmatic airway inflammation.