The application of physiological oxygen (physoxia) concentrations is becoming increasingly commonplace within a mammalian stem cell culture. Human mesenchymal stem cells (hMSCs) attract widespread interest for clinical application due to their unique immunomodulatory, multi-lineage potential, and regenerative capacities. Descriptions of the impact of physoxia on global DNA methylation patterns in hMSCs and the activity of enzymatic machinery responsible for its regulation remain limited. Human bone marrow-derived mesenchymal stem cells (BM-hMSCs, passage 1) isolated in reduced oxygen conditions displayed an upregulation of SOX2 in reduced oxygen conditions vs. air oxygen (21% O2, AO), while no change was noted for either OCT-4 or NANOG. DNA methylation marks 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) showed decreases in 2% O2 environment (workstation) (2% WKS). DNMT3B (DNA methyltransferase 3B) and TET1 (Ten-eleven translocation enzyme 1) displayed reduced transcription in physoxia. Consistent with transcriptional downregulation, we noted increased promoter methylation levels of DNMT3B in 2% WKS accompanied by reduced DNMT3B and TET1 protein expression. Finally, a decrease in HIF1A (Hypoxia-inducible factor 1A) gene expression in 2% WKS environment correlated with protein levels, while HIF2A was significantly higher in physoxia correlated with protein expression levels vs. AO. Together, these data have demonstrated, for the first time, that global 5mC, 5hmC, and DNMT3B are oxygen-sensitive in hMSCs. Further insights into the appropriate epigenetic regulation within hMSCs may enable increased safety and efficacy development within the therapeutic ambitions.
Asthma is chronic inflammatory disease affecting 5% of world population. Characterized by eosinophilic type2 inflammation. FKBP51 immunophilin, important modular protein of glucocorticoid receptor (GR). We aimed to evaluate immunocytochemical localization of GR and FKBP51 in induced sputum cells by using immunocytochemical method and immunofluorescent ant-FKBP51 and anti –GR antibody and estimation of IgE and Type 2 inflammatory cytokine IL-5,IL-13 by ELISA technique.GR in the sputum show non-significant decrease of cytoplasmic distribution of the patient groups and highly significant increase in steroid treated patients and non-significant increase in nuclear distribution in non-steroid, FKBP51 nuclear localization show non-significant i
... Show MoreFrançois Mauriac’s novel The Desert of Love (1949) puts the reader before an experienced sociologist who is skillfully able to analyze the most mysterious human emotions and feelings. The writer's starting point is that people are similar in feelings but different in behavior. He severely criticized the aristocratic class and uncovered its defects and faults.
The novelist presents Courege's family as an example of the aristocratic class. It is a family torn by hatred, selfishness and disagreements due to absence of intimacy and love. This poisoned environment pushes the father and his son, Raymond, to search away for emotional ventures and banned relations
... Show MoreEn el contexto iraquí, el análisis de las dificultades léxicas de los estudiantes de ELE es fundamental para poder llevar a cabo prácticas que respondan dos necesidades concretas. Por un lado, ofrecer experiencias de aula que garanticen el desarrollo de competencias comunicativas que optimicen el uso adecuado de la lengua española (L2); por otro, atender a las exigencias que se hacen desde el PCIC y el MCER para tener unos parámetros claros de evaluación. Así las cosas, en este artículo se propone la caracterización de la competencia léxica como parte de las competencias lingüísticas desde la perspectiva del MCER, para señalar cuál es el alcance de su optimización para los estudiantes arabófonos en general y los ira
... Show MoreEl Lázarillo señala a fines del reinado del emperador, el comienzo de un
nuevo género en la literatura castellana. A través de sus páginas nos adentró en un
mundo de pobreza, de
hambre secular, de hipocresía, y rodeado de problemas.
Lázaro cuenta en primera persona sus aventuras comenzando por su nacimiento, en
una aceña de las riberas del río Tormes. Condenando su padre como ladrón y, su
madre se entrega al mas vil morisco - cuya conducta deja también que desea –
haber pasado hambre y le entrega, siendo todavía un niño, a un ciego de alma ruin
para que, acompañándole, se gana la vida. Para aplacar el hambre, pues el ciego le
daba poco de comer, el muchacho le hace objeto, de repetidas tretas.
Lawful protection of the human gene conceded a moral concern regarding the future of existence human. After the discovery of the human genetic map, scientific experiments and research related to the human gene increased, negative applications of genetic engineering in particular that violate essential human rights, the right to human dignity to be specific. These practices represent actual challenges to the existence and diversity of current and future generations. Therefore, the presence of legal rules at the domestic and global levels is an absolute necessity to prohibit these threats and determine civil and criminal accountability for those who infringe any laws related to this issue.
Abstract
The research was limited to those whom Imam Abu Dawood
described in his Sunan as weak, so this research does not include
narrators who carried descriptions indicating weakness such as
ignorance or others, nor does it include hadiths that the Imam
described as weak.
The number of narrators whom Imam Abu Dawood described as
weak has reached six narrators, and my methodology was to
mention the words of Imam Abu Dawood, then transfer the
sayings of other advanced scholars, as well as the sayings of
Imam Abu Dawood in his other books, if any, to show the extent
of compatibility between these sayings.
I have reached the following resul
... Show Moreالمستخلص [English] Peace-building is a science that has its foundations and needs mechanisms, components, studies and plans based on the needs of the parties responsible for achieving peace and meeting the necessary needs of conflict societies, as it has become a goal sought by many local and regional actors and parties. The State of South Africa has realized this fact and has devoted space in its conception and planning to addressing the issues of conflict and war within the framework of its unitary work.Since security and stability in general seek to create peaceful and legal means through which existing problems can be expressed and addressed. The differences have varied to build peace and create cooperation between groups and th
... Show MoreThe formula is effective in Surat Nisa
(A study of gramophone)
in the name of o Allah the Merciful
Praise be to Allah, Lord of the Worlds, and prayers and peace be upon the Seal of the Prophets and Messengers. The envoy is a mercy to the worlds Muhammad Sadiq Al - Amin and to the pure and good companions of the Tayyibites.
The formula of the morphological formulas, which have diverged from other meanings, whether lexicon or contextual and what this formula contains many meanings (effective source) and (effective in the sense of effective) and (effective sense reactor) and (effective sense) and ( (F) in the sense of a similar character) and ((the name of the) (collect). This was dealt with in the formula in Surat al-Nisaa