X Inactivation Lessons from Differentiating Mouse Embryonic Stem Cells

X chromosome inactivation (XCI) is the dosage compensation mechanism that evolved in female mammals to correct the genetic imbalance of X-linked genes between sexes. X chromosome inactivation occurs in early development when one of the two X chromosomes of females is nearly-completely silenced. Differentiating Embryonic Stem cells (ESC) are regarded as a useful tool to study XCI, since they recapitulate many events occurring during early development. In this review we aim to summarise the advances in the field and to discuss the close connection between cell differentiation and X chromosome inactivation, with a particular focus on mouse ESCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12015-015-9597-5) contains supplementary material, which is available to authorized users

Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing

The Xist long noncoding RNA orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing by recruiting the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the 3D structure of DNA, enabling Xist and its silencing proteins to spread across the X to silence transcription

Magnetic Resonance features of pyogenic brain abscesses and differential diagnosis using morphological and functional imaging studies: a pictorial essay.

The aim of this paper is to illustrate the potential of magnetic resonance imaging (MRI) in diagnosis, differential diagnosis, treatment planning and evaluation of therapy effectiveness of pyogenic brain abscesses, through the use of morphological (or conventional) and functional (or advanced) sequences. Conventional MRI study is useful for the identification of lesions, to determine the location and morphology and allows a correct hypothesis of nature in the most typical cases. However, the differential diagnosis from other brain lesions such as non pyogenic abscesses or necrotic tumors (high-grade gliomas and metastases) is often only possible through the use of functional sequences, as the measurement of diffusion with apparent diffusion coefficient (DWI-ADC), proton magnetic resonance spectroscopy (1H-MRS) and perfusion weighted imaging (PWI), which complement the morphological sequences and provide essential information on structural, metabolic and hemodynamic characteristics allowing greater neuroradiological confidence. Modern diagnostic MRI of pyogenic brain abscesses cannot be separated from knowledge, integration and proper use of the morphological and functional sequences

Awakening the sleeping giant: methods for reactivating the inactive X chromosome as clinical treatment for X-linked disorders

No abstract availabl

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part I, the solid gland.

Differentiation between normal solid (non-cystic) pineal glands and pineal pathologies on brain MRI is difficult. The aim of this study was to assess the size of the solid pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. We retrospectively analyzed the size (width, height, planimetric area) of solid pineal glands in 184 non-retinoblastoma patients (73 female, 111 male) aged 0-5 years on MRI. The effect of age and gender on gland size was evaluated. Linear regression analysis was performed to analyze the relation between size and age. Ninety-nine percent prediction intervals around the mean were added to construct a normal size range per age, with the upper bound of the predictive interval as the parameter of interest as a cutoff for normalcy. There was no significant interaction of gender and age for all the three pineal gland parameters (width, height, and area). Linear regression analysis gave 99 % upper prediction bounds of 7.9, 4.8, and 25.4 mm(2), respectively, for width, height, and area. The slopes (size increase per month) of each parameter were 0.046, 0.023, and 0.202, respectively. Ninety-three percent (95 % CI 66-100 %) of asymptomatic solid pineoblastomas were larger in size than the 99 % upper bound. This study establishes norms for solid pineal gland size in non-retinoblastoma children aged 0-5 years. Knowledge of the size of the normal pineal gland is helpful for detection of pineal gland abnormalities, particularly pineoblastoma

Investigating the Structure and Meaning of Public Service Motivation across Populations: Developing an International Instrument and Addressing Issues of Measurement Invariance

The growth in international research on public service motivation (PSM) raises a number of important questions about the degree to which the theory and research developed in one country can contribute to our understanding of PSM in other counties. To help address this issue, this study revisits the conceptual and operational definitions of PSM to address weaknesses previously noted in the literature. Although some important steps have been taken to both improve and internationalize the PSM scale, this work has been done incrementally. In contrast, this study takes a more systematic and comprehensive approach by combining the efforts of international PSM scholars to develop and then test a revised measurement instrument for PSM in 12 countries. Although the resulting four dimensional 16-item measure of PSM reported here provides a better theoretical and empirical foundation for the measurement of PSM, our results suggest that the exact meaning and scaling of PSM dimensions are likely to differ across cultures and languages. These results raise serious concerns regarding the ability to develop a single universal scale of PSM, or making direct comparisons of PSM across countrie

Investigating the structure and meaning of public service motivation across populations: Developing an international instrument and addressing issues of measurement invariance

The growth in international research on public service motivation (PSM) raises a number of important questions about the degree to which the theory and research developed in one country can contribute to our understanding of PSM in other counties. To help address this issue, this study revisits the conceptual and operational definitions of PSM to address weaknesses previously noted in the literature. Although some important steps have been taken to both improve and internationalize the PSM scale, this work has been done incrementally. In contrast, this study takes a more systematic and comprehensive approach by combining the efforts of international PSM scholars to develop and then test a revised measurement instrument for PSM in 12 countries. Although the resulting four dimensional 16-item measure of PSM reported here provides a better theoretical and empirical foundation for the measurement of PSM, our results suggest that the exact meaning and scaling of PSM dimensions are likely to differ across cultures and languages. These results raise serious concerns regarding the ability to develop a single universal scale of PSM, or making direct comparisons of PSM across countries. © 2012 The Author

Tightropes and tripwires: a Buddhist interpretation of suffering through attachment in Kafka’s work

The aim of the dissertation is to challenge perceptions of Kafka’s work as negative by developing more constructive readings of the accounts of suffering and abandonment which form an undeniable feature of his writing. The term ‘Kafkaesque’ is now in widespread use to indicate a situation or event characterised by frustration and torment, but this designation paints an unnecessarily bleak picture of Kafka’s fictional landscapes. One path towards a brighter view of his art is offered by Buddhism, which puts suffering at the centre of its philosophy and yet develops a positive spiritual outlook on life. It does so by giving clear reasons for suffering based on natural causes, leaving no room for mysterious or irresistible forces. From a Buddhist standpoint, the most formidable barrier to alleviating suffering is not presented by a powerful Court or an impregnable Castle, but by the human self or – more precisely – attachment to self. The Buddhist approach to Kafka reads his works in two complementary ways, for content (information) and form (expression). The first examines the close parallels between key Buddhist teachings (such as on suffering and emptiness) and predominant themes from Kafka’s writing (such as futile quests after recognition and justice); the second explores the gaps and paradoxes that confront Kafka’s characters and readers, and measures them against the absurd, nonsensical utterances (koans) used by Zen masters to nonplus their students and loosen their dependency on conventional modes of thinking. In this way, it will be shown that the suffering Kafka describes so relentlessly can be traced back to personal attachments rather than intervention by external agencies

Long non-coding rna (Lncrna) roles in cell biology, neurodevelopment and neurological disorders

Development is a complex process regulated both by genetic and epigenetic and environmental clues. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several tissues including the brain. Altered expression of lncRNAs has been linked to several neurodegenerative, neurodevelopmental and mental disorders. The identification and characterization of lncRNAs that are deregulated or mutated in neurodevelopmental and mental health diseases are fundamental to understanding the complex transcriptional processes in brain function. Crucially, lncRNAs can be exploited as a novel target for treating neurological disorders. In our review, we first summarize the recent advances in our understanding of lncRNA functions in the context of cell biology and then discussing their association with selected neuronal development and neurological disorders

Long Non-Coding RNA (lncRNA) Roles in Cell Biology, Neurodevelopment and Neurological Disorders.

Development is a complex process regulated both by genetic and epigenetic and environmental clues. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several tissues including the brain. Altered expression of lncRNAs has been linked to several neurodegenerative, neurodevelopmental and mental disorders. The identification and characterization of lncRNAs that are deregulated or mutated in neurodevelopmental and mental health diseases are fundamental to understanding the complex transcriptional processes in brain function. Crucially, lncRNAs can be exploited as a novel target for treating neurological disorders. In our review, we first summarize the recent advances in our understanding of lncRNA functions in the context of cell biology and then discussing their association with selected neuronal development and neurological disorders