Molecular characterisation of congenital myasthenic syndromes in Southern Brazil

Objective To perform genetic testing of patients with congenital myasthenic syndromes (CMS) from the Southern Brazilian state of Parana. Patients and methods Twenty-five CMS patients from 18 independent families were included in the study. Known CMS genes were sequenced and restriction digest for the mutation RAPSN p.N88K was performed in all patients. Results We identified recessive mutations of CHRNE in ten families, mutations in DOK7 in three families and mutations in COLQ, CHRNA1 and CHRNB1 in one family each. The mutation CHRNE c. 70insG was found in six families. We have repeatedly identified this mutation in patients from Spain and Portugal and haplotype studies indicate that CHRNE c. 70insG derives from a common ancestor. Conclusions Recessive mutations in CHRNE are the major cause of CMS in Southern Brazil with a common mutation introduced by Hispanic settlers. The second most common cause is mutations in DOK7. The minimum prevalence of CMS in Parana is 0.18/100 000

Numerical evolution of Brill waves

We report a numerical evolution of axisymmetric Brill waves. The numerical algorithm has new features, including (i) a method for keeping the metric regular on the axis and (ii) the use of coordinates that bring spatial infinity to the edge of the computational grid. The dependence of the evolved metric on both the amplitude and shape of the initial data is found.Comment: added more discussion of results and several reference

Molecular characterisation of congenital myasthenic syndromes in Southern Brazil

Objective To perform genetic testing of patients with congenital myasthenic syndromes (CMS) from the Southern Brazilian state of Parana. Patients and methods Twenty-five CMS patients from 18 independent families were included in the study. Known CMS genes were sequenced and restriction digest for the mutation RAPSN p.N88K was performed in all patients. Results We identified recessive mutations of CHRNE in ten families, mutations in DOK7 in three families and mutations in COLQ, CHRNA1 and CHRNB1 in one family each. The mutation CHRNE c. 70insG was found in six families. We have repeatedly identified this mutation in patients from Spain and Portugal and haplotype studies indicate that CHRNE c. 70insG derives from a common ancestor. Conclusions Recessive mutations in CHRNE are the major cause of CMS in Southern Brazil with a common mutation introduced by Hispanic settlers. The second most common cause is mutations in DOK7. The minimum prevalence of CMS in Parana is 0.18/100 000

The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis

Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells (ESCs) with a differentiation-resistant, “hyper-pluripotent” state, which readily reprograms to a naive state resembling the preimplantation embryo. We further demonstrate that DDX6 plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner. Mechanistically, DDX6 mediates the translational suppression of target mRNAs in P-bodies. Upon loss of DDX6 activity, P-bodies dissolve and release mRNAs encoding fate-instructive transcription and chromatin factors that re-enter the ribosome pool. Increased translation of these targets impacts cell fate by rewiring the enhancer, heterochromatin, and DNA methylation landscapes of undifferentiated cell types. Collectively, our data establish a link between P-body homeostasis, chromatin organization, and stem cell potency

Spin relaxation of localized electrons in n-type semiconductors

The mechanisms that determine spin relaxation times of localized electrons in impurity bands of n-type semiconductors are considered theoretically and compared with available experimental data. The relaxation time of the non-equilibrium angular momentum is shown to be limited either by hyperfine interaction, or by spin-orbit interaction in course of exchange-induced spin diffusion. The energy relaxation time in the spin system is governed by phonon-assisted hops within pairs of donors with an optimal distance of about 4 Bohr radii. The spin correlation time of the donor-bound electron is determined either by exchange interaction with other localized electrons, or by spin-flip scattering of free conduction-band electrons. A possibility of optical cooling of the spin system of localized electrons is discussed.Comment: Submitted to the special issue "Optical Orientation", Semiconductor Science and Technolog

Wigs, disguises and child's play : solidarity in teacher education

It is generally acknowledged that much contemporary education takes place within a dominant audit culture, in which accountability becomes a powerful driver of educational practices. In this culture both pupils and teachers risk being configured as a means to an assessment and target-driven end: pupils are schooled within a particular paradigm of education. The article discusses some ethical issues raised by such schooling, particularly the tensions arising for teachers, and by implication, teacher educators who prepare and support teachers for work in situations where vocational aims and beliefs may be in in conflict with instrumentalist aims. The article offers De Certeau’s concept of ‘la perruque’ to suggest an opening to playful engagement for human ends in education, as a way of contending with and managing the tensions generated. I use the concept to recover a concept of solidarity for teacher educators and teachers to enable ethical teaching in difficult times

Global services and support for children with developmental delays and disabilities: Bridging research and policy gaps

Summary: 1. The United Nations Sustainable Development Goals and the UN Convention on the Rights of the Child (CRC) envision an inclusive society in which health and education contribute to the well-being of all. To achieve this vision, children with developmental delays and behavioral, cognitive, mental, and neurological disabilities need greater access to health care, early childhood care and development services, and education. 2. Improved population-level detection, alongside screening, assessment, and linkage to evidence-based, intersectoral services in the first years of life, can help maximize capabilities and increase the chances of social inclusion for children with developmental delays and disabilities. 3. Educational programs for children with delays and disabilities whose service delivery structure supports the ability of parents to work should be encouraged so that parents can participate in achieving children’s educational goals while also meeting their financial needs. 4. Parents and caregivers who receive training in psychosocial interventions and ongoing support can help children with delays and disabilities thrive in family contexts. 5. Family mental health influences the developmental trajectory of children. Ensuring that parents and caregivers have access to affordable, quality mental health services helps to prevent poor outcomes for children. 6. Rigorous evaluation, continuous quality improvement, and regular monitoring of the programmatic outcomes of services and policy approaches targeting children and caregivers would inform their implementation and serve to disseminate lessons learned from successful policy and program implementation

Numerical Relativity: A review

Computer simulations are enabling researchers to investigate systems which are extremely difficult to handle analytically. In the particular case of General Relativity, numerical models have proved extremely valuable for investigations of strong field scenarios and been crucial to reveal unexpected phenomena. Considerable efforts are being spent to simulate astrophysically relevant simulations, understand different aspects of the theory and even provide insights in the search for a quantum theory of gravity. In the present article I review the present status of the field of Numerical Relativity, describe the techniques most commonly used and discuss open problems and (some) future prospects.Comment: 2 References added; 1 corrected. 67 pages. To appear in Classical and Quantum Gravity. (uses iopart.cls

Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity