53 research outputs found
Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo
GLE1 mutations cause lethal congenital contracture syndrome 1 (LCCS1), a severe autosomal recessive fetal motor neuron disease, and more recently have been associated with amyotrophic lateral sclerosis (ALS). The gene encodes a highly conserved protein with an essential role in mRNA export. The mechanism linking Gle1 function to motor neuron degeneration in humans has not been elucidated, but increasing evidence implicates abnormal RNA processing as a key event in the pathogenesis of several motor neuron diseases. Homozygous gle1−/− mutant zebrafish display various aspects of LCCS, showing severe developmental abnormalities including motor neuron arborization defects and embryonic lethality. A previous gene expression study on spinal cord from LCCS fetuses indicated that oligodendrocyte dysfunction may be an important factor in LCCS. We therefore set out to investigate the development of myelinating glia in gle1−/− mutant zebrafish embryos. While expression of myelin basic protein (mbp) in hindbrain oligodendrocytes appeared relatively normal, our studies revealed a prominent defect in Schwann cell precursor proliferation and differentiation in the posterior lateral line nerve. Other genes mutated in LCCS have important roles in Schwann cell development, thereby suggesting that Schwann cell deficits may be a common factor in LCCS pathogenesis. These findings illustrate the potential importance of glial cells such as myelinating Schwann cells in motor neuron diseases linked to RNA processing defects
Massive binary black holes in galactic nuclei and their path to coalescence
Massive binary black holes form at the centre of galaxies that experience a
merger episode. They are expected to coalesce into a larger black hole,
following the emission of gravitational waves. Coalescing massive binary black
holes are among the loudest sources of gravitational waves in the Universe, and
the detection of these events is at the frontier of contemporary astrophysics.
Understanding the black hole binary formation path and dynamics in galaxy
mergers is therefore mandatory. A key question poses: during a merger, will the
black holes descend over time on closer orbits, form a Keplerian binary and
coalesce shortly after? Here we review progress on the fate of black holes in
both major and minor mergers of galaxies, either gas-free or gas-rich, in
smooth and clumpy circum-nuclear discs after a galactic merger, and in
circum-binary discs present on the smallest scales inside the relic nucleus.Comment: Accepted for publication in Space Science Reviews. To appear in hard
cover in the Space Sciences Series of ISSI "The Physics of Accretion onto
Black Holes" (Springer Publisher
Relation between the level of self-mutilation and theconcentration of fecal metabolites of glucocorticoids incaptive chimpanzees (Pan troglodytes)
An algorithm for large scale quadratic programming
SIGLEAvailable from British Library Document Supply Centre- DSC:9091.9(CSS--219) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
On the use of element-by-element preconditioners to solve large scale partially separable optimization problems
SIGLEAvailable from British Library Document Supply Centre- DSC:8053.4153(RAL--95-010) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
New crash procedures for large systems of linear constraints
SIGLEAvailable from British Library Document Supply Centre- DSC:9091.9(CSS--226) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
A globally convergent augmented Lagrangian algorithm for optimization with general constraints and simple bounds
SIGLEAvailable from British Library Document Supply Centre- DSC:9091.9(CSS--230) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Convergence of quasi-Newton matrices generated by the symmetric rank one update
Available from British Library Document Supply Centre- DSC:9091.9(CSS--208) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
Testing a class of methods for solving minimization problems with simple bounds on the variables (revised)
SIGLEAvailable from British Library Document Supply Centre- DSC:9091.9(CSS--203) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
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