Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger-Huet anomaly

The nature of the wild-type gene product at the mouse ichthyosis (ic) locus has been of great interest because mutations at this locus cause marked abnormalities in nuclear heterochromatin, similar to those observed in Pelger-Huët anomaly (PHA). We recently found that human PHA is caused by mutations in the gene (LBR) encoding lamin B receptor, an evolutionarily conserved inner nuclear membrane protein involved in nuclear assembly and chromatin binding. Mice homozygous for deleterious alleles at the ichthyosis (ic) locus present with a blood phenotype similar to PHA, and develop other phenotypic abnormalities, including alopecia, variable expression of syndactyly and hydrocephalus. The ic locus on mouse chromosome 1 shares conserved synteny with the chromosomal location of the human LBR locus on human chromosome 1. In this study, we identified one nonsense (815ins) and two frameshift mutations (1088insCC and 1884insGGAA) within the Lbr gene of mice homozygous for either of three independent mutations (ic, ic(J) and ic(4J), respectively) at the ichthyosis locus. These allelic mutations are predicted to result in truncated or severely impaired LBR protein. Our studies of mice homozygous for the ic(J) mutation revealed a complete loss of LBR protein as shown by immunofluorescence microscopy and immunoblotting. The findings provide the molecular basis for the heterochromatin clumping and other distinct phenotypes caused by ic mutations. These spontaneous Lbr mutations confirm the molecular basis of human PHA and provide a small animal model for determination of the precise function of LBR in normal and pathological states

Hypoxic adaptation during development: relation to pattern of neurological presentation and cognitive disability

Children with acute hypoxic-ischaemic events (e.g. stroke) and chronic neurological conditions associated with hypoxia frequently present to paediatric neurologists. Failure to adapt to hypoxia may be a common pathophysiological pathway linking a number of other conditions of childhood with cognitive deficit. There is evidence that congenital cardiac disease, asthma and sleep disordered breathing, for example, are associated with cognitive deficit, but little is known about the mechanism and whether there is any structural change. This review describes what is known about how the brain reacts and adapts to hypoxia, focusing on epilepsy and sickle cell disease (SCD). We prospectively recorded overnight oxyhaemoglobin saturation (SpO 2) in 18 children with intractable epilepsy, six of whom were currently or recently in minor status (MS). Children with MS were more likely to have an abnormal sleep study defined as either mean baseline SpO2 &lt;94 or &gt;4 dips of &gt;4 in SpO2/hour (p = .04). In our series of prospectively followed patients with SCD who subsequently developed acute neurological symptoms and signs, mean overnight SpO2 was lower in those with cerebrovascular disease on magnetic resonance angiography (Mann-Whitney, p = .01). Acute, intermittent and chronic hypoxia may have detrimental effects on the brain, the clinical manifestations perhaps depending on rapidity of presentation and prior exposure.</p

Quantum Turbulence: Achievements and Challenges

The paper is, for the most part, a review, written in its original form for an International Workshop on Vortices, Superfluid Dynamics, and Quantum Turbulence, held in Lammi, Finland, in 2010. Achievements are reviewed, and a strong emphasis is placed on problems that are either unsolved or still the subject of active discussion. These problems often call for more powerful experimental techniques, including local probes and actual visualization of the turbulent motion. Special emphasis is placed on recent progress in the development of visualization