Reduced Gamma Oscillations in a Mouse Model of Intellectual Disability: A Role for Impaired Repetitive Neurotransmission?

Intellectual disability affects 2–3% of the population; mutations of the X-chromosome are a major cause of moderate to severe cases. The link between the molecular consequences of the mutation and impaired cognitive function remains unclear. Loss of function mutations of oligophrenin-1 (OPHN1) disrupt Rho-GTPase signalling. Here we demonstrate abnormal neurotransmission at CA3 synapses in hippocampal slices from Ophn1 ^-/y mice, resulting from a substantial decrease in the readily releasable pool of vesicles. As a result, synaptic transmission fails at high frequencies required for oscillations associated with cognitive functions. Both spontaneous and KA-induced gamma oscillations were reduced in Ophn1 ^-/y hippocampal slices. Spontaneous oscillations were rapidly rescued by inhibition of the downstream signalling pathway of oligophrenin-1. These findings suggest that the intellectual disability due to mutations of oligophrenin-1 results from a synaptopathy and consequent network malfunction, providing a plausible mechanism for the learning disabilities. Furthermore, they raise the prospect of drug treatments for affected individuals.     

Reproductive development and nuclear DNA content in angiosperms

Correlates of nuclear DNA content in angiosperms have been noted previously for a range of features, cellular to geographic. A new hypothesis, the correlation between nuclear DNA content and reproductive developmental features (after Cavalier-Smith, Journal of Cell Science 34, 247–268, 1978) is posed and tested here. Of three features tested (megasporogenesis, microsporogenesis, and endosperm development), megasporogenesis alone was shown to be correlated with nuclear DNA amount. The hypothesis was examined in 107 families of angiosperms using nonparametric statistics, and in 53 families of monocotyledons and outgroups using a phylogenetic test of association. A correlation was found between large genomes and successive microsporogenesis for all angiosperms, but not for monocots and dicots analyzed separately, thus underlining the importance of taking into account phylogenetic relationships in such studies. A correlation between cellular endosperm and large genomes in dicotyledons needs to be confirmed in a phylogenetic context. A tendency for deviations from monosporic megasporogenesis to occur in taxa that have a nuclear DNA content of over 9.0 pg/C was demonstrated using both phylogenetic and nonphylogenetic tests. It is hypothesized that cytoskeleton dynamics are affected in reproductive cells, enabling decoupling between nuclear and cytoplasmic cell cycles and leading to variation in reproductive development.     

'Fiber 7' supplement as an alternative to laxatives in a nursing home

Background: Chronic constipation is a common and bothersome problem in elderly nursing home patients. Although fibre has a known role in the treatment of constipation, laxatives are still widely used in nursing home patients. Objective: To determine whether the addition of a fibre supplement to oral diet can reduce the use of laxatives in a long‐term care facility. Participants and methods: Oral diet of 92 nursing home residents (all older than 65) on chronic laxatives (docusate, milk of magnesia with Cascara, psyllium) was supplemented with ‘Fiber 7’, a natural powder fibre (7 g per meal twice a day). During the next 2.5 years discontinuation of laxatives was attempted. Results: Laxatives were successfully discontinued in 63 of the 92 patients (68.5%, 95% confidence interval 59–78%). The fibre supplement was well tolerated. The cost of care was decreased by $3.5 per patient every month or by $220/month for the 63 patients. Conclusions: Use of ‘Fiber 7’ allowed discontinuation of laxatives in 63 of 92 nursing home residents. The fibre supplement was a safe and convenient alternative to laxatives and decreased the cost of medical care.     

Phylogenetic relationships and evolution of the KNOTTED class of plant homeodomain proteins.

Knotted-like (KNOX) proteins constitute a group of homeodomain proteins involved in pattern formation in developing tissues of angiosperms and other green plants. We conducted phylogenetic analyses of nucleotide and amino acid sequences of all known KNOX proteins in order to examine their evolution. Our analyses reveal two groups of KNOX proteins, classes I and II. Dicot and monocot sequences occur in both classes, indicating that the protein classes arose prior to the origin of the monocots. A conifer (Picea) sequence is nested within class I, suggesting that there are likely to be other copies of KNOX genes in this and other conifers. The orthology of several grass genes (including Zea Kn1, ZMKN1) is strongly supported by phylogenetic and synteny analyses. However, no compelling evidence supports the hypothesis of orthology previously proposed for several dicot genes and ZMKN1. Analysis of expression patterns suggests that the ancestral KNOX gene was expressed in all plant parts and that the propensity to be downregulated in roots and leaves evolved in the class I genes.     

Nuclear DNA content of monocotyledons and related taxa

Nuclear DNA content of 62 species of angiosperms including 52 monocotyledons and ten dicotyledons has been estimated by flow cytometry using Nicotiana tabacum var. Xanthi as the internal standard. These data, considered together with previous data on diploid species, suggest the following: 1) Most families and orders of monocotyledons have small genomes. Contrary to the general impression that monocotyledons are a group characterized by large genomes, genomes of over 20 pg/2C nucleus occur only in the Liliiflorae, Commelinales, Alismatales, and Araceae. 2) Variation within families ranges from two- to 56-fold, but is two- to fivefold in most families. Thus extraordinary variation in genome size appears to be limited to particular lineages, perhaps owing to some shared feature that facilitates such variation. 3) Endopolyploidy is not observed in the leaves of the species studied, although it has been reported to occur in the roots of several monocotyledons. This suggests that an examination of the basis for this difference between the roots and leaves of monocotyledons may provide clues to the mechanisms that regulate endopolyploidization in these organs.