Long-term plasticity in hippocampal place-cell representation of environmental geometry

The hippocampus is widely believed to be involved in the storage or consolidation of long-term memories. Several reports have shown short-term changes in single hippocampal unit activity during memory and plasticity experiments, but there has been no experimental demonstration of long-term persistent changes in neuronal activity in any region except primary cortical areas. Here we report that, in rats repeatedly exposed to two differently shaped environments, the hippocampal-place-cell representations of those environments gradually and incrementally diverge; this divergence is specific to environmental shape, occurs independently of explicit reward, persists for periods of at least one month, and transfers to new enclosures of the same shape. These results indicate that place cells may be a neural substrate for long-term incidental learning, and demonstrate the long-term stability of an experience-dependent firing pattern in the hippocampal formation.     

Aerosol formation: atmospheric particles from organic vapours

Aerosol particles produced over forested areas may affect climate by acting as nuclei for cloud condensation, but their composition (and hence the chemical species that drive their production) remains an open question. Here we show, to our knowledge for the first time, that these newly formed particles (3-5 nm in diameter) are composed primarily of organic species, such as cis-pinonic acid and pinic acid, produced by oxidation of terpenes in organic vapours released from the canopy.     

A progeroid syndrome in mice is caused by defects in A-type lamins

Numerous studies of the underlying causes of ageing have been attempted by examining diseases associated with premature ageing, such as Werner's syndrome and Hutchinson-Gilford progeria syndrome (HGPS). HGPS is a rare genetic disorder resulting in phenotypes suggestive of accelerated ageing, including shortened stature, craniofacial disproportion, very thin skin, alopecia and osteoporosis, with death in the early teens predominantly due to atherosclerosis. However, recent reports suggest that developmental abnormalities may also be important in HGPS. Here we describe the derivation of mice carrying an autosomal recessive mutation in the lamin A gene (Lmna) encoding A-type lamins, major components of the nuclear lamina. Homozygous mice display defects consistent with HGPS, including a marked reduction in growth rate and death by 4 weeks of age. Pathologies in bone, muscle and skin are also consistent with progeria. The Lmna mutation resulted in nuclear morphology defects and decreased lifespan of homozygous fibroblasts, suggesting premature cell death. Here we present a mouse model for progeria that may elucidate mechanisms of ageing and development in certain tissue types, especially those developing from the mesenchymal cell lineage.     

Carbon loss by deciduous trees in a CO2-rich ancient polar environment

Fossils demonstrate that deciduous forests covered the polar regions for much of the past 250 million years when the climate was warm and atmospheric CO2 high. But the evolutionary significance of their deciduous character has remained a matter of conjecture for almost a century. The leading hypothesis argues that it was an adaptation to photoperiod, allowing the avoidance of carbon losses by respiration from a canopy of leaves unable to photosynthesize in the darkness of warm polar winters. Here we test this proposal with experiments using 'living fossil' tree species grown in a simulated polar climate with and without CO2 enrichment. We show that the quantity of carbon lost annually by shedding a deciduous canopy is significantly greater than that lost by evergreen trees through wintertime respiration and leaf litter production, irrespective of growth CO2 concentration. Scaling up our experimental observations indicates that the greater expense of being deciduous persists in mature forests, even up to latitudes of 83 degrees N, where the duration of the polar winter exceeds five months. We therefore reject the carbon-loss hypothesis as an explanation for the deciduous nature of polar forests.     

Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).     

Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD)

Infantile myopathies with diaphragmatic paralysis are genetically heterogeneous, and clinical symptoms do not assist in differentiating between them. We used phased haplotype analysis with subsequent targeted exome sequencing to identify MEGF10 mutations in a previously unidentified type of infantile myopathy with diaphragmatic weakness, areflexia, respiratory distress and dysphagia. MEGF10 is highly expressed in activated satellite cells and regulates their proliferation as well as their differentiation and fusion into multinucleated myofibers, which are greatly reduced in muscle from individuals with early onset myopathy, areflexia, respiratory distress and dysphagia.     

The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat

Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin.     

CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium

Tubulin glutamylation is a post-translational modification that occurs predominantly in the ciliary axoneme and has been suggested to be important for ciliary function. However, its relationship to disorders of the primary cilium, termed ciliopathies, has not been explored. Here we mapped a new locus for Joubert syndrome (JBTS), which we have designated as JBTS15, and identified causative mutations in CEP41, which encodes a 41-kDa centrosomal protein. We show that CEP41 is localized to the basal body and primary cilia, and regulates ciliary entry of TTLL6, an evolutionarily conserved polyglutamylase enzyme. Depletion of CEP41 causes ciliopathy-related phenotypes in zebrafish and mice and results in glutamylation defects in the ciliary axoneme. Our data identify CEP41 mutations as a cause of JBTS and implicate tubulin post-translational modification in the pathogenesis of human ciliary dysfunction.