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.     

A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance

Biofilms are surface-attached microbial communities with characteristic architecture and phenotypic and biochemical properties distinct from their free-swimming, planktonic counterparts. One of the best-known of these biofilm-specific properties is the development of antibiotic resistance that can be up to 1,000-fold greater than planktonic cells. We report a genetic determinant of this high-level resistance in the Gram-negative opportunistic pathogen, Pseudomonas aeruginosa. We have identified a mutant of P. aeruginosa that, while still capable of forming biofilms with the characteristic P. aeruginosa architecture, does not develop high-level biofilm-specific resistance to three different classes of antibiotics. The locus identified in our screen, ndvB, is required for the synthesis of periplasmic glucans. Our discovery that these periplasmic glucans interact physically with tobramycin suggests that these glucose polymers may prevent antibiotics from reaching their sites of action by sequestering these antimicrobial agents in the periplasm. Our results indicate that biofilms themselves are not simply a diffusion barrier to these antibiotics, but rather that bacteria within these microbial communities employ distinct mechanisms to resist the action of antimicrobial agents.     

Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding

During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round. Mitotic cell rounding is thought to facilitate organization within the mitotic cell and be necessary for the geometric requirements of division. However, the forces that drive this shape change remain poorly understood in the presence of external impediments, such as a tissue environment. Here we use cantilevers to track cell rounding force and volume. We show that cells have an outward rounding force, which increases as cells enter mitosis. We find that this mitotic rounding force depends both on the actomyosin cytoskeleton and the cells' ability to regulate osmolarity. The rounding force itself is generated by an osmotic pressure. However, the actomyosin cortex is required to maintain this rounding force against external impediments. Instantaneous disruption of the actomyosin cortex leads to volume increase, and stimulation of actomyosin contraction leads to volume decrease. These results show that in cells, osmotic pressure is balanced by inwardly directed actomyosin cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent surface tension and globally regulating osmotic pressure, cells can control their volume, shape and mechanical properties.     

Mapping copy number variation by population-scale genome sequencing

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.     

Isozymes of an autopolyploid shrub, Atriplex canescens (Chenopodiaceae)

Diploid, tetraploid, and hexaploid populations of Atriplex canescens ( x =9) were examined for 18 isozyme systems. Of 24 interpretable loci, only one locus (Per 1 ) was polymorphic. Another locus (Per 2 ) showed a dosage effect. Genetic distance values, D, ranged from near 0 to 0.05, which are in the normal range for local species races. Results from clonal ramets gave identical results. The data and analyses support an essentially autopolyploid origin for the polyploid populations examined.     

Food habits and dietary overlap of nongame insectivorous fishes in Flint Creek, Oklahoma, a western Ozark foothills stream

Insectivorous fishes were sampled from March, 1983 to February 1984, in Flint Creek, Delaware Co., Oklahoma. There was insignificant habitat segregation between Etheostoma spectabile and E. punctulatum and seasonal habitat partitioning between Cottus carolinae and both darters. Mature E. spectabile ate primarily chironomids and mayflies, whereas juveniles fed primarily on microcrustaceans. Mature E. punctulatum consumed fewer Ephemerella and Leptophlebia than E. spectabile , feeding on Stenonema and other crustaceans. Juvenile E. punctulatum fed mainly on amphipods and mayflies, and juvenile E. spectabile ate primarily microcrustaceans. Cottus carolinae elected primarily mayflies in spring - summer and chironomids in January - February. Coefficients of dietary overlap were highest between larger E. spectabile and juvenile E. punctulatum and lowest between immature E. spectabile and mature E. punctulatum . Overlap between the two darters was significantly correlated with differences in mean prey size (p E. spectabile was also significantly correlated to differences in mean prey sizes. Etheostoma spectabile generally preferred smaller prey than E. punctulatum . All three species avoided Stenelmis . Cottus carolinae avoided microcrustaceans. The study showed that resource partitioning among these three insectivorous fishes is affected by complex interactions of habitat and prey electivity, and prey size selectivity.         

Three new species of Nearctic Isoperla (Plecoptera)

Nymphs and adults of three new species of Isoperla are described from reared material. I. sagittata is known only from southeastern Texas, I. Coushatta has been collected in East Texas and Oklahoma, and I. jewetti occurs in the Basin and Range Mountains of West Texas. The male aedeagii, female subgenital plates, and nymphal mouthparts are diagnostic in all three species.     

Taxonomic and nomenclatural rearrangements in Artemisia subgen. Tridentatae, including a redefinition of Sphaeromeria (Asteraceae, Anthemideae)

A recent molecular phylogenetic study of all members of Artemisia subgenus Tridentatae, as well as most of the other New World endemic Artemisia and the allied genera Sphaeromeria and Picrothamnus, raised the necessity of revising the taxonomic framework of the North American endemic Artemisia. Composition of the subgenus Tridentatae is enlarged to accommodate other North American endemics and is organized into 3 sections: Tridentatae, Nebulosae, and Filifoliae. This paper deals with the combination of one section, the amendment of 2 more sections, and the combination in or the reversion to Artemisia of some Sphaeromeria and Picrothamnus species. The new names given for previous Sphaeromeria species are Artemisia macarthurii (for S. argentea ), A. albicans (for S. cana ), A. constricta (for S. compacta ), and A. inaequifolia (for S. diversifolia ). The other Sphaeromeria we studied ( S. capitata, S. potentilloides, S. ruthiae, and S. simplex ) had been formerly considered Artemisia (respectively, A. capitata, A. potentilloides, A. ruthiae, and A. simplex ), and their previous nomenclature is therefore recommended. Un estudio reciente sobre la filogenia molecular de todos los miembros del subgénero Tridentatae de Artemisia, así como de la mayoría de las otras especies de Artemisia endémicas del Nuevo Mundo y los géneros afines Sphaeromeria y Picrothamnus, hizo ver la necesidad de revisar el marco taxonómico de las especies de Artemisia endémicas a Norteamérica. La composición del subgénero Tridentatae se ha ampliado para dar cabida a las otras especies endémicas de Norteamérica, y está organizado en 3 secciones: Tridentatae, Nebulosae y Filifoliae. El presente artículo trata sobre la combinación de una sección y la enmienda de 2 más, y propone la incorporación o reversión a Artemisia de algunas especies de Sphaeromeria y Picrothamnus. Los nuevos nombres de las especies previamente asignadas a Sphaeromeria son Artemisia macarthurii (para S. argentea ), A. albicans (para S. cana ), A. constricta (para S. compacta ) y A. inaequifolia (para S. diversifolia ). Las otras especies de Sphaeromeria estudiadas ( S. capitata, S. potentilloides, S. ruthiae y S. simplex ) habían sido previamente consideradas como miembros de Artemisia ( A. capitata, A. potentilloides, A. ruthiae y A. simplex, respectivamente), por lo quese recomienda utilizar su nomenclatura anterior.     

Randomly amplified polymorphic DNA analysis (RAPD) of Artemisia subgenus Tridentatae species and hybrids

Species of Artemisia (subgenus Tridentatae ) dominate much of western North America. The genetic variation that allows this broad ecological adaptation is facilitated by hybridization and polyploidization. Three separate studies were performed in this group using randomly amplified polymorphic DNA (RAPD). Fifty-seven 10-mer primers generated nearly 400 markers from genomic DNA obtained from leaf tissue. These studies were (1) a measure of the variability of plants within and between populations and between subspecies using 5 A. tridentata ssp. wyomingensis populations, 2 A. cana ssp. cana populations, and 1 A. cana ssp. viscidula population; (2) an examination of the hypothesis that tetraploid (4 x ) Artemisia tridentata spp. vaseyana derives de novo from diploid (2 x ) populations via antopolyploidy; and (3) an examination of the validity of the status of putative hybrids that have been produced by controlled pollination. These later hybrid combinations- A. tridentata ssp. tridentata × A. t. ssp. vaseyana , A. t. ssp. wyomingensis × A. tripartita , and A. cana ssp. cana A. tridentata ssp. wyomingensis - were made to combine traits of parental taxa in unique combinations with possible management application. RAPD marker data were subjected to similarity and UPGMA clustering analyses. RAPD markers were effective in measuring genetic diversity at different systematic levels. Individual plants within a population were approximately 55% to > 80% similar to one another; populations within subspecies gave corresponding values of similarity, probably a result of the combined effects of large population sizes and wind pollination. The 2 subspecies of A. cana were approximately 45% similar. At least some 4 x populations of A. tridentata ssp. vaseyana apparently derive de novo from 2 x plants based on their being embedded in 2 x phenogram groups, thus reinforcing evidence that autopolyploidy plays an important role in Tridentatae population biology. Two ( A. tridentata ssp. tridentata × A. t. ssp. vaseyana and A. cana ssp. cana × A. tridentata ssp. wyomingensis ) of the 3 putative hybrid combinations were confirmed to include hybrids. These hybrids may have potential in management applications. Additional use of RAPD technology combined with other techniques may be useful in delimiting genetic characteristics and in guiding artificial selection in Tridentatae .