Structure of PTB bound to RNA: specific binding and implications for splicing regulation

The polypyrimidine tract binding protein (PTB) is a 58-kilodalton RNA binding protein involved in multiple aspects of messenger RNA metabolism, including the repression of alternative exons. We have determined the solution structures of the four RNA binding domains (RBDs) of PTB, each bound to a CUCUCU oligonucleotide. Each RBD binds RNA with a different binding specificity. RBD3 and RBD4 interact, resulting in an antiparallel orientation of their bound RNAs. Thus, PTB will induce RNA looping when bound to two separated pyrimidine tracts within the same RNA. This leads to structural models for how PTB functions as an alternative-splicing repressor.     

Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees

The determination of the chimpanzee genome sequence provides a means to study both structural and functional aspects of the evolution of the human genome. Here we compare humans and chimpanzees with respect to differences in expression levels and protein-coding sequences for genes active in brain, heart, liver, kidney, and testis. We find that the patterns of differences in gene expression and gene sequences are markedly similar. In particular, there is a gradation of selective constraints among the tissues so that the brain shows the least differences between the species whereas liver shows the most. Furthermore, expression levels as well as amino acid sequences of genes active in more tissues have diverged less between the species than have genes active in fewer tissues. In general, these patterns are consistent with a model of neutral evolution with negative selection. However, for X-chromosomal genes expressed in testis, patterns suggestive of positive selection on sequence changes as well as expression changes are seen. Furthermore, although genes expressed in the brain have changed less than have genes expressed in other tissues, in agreement with previous work we find that genes active in brain have accumulated more changes on the human than on the chimpanzee lineage.     

Axonal neuregulin-1 regulates myelin sheath thickness

In the nervous system of vertebrates, myelination is essential for rapid and accurate impulse conduction. Myelin thickness depends on axon fiber size. We use mutant and transgenic mouse lines to show that axonal Neuregulin-1 (Nrg1) signals information about axon size to Schwann cells. Reduced Nrg1 expression causes hypomyelination and reduced nerve conduction velocity. Neuronal overexpression of Nrg1 induces hypermyelination and demonstrates that Nrg1 type III is the responsible isoform. We suggest a model by which myelin-forming Schwann cells integrate axonal Nrg1 signals as a biochemical measure of axon size.     

Mutations in dynein link motor neuron degeneration to defects in retrograde transport

Degenerative disorders of motor neurons include a range of progressive fatal diseases such as amyotrophic lateral sclerosis (ALS), spinal-bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Although the causative genetic alterations are known for some cases, the molecular basis of many SMA and SBMA-like syndromes and most ALS cases is unknown. Here we show that missense point mutations in the cytoplasmic dynein heavy chain result in progressive motor neuron degeneration in heterozygous mice, and in homozygotes this is accompanied by the formation of Lewy-like inclusion bodies, thus resembling key features of human pathology. These mutations exclusively perturb neuron-specific functions of dynein.     

Identification and quantification of zeaxanthin esters in plants using liquid chromatography-mass spectrometry

It has been suggested that lutein and zeaxanthin may decrease the risk for age-related macular degeneration. Surprisingly, oleoresins rich in zeaxanthin are not yet available on the market. Several authors have reported enhanced stability of esterified xanthophylls, so plants containing zeaxanthin esters were investigated to establish valuable sources for the production of durable oleoresins. Liquid chromatography-atmospheric pressure chemical ionization mass spectrometry [LC-(APCI)MS] was used to unequivocally identify zeaxanthin esters of a standard mixture and in several plant extracts. Zeaxanthin esters were quantified on the basis of their respective molecular masses using zeaxanthin for calibration; total zeaxanthin was determined after saponification of aliquots of the extracts. Thus, dried wolfberries (Lycium barbarum), Chinese lanterns (Physalis alkekengi), orange pepper (Capsicum annuum), and sea buckthorn (Hippophae rhamnoides) proved to be valuable zeaxanthin ester sources. The present LC-MS method allows for an even more detailed analysis of zeaxanthin esters than reported previously.     

Vernachlässigte Phosphor‐ und Kaliumdüngung im ökologischen Landbau senkt die biologische Stickstofffixierung bei Rotklee und den Kornertrag bei nachfolgendem Hafer

Neglected P and K fertilization in organic farming reduces N₂ fixation and grain yield in a red clover‐oat rotation N₂ fixation is the most important N source in organic farming. An insufficient P, K, and S supply to legumes may reduce their N₂ fixation capacity. Consequently, the total yield of plant production may also be reduced. This problem was studied in a pot experiment with red clover followed by oat. Soil was taken from a field where organic farming had been practiced for more than 30 years without applying any mineral fertilizers or buying additional fodder. The soil (luvisol from loess) was characterized by: pH (CaCl₂) 5.4; lactate‐soluble (CAL) P 5 mg kg^–1 and K 110 mg kg^–1. 6 kg dry soil were mixed with 400 mg P applied as (i) triplesuperphosphate (TSP), (ii) rock phosphate (RP) or (iii) compost from organic household residues (BAK). An additional treatment (iv) with TSP received 1000 mg K as K₂SO₄ (TSP+K) and an additional treatment with RP (v) received only 200 mg P (RP/2). A control treatment received no fertilizer. P application significantly improved the P nutritional status of the plants (P content) and increased the N amount in the shoots of red clover (with 400 mg P per pot by 64 % to 139 % as compared to the control) and the dry matter (DM) yield by 60 % to 130 %. No significant differences between TSP and RP were found. The application of BAK resulted in a significantly higher N yield than the application of RP and TSP. The treatment TSP+K resulted in the highest DM yield (230 %), removal of P was 343 %, of K 228 %, and of N 239 % as compared to the control plants. This indicates a synergistic effect of P, K, and S on N₂ fixation, which was also found with BAK. Oat grown after red clover increased its grain yield by 132 % (200 mg P as RP) to 165 % (400 mg P treatments). This was mainly due to a higher P uptake (up to 172 %) and a higher N uptake (up to 172 %) as compared to the control.     

Use of the caudolateral curvilinear osteophyte as an early marker for future development of osteoarthritis associated with hip dysplasia in dogs

OBJECTIVE: To determine the relationship between the caudolateral curvilinear osteophyte (CCO) and osteoarthritis associated with hip dysplasia in dogs. DESIGN: Longitudinal cohort study. ANIMALS: 48 Labrador Retrievers from 7 litters. PROCEDURE: In each of 24 sex- and size-matched pairs fed the same diet, a restricted-fed dog was fed 25% less than a control dog for life. The dogs' hips were evaluated in the standard ventrodorsal hip-extended radiographic projection at 16, 30, and 52 weeks of age and then yearly for life. Histologic examination of hip joint tissues was performed on 45 dogs. RESULTS: Median age at death was 11.2 years. Adjusting for feeding group, dogs with a CCO were 3.7 times as likely to develop radiographic signs of osteoarthritis than those without a CCO. Stratified by diet, 100% of the control dogs with a CCO developed radiographic signs of osteoarthritis and 55% of restricted-fed dogs with a CCO developed radiographic signs of osteoarthritis. The CCO was the first radiographic change seen in 22 of 29 (76%) dogs with osteoarthritis. Overall, 35 of 37 (95%) dogs with a CCO had histopathologic lesions of osteoarthritis. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate a relationship between a CCO on the femoral neck and subsequent development of radiographic signs of osteoarthritis in Labrador Retrievers evaluated over their life span. A CCO is an important early radiographic indication of osteoarthritis associated with canine hip dysplasia.     

Impact features on Stardust: implications for comet 81P/Wild 2 dust

Particles emanating from comet 81P/Wild 2 collided with the Stardust spacecraft at 6.1 kilometers per second, producing hypervelocity impact features on the collector surfaces that were returned to Earth. The morphologies of these surprisingly diverse features were created by particles varying from dense mineral grains to loosely bound, polymineralic aggregates ranging from tens of nanometers to hundreds of micrometers in size. The cumulative size distribution of Wild 2 dust is shallower than that of comet Halley, yet steeper than that of comet Grigg-Skjellerup.