Determination of the tissue distribution and excretion by accelerator mass spectrometry of the nonadecapeptide 14C-Moli1901 in beagle dogs after intratracheal instillation

Moli1901 is a 19 residue polycyclic peptide antibiotic which increases chloride transport and water mobilization in airway epithelium. These properties suggest that it may be a useful treatment for cystic fibrosis (CF). In this study, we used accelerator mass spectrometry (AMS) to quantify Moli1901 following administration of only 0.045 microCi of 14C-Moli1901 per dog. Limits of quantitation of AMS were 0.03 (urine) to 0.3 (feces) ng equiv. Moli1901/g. Administration of 14C-Moli1901 by intratracheal instillation (approximately 100 microg) into the left cranial lobe of the lung of beagle dogs resulted in retention of 64% of the dose in the left cranial lobe for up to 28 days. Whole blood and plasma concentrations of 14C were <5 ng/ml at all times after the dose. Concentrations of 14C in whole blood and plasma declined over the first day after the dose and rose thereafter, with the rise in plasma concentrations lagging behind those in whole blood. During the first 3 days after the dose, plasma accounted for the majority of 14C in whole blood, but after that time, plasma accounted for only 25-30% of the 14C in whole blood. Tissue (left and right caudal lung lobe, liver, kidney, spleen, brain) and bile concentrations were low, always less than 0.25% the concentrations found in the left cranial lung lobe. Approximately 13% of the dose was eliminated in urine and feces in 28 days, with fecal elimination accounting for about 10% of the dose. The data presented here are consistent with that obtained in other species. Moli1901 is slowly absorbed and excreted from the lung, and it does not accumulate in other tissues. Moli1901 is currently in the clinic and has proven to be safe in single dose studies in human volunteers and cystic fibrosis patients by the inhalation route. No information on the disposition of the compound in humans is available. This study in dogs demonstrates the feasibility of obtaining that information using 14C-Moli1901 and AMS.     

Redistribution of myosin heavy chain mRNA in the midregion of stretched muscle fibers

Summary Myosin mRNA distribution was compared to the distribution of striations, nuclei, and cytoskeletal components in normal fibers and in fibers undergoing growth and repair processes in response to stretch. Plantarflexion of rabbit lower hindlimb for 4 or 6 days resulted in a 35% increase in weight of the tibialis anterior muscle. Slow myosin expression in stretched fibers increased such that the proportion of fibers shifted from the fast type towards an intermediate type. Semi-quantitative in situ hybridization revealed a large increase in concentration of slow myosin mRNA in stretched fibers. Polysomes translating myosin heavy chain were excluded from the intact myofibrillar lattice. Significant increases of myosin mRNA concentration occurred only in the outer 8 m subsarcolemmal annulus of these stretched fibers (P<0.001) where myofibril formation also was evident. In some fibers, stretch caused myofibrillar disorder where nuclei became centrally located, and focal concentrations of myosin mRNA also occurred. We discuss mechanisms for mRNA accumulation and favor free diffusion to loosely packed cytoplasmic regions where myosin is needed for myofibrillar growth and repair.     

Topology independent protein structural alignment

Background  

Identifying structurally similar proteins with different chain topologies can aid studies in homology modeling, protein folding, protein design, and protein evolution. These include circular permuted protein structures, and the more general cases of non-cyclic permutations between similar structures, which are related by non-topological rearrangement beyond circular permutation. We present a method based on an approximation algorithm that finds sequence-order independent structural alignments that are close to optimal. We formulate the structural alignment problem as a special case of the maximum-weight independent set problem, and solve this computationally intensive problem approximately by iteratively solving relaxations of a corresponding integer programming problem. The resulting structural alignment is sequence order independent. Our method is also insensitive to insertions, deletions, and gaps.     

我国巴拉巴按蚊形态描述

白踝按蚊种团是由很多形态近似的蚊种组成,其中巴拉巴按蚊和白踝按蚊均为东南亚一带的重要传疟媒介。我国过去资料均记载为白踝按蚊,但未从形态上详细鉴定。为了确定该种的分类地位,1963年作者等在海南岛万宁县兴隆附近山林区采集“白踝按蚊”全套标本10批共150多套,1971年后从云南省采集少数标本进行形态鉴定,发现其与Colless(1956,1957)所描述的白踝按蚊Anopheles leucosphyrus leucosphyrus Donitz(1901)有很明显的差别,而与巴拉巴按蚊A.balabacensis balabacensis Balsas(1936)除某些特征略有差异外,余均完全一致。按Colless的分类法,过去我国记载的“白踝按蚊”,应鉴定为巴拉巴按蚊A.balabacensis balabacensis Baisas。     

Evolutionary origins of Brassicaceae specific genes in Arabidopsis thaliana

Background  

All sequenced genomes contain a proportion of lineage-specific genes, which exhibit no sequence similarity to any genes outside the lineage. Despite their prevalence, the origins and functions of most lineage-specific genes remain largely unknown. As more genomes are sequenced opportunities for understanding evolutionary origins and functions of lineage-specific genes are increasing.