Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors

Different isoforms of serotonin subtype 2C receptor (5-HT(2C)R) with altered G protein-coupling efficacy are generated by RNA editing, which converts genomically encoded adenosine residues into inosines. In combination, editing of five sites all located within the second intracellular loop region of 5-HT(2C)R mRNA changes the gene-encoded Ile, Asn, and Ile at positions 156, 158, and 160, respectively. We analyzed the G protein-coupling functions of previously unreported editing isoform receptors. An approximately 13-fold reduction in the agonist potency for G protein-coupling stimulation as well as a significantly reduced basal level activity was observed with the thalamus-specific isoform carrying Ile156, Gly158, and Val160 (5-HT(2C)R-IGV). In contrast, the agonist was four- to five-fold less potent with 5-HT(2C)R-MSV and -IDV, detected in the amygdala and choroid plexus, respectively, indicating a dominant role for the amino acid residue at position 158 in receptor functions. We also identified a splicing variant receptor with a truncated C terminus that displayed no ligand binding capacity or G protein-coupling activity. Examination of the alternatively spliced RNA encoding this truncated receptor suggests that editing of this variant RNA occurs after completion of splicing, resulting in complete editing at all five sites.     

美国奥巴马政府新医改法案及启示

对美国医改法案中巨额医保资金的来源、法案即时生效的主要条款、法案的主要内容等进行了简要梳理,以期为我国医药卫生体制改革工作提供参考。     

Microsatellite DNA variation in Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus) and cross-species amplification in the Acipenseridae

Overharvest and habitat alteration have led toa collapse of most commercial Atlantic sturgeon(Acipenser oxyrinchus oxyrinchus)fisheries while pushing the species to rarityor extirpation in most of its historical range. A biologically sound conservation program forthis species requires knowledge of its geneticdiversity and of the evolutionary relationshipsamong geographic populations. To address theseresearch needs, six microsatellite loci wereisolated from A. o. oxyrinchus. Pedigreeanalysis suggested that all are inherited in acodominant Mendelian pattern. The six lociwere tested in ten additional sturgeon speciesfrom three genera and three apparent ploidylevels (4n, 8n, 16n). Approximately 70% ofsuccessful locus-species amplifications werepolymorphic. Polysomy was observed most oftenin 8n and 16n species. Genetic diversity andpopulation structure of A. o. oxyrinchuswere assayed using three polymorphic Aoxmarkers and four markers developed from lakesturgeon (A. fulvescens). A. o.oxyrinchus were sampled from the AltamahaRiver, Georgia, USA north to the St. LawrenceRiver, Quebec, Canada. Gulf sturgeon, A.o. desotoi, were sampled from the SuwanneeRiver, Florida, USA, to assess differentiationbetween the subspecies. Seventy-seven alleleswere observed to segregate into uniquemultilocus genotypes for each of the 392individuals assayed. Mean diversity wasgreatest in the Chesapeake Bay (9.7 alleles perlocus) and Delaware River (7.4 alleles perlocus) collections, and lowest in the St.Lawrence River (4.6 alleles per locus). Meanheterozygosity across seven loci ranged from44.3% (St. Lawrence River) to 62.6% (Altamaha River). Significant allelic heterogeneity wasobserved in 82% of pairwise comparisons aswell as a global test (p < 0.0001) for A.o. oxyrinchus collections. Genetic distancesuggests the presence of at least sixsubpopulations in A. o. oxyrinchus: St.Lawrence River, St. John River, Hudson River,Delaware River, Albemarle Sound, and AltamahaRiver. Genetic and geographic distances werepositively correlated (r = 0.57, p < 0.03) amongA. o. oxyrinchus, suggesting isolation bydistance and philopatry. Hierarchical genediversity analysis indicated significantgenetic population structure at every level. Maximum likelihood assignment tests correctlyassigned individual fish to collection with ahigh rate of success (mean = 87.5%); this andother lines of evidence indicated that theChesapeake Bay collection represents a mixedpopulation of sub-adult sturgeon from northernand southern Atlantic coast populations. Population structure was correlated with thatsuggested by earlier mitochondrial (mt) DNAanalyses. Significant diversity was observedbetween two Canadian populations from whichonly a single mtDNA haplotype has beenreported.     

The Unknown Vygotsky: On the Experience of a Literary Translation from Hebrew

Following is the first publication of a previously unknown translation by L.S. Vygotsky from Hebrew of a fictional short story by M.J. Berdyczewski, a Jewish writer popular at the beginning of the twentieth century. The commentary by the authors of this article reconstructs the context of Vygotsky’s life situation during the prerevolutionary period. Particular attention is focused on the questions of ethnic and cultural self-determination that were confronting him. The cultural contexts essential for an understanding and interpretation of the artistic and world-view features of the text of the short story are explored. A comparison is drawn to show the connection between the themes addressed in the story and the substantive problems that Vygotsky would subsequently deal with as a professional psychology: the artistic inner experience, moral choice, and cultural mediation.     

Release of the inhibition of messenger RNA translation in extracts of interferon-treated Ehrlich ascites tumor cells by added transfer RNA

In an extract of Ehrlich ascites tumor (EAT) cells which had been “preincubated” for 45 min to lower endogenous protein synthesis (S30_C) the translation of exogenous encephalomyocarditis (EMC) viral mRNA proceeds at a constant rate for over 90 min. In a similarly treated extract of interferon-treated EAT cells (S30_INT) the translation proceeds at a lower rate than in the S30_C for about 30 min and then stops. The impairment of the translation in the S30_INT is mediated by one or more inhibitors. After the cessation of translation the viral mRNA in the S30_INT is in large polysomes. The size of these changes little (if any) during a further 15 min incubation. The addition of mouse tRNA (but not ribosomal RNA or $\text{E. coli}$ tRNA) to the S30_INT after the cessation of viral mRNA translation results in the restart of translation at a rate close to that in the S30_C. This effect of tRNA is diminished by pactamycin, which inhibits peptide chain initiation but not elongation. These results indicate that addition of tRNA allows the elongation of incomplete peptide chains and the initiation of new chains. The need for added tRNA may be due to the fact that in S30_INT the amino acid acceptance of some of the endogenous tRNA species (but not of added tRNAs) is impaired. This impairment is pronounced for leucine and very slight, if any, for five other amino acids tested (i.e. isoleucine, methionine, phenylalanine, threonine, and valine).     

The Study of Children’s Play within the Context of Cultural-Historical Psychology: Experience and Prospects

The paper reconstructs the history of the problem of mental development using material from children’s play. This study shows how researchers in the school of cultural-historical psychology identified the developmental function of play, established a qualitative leap in its development and attempted to re-create it, beginning with the works of L.S. Vygotsky, then of his followers (the activity-based approach in the interpretation of narrative role-playing: A.N. Leontiev, D.B. Elkonin, N.Ia. Mikhailenko, N.A. Korotkova, etc.), and, finally, of the researchers who studied a specific act of development in play (L.I. El’koninova, T.V. Bazhanova, K.O. Iur’eva). This research presents the view that the concept of the cultural form of play, containing a Challenge (defined by the boundaries of the possibilities of action and by risk) and the subsequent Response is the basis not only of narrative role-playing but also of games with rules, as well as computer games. The Challenge entails action that changes the action situation; it typifies all forms of play, which are supposed to tie together what is disjointed in a child’s daily life into a semantic knot.     

Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis

Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-β, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining.ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-β and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines.Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.     

Coastal Wetlands Planning, Protection, and Restoration Act: A programmatic application of adaptive management

The Coastal Wetlands Planning, Protection, and Restoration Act (CWPPRA), commonly referred to as ‘The Breaux Act’, has provided some of the resources necessary to begin implementing a comprehensive, large-scale, long-term coastal wetland restoration program for Louisiana USA. Due to the dynamic nature of this ecosystem and the uncertainty associated with large-scale restoration, adaptive management principles were embedded throughout CWPPRA’s organizational structure, planning process, project implementation, and monitoring program to facilitate achieving the mandates associated with the Breaux Act. Feedback loops were established within and between each of the programmatic components to encourage continuous learning, which is central to adaptive management. The knowledge gained has led to institutionalized change in projects as well as the program. This paper describes how the formation of the CWPPRA Task Force and associated committees and groups resulted in an integrated coast-wide process for planning, selection, construction, operation, maintenance, monitoring, and scientific evaluation of 84 restoration projects implemented or scheduled for implementation throughout coastal Louisiana.     

Resistance of Hibiscus esculentus L. and Vigna sinensis (L.) Endl. to Pseudocercospora and plant peroxidase activity in relation to infection

Five cultivars of Hibiscus esculentus L. and six cultivars of Vigna sinensis (L.) Endl. were tested for their relative resistance to Pseudocercospora spp. Differences in susceptibility to the leaf spot pathogen were observed in both host and non-host interactions. The H. esculentus cv. South Sea and V. sinensis cv. Purple Mart were most susceptible to Pseudocercospora abelmoschi and P. cruenta, respectively. The H. esculentus cv. Pure Luck was most tolerant to P. abelmoschi while the V. sinensis cv. KY Bush was highly resistant to P. cruenta. A distinct host-specific interaction was observed among the different species of Pseudocercospora. Cultivar specific interactions were most pronounced between V. sinensis and P. cruenta. A direct correlation was observed between the variation in peroxidase activity in the soluble fraction of inoculated leaves and resistance to infection in H. esculentus and V. sinensis cultivars. The soluble fraction of inoculated leaves had higher peroxidase activity than either mitochondrial or chloroplast extracts.