Distinct functions of the two isoforms of dopamine D2 receptors

Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms, D2S and D2L, previously thought to have the same function. Here we show that these receptors have distinct functions in vivo; D2L acts mainly at postsynaptic sites and D2S serves presynaptic autoreceptor functions. The cataleptic effects of the widely used antipsychotic haloperidol are absent in D2L-deficient mice. This suggests that D2L is targeted by haloperidol, with implications for treatment of neuropsychiatric disorders. The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors.     

The role of the substantia nigra on the rage reaction elicited by hypothalamic stimulation,in the cat

Summary The effects of substantia nigra stimulation on the rage reaction evoked by hypothalamic activation were studied. The reference value of the rage reaction was the latency of the hissing, which was constant in all animals when hypothalamic stimulation was performed with the same parameters. Simultaneous activation of substantia nigra and hypothalamus determined a significant decrease in hissing latency. The influence of the substantia nigra on the affective components of the aggressive behavior is underlined.This work was supported by a grant from the Consiglio Nazionale delle Ricerche Roma, Italy.     

The role of the substantia nigra on the rage reaction elicited by hypothalamic stimulation, in the cat

The effects of substantia nigra stimulation on the rage reaction evoked by hypothalamic activation were studied. The reference value of the rage reaction was the latency of the hissing, which was constant in all animals when hypothalamic stimulation was performed with the same parameters. Simultaneous activation of substantia nigra and hypothalamus determined a significant decrease in hissing latency. The influence of the substantia nigra on the affective components of the aggressive behavior is underlined.     

打开中国遗传学历史之门

我国6个单位即中国医学科学院医学生物学研究所、上海复旦大学、哈尔滨医科大学、中国科学院遗传所、医科院肿瘤所和上海第二医科大学附属瑞金医院的遗传学家大力协作，利用高度多态性的遗传学标志对中国各民族的源流关系及其与世界各民族的进化关系进行了分析，是中国人类基因组多样性计划的一个重大成果，不仅发表于《美国国家科学院院报》（ProceedingsoftheNationalAcademyofSciences）上，赢得了世界人类基因组多样性计划的权威Cavalli－Sforza和Riazza分别在《美国国家科学院院报》和《自然》（Nature）上撰文评述，而且还入选了…     

Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia

Hair cells of the inner ear are not normally replaced during an animal's life, and must continually renew components of their various organelles. Among these are the stereocilia, each with a core of several hundred actin filaments that arise from their apical surfaces and that bear the mechanotransduction apparatus at their tips. Actin turnover in stereocilia has previously been studied by transfecting neonatal rat hair cells in culture with a β-actin-GFP fusion, and evidence was found that actin is replaced, from the top down, in 2-3 days. Overexpression of the actin-binding protein espin causes elongation of stereocilia within 12-24 hours, also suggesting rapid regulation of stereocilia lengths. Similarly, the mechanosensory 'tip links' are replaced in 5-10 hours after cleavage in chicken and mammalian hair cells. In contrast, turnover in chick stereocilia in vivo is much slower. It might be that only certain components of stereocilia turn over quickly, that rapid turnover occurs only in neonatal animals, only in culture, or only in response to a challenge like breakage or actin overexpression. Here we quantify protein turnover by feeding animals with a (15)N-labelled precursor amino acid and using multi-isotope imaging mass spectrometry to measure appearance of new protein. Surprisingly, in adult frogs and mice and in neonatal mice, in vivo and in vitro, the stereocilia were remarkably stable, incorporating newly synthesized protein at <10% per day. Only stereocilia tips had rapid turnover and no treadmilling was observed. Other methods confirmed this: in hair cells expressing β-actin-GFP we bleached fiducial lines across hair bundles, but they did not move in 6 days. When we stopped expression of β- or γ-actin with tamoxifen-inducible recombination, neither actin isoform left the stereocilia, except at the tips. Thus, rapid turnover in stereocilia occurs only at the tips and not by a treadmilling process.     

Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni

Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampling of an estimated 14,000 gene complement. By analyzing automated Gene Ontology assignments, we provide a detailed view of important S. mansoni biological systems, including characterization of metazoa-specific and eukarya-conserved genes. Phylogenetic analysis suggests an early divergence from other metazoa. The data set provides insights into the molecular mechanisms of tissue organization, development, signaling, sexual dimorphism, host interactions and immune evasion and identifies novel proteins to be investigated as vaccine candidates and potential drug targets.     

Migration rates of human populations from surname distributions

Migration is an important factor in the biological evolution of human populations, and surnames provide one of the simplest records of identification. The distribution of surnames can supply quantitative information on the structure of human populations. Surnames considered as alleles of a gene transmitted only by the male line can be assumed to be neutral markers and therefore satisfy the expectations of the neutral theory of evolution, which is entirely described by random genetic drift, mutation and migration. As data on surnames are easier to collect than those from genes, the information yield is potentially increased, but the validity of the conclusions must be tested in actual samples. The purpose of this report is to compare the estimates of migration rates in Italy, as inferred by the surname distribution found in the telephone directories and other sources, with the corresponding estimates from official demographic sources. Our findings show that in these samples the ratio of surnames to individuals makes it possible to calculate reliable estimates of migration rates.