Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The effects of haloperidol treatment on the distribution of NK1 receptor immunoreactive neurons in guinea-pig brain (Short communication)

Previous studies have observed increased tachykinin NK1 receptor immunoreactivity (NK1-IR) in the prefrontal cortex in subjects with schizophrenia. Since the subjects were medicated the possibility of a treatment effect could not be excluded. Thus, the present study was undertaken to determine the effect of chronic treatment with the antipsychotic drug, haloperidol, on the distribution of NK1-IR neurons in the guinea-pig brain. Guinea pigs were treated each day for 21 days with either haloperidol (1 mg/kg) or vehicle and the brains were then processed for immumohistochemistry using an NK1 receptor-specific polyclonal antibody. NK1-IR neurons and fibres were abundant in the forebrain cortex and caudate putamen and more sparsely distributed in a number of other brain regions. The relative density of NK1-IR neurons was significantly increased in the forebrain cortex, but not in the caudate putamen in guinea pigs treated with haloperidol. This study has shown that haloperidol causes region-specific changes to the density of NK1-IR neurons. Whether these changes are related to the therapeutic effects or to the side effects of haloperidol in individuals with schizophrenia, remains to be determined. (c) 2005 Elsevier Ireland Ltd. All rights reserved

Effect of subchronic administration of tachykinin antagonists on response of guinea-pigs to mild and severe stress

The effects of subchronic subcutaneous treatment with tachykinin receptor antagonists over nine days on the repeated mild stress response induced by daily subcutaneous injections and on the severe acute stress induced by morphine withdrawal were investigated in guinea-pigs. The NK₁ receptor antagonist, L733,060, 0.25 mg/kg, significantly increased locomotor activity of guinea-pigs compared with animals subjected to repeated injection of the inactive enantiomer, but inhibited Fos-like immunoreactivity (Fos-LI) in the hypothalamus. In animals subjected to the acute severe stress of naltrexone-induced morphine withdrawal, treatment with the NK₁ antagonist, L733,060, produced reductions in Fos-LI in the spinal dorsal horn, whereas those treated with the NK₃ antagonist, SSR146,977, 0.3 mg/kg, had reduced Fos-LI in the dorsal horn, adrenal medulla, nucleus accumbens, ventral tegmental area and periaqueductal grey. Those animals treated with both NK₁ and NK₃ antagonists also had reduced Fos-LI in the amygdala and paraventricular nucleus of the thalamus. It was concluded that the NK₁ antagonist reduced the hypothalamic response to mild stress but the NK₃ antagonist was more effective in reducing the severe stress response to morphine withdrawal. Furthermore, combination of NK₁ and NK₃ antagonists was more effective than either antagonist in reducing the Fos-LI response to morphine withdrawal

Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

1. Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. 2. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg(−1) subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. 3. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. 4. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. 5. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. 6. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia