Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells

Overexpression of Hoxb4 in bone marrow cells promotes expansion of hematopoietic stem cell (HSC) populations in vivo and in vitro, indicating that this homeoprotein can activate the genetic program that determines self-renewal. However, this function cannot be solely attributed to Hoxb4 because Hoxb4(-/-) mice are viable and have an apparently normal HSC number. Quantitative polymerase chain reaction analysis showed that Hoxb4(-/-) c-Kit(+) fetal liver cells expressed moderately higher levels of several Hoxb cluster genes than control cells, raising the possibility that normal HSC activity in Hoxb4(-/-) mice is due to a compensatory up-regulation of other Hoxb genes. In this study, we investigated the competitive repopulation potential of HSCs lacking Hoxb4 alone, or in conjunction with 8 other Hoxb genes. Our results show that Hoxb4(-/-) and Hoxb1-b9(-/-) fetal liver cells retain full competitive repopulation potential and the ability to regenerate all myeloid and lymphoid lineages. Quantitative Hox gene expression profiling in purified c-KIt(+) Hoxb1-bg(-/-) fetal liver cells revealed an interaction between the Hoxa, b, and c clusters with variation in expression levels of Hoxa4, -a11, and -c4. Together, these studies show a complex network of genetic interactions between several Hox genes in primitive hematopoietic cells and demonstrate that HSCs lacking up to 30% of the active Hox genes remain fully competent.

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

Rapid Fluctuations in the Lower Solar Atmosphere

The Rapid Oscillations in the Solar Atmosphere instrument reveals solar atmospheric fluctuations at high frequencies. Spectra of variations of the G-band intensity (IG ) and Ca II K-line intensity (IK ) show correlated fluctuations above white noise to frequencies beyond 300 mHz and 50 mHz, respectively. The noise-corrected G-band spectrum for f = 28-326 mHz shows a power law with exponent -1.21 ± 0.02, consistent with the presence of turbulent motions. G-band spectral power in the 25-100 mHz ("UHF") range is concentrated at the locations of magnetic bright points in the intergranular lanes and is highly intermittent in time. The intermittence of the UHF G-band fluctuations, shown by a positive kurtosis ?, also suggests turbulence. Combining values of IG , IK , UHF power, and ? reveals two distinct states of the solar atmosphere. State 1, including almost all the data, is characterized by low IG , IK , and UHF power and ? ˜ 6. State 2, including only a very small fraction of the data, is characterized by high IG , IK , and UHF power and ? ˜ 3. Superposed epoch analysis shows that the UHF power peaks simultaneously with spatio-temporal IG maxima in either state. For State 1, IK shows 3.5 minute chromospheric oscillations with maxima occurring 21 s after IG maxima implying a 150-210 km effective height difference. However, for State 2 the IK and IG maxima are simultaneous; in this highly magnetized environment sites of G-band and K-line emission may be spatially close together.