The intranuclear position of many genes has been correlated with their activity state, suggesting that migration to functional subcompartments may influence gene expression. Indeed, nascent RNA production and RNA polymerase II seem to be localized into discrete foci or 'transcription factories'. Current estimates from cultured cells indicate that multiple genes could occupy the same factory, although this has not yet been observed. Here we show that, during transcription in vivo, distal genes colocalize to the same transcription factory at high frequencies. Active genes are dynamically organized into shared nuclear subcompartments, and movement into or out of these factories results in activation or abatement of transcription. Thus, rather than recruiting and assembling transcription complexes, active genes migrate to preassembled transcription sites.The activity state of a gene can often be correlated with its intranuclear localization to specific subregions or its position relative to constitutive heterochromatin [1][2][3][4][5][6] ; however, it is unclear whether activation or repression of an individual gene is a cause or consequence of intranuclear position. Transcriptionally active genes have been proposed to associate with transcription factories, discrete nuclear sites of nascent RNA production and concentrated transcriptional components, such as RNA polymerase [7][8][9][10][11][12] . Calculations using the number of RNA polymerase II (RNAP II) transcription factories in HeLa cells (several thousand per nucleus) and estimates of the number of transcription units suggest that several active genes could occupy the same factory 10

We have developed a technique to systematically discover and study high-redshift supernovae that can be used to measure the cosmological parameters. We report here results based on the initial seven of more than 28 supernovae discovered to date in the high-redshift supernova search of the Supernova Cosmology Project. We Ðnd an observational dispersion in peak magnitudes of this disperp MB \ 0.27 ; sion narrows to after "" correcting ÏÏ the magnitudes using the light-curve "" widthp MB,corr \ 0.19 luminosity ÏÏ relation found for nearby (z ¹ 0.1) Type Ia supernovae from the Cala n/Tololo survey (Hamuy et al.). Comparing light-curve widthÈcorrected magnitudes as a function of redshift of our distant (z \ 0.35È0.46) supernovae to those of nearby Type Ia supernovae yields a global measurement of the mass density, for a " \ 0 cosmology. For a spatially Ñat universe (i.e., not correspond to a unique value of the deceleration parameterWe present analyses and checks q 0 . for statistical and systematic errors and also show that our results do not depend on the speciÐcs of the width-luminosity correction. The results for are inconsistent with "-dominated, low-) " -versus-) M density, Ñat cosmologies that have been proposed to reconcile the ages of globular cluster stars with higher Hubble constant values.

BackgroundFecal bacteriotherapy (‘stool transplant’) can be effective in treating recurrent Clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent C. difficile infection that had failed repeated standard antibiotics. Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon. Pre-treatment and post-treatment stool samples were analyzed by 16 S rRNA gene sequencing using the Ion Torrent platform.ResultsBoth patients were infected with the hyper virulent C. difficile strain, ribotype 078. Following stool substitute treatment, each patient reverted to their normal bowel pattern within 2 to 3 days and remained symptom-free at 6 months. The analysis demonstrated that rRNA sequences found in the stool substitute were rare in the pre-treatment stool samples but constituted over 25% of the sequences up to 6 months after treatment.ConclusionThis proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture.Trial registrationClinical trial registration number: CinicalTrials.gov NCT01372943

Communication between distal chromosomal elements is essential for control of many nuclear processes. For example, genes in higher eukaryotes often require distant enhancer sequences for high-level expression. The mechanisms proposed for long-range enhancer action fall into two basic categories. Non-contact models propose that enhancers act at a distance to create a favorable environment for gene transcription, or act as entry sites or nucleation points for factors that ultimately communicate with the gene. Contact models propose that communication occurs through direct interaction between the distant enhancer and the gene by various mechanisms that 'loop out' the intervening sequences. Although much attention has focused on contact models, the existence and nature of long-range interactions is still controversial and speculative, as there is no direct evidence that distant sequences physically interact in vivo. Here, we report the development of a widely applicable in situ technique to tag and recover chromatin in the immediate vicinity of an actively transcribed gene. We show that the classical enhancer element, HS2 of the prototypical locus control region (LCR) of the beta-globin gene cluster, is in close physical proximity to an actively transcribed HBB (beta-globin) gene located over 50 kb away in vivo, suggesting a direct regulatory interaction. The results give unprecedented insight into the in vivo structure of the LCR-gene interface and provide the first direct evidence of long-range enhancer communication.