Brain connectivity changes after osteopathic manipulative treatment: A randomized manual placebo-controlled trial

The effects of osteopathic manipulative treatment (OMT) on functional brain connectivity in healthy adults is missing in the literature. To make up for this lack, we applied advanced network analysis methods to analyze resting state functional magnetic resonance imaging (fMRI) data, after OMT and Placebo treatment (P) in 30 healthy asymptomatic young participants randomized into OMT and placebo groups (OMTg; Pg). fMRI brain activity measures, performed before (T0), immediately after (T1) and three days after (T2) OMT or P were used for inferring treatment effects on brain circuit functional organization. Repeated measures ANOVA and post-hoc analysis demonstrated that Right Precentral Gyrus (F (2, 32) = 5.995, p < 0.005) was more influential over the information flow immediately after the OMT, while decreased betweenness centrality in Left Caudate (F (2, 32) = 6.496, p < 0.005) was observable three days after. Clustering coefficient showed a distinct time-point and group effect. At T1, reduced neighborhood connectivity was observed after OMT in the Left Amygdala (L-Amyg) (F(2, 32) = 7.269, p < 0.005) and Left Middle Temporal Gyrus (F(2, 32) = 6.452, p < 0.005), whereas at T2 the L-Amyg and Vermis-III (F(2, 32) = 6.772, p < 0.005) increased functional interactions. Data demonstrated functional connectivity re-arrangement after OMT

The spliceosome U2 snRNP factors promote genome stability through distinct mechanisms; transcription of repair factors and R-loop processing

Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress

Three Prochlorococcus cyanophage genomes : signature features and ecological interpretations

© 2005 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The definitive version was published in PLoS Biology 3 (2005): e144, doi:10.1371/journal.pbio.0030144.The oceanic cyanobacteria Prochlorococcus are globally important, ecologically diverse primary producers. It is thought that their viruses (phages) mediate population sizes and affect the evolutionary trajectories of their hosts. Here we present an analysis of genomes from three Prochlorococcus phages: a podovirus and two myoviruses. The morphology, overall genome features, and gene content of these phages suggest that they are quite similar to T7-like (P-SSP7) and T4-like (P-SSM2 and P-SSM4) phages. Using the existing phage taxonomic framework as a guideline, we examined genome sequences to establish ‘‘core’’ genes for each phage group. We found the podovirus contained 15 of 26 core T7-like genes and the two myoviruses contained 43 and 42 of 75 core T4-like genes. In addition to these core genes, each genome contains a significant number of ‘‘cyanobacterial’’ genes, i.e., genes with significant best BLAST hits to genes found in cyanobacteria. Some of these, we speculate, represent ‘‘signature’’ cyanophage genes. For example, all three phage genomes contain photosynthetic genes (psbA, hliP) that are thought to help maintain host photosynthetic activity during infection, as well as an aldolase family gene (talC) that could facilitate alternative routes of carbon metabolism during infection. The podovirus genome also contains an integrase gene (int) and other features that suggest it is capable of integrating into its host. If indeed it is, this would be unprecedented among cultured T7-like phages or marine cyanophages and would have significant evolutionary and ecological implications for phage and host. Further, both myoviruses contain phosphate-inducible genes (phoH and pstS) that are likely to be important for phage and host responses to phosphate stress, a commonly limiting nutrient in marine systems. Thus, these marine cyanophages appear to be variations of two well-known phages—T7 and T4—but contain genes that, if functional, reflect adaptations for infection of photosynthetic hosts in low-nutrient oceanic environments.This research was supported by the US DOE under grant numbers DEFG02– 99ER62814 and DE-FG02–02ER63445, and the National Science Foundation under grant number OCE-9820035 (to SWC)

Viral capsids: Mechanical characteristics, genome packaging and delivery mechanisms

The main functions of viral capsids are to protect, transport and deliver their genome. The mechanical properties of capsids are supposed to be adapted to these tasks. Bacteriophage capsids also need to withstand the high pressures the DNA is exerting onto it as a result of the DNA packaging and its consequent confinement within the capsid. It is proposed that this pressure helps driving the genome into the host, but other mechanisms also seem to play an important role in ejection. DNA packaging and ejection strategies are obviously dependent on the mechanical properties of the capsid. This review focuses on the mechanical properties of viral capsids in general and the elucidation of the biophysical aspects of genome packaging mechanisms and genome delivery processes of double-stranded DNA bacteriophages in particular

Genome-Wide Distribution of RNA-DNA Hybrids Identifies RNase H Targets in tRNA Genes, Retrotransposons and Mitochondria

During transcription, the nascent RNA can invade the DNA template, forming extended RNA-DNA duplexes (R-loops). Here we employ ChIP-seq in strains expressing or lacking RNase H to map targets of RNase H activity throughout the budding yeast genome. In wild-type strains, R-loops were readily detected over the 35S rDNA region, transcribed by Pol I, and over the 5S rDNA, transcribed by Pol III. In strains lacking RNase H activity, R-loops were elevated over other Pol III genes, notably tRNAs, SCR1 and U6 snRNA, and were also associated with the cDNAs of endogenous TY1 retrotransposons, which showed increased rates of mobility to the 5'-flanking regions of tRNA genes. Unexpectedly, R-loops were also associated with mitochondrial genes in the absence of RNase H1, but not of RNase H2. Finally, R-loops were detected on actively transcribed protein-coding genes in the wild-type, particularly over the second exon of spliced ribosomal protein genes