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Two recent studies in Molecular Cell 1 and Nature 2 show that evicted RNA polymerases reassociate rapidly with post-replicative chromatin and proceed into an unusual transcription cycle, bypassing regular controls and creating a temporary window for altered gene expression. Two recent studies in Molecular Cell and Nature show that evicted RNA polymerases reassociate rapidly with post-replicative chromatin and proceed into an unusual transcription cycle, bypassing regular controls and creating a temporary window for altered gene expression. [ABSTRACT FROM AUTHOR]

The description of perturbed particle conformations needs as a prerequisite the algorithm of unperturbed chains which is outlined in Paper I [J. Chem. Phys. 143, 114906 (2015)]. The mean square segment length 〈r²(n)〉= b²n2ν with ν = 0.588 for linear chains in a good solvent is used as an approximation also for branched samples. The mean square radius of gyration is easily derived, but for the hydrodynamic, the segment distribution by Domb et al. [Proc. Phys. Soc., London 85, 624 (1965)] is required. Both radii can analytically be expressed by Gamma functions. For the angular dependence of scattered light, the Fourier transform of the Domb distribution for self-avoiding random walk is needed, which cannot be obtained as an analytical function and was derived by numerical integration. The summation over all segment length in the particle was performed with an analytic fit-curve for the Fourier transform and was carried out numerically. Results were derived (i) for uniform and polydisperse linear chains, (ii) or f -functional randomly branched polymers and their monodisperse fractions, (iii) for random A3B2 co-polymers, and (iv) for AB2 hyper-branched samples. The deviation of the Gaussian approximation with the variance of 〈r²(n)〉= b²n2ν slightly overestimates the excluded volume interaction but still remains a fairly good approximation for region of qRg < 10. [ABSTRACT FROM AUTHOR]

The chromatin environment at origins of replication is thought to influence DNA replication initiation in eukaryotic genomes. However, it remains unclear how and which chromatin features control the firing of early-efficient (EE) or late-inefficient (LI) origins. Here, we use site-specific recombination and single-locus chromatin isolation to purify EE and LI replication origins in Saccharomyces cerevisiae. Using mass spectrometry, we define the protein composition of native chromatin regions surrounding the EE and LI replication start sites. In addition to known origin interactors, we find the microtubule-binding Ask1/DASH complex as an origin-regulating factor. Strikingly, tethering of Ask1 to individual origin sites advances replication timing (RT) of the targeted chromosomal domain. Targeted degradation of Ask1 globally changes RT of a subset of origins, which can be reproduced by inhibiting microtubule dynamics. Thus, our findings mechanistically connect RT and chromosomal organization via Ask1/DASH with the microtubule cytoskeleton. [Display omitted] • Single-locus chromatin isolation shows distinct protein interactions at EE/LI origins • Ask1/DASH complex can regulate replication timing of ∼450 chromosomal locations • Ask1-activated regions are enriched for EE replication origins • Ask1-repressed regions are preferentially located at LI and inter-origin locations Weiβ et al. establish a system of native single-locus chromatin isolation in yeast to identify proteins associated with distinct early-efficient (EE) or late-inefficient (LI) replication origins. The results identify the microtubule-binding Ask1/DASH complex as an origin-regulating factor that connects chromosomal organization in the nucleus with replication timing control. [ABSTRACT FROM AUTHOR]

Transcription–replication conflicts occur when the two critical cellular machineries responsible for gene expression and genome duplication collide with each other on the same genomic location. Although both prokaryotic and eukaryotic cells have evolved multiple mechanisms to coordinate these processes on individual chromosomes, it is now clear that conflicts can arise due to aberrant transcription regulation and premature proliferation, leading to DNA replication stress and genomic instability. As both are considered hallmarks of aging and human diseases such as cancer, understanding the cellular consequences of conflicts is of paramount importance. In this article, we summarize our current knowledge on where and when collisions occur and how these encounters affect the genome and chromatin landscape of cells. Finally, we conclude with the different cellular pathways and multiple mechanisms that cells have put in place at conflict sites to ensure the resolution of conflicts and accurate genome duplication. [ABSTRACT FROM AUTHOR]

The article discusses the process by which the former website of the archived cabinet protocols of the 1966-1970 state government of North Rhine-Westphalia, Germany http://protokolle.archive.nrw.de/ was updated using the screenshot archiving software tools Pablo, HTTrack, and Heritrix. Alleged difficulties associated with long-term online digital archiving are identified along with intricacies of preserving dynamic web content and linking.

Background: The incidence and prevalence of acute and chronic pancreatitis have increased in Western countries. It is likely, the number of hospital admissions has increased correspondingly., Aims: To analyze the trends in hospital admissions in the Netherlands for acute and chronic pancreatitis from 1992 to 2004 and to forecast the number of admissions up to 2010., Methods: Analysis of hospital admissions for acute and chronic pancreatitis accumulated in a nationwide database. Curve fitting regression models were used to explore future trends., Results: The number of acute pancreatitis admissions rose in 1992-2004 from 1,785 to 3,120 (74.8% increase). The overall 'annual number' of acute pancreatitis admissions increased from 11.8 to 19.2 per 100,000 person-years. The linear regression model predicted 3,205 [95% confidence intervals (CI), 3,111-3,299] and 3,537 (95% CI, 3,429-3,645) admissions for 2007 and 2010, respectively, a further increase of at least 9.9% in 2010 compared with 2004. In the 12-year time period, chronic pancreatitis admissions showed an increase of 75.4% (from 790 to 1,386). The overall 'annual number' of chronic pancreatitis admissions increased from 5.2 to 8.5 per 100,000 person-years. The cubic regression model predicted 1868 (95% CI, 1,619-2,117) and 3,173 (95% CI, 2,456-3,890) admissions for 2007 and 2010, respectively, an additional increase of 77.2% in 2010 compared with 2004., Conclusion: Hospital admissions for acute and chronic pancreatitis have increased substantially from 1992-2004. This trend will most likely continue for the near future and the burden and costs to the Dutch health care system will increase accordingly.