A Polynomial-time Bicriteria Approximation Scheme for Planar Bisection

Given an undirected graph with edge costs and node weights, the minimum bisection problem asks for a partition of the nodes into two parts of equal weight such that the sum of edge costs between the parts is minimized. We give a polynomial time bicriteria approximation scheme for bisection on planar graphs. Specifically, let $W$ be the total weight of all nodes in a planar graph $G$. For any constant $\varepsilon > 0$, our algorithm outputs a bipartition of the nodes such that each part weighs at most $W/2 + \varepsilon$ and the total cost of edges crossing the partition is at most $(1+\varepsilon)$ times the total cost of the optimal bisection. The previously best known approximation for planar minimum bisection, even with unit node weights, was $O(\log n)$. Our algorithm actually solves a more general problem where the input may include a target weight for the smaller side of the bipartition.Comment: To appear in STOC 201

Nuclear organisation and replication timing are coupled through RIF1-PP1 interaction

Three-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing programme and, if so, how. Here we demonstrate that RIF1 is a molecular hub that co-regulates both processes. Both nuclear organisation and replication timing depend upon the interaction between RIF1 and PP1. However, whereas nuclear architecture requires the full complement of RIF1 and its interaction with PP1, replication timing is not sensitive to RIF1 dosage. The role of RIF1 in replication timing also extends beyond its interaction with PP1. Availing of this separation-of-function approach, we have therefore identified in RIF1 dual function the molecular bases of the co-dependency of the replication-timing programme and nuclear architecture

Cohesin depleted cells pass through mitosis and reconstitute a functional nuclear architecture

The human genome forms thousands of “contact domains”, which are intervals of enhanced contact frequency. Some, called “loop domains” are thought to form by cohesin-mediated loop extrusion. Others, called “compartmental domains”, form due to the segregation of active and inactive chromatin into A and B compartments. Recently, Hi-C studies revealed that the depletion of cohesin leads to the disappearance of all loop domains within a few hours, but strengthens compartment structure. Here, we combine live cell microscopy, super-resolution microscopy, Hi-C, and studies of replication timing to examine the longer-term consequences of cohesin degradation in HCT-116 human colorectal carcinoma cells, tracking cells for up to 30 hours. Surprisingly, cohesin depleted cells proceed through an aberrant mitosis, yielding a single postmitotic cell with a multilobulated nucleus. Hi-C reveals the continued disappearance of loop domains, whereas A and B compartments are maintained. In line with Hi-C, microscopic observations demonstrate the reconstitution of chromosome territories and chromatin domains. An interchromatin channel system (IC) expands between chromatin domain clusters and carries splicing speckles. The IC is lined by active chromatin enriched for RNA Pol II and depleted in H3K27me3. Moreover, the cells exhibit typical early-, mid-, and late- DNA replication timing patterns. Our observations indicate that the functional nuclear compartmentalization can be maintained in cohesin depleted pre- and postmitotic cells. However, we find that replication foci – sites of active DNA synthesis – become physically larger consistent with a model where cohesin dependent loop extrusion tends to compact intervals of replicating chromatin, whereas their genomic boundaries are associated with compartmentalization, and do not change.3D FISH3D fluorescence in situ hybridization3D SIM3D structured illumination microscopyAIDauxin inducible degronANC / INCactive / inactive nuclear compartmentCTchromosome territoryCD(C)chromatin domain (cluster)CTCFCCCTC binding factorDAPI4’,6-diamidino-2-phenylindoleEdU5-Ethynyl-2’-deoxyuridineHi-Cchromosome conformation capturing combined with deep sequencingICinterchromatin compartmentMLNmultilobulated nucleusNCnucleosome clusterPBSphosphate buffered salinePBSTphosphate buffered saline with 0.02% TweenPRperichromatin regionRDreplication domainRLreplication labelingTADtopologically associating domai

Cohesin depleted cells rebuild functional nuclear compartments after endomitosis

Cohesin plays an essential role in chromatin loop extrusion, but its impact on a compartmentalized nuclear architecture, linked to nuclear functions, is less well understood. Using live-cell and super-resolved 3D microscopy, here we find that cohesin depletion in a human colon cancer derived cell line results in endomitosis and a single multilobulated nucleus with chromosome territories pervaded by interchromatin channels. Chromosome territories contain chromatin domain clusters with a zonal organization of repressed chromatin domains in the interior and transcriptionally competent domains located at the periphery. These clusters form microscopically defined, active and inactive compartments, which likely correspond to A/B compartments, which are detected with ensemble Hi-C. Splicing speckles are observed nearby within the lining channel system. We further observe that the multilobulated nuclei, despite continuous absence of cohesin, pass through S-phase with typical spatio-temporal patterns of replication domains. Evidence for structural changes of these domains compared to controls suggests that cohesin is required for their full integrity

Static charged perfect fluid spheres in general relativity

Interior perfect fluid solutions for the Reissner-Nordstrom metric are studied on the basis of a new classification scheme. General formulas are found in many cases. Explicit new global solutions are given as illustrations. Known solutions are briefly reviewed.Comment: 23 pages, Revtex (galley), journal version, to appear in Phys.Rev.

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation o

Replication timing maintains the global epigenetic state in human cells

ACKNOWLEDGMENTS We thank R. Didier and B. Alexander of the FSU Flow Cytometry and Confocal Microscopy Facilities for their help with flow cytometry and fluorescence-activated cell sorting for this project. Thanks to A. Brown of the FSU Biological Science Core Labs and to Y. Yang and C. Vied of the FSU Translational Labs. Thanks to S. R. Westermann of SCIGRAPHIX for generating the model figure. Thanks to B. van Steensel, J. Phillips-Cremins, and P. Fraser for critical reading of the manuscript. Funding: This work was supported by NIH grant GM083337 to D.M.G., GM035463 to V.G.C., and GM085354 to D.M.G., S.D., and V.G.C. D.L. is supported by the Hong Kong Research Grant Council (ECS 26104216). T.B. is supported by the William C. and Joyce C. O’Neil Charitable Trust, Memorial Sloan Kettering Single Cell Sequencing InitiativePeer reviewedPostprin

Pionska apsorpcija u 4He

This paper presents a large solid angle measurement of the positive pion absorption cross-section on 4He and its decomposition into partial channels. A large fraction of the absorption cross-section at incident pion kinetic energies of Tπ+ =70, 118, 162, 239, and 330 MeV is due to multinucleon channels.Daju se ishodi mjerenja pod velikim prostornim kutom udarnog presjeka za apsorpciju pozitivnih piona u He4 i razdjela na pojedine kanale. Velik dio apsorpcijskog udarnog presjeka za energije upadnih piona od Tπ+ =70, 118, 162, 239 i 330 MeV je posljedica višenukleonskih kanala

Pionska apsorpcija u 4He

This paper presents a large solid angle measurement of the positive pion absorption cross-section on 4He and its decomposition into partial channels. A large fraction of the absorption cross-section at incident pion kinetic energies of Tπ+ =70, 118, 162, 239, and 330 MeV is due to multinucleon channels.Daju se ishodi mjerenja pod velikim prostornim kutom udarnog presjeka za apsorpciju pozitivnih piona u He4 i razdjela na pojedine kanale. Velik dio apsorpcijskog udarnog presjeka za energije upadnih piona od Tπ+ =70, 118, 162, 239 i 330 MeV je posljedica višenukleonskih kanala