572 research outputs found
Reconstitution of licensed replication origins on Xenopus sperm nuclei using purified proteins
BACKGROUND: In order to ensure precise chromosome duplication, eukaryotes "license" their replication origins during late mitosis and early G1 by assembling complexes of Mcm2-7 onto them. Mcm2-7 are essential for DNA replication, but are displaced from origins as they initiate, thus ensuring that no origin fires more than once in a single cell cycle. RESULTS: Here we show that a combination of purified nucleoplasmin, the origin recognition complex (ORC), Cdc6, RLF-B/Cdt1 and Mcm2-7 can promote functional origin licensing and the assembly of Mcm2-7 onto Xenopus sperm nuclei. The reconstituted reaction is inhibited by geminin, a specific RLF-B/Cdt1 inhibitor. Interestingly, the purified ORC used in the reconstitution had apparently lost the Orc6 subunit, suggesting that Orc6 is not essential for replication licensing. We use the reconstituted system to make a preliminary analysis of the different events occuring during origin assembly, and examine their nucleotide requirements. We show that the loading of Xenopus ORC onto chromatin is strongly stimulated by both ADP, ATP and ATP-γ-S whilst the loading of Cdc6 and Cdt1 is stimulated only by ATP or ATP-γ-S. CONCLUSIONS: Nucleoplasmin, ORC, Cdc6, RLF-B/Cdt1 and Mcm2-7 are the only proteins required for functional licensing and the loading of Mcm2-7 onto chromatin. The requirement for nucleoplasmin probably only reflects a requirement to decondense sperm chromatin before ORC can bind to it. Use of this reconstituted system should allow a full biochemical analysis of origin licensing and Mcm2-7 loading
Incommensurate antiferromagnetic order in the manifoldly-frustrated SrTbO with transition temperature up to 4.28 K
The Nel temperature of the new frustrated family of
Sr\emph{RE}O (\emph{RE} = rare earth) compounds is yet limited to
0.9 K, which more or less hampers a complete understanding of the
relevant magnetic frustrations and spin interactions. Here we report on a new
frustrated member to the family, SrTbO with a record =
4.28(2) K, and an experimental study of the magnetic interacting and
frustrating mechanisms by polarized and unpolarized neutron scattering. The
compound SrTbO displays an incommensurate antiferromagnetic (AFM) order
with a transverse wave vector \textbf{Q} = (0.5924(1),
0.0059(1), 0) albeit with partially-ordered moments, 1.92(6) at
0.5 K, stemming from only one of the two inequivalent Tb sites mainly by virtue
of their different octahedral distortions. The localized moments are confined
to the \emph{bc} plane, 11.9(66) away from the \emph{b} axis probably
by single-ion anisotropy. We reveal that this AFM order is dominated mainly by
dipole-dipole interactions and disclose that the octahedral distortion,
nearest-neighbour (NN) ferromagnetic (FM) arrangement, different next NN FM and
AFM configurations, and in-plane anisotropic spin correlations are vital to the
magnetic structure and associated multiple frustrations. The discovery of the
thus far highest AFM transition temperature renders SrTbO a new
friendly frustrated platform in the family for exploring the nature of magnetic
interactions and frustrations.Comment: 19 pages, 8 Figures, 1 Tabl
Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb
The behavior of adult-born cells can be easily monitored in cell culture or in lower model organisms, but longitudinal observation of individual mammalian adult-born cells in their native microenvironment still proves to be a challenge. Here we have established an approach named optical cell positioning system for long-term in vivo single-cell tracking, which integrates red-green-blue cell labeling with repeated angiography. By combining this approach with in vivo two-photon imaging technique, we characterized the in vivo migration patterns of adult-born neurons in the olfactory bulb. In contrast to the traditional view of mere radial migration of adult-born cells within the bulb, we found that juxtaglomerular cells switch from radial migration to long distance lateral migration upon arrival in their destination layer. This unique long-distance lateral migration has characteristic temporal (stop-and-go) and spatial (migratory, unidirectional or multidirectional) patterns, with a clear cell age-dependent decrease in the migration speed. The active migration of adult-born cells coincides with the time period of initial fate determination and is likely to impact on the integration sites of adult-born cells, their odor responsiveness, as well as their survival rate
An optimal series expansion of the multiparameter fractional Brownian motion
We derive a series expansion for the multiparameter fractional Brownian
motion. The derived expansion is proven to be rate optimal.Comment: 21 pages, no figures, final version, to appear in Journal of
Theoretical Probabilit
Bright fluorogenic squaraines with tuned cell entry for selective imaging of plasma membrane vs. endoplasmic reticulum
Novel loci and pathways significantly associated with longevity
Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(−5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity
Instabilities in extreme magnetoconvection
Thermal convection in an electrically conducting fluid (for example, a liquid
metal) in the presence of a static magnetic field is considered in this
chapter. The focus is on the extreme states of the flow, in which both buoyancy
and Lorentz forces are very strong. It is argued that the instabilities
occurring in such flows are often of unique and counter-intuitive nature due to
the action of the magnetic field, which suppresses conventional turbulence and
gives preference to two-dimensional instability modes not appearing in more
conventional convection systems. Tools of numerical analysis suitable for such
flows are discussed
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