Identification of an interchromosomal compartment by polymerization of nuclear-targeted vimentin

A number of structural and functional subnuclear compartments have been described, including regions exclusive of chromosomes previously hypothesized to form a reactive nuclear space. We have now explored this accessible nuclear space and interchromosomal nucleoplasmic domains experimentally using Xenopus vimentin engineered to contain a nuclear localization signal (NLS-vimentin). In stably transfected human cells incubated at 37°C, the NLS-vimentin formed a restricted number of intranuclear speckles. At 28°C, the optimal temperature for assembly of the amphibian protein, NLSvimentin progressively extended with time out from the speckles into strictly orientated intranuclear filamentous arrays. This enabled us to observe the development of a system of interconnecting channel-like areas. Quantitative analysis based on 3-D imaging microscopy revealed that these arrays were localized almost exclusively outside of chromosome territories. During mitosis the filaments disassembled and dispersed throughout the cytoplasm, while in anaphase-telophase the vimentin was recruited back into the nucleus and reassembled into filaments at the chromosome surfaces, in distributions virtually identical to those observed in the previous interphase. The filaments also colocalized with specific nuclear RNAs, coiled bodies and PML bodies, all situated outside of chromosome territories, thereby interlinking these structures. This strongly implies that these nuclear entities coexist in the same interconnected nuclear compartment. The assembling NLS-vimentin is restricted to and can be used to delineate, at least in part, the formerly proposed reticular interchromosomal domain compartment (ICD). The properties of NLS-vimentin make it an excellent tool for performing structural and functional studies on this compartment

Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

Nuclear astrophysics studies with ultra-peripheral heavy-ion collisions

I describe in very simple terms the theoretical tools needed to investigate ultra-peripheral nuclear reactions for nuclear astrophysics purposes. For a more detailed account, see arXiv:0908.4307.Comment: 12 pages, 8 figures, Lecture notes presented at the 5th European Summer School on Experimental Nuclear Astrophysics, Sep. 20- 27, 2009, Santa Tecla, Sicily, Italy. AIP proceedings, to be publishe

Manifestation of finite temperature size effects in nanogranular magnetic graphite

In addition to the double phase transition (with the Curie temperatures T_C=300K and T_{Ct}=144K), a low-temperature anomaly in the dependence of the magnetization is observed in the bulk magnetic graphite (with an average granular size of L=10nm), which is attributed to manifestation of the size effects below the quantum temperature. The best fits of the high-temperature data (using the mean-field Curie-Weiss and Bloch expressions) produced reasonable estimates for the model parameters, such as defects mediated effective spin exchange energy J=12meV (which defines the intragranular Curie temperature T_C) and proximity mediated interactions between neighboring grains (through potential barriers created by thin layers of non-magnetic graphite) with energy J_t=exp(-d/s)J=5.8meV (which defines the intergranular Curie temperature T_{Ct}) with d=1.5nm and s=2nm being the intergranular distance and characteristic length, respectively

Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain

Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation