De Sitter and Schwarzschild-De Sitter According to Schwarzschild and De Sitter

When de Sitter first introduced his celebrated spacetime, he claimed, following Schwarzschild, that its spatial sections have the topology of the real projective space RP^3 (that is, the topology of the group manifold SO(3)) rather than, as is almost universally assumed today, that of the sphere S^3. (In modern language, Schwarzschild was disturbed by the non-local correlations enforced by S^3 geometry.) Thus, what we today call "de Sitter space" would not have been accepted as such by de Sitter. There is no real basis within classical cosmology for preferring S^3 to RP^3, but the general feeling appears to be that the distinction is in any case of little importance. We wish to argue that, in the light of current concerns about the nature of de Sitter space, this is a mistake. In particular, we argue that the difference between "dS(S^3)" and "dS(RP^3)" may be very important in attacking the problem of understanding horizon entropies. In the approach to de Sitter entropy via Schwarzschild-de Sitter spacetime, we find that the apparently trivial difference between RP^3 and S^3 actually leads to very different perspectives on this major question of quantum cosmology.Comment: 26 pages, 8 figures, typos fixed, references added, equation numbers finally fixed, JHEP versio

CENP-E Function at Kinetochores Is Essential for Chromosome Alignment

CENP-E is a kinesin-like protein that binds to kinetochores and may provide functions that are critical for normal chromosome motility during mitosis. To directly test the in vivo function of CENP-E, we microinjected affinity-purified antibodies to block the assembly of CENP-E onto kinetochores and then examined the behavior of these chromosomes. Chromosomes lacking CENP-E at their kinetochores consistently exhibited two types of defects that blocked their alignment at the spindle equator. Chromosomes positioned near a pole remained mono-oriented as they were unable to establish bipolar microtubule connections with the opposite pole. Chromosomes within the spindle established bipolar connections that supported oscillations and normal velocities of kinetochore movement between the poles, but these bipolar connections were defective because they failed to align the chromosomes into a metaphase plate

Histone Deacetylase Inhibitors Trigger a G2 Checkpoint in Normal Cells That Is Defective in Tumor Cells

Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic integrity. An increasing number of tumor suppressors are being demonstrated to have roles in checkpoint mechanisms, implying that checkpoint dysfunction is likely to be a common feature of cancers. Here we report that histone deacetylase inhibitors, in particular azelaic bishydroxamic acid, triggers a G2 phase cell cycle checkpoint response in normal human cells, and this checkpoint is defective in a range of tumor cell lines. Loss of this G2 checkpoint results in the tumor cells undergoing an aberrant mitosis resulting in fractured multinuclei and micronuclei and eventually cell death. This histone deacetylase inhibitor-sensitive checkpoint appears to be distinct from G2/M checkpoints activated by genotoxins and microtubule poisons and may be the human homologue of a yeast G2 checkpoint, which responds to aberrant histone acetylation states. Azelaic bishydroxamic acid may represent a new class of anticancer drugs with selective toxicity based on its ability to target a dysfunctional checkpoint mechanism in tumor cells

Human MPS1 Kinase Is Required for Mitotic Arrest Induced by the Loss of CENP-E from Kinetochores

We have determined that the previously identified dual-specificity protein kinase TTK is the human orthologue of the yeast MPS1 kinase. Yeast MPS1 (monopolar spindle) is required for spindle pole duplication and the spindle checkpoint. Consistent with the recently identified vertebrate MPS1 homologues, we found that hMPS1 is localized to centrosomes and kinetochores. In addition, hMPS1 is part of a growing list of kinetochore proteins that are localized to nuclear pores. hMPS1 is required by cells to arrest in mitosis in response to spindle defects and kinetochore defects resulting from the loss of the kinesin-like protein, CENP-E. The pattern of kinetochore localization of hMPS1 in CENP-E defective cells suggests that their interaction with the kinetochore is sensitive to microtubule occupancy rather than kinetochore tension. hMPS1 is required for MAD1, MAD2 but not hBUB1, hBUBR1 and hROD to bind to kinetochores. We localized the kinetochore targeting domain in hMPS1 and found that it can abrogate the mitotic checkpoint in a dominant negative manner. Last, hMPS1 was found to associate with the anaphase promoting complex, thus raising the possibility that its checkpoint functions extend beyond the kinetochore

Dengue

Lecture 49 ISBN e-book : 9781615045754International audienc