A dynamic mode of mitotic bookmarking by transcription factors.

During mitosis, transcription is shut off, chromatin condenses, and most transcription factors (TFs) are reported to be excluded from chromosomes. How do daughter cells re-establish the original transcription program? Recent discoveries that a select set of TFs remain bound on mitotic chromosomes suggest a potential mechanism for maintaining transcriptional programs through the cell cycle termed mitotic bookmarking. Here we report instead that many TFs remain associated with chromosomes in mouse embryonic stem cells, and that the exclusion previously described is largely a fixation artifact. In particular, most TFs we tested are significantly enriched on mitotic chromosomes. Studies with Sox2 reveal that this mitotic interaction is more dynamic than in interphase and is facilitated by both DNA binding and nuclear import. Furthermore, this dynamic mode results from lack of transcriptional activation rather than decreased accessibility of underlying DNA sequences in mitosis. The nature of the cross-linking artifact prompts careful re-examination of the role of TFs in mitotic bookmarking

A Survey for EHB Stars in the Galactic Bulge

We present a progress report on an extensive survey to find and characterize all types of blue horizontal-branch stars in the nuclear bulge of the Galaxy. We have obtained wide, shallow imaging in UBV of ~12 square degrees in the bulge, with follow-up spectroscopy for radial velocities and metal abundance determinations. We have discovered a number of metal-rich blue HB stars, whose presence in the bulge is expected by the interpretation of the extragalactic ultraviolet excess. Very deep images have been obtained in UBV and SDSS u along the bulge minor axis, which reveal a significant number of EHB candidates fainter than B = 19, i.e., with the same absolute magnitudes as EHB stars in several globular clusters.Comment: To appear in "Extreme Horizontal Branch Stars and Related Objects", Astrophysics and Space Science, Kluwer Academic Publishers, proceedings of the meeting held in Keele, UK, June 16-20, 200

Pyrrolidine Derivative Targets Actin Cytoskeleton in MCF-7 Breast Cancer Cells

Recent research has brought pyrrolidine derivatives into consideration for the development of anticancer drugs with high efficacy and low toxicity. Dr. Hansen’s lab at DePauw has synthesized a pyrrolidine derivative that demonstrated anticancer activity. However, there are many ways a compound can affect cancer cells. In this research, we decided to investigate the mechanism of action of this new compound, specifically on MCF-7 breast cancer cell line. Based on the results, we believe that there is a great likelihood that the pyrrolidine derivative can induce apoptosis (cell death) and disrupt cell movement in MCF-7 cells. In other words, these are strong indicators that this compound can inhibit both early and late-stage cancer cells

Automatic cell segmentation by adaptive thresholding (ACSAT) for large-scale calcium imaging datasets

Advances in calcium imaging have made it possible to record from an increasingly larger number of neurons simultaneously. Neuroscientists can now routinely image hundreds to thousands of individual neurons. An emerging technical challenge that parallels the advancement in imaging a large number of individual neurons is the processing of correspondingly large datasets. One important step is the identification of individual neurons. Traditional methods rely mainly on manual or semimanual inspection, which cannot be scaled for processing large datasets. To address this challenge, we focused on developing an automated segmentation method, which we refer to as automated cell segmentation by adaptive thresholding (ACSAT). ACSAT works with a time-collapsed image and includes an iterative procedure that automatically calculates global and local threshold values during successive iterations based on the distribution of image pixel intensities. Thus, the algorithm is capable of handling variations in morphological details and in fluorescence intensities in different calcium imaging datasets. In this paper, we demonstrate the utility of ACSAT by testing it on 500 simulated datasets, two wide-field hippocampus datasets, a wide-field striatum dataset, a wide-field cell culture dataset, and a two-photon hippocampus dataset. For the simulated datasets with truth, ACSAT achieved >80% recall and precision when the signal-to-noise ratio was no less than ∼24 dB.DP2 NS082126 - NINDS NIH HHSPublished versio

Impact of exercise-nutritional state interactions in patients with type 2 diabetes

Introduction This study examines the role of nutritional status during exercise training in patients with type 2 diabetes mellitus by investigating the effect of endurance-type exercise training in the fasted versus the fed state on clinical outcome measures, glycemic control, and skeletal muscle characteristics in male type 2 diabetes patients. Methods Twenty-five male patients (glycated hemoglobin (HbA1c), 57 ± 3 mmol·mol−1 (7.4% ± 0.3%)) participated in a randomized 12-wk supervised endurance-type exercise intervention, with exercise being performed in an overnight-fasted state (n = 13) or after consuming breakfast (n = 12). Patients were evaluated for glycemic control, blood lipid profiles, body composition and physical fitness, and skeletal muscle gene expression. Results Exercise training was well tolerated without any incident of hypoglycemia. Exercise training significantly decreased whole-body fat mass (−1.6 kg) and increased high-density lipoprotein concentrations (+2 mg·dL−1), physical fitness (+1.7 mL·min−1·kg−1), and fat oxidation during exercise in both groups (PTIME 0.05). HbA1c concentrations significantly decreased after exercise training (PTIME < 0.001), with a significant greater reduction after consuming breakfast (−0.30% ± 0.06%) compared with fasted state (−0.08% ± 0.06%; mean difference, 0.21%; PTIME × GROUP = 0.016). No interaction effects were observed for skeletal muscle genes related to lipid metabolism or oxidative capacity. Conclusions Endurance-type exercise training in the fasted or fed state do not differ in their efficacy to reduce fat mass, increase fat oxidation capacity, and increase cardiorespiratory fitness and high-density lipoprotein concentrations or their risk of hypoglycemia in male patients with type 2 diabetes. HbA1c seems to be improved more with exercise performed in the postprandial compared with the postabsorptive state

An attractor for dark matter structures

Cosmological simulations of dark matter structures have identified a set of universal profiles, and similar characteristics have been seen in non-cosmological simulations. It has therefore been speculated whether these profiles of collisionless systems relate to accretion and merger history, or if there is an attractor for the dark matter systems. Here we identify such a 1-dimensional attractor in the 3-dimensional space spanned by the 2 radial slopes of the density and velocity dispersion, and the velocity anisotropy. This attractor effectively removes one degree of freedom from the Jeans equation. It also allows us to speculate on a new fluid interpretation for the Jeans equation, with an effective polytropic index for the dark matter particles between 1/2 and 3/4. If this attractor solution holds for other collisionless structures, then it may hold the key to break the mass-anisotropy degeneracy, which presently prevents us from measuring the mass profiles in dwarf galaxies uniquely.Comment: 7 pages, 2 figures, comments welcom

Dynamical models with a general anisotropy profile

Both numerical simulations and observational evidence indicate that the outer regions of galaxies and dark matter haloes are typically mildly to significantly radially anisotropic. The inner regions can be significantly non-isotropic, depending on the dynamical formation and evolution processes. In an attempt to break the lack of simple dynamical models that can reproduce this behaviour, we explore a technique to construct dynamical models with an arbitrary density and an arbitrary anisotropy profile. We outline a general construction method and propose a more practical approach based on a parameterized anisotropy profile. This approach consists of fitting the density of the model with a set of dynamical components, each of which have the same anisotropy profile. Using this approach we avoid the delicate fine-tuning difficulties other fitting techniques typically encounter when constructing radially anisotropic models. We present a model anisotropy profile that generalizes the Osipkov-Merritt profile, and that can represent any smooth monotonic anisotropy profile. Based on this model anisotropy profile, we construct a very general seven-parameter set of dynamical components for which the most important dynamical properties can be calculated analytically. We use the results to look for simple one-component dynamical models that generate simple potential-density pairs while still supporting a flexible anisotropy profile. We present families of Plummer and Hernquist models in which the anisotropy at small and large radii can be chosen as free parameters. We also generalize these two families to a three-parameter family that self-consistently generates the set of Veltmann potential-density pairs. (Abridged...)Comment: 18 pages, accepted for publication in A&

A simple analytical model for dark matter halo structure and adiabatic contraction

A simple analytical model for describing inner parts of dark matter halo is considered. It is assumed that dark matter density is power-law. The model deals with dark matter distribution function in phase space of adiabatic invariants (radial action and angular momentum). Two variants are considered for the angular part of the distribution function: narrow and broad distribution. The model allows to describe explicitly the process of adiabatic contraction of halo due to change of gravitational potential caused by condensation of baryonic matter in the centre. The modification of dark matter density in the centre is calculated, and is it shown that the standard algorithm of adiabatic contraction calculation overestimates the compressed halo density, especially in the case of strong radial anisotropy.Comment: 5 pages, 3 figures. v3 - major improvements, another halo model introduced, discussion extende

A statistical-mechanical explanation of dark matter halo properties

Cosmological N-body simulations have revealed many empirical relationships of dark matter halos, yet the physical origin of these halo properties still remains unclear. On the other hand, the attempts to establish the statistical mechanics for self-gravitating systems have encountered many formal difficulties, and little progress has been made for about fifty years. The aim of this work is to strengthen the validity of the statistical-mechanical approach we have proposed previously to explain the dark matter halo properties. By introducing an effective pressure instead of the radial pressure to construct the specific entropy, we use the entropy principle and proceed in a similar way as previously to obtain an entropy stationary equation. An equation of state for equilibrated dark halos is derived from this entropy stationary equation, by which the dark halo density profiles with finite mass can be obtained. We also derive the anisotropy parameter and pseudo-phase-space density profile. All these predictions agree well with numerical simulations in the outer regions of dark halos. Our work provides further support to the idea that statistical mechanics for self-gravitating systems is a viable tool for investigation.Comment: 5 pages, 4 figures, Accepted by A&