TTC5 is required to prevent apoptosis of acute myeloid leukemia stem cells

Using a screening strategy, we identified the tetratricopeptide repeat (TPR) motif protein, Tetratricopeptide repeat domain 5 (TTC5, also known as stress responsive activator of p300 or Strap) as required for the survival of human acute myeloid leukemia (AML) cells. TTC5 is a stress-inducible transcription cofactor known to interact directly with the histone acetyltransferase EP300 to augment the TP53 response. Knockdown (KD) of TTC5 induced apoptosis of both murine and human AML cells, with concomitant loss of clonogenic and leukemia-initiating potential; KD of EP300 elicited a similar phenotype. Consistent with the physical interaction of TTC5 and EP300, the onset of apoptosis following KD of either gene was preceded by reduced expression of BCL2 and increased expression of pro-apoptotic genes. Forced expression of BCL2 blocked apoptosis and partially rescued the clonogenic potential of AML cells following TTC5 KD. KD of both genes also led to the accumulation of MYC, an acetylation target of EP300, and the form of MYC that accumulated exhibited relative hypoacetylation at K148 and K157, residues targeted by EP300. In view of the ability of excess cellular MYC to sensitize cells to apoptosis, our data suggest a model whereby TTC5 and EP300 cooperate to prevent excessive accumulation of MYC in AML cells and their sensitization to cell death. They further reveal a hitherto unappreciated role for TTC5 in leukemic hematopoiesis

The nature of the ISM in galaxies during the star-formation activity peak of the Universe

We combine a semi-analytic model of galaxy formation, tracking atomic and molecular phases of cold gas, with a three-dimensional radiative-transfer and line tracing code to study the sub-mm emission from atomic and molecular species (CO, HCN, [CI], [CII], [OI]) in galaxies. We compare the physics that drives the formation of stars at the epoch of peak star formation (SF) in the Universe (z = 2.0) with that in local galaxies. We find that normal star-forming galaxies at high redshift have much higher CO-excitation peaks than their local counterparts and that CO cooling takes place at higher excitation levels. CO line ratios increase with redshift as a function of galaxy star-formation rate, but are well correlated with H2 surface density independent of redshift. We find an increase in the [OI]/[CII] line ratio in typical star-forming galaxies at z = 1.2 and z = 2.0 with respect to counterparts at z = 0. Our model results suggest that typical star-forming galaxies at high redshift consist of much denser and warmer star-forming clouds than their local counterparts. Galaxies belonging to the tail of the SF activity peak at z = 1.2 are already less dense and cooler than counterparts during the actual peak of SF activity (z = 2.0). We use our results to discuss how future ALMA surveys can best confront our predictions and constrain models of galaxy formation.Comment: 19 pages, 14 figures, accepted for publication in MNRA

Spatial Modelling of Within-Field Weed Populations - a Review

Concerns around herbicide resistance, human risk, and the environmental impacts of current weed control strategies have led to an increasing demand for alternative weed management methods. Many new weed management strategies are under development; however, the poor availability of accurate weed maps, and a lack of confidence in the outcomes of alternative weed management strategies, has hindered their adoption. Developments in field sampling and processing, combined with spatial modelling, can support the implementation and assessment of new and more integrated weed management strategies. Our review focuses on the biological and mathematical aspects of assembling within-field weed models. We describe both static and spatio-temporal models of within-field weed distributions (including both cellular automata (CA) and non-CA models), discussing issues surrounding the spatial processes of weed dispersal and competition and the environmental and anthropogenic processes that affect weed spatial and spatio-temporal distributions. We also examine issues surrounding model uncertainty. By reviewing the current state-of-the-art in both static and temporally dynamic weed spatial modelling we highlight some of the strengths and weaknesses of current techniques, together with current and emerging areas of interest for the application of spatial models, including targeted weed treatments, economic analysis, herbicide resistance and integrated weed management, the dispersal of biocontrol agents, and invasive weed species

Can Photoionization Squelching Resolve the Sub-structure Crisis?

Cold Dark Matter theory predicts that the Local Group should contain many more dwarf-sized objects than the observed number of dwarf galaxies --- the so-called sub-structure problem. We investigate whether the suppression of star formation in these small objects due to the presence of a photoionizing background can resolve the problem. We make use of results from recent hydrodynamic simulations to build a recipe for the suppression of gas infall into semi-analytic galaxy formation models, and use these to predict the luminosity function of dwarf galaxies in the Local Group. In the models without photoionization ``squelching'', we predict a large excess of faint dwarf galaxies compared with the observed number in the Local Group --- thus, the usual recipe for supernovae feedback used in semi-analytic models does not solve the sub-structure problem on its own. When we include photoionization squelching, we find good agreement with the observations. We have neglected tidal destruction, which probably further reduces the number of dwarf galaxies. We conclude that photoionizing squelching easily solves the sub-structure problem. In fact, it is likely that once this effect is taken into account, models with reduced small-scale power (e.g. Warm Dark Matter) would underproduce dwarf galaxies.Comment: LaTeX, 5 pages, 2 figures, Submitted to ApJ Letter

On the Distribution of Haloes, Galaxies and Mass

The stochasticity in the distribution of dark haloes in the cosmic density field is reflected in the distribution function $P_V(N_h|\delta_m)$ which gives the probability of finding $N_h$ haloes in a volume $V$ with mass density contrast $\delta_m$. We study the properties of this function using high-resolution $N$-body simulations, and find that $P_V(N_n|\delta_m)$ is significantly non-Poisson. The ratio between the variance and the mean goes from $\sim 1$ (Poisson) at $1+\delta_m\ll 1$ to $<1$ (sub-Poisson) at $1+\delta_m\sim 1$ to $>1$ (super-Poisson) at $1+\delta_m\gg 1$. The mean bias relation is found to be well described by halo bias models based on the Press-Schechter formalism. The sub-Poisson variance can be explained as a result of halo-exclusion while the super-Poisson variance at high $\delta_m$ may be explained as a result of halo clustering. A simple phenomenological model is proposed to describe the behavior of the variance as a function of $\delta_m$. Galaxy distribution in the cosmic density field predicted by semi-analytic models of galaxy formation shows similar stochastic behavior. We discuss the implications of the stochasticity in halo bias to the modelling of higher-order moments of dark haloes and of galaxies.Comment: 10 pages, 6 figures, Latex using MN2e style. Minor changes. Accepted for publication in MNRA

The Medial Prefrontal Cortex and the Emergence of Self-Conscious Emotion in Adolescence

In the present study, we examined the relationship between developmental modulation of socioaffective brain systems and adolescents’ preoccupation with social evaluation. Child, adolescent, and adult participants viewed cues indicating that a camera was alternately off, warming up, or projecting their image to a peer during the acquisition of behavioral-, autonomic-, and neural-response (functional MRI) data. Believing that a peer was actively watching them was sufficient to induce self-conscious emotion that rose in magnitude from childhood to adolescence and partially subsided into adulthood. Autonomic arousal was uniquely heightened in adolescents. These behavioral patterns were paralleled by emergent engagement of the medial prefrontal cortex (MPFC) and striatum-MPFC connectivity during adolescence, which are thought to promote motivated social behavior in adolescence. These findings demonstrate that adolescents’ self-consciousness is related to age-dependent sensitivity of brain systems critical to socioaffective processes. Further, unique interactions between the MPFC and striatum may provide a mechanism by which social-evaluation contexts influence adolescent behavior.Psycholog

The Role of Ram Pressure Stripping in the Quenching of Cluster Star Formation

Recent observations of galaxy clusters have shown that environmental effects apparently associated with the cluster begin to lower the star formation rates of galaxies at distances as great as three times the cluster virial radius. These observations may indicate preprocessing of cluster galaxies in groups or in the cluster core for galaxies on highly elliptical orbits, but may also imply that the environmental effects due to the cluster are directly affecting galaxies on their first infall. To explore these issues, we investigate different models of ram pressure stripping as it acts on satellite galaxies in clusters, and compare to observations of the radial star formation gradient in clusters. We calculate the location of the accretion shock around model clusters, and use this as the radius of onset of ram pressure stripping in the GALFORM semi-analytic model of galaxy formation. Comparison of the results of our model, and previously considered, simpler ram pressure models, with recent observations indicates that current data is unable to strongly discriminate between models of ram pressure stripping due to the complex interplay of preprocessing effects at work. However, future observations of a larger sample of clusters will likely be able to place stronger constraints on the process of ram pressure stripping and its role in shaping radial trends in and around clusters.Comment: 10 pages, 4 figures, published in the Astrophysical Journa