Calcium signalling links MYC to NUAK1

NUAK1 is a member of the AMPK-related family of kinases. Recent evidence suggests that NUAK1 is an important regulator of cell adhesion and migration, cellular and organismal metabolism, and regulation of TAU stability. As such, NUAK1 may play key roles in multiple diseases ranging from neurodegeneration to diabetes and metastatic cancer. Previous work revealed a crucial role for NUAK1 in supporting viability of tumour cells specifically when MYC is overexpressed. This role is surprising, given that NUAK1 is activated by the tumour suppressor LKB1. Here we show that, in tumour cells lacking LKB1, NUAK1 activity is maintained by an alternative pathway involving calcium-dependent activation of PKCα. Calcium/PKCα-dependent activation of NUAK1 supports engagement of the AMPK-TORC1 metabolic checkpoint, thereby protecting tumour cells from MYC-driven cell death, and indeed, MYC selects for this pathway in part via transcriptional regulation of PKCα and ITPR. Our data point to a novel role for calcium in supporting tumour cell viability and clarify the synthetic lethal interaction between NUAK1 and MYC

The SseC translocon component in Salmonella enterica serovar Typhimurium is chaperoned by SscA

Background: Salmonella enterica is a causative agent of foodborne gastroenteritis and the systemic disease known as typhoid fever. This bacterium uses two type three secretion systems (T3SSs) to translocate protein effectors into host cells to manipulate cellular function. Salmonella pathogenicity island (SPI)-2 encodes a T3SS required for intracellular survival of the pathogen. Genes in SPI-2 include apparatus components, secreted effectors and chaperones that bind to secreted cargo to coordinate their release from the bacterial cell. Although the effector repertoire secreted by the SPI-2 T3SS is large, only three virulence-associated chaperones have been characterized. Results: Here we report that SscA is the chaperone for the SseC translocon component. We show that SscA and SseC interact in bacterial cells and that deletion of sscA results in a loss of SseC secretion, which compromises intracellular replication and leads to a loss of competitive fitness in mice. Conclusions: This work completes the characterization of the chaperone complement within SPI-2 and identifies SscA as the chaperone for the SseC translocon

Production of Milky Way structure by the Magellanic Clouds

Previous attempts at disturbing the galactic disk by the Magellanic Clouds relied on direct tidal forcing. However, by allowing the halo to actively respond rather than remain a rigid contributor to the rotation curve, the Clouds may produce a wake in the halo which then distorts the disk. Recent work reported here suggests that the Magellanic Clouds use this mechanism to produce disk distortions sufficient to account for both the radial location, position angle and sign of the HI warp and observed anomalies in stellar kinematics towards the galactic anticenter and LSR motion.Comment: 8 pages, uuencoded compressed PostScript, no figures, html version with figures and mpeg simulations available at http://www-astro.phast.umass.edu/Preprints/martin/martin1/lmc_online.htm

Online discussion compensates for suboptimal timing of supportive information presentation in a digitally supported learning environment

This study used a sequential set-up to investigate the consecutive effects of timing of supportive information presentation (information before vs. information during the learning task clusters) in interactive digital learning materials (IDLMs) and type of collaboration (personal discussion vs. online discussion) in computer-supported collaborative learning (CSCL) on student knowledge construction. Students (N = 87) were first randomly assigned to the two information presentation conditions to work individually on a case-based assignment in IDLM. Students who received information during learning task clusters tended to show better results on knowledge construction than those who received information only before each cluster. The students within the two separate information presentation conditions were then randomly assigned to pairs to discuss the outcomes of their assignments under either the personal discussion or online discussion condition in CSCL. When supportive information had been presented before each learning task cluster, online discussion led to better results than personal discussion. When supportive information had been presented during the learning task clusters, however, the online and personal discussion conditions had no differential effect on knowledge construction. Online discussion in CSCL appeared to compensate for suboptimal timing of presentation of supportive information before the learning task clusters in IDLM

Peripheral blood lymphocyte number and phenotype prior to therapy correlate with response in subcutaneously applied rIL-2 therapy of renal cell carcinoma.

The phenotype of peripheral blood lymphocytes of 27 renal cell carcinoma patients before and at the end of subcutaneously given rIL-2 therapy was determined by two colour flow cytometry. Therapy induced changes in peripheral blood leucocyte composition and phenotypes were comparable to those reported for intravenously given rIL-2. The present paper shows a correlation between the 'activation status' of the patient before therapy and eventual response

Density Waves Inside Inner Lindblad Resonance: Nuclear Spirals in Disk Galaxies

We analyze formation of grand-design two-arm spiral structure in the nuclear regions of disk galaxies. Such morphology has been recently detected in a number of objects using high-resolution near-infrared observations. Motivated by the observed (1) continuity between the nuclear and kpc-scale spiral structures, and by (2) low arm-interarm contrast, we apply the density wave theory to explain the basic properties of the spiral nuclear morphology. In particular, we address the mechanism for the formation, maintenance and the detailed shape of nuclear spirals. We find, that the latter depends mostly on the shape of the underlying gravitational potential and the sound speed in the gas. Detection of nuclear spiral arms provides diagnostics of mass distribution within the central kpc of disk galaxies. Our results are supported by 2D numerical simulations of gas response to the background gravitational potential of a barred stellar disk. We investigate the parameter space allowed for the formation of nuclear spirals using a new method for constructing a gravitational potential in a barred galaxy, where positions of resonances are prescribed.Comment: 18 pages, 9 figures, higher resolution available at http://www.pa.uky.edu/~ppe/papers/nucsp.ps.g

Early sCD8 plasma levels during subcutaneous rIl-2 therapy in patients with renal cell carcinoma correlate with response.

Plasma sIl-2R and sCD8 levels of 12 patients with renal cell carcinoma were determined before and during subcutaneous rIl-2 therapy. Patients with a complete/partial remission showed a significantly stronger initial increase of sCD8 compared to patients with stable disease or tumour progression