Identification of a predicted partner-switching system that affects production of the gene transfer agent RcGTA and stationary phase viability in Rhodobacter capsulatus

Background: Production of the gene transfer agent RcGTA in the α-proteobacterium Rhodobacter capsulatus is dependent upon the response regulator protein CtrA. Loss of this regulator has widespread effects on transcription in R. capsulatus, including the dysregulation of numerous genes encoding other predicted regulators. This includes a set of putative components of a partner-switching signaling pathway with sequence homology to the σ-regulating proteins RsbV, RsbW, and RsbY that have been extensively characterized for their role in stress responses in gram-positive bacteria. These R. capsulatus homologues, RbaV, RbaW, and RbaY, have been investigated for their possible role in controlling RcGTA gene expression. Results: A mutant strain lacking rbaW showed a significant increase in RcGTA gene expression and production. Mutation of rbaV or rbaY led to a decrease in RcGTA gene expression and production, and these mutants also showed decreased viability in the stationary phase and produced unusual colony morphologies. In vitro and in vivo protein interaction assays demonstrated that RbaW and RbaV interact. A combination of gene disruptions and protein-protein interaction assays were unsuccessful in attempts to identify a cognate σ factor, and the genetic data support a model where the RbaV protein that is the determinant regulator of RcGTA gene expression in this system. Conclusions: These findings provide new information about RcGTA regulation by a putative partner-switching system and further illustrate the integration of RcGTA production into R. capsulatus physiology

Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling.

Matriptase is an epithelia-specific membrane-anchored serine protease that has received considerable attention in recent years because of its consistent dysregulation in human epithelial tumours, including breast cancer. Mice with reduced levels of matriptase display a significant delay in oncogene-induced mammary tumour formation and blunted tumour growth. The abated tumour growth is associated with a decrease in cancer cell proliferation. Here we demonstrate by genetic deletion and silencing that the proliferation impairment in matriptase-deficient breast cancer cells is caused by their inability to initiate activation of the c-Met signalling pathway in response to fibroblast-secreted pro-HGF. Similarly, inhibition of matriptase catalytic activity using a selective small-molecule inhibitor abrogates the activation of c-Met, Gab1 and AKT, in response to pro-HGF, which functionally leads to attenuated proliferation in breast carcinoma cells. We conclude that matriptase is critically involved in breast cancer progression and represents a potential therapeutic target in breast cancer

The electromagnetic field near a dielectric half-space

We compute the expectations of the squares of the electric and magnetic fields in the vacuum region outside a half-space filled with a uniform non-dispersive dielectric. This gives predictions for the Casimir-Polder force on an atom in the `retarded' regime near a dielectric. We also find a positive energy density due to the electromagnetic field. This would lead, in the case of two parallel dielectric half-spaces, to a positive, separation-independent contribution to the energy density, besides the negative, separation-dependent Casimir energy. Rough estimates suggest that for a very wide range of cases, perhaps including all realizable ones, the total energy density between the half-spaces is positive.Comment: Latex2e, IOP macros, 15 pages, 2 eps figure

An explicit height bound for the classical modular polynomial

For a prime m, let Phi_m be the classical modular polynomial, and let h(Phi_m) denote its logarithmic height. By specializing a theorem of Cohen, we prove that h(Phi_m) <= 6 m log m + 16 m + 14 sqrt m log m. As a corollary, we find that h(Phi_m) <= 6 m log m + 18 m also holds. A table of h(Phi_m) values is provided for m <= 3607.Comment: Minor correction to the constants in Theorem 1 and Corollary 9. To appear in the Ramanujan Journal. 17 pages

21-cm synthesis observations of VIRGOHI 21 - a possible dark galaxy in the Virgo Cluster

Many observations indicate that dark matter dominates the extra-galactic Universe, yet no totally dark structure of galactic proportions has ever been convincingly identified. Previously we have suggested that VIRGOHI 21, a 21-cm source we found in the Virgo Cluster using Jodrell Bank, was a possible dark galaxy because of its broad line-width (~200 km/s) unaccompanied by any visible gravitational source to account for it. We have now imaged VIRGOHI 21 in the neutral-hydrogen line and find what could be a dark, edge-on, spinning disk with the mass and diameter of a typical spiral galaxy. Moreover, VIRGOHI 21 has unquestionably been involved in an interaction with NGC 4254, a luminous spiral with an odd one-armed morphology, but lacking the massive interactor normally linked with such a feature. Numerical models of NGC 4254 call for a close interaction ~10^8 years ago with a perturber of ~10^11 solar masses. This we take as additional evidence for the massive nature of VIRGOHI 21 as there does not appear to be any other viable candidate. We have also used the Hubble Space Telescope to search for stars associated with the HI and find none down to an I band surface brightness limit of 31.1 +/- 0.2 mag/sq. arcsec.Comment: 8 pages, accepted to ApJ, uses emulateapj.cls. Mpeg animation (Fig. 2) available at ftp://ftp.naic.edu/pub/publications/minchin/video2.mp

Cardiovascular Effects of Urocortin 2 and Urocortin 3 in Patients with Chronic Heart Failure

Aims: Urocortin 2 and urocortin 3 may play a role in the pathophysiology of heart failure and are emerging therapeutic targets. We aimed to examine the local and systemic cardiovascular effects of urocortin 2 and urocortin 3 in healthy subjects and patients with heart failure. Methods: Patients with heart failure (n = 8) and age and gender-matched healthy subjects (n = 8) underwent bilateral forearm arterial blood flow measurement using forearm venous occlusion plethysmography during intra-arterial infusions of urocortin 2 (3.6–36 pmol min−1), urocortin 3 (360–3600 pmol min−1) and substance P (2–8 pmol min−1). Heart failure patients (n = 9) and healthy subjects (n = 7) underwent non-invasive impedance cardiography during incremental intravenous infusions of sodium nitroprusside (573–5730 pmol kg−1 min−1 ), urocortin 2 (36–360 pmol min−1 ), urocortin 3 (1.2–12 nmol min−1) and saline placebo. Results: Urocortin 2, urocortin 3 and substance P induced dose-dependent forearm arterial vasodilatation in both groups (P &#60; 0.05 for both) with no difference in magnitude of vasodilatation between patients and healthy subjects. During systemic intravenous infusions, urocortin 3 increased heart rate and cardiac index and reduced mean arterial pressure and peripheral vascular resistance index in both groups (P &#60; 0.01 for all). Urocortin 2 produced similar responses to urocortin 3, although increases in cardiac index and heart rate were only significant in heart failure (P &#60; 0.05) and healthy subjects (P &#60; 0.001), respectively. Conclusion: Urocortins 2 and 3 cause vasodilatation, reduce peripheral vascular resistance and increase cardiac output in both health and disease. These data provide further evidence to suggest that urocortins 2 and 3 continue to hold promise for the treatment of heart failure

Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men.

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment

Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis

Granulocytes are pivotal regulators of tissue injury. However, the transcriptional mechanisms that regulate granulopoiesis under inflammatory conditions are poorly understood. Here we show that the transcriptional coregulator B cell leukemia/lymphoma 3 (Bcl3) limits granulopoiesis under emergency (i.e., inflammatory) conditions, but not homeostatic conditions. Treatment of mouse myeloid progenitors with G-CSF — serum concentrations of which rise under inflammatory conditions — rapidly increased Bcl3 transcript accumulation in a STAT3-dependent manner. Bcl3-deficient myeloid progenitors demonstrated an enhanced capacity to proliferate and differentiate into granulocytes following G-CSF stimulation, whereas the accumulation of Bcl3 protein attenuated granulopoiesis in an NF-κB p50–dependent manner. In a clinically relevant model of transplant-mediated lung ischemia reperfusion injury, expression of Bcl3 in recipients inhibited emergency granulopoiesis and limited acute graft damage. These data demonstrate a critical role for Bcl3 in regulating emergency granulopoiesis and suggest that targeting the differentiation of myeloid progenitors may be a therapeutic strategy for preventing inflammatory lung injury

De groeiende aardappelwereld

Nederland exporteert meer pootaardappelen dan alle andere landen samen. Goed nieuws, want de aardappel heeft nog een grote toekomst voor zich, denkt onderzoeker Anton Haverkort van Plant Research International, onderdeel van Wageningen UR. In opkomende economieën groeit de vraag naar aardappelen snel