A DNA damage and stress inducible G protein-coupled receptor blocks cells in G2/M

Cell cycle progression is monitored by highly coordinated checkpoint machinery, which is activated to induce cell cycle arrest until defects like DNA damage are corrected. We have isolated an anti-proliferative cell cycle regulator named G2A (for G2 accumulation), which is predominantly expressed in immature T and B lymphocyte progenitors and is a member of the seven membrane-spanning G protein-coupled receptor family. G2A overexpression attenuates the transformation potential of BCR-ABL and other oncogenes, and leads to accumulation of cells at G2/M independently of p53 and c-Abl. G2A can be induced in lymphocytes and to a lesser extent in nonlymphocyte cell lines or tissues by multiple stimuli including different classes of DNA-damaging agents and serves as a response to damage and cellular stimulation which functions to slow cell cycle progression.

CIKS, a connection to IκB kinase and stress-activated protein kinase

Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-κB and AP-1/ATF families. Activation of NF-κB factors is thought to be mediated primarily via IκB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKα and IKKβ are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-κB essential modulator)/IKKγ. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKγ in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-κB-dependent reporter. Activation of NF-κB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins.

A Selaginella lepidophylla Trehalose-6-Phosphate Synthase Complements Growth and Stress-Tolerance Defects in a Yeast tps1 Mutant1

The accumulation of the disaccharide trehalose in anhydrobiotic organisms allows them to survive severe environmental stress. A plant cDNA, SlTPS1, encoding a 109-kD protein, was isolated from the resurrection plant Selaginella lepidophylla, which accumulates high levels of trehalose. Protein-sequence comparison showed that SlTPS1 shares high similarity to trehalose-6-phosphate synthase genes from prokaryotes and eukaryotes. SlTPS1 mRNA was constitutively expressed in S. lepidophylla. DNA gel-blot analysis indicated that SlTPS1 is present as a single-copy gene. Transformation of a Saccharomyces cerevisiae tps1Δ mutant disrupted in the ScTPS1 gene with S. lepidophylla SlTPS1 restored growth on fermentable sugars and the synthesis of trehalose at high levels. Moreover, the SlTPS1 gene introduced into the tps1Δ mutant was able to complement both deficiencies: sensitivity to sublethal heat treatment at 39°C and induced thermotolerance at 50°C. The osmosensitive phenotype of the yeast tps1Δ mutant grown in NaCl and sorbitol was also restored by the SlTPS1 gene. Thus, SlTPS1 protein is a functional plant homolog capable of sustaining trehalose biosynthesis and could play a major role in stress tolerance in S. lepidophylla.

Ergodic theorems along sequences and Hardy fields.

Let a(x) be a real function with a regular growth as x --> infinity. [The precise technical assumption is that a(x) belongs to a Hardy field.] We establish sufficient growth conditions on a(x) so that the sequence ([a(n)])(infinity)(n=1) is a good averaging sequence in L2 for the pointwise ergodic theorem. A sequence (an) of positive integers is a good averaging sequence in L2 for the pointwise ergodic theorem if in any dynamical system (Omega, Sigma, m, T) for f [symbol, see text] in L2(Omega) the averages [equation, see text] converge for almost every omicron in. Our result implies that sequences like ([ndelta]), where delta > 1 and not an integer, ([n log n]), and ([n2/log n]) are good averaging sequences for L2. In fact, all the sequences we examine will turn out to be good averaging for Lp, p > 1; and even for L log L. We will also establish necessary and sufficient growth conditions on a(x) so that the sequence ([a(n)]) is good averaging for mean convergence. Note that for some a(x) (e.g., a(x) = log2 x), ([a(n)]) may be good for mean convergence without being good for pointwise convergence.

Cosmic velocity fields and their interpretation

We review the current status of our knowledge of cosmic velocity fields, on both small and large scales. A new statistic is described that characterizes the incoherent, thermal component of the velocity field on scales less than 2h−1 Mpc (h is H0/100 km·s−1·Mpc−1, where H0 is the Hubble constant and 1 Mpc = 3.09 × 1022 m) and smaller. The derived velocity is found to be quite stable across different catalogs and is of remarkably low amplitude, consistent with an effective Ω ∼ 0.15 on this scale. We advocate the use of this statistic as a standard diagnostic of the small-scale kinetic energy of the galaxy distribution. The analysis of large-scale flows probes the velocity field on scales of 10–60 h−1 Mpc and should be adequately described by linear perturbation theory. Recent work has focused on the comparison of gravity or density fields derived from whole-sky redshift surveys of galaxies [e.g., the Infrared Astronomical Satellite (IRAS)] with velocity fields derived from a variety of sources. All the algorithms that directly compare the gravity and velocity fields suggest low values of the density parameter, while the POTENT analysis, using the same data but comparing the derived IRAS galaxy density field with the Mark-III derived matter density field, leads to much higher estimates of the inferred density. Since the IRAS and Mark-III fields are not fully consistent with each other, the present discrepancies might result from the very different weighting applied to the data in the competing methods.

The sigma factor sigma s affects antibiotic production and biological control activity of Pseudomonas fluorescens Pf-5.

Pseudomonas fluorescens Pf-5, a rhizosphere-inhabiting bacterium that suppresses several soilborne pathogens of plants, produces the antibiotics pyrrolnitrin, pyoluteorin, and 2,4-diacetylphloroglucinol. A gene necessary for pyrrolnitrin production by Pf-5 was identified as rpoS, which encodes the stationary-phase sigma factor sigma s. Several pleiotropic effects of an rpoS mutation in Escherichia coli also were observed in an RpoS- mutant of Pf-5. These included sensitivities of stationary-phase cells to stresses imposed by hydrogen peroxide or high salt concentration. A plasmid containing the cloned wild-type rpoS gene restored pyrrolnitrin production and stress tolerance to the RpoS- mutant of Pf-5. The RpoS- mutant overproduced pyoluteorin and 2,4-diacetyl-phloroglucinol, two antibiotics that inhibit growth of the phytopathogenic fungus Pythium ultimum, and was superior to the wild type in suppression of seedling damping-off of cucumber caused by Pythium ultimum. When inoculated onto cucumber seed at high cell densities, the RpoS- mutant did not survive as well as the wild-type strain on surfaces of developing seedlings. Other stationary-phase-specific phenotypes of Pf-5, such as the production of cyanide and extracellular protease(s) were expressed by the RpoS- mutant, suggesting that sigma s is only one of the sigma factors required for the transcription of genes in stationary-phase cells of P. fluorescens. These results indicate that a sigma factor encoded by rpoS influences antibiotic production, biological control activity, and survival of P. fluorescens on plant surfaces.