Maize Unstable factor for orange1 Is Required for Maintaining Silencing Associated with Paramutation at the pericarp color1 and booster1 Loci

To understand the molecular mechanisms underlying paramutation, we examined the role of Unstable factor for orange1 (Ufo1) in maintaining paramutation at the maize pericarp color1 (p1) and booster1 (b1) loci. Genetic tests revealed that the Ufo1-1 mutation disrupted silencing associated with paramutation at both p1 and b1. The level of up regulation achieved at b1 was lower than that at p1, suggesting differences in the role Ufo1-1 plays at these loci. We characterized the interaction of Ufo1-1 with two silenced p1 epialleles, P1-rr′ and P1-pr^TP, that were derived from a common P1-rr ancestor. Both alleles are phenotypically indistinguishable, but differ in their paramutagenic activity; P1-rr′ is paramutagenic to P1-rr, while P1-pr^TP is non-paramutagenic. Analysis of cytosine methylation revealed striking differences within an enhancer fragment that is required for paramutation; P1-rr′ exhibited increased methylation at symmetric (CG and CHG) and asymmetric (CHH) sites, while P1-pr^TP was methylated only at symmetric sites. Both silenced alleles had higher levels of dimethylation of lysine 9 on histone 3 (H3K9me2), an epigenetic mark of silent chromatin, in the enhancer region. Both epialleles were reactivated in the Ufo1-1 background; however, reactivation of P1-rr′ was associated with dramatic loss of symmetric and asymmetric cytosine methylation in the enhancer, while methylation of up-regulated P1-pr^TP was not affected. Interestingly, Ufo1-1–mediated reactivation of both alleles was accompanied with loss of H3K9me2 mark from the enhancer region. Therefore, while earlier studies have shown correlation between H3K9me2 and DNA methylation, our study shows that these two epigenetic marks are uncoupled in the Ufo1-1–reactivated p1 alleles. Furthermore, while CHH methylation at the enhancer region appears to be the major distinguishing mark between paramutagenic and non-paramutagenic p1 alleles, H3K9me2 mark appears to be important for maintaining epigenetic silencing.     

Antimicrobial potential of deep surface sediment associated bacteria from the Sea of Japan

The aim of this study was to survey microorganisms from the deep surface sediment samples collected from the Sea of Japan and to screen them for antimicrobial and antagonistic effects. Phylogenetic analysis revealed most isolates sharing 98–100 % sequence similarity to recognized species, including those recovered previously from marine or saline environments. Alteromonas, Halomonas, Marinobacter, Pseudoalteromonas, Salinicola, within the class Gammaproteobacteria, Sulfitobacter (Alphaproteobacteria), Bacillus, Paenibacillus and Paenisporosarcina (Firmicutes), Nocardiopsis and Streptomyces (Actinobacteria) occurred abundantly in all sediment samples. Antimicrobial screening revealed twenty three strains (13 %) capable to inhibit growth of one to eight test cultures and deep sediment isolates. Based on phylogenetic analysis mostly active strains belonged to the genera Bacillus, Brevibacillus, Nocardiopsis, Paenibacillus and Streptomyces. Antimicrobial substances (1–3) were isolated from strain Paenibacillus sp. Sl 79w showing a high inhibitory activity. On the basis of combined spectral analyses (IR, UV, ¹H and ¹³C NMR) the compounds 1, 2 and 3 with [M + H]⁺ at 409.1 and 409.2 m/z, and with [M + Na]⁺ at 822.5 m/z were found to have a carbon skeleton of isocoumarin and peptide antibiotics, respectively. Our findings demonstrated that the deep surface sediments of the Sea of Japan represent an untapped source of diverse microorganisms capable of antimicrobial metabolite production.     

Law of the Minimum Paradoxes

The “Law of the Minimum” states that growth is controlled by the scarcest resource (limiting factor). This concept was originally applied to plant or crop growth (Justus von Liebig, 1840, Salisbury, Plant physiology, 4th edn., Wadsworth, Belmont, 1992) and quantitatively supported by many experiments. Some generalizations based on more complicated “dose-response” curves were proposed. Violations of this law in natural and experimental ecosystems were also reported. We study models of adaptation in ensembles of similar organisms under load of environmental factors and prove that violation of Liebig’s law follows from adaptation effects. If the fitness of an organism in a fixed environment satisfies the Law of the Minimum then adaptation equalizes the pressure of essential factors and, therefore, acts against the Liebig’s law. This is the the Law of the Minimum paradox: if for a randomly chosen pair “organism–environment” the Law of the Minimum typically holds, then in a well-adapted system, we have to expect violations of this law.     

Abnormal mitosis triggers p53-dependent cell cycle arrest in human tetraploid cells

Erroneously arising tetraploid mammalian cells are chromosomally instable and may facilitate cell transformation. An increasing body of evidence shows that the propagation of mammalian tetraploid cells is limited by a p53-dependent arrest. The trigger of this arrest has not been identified so far. Here we show by live cell imaging of tetraploid cells generated by an induced cytokinesis failure that most tetraploids arrest and die in a p53-dependent manner after the first tetraploid mitosis. Furthermore, we found that the main trigger is a mitotic defect, in particular, chromosome missegregation during bipolar mitosis or spindle multipolarity. Both a transient multipolar spindle followed by efficient clustering in anaphase as well as a multipolar spindle followed by multipolar mitosis inhibited subsequent proliferation to a similar degree. We found that the tetraploid cells did not accumulate double-strand breaks that could cause the cell cycle arrest after tetraploid mitosis. In contrast, tetraploid cells showed increased levels of oxidative DNA damage coinciding with the p53 activation. To further elucidate the pathways involved in the proliferation control of tetraploid cells, we knocked down specific kinases that had been previously linked to the cell cycle arrest and p53 phosphorylation. Our results suggest that the checkpoint kinase ATM phosphorylates p53 in tetraploid cells after abnormal mitosis and thus contributes to proliferation control of human aberrantly arising tetraploids.     

«Salivaomics» of Different Molecular Biological Subtypes of Breast Cancer

The aim of the study was to determine the metabolic characteristics of saliva depending on the molecular biological subtype of breast cancer, as well as depending on the expression levels of HER2, estrogen receptors (ER), and progesterone receptors (PR). The study included 487 patients with morphologically verified breast cancer and 298 volunteers without breast pathologies. Saliva samples were obtained from all patients strictly before the start of treatment and the values of 42 biochemical indicators were determined. It has been established that the saliva of healthy volunteers and patients with various molecular biological subtypes of breast cancer differs in 12 biochemical indicators: concentrations of protein, urea, nitric oxide, malondialdehyde, total amino acid content, and activity of lactate dehydrogenase, alkaline phosphatase, gamma-glutamyltransferase, catalase, amylase, superoxide dismutase, and peroxidases. The saliva composition of patients with basal-like breast cancer differs from other subtypes in terms of the maximum number of indicators. Changes in biochemical indicators indicated an increase in the processes of lipid peroxidation and endogenous intoxication and a weakening of antioxidant protection, which correlates with the severity of the disease and the least favorable prognosis for this subtype of breast cancer. An analysis was made of the individual contribution of the expression level of HER2, estrogen, and progesterone receptors to changes in the biochemical composition of saliva. The HER2 (−)/HER2 (+) group, which should be considered as a single group, as well as ER-positive breast cancer, differ statistically significantly from the control group. For ER/PR-positive breast cancer, a more favorable ratio of saliva biochemical indicators was also noted compared to ER/PR-negative breast cancer.     

Cutting edge: serotonin is a chemotactic factor for eosinophils and functions additively with eotaxin

Elevated levels of serotonin (5-hydroxytryptamine, 5-HT) are observed in the serum of asthmatics. Herein, we demonstrate that 5-HT functions independently as an eosinophil chemoattractant that acts additively with eotaxin. 5-HT2A receptor antagonists (including MDL-100907 and cyproheptadine (CYP)) were found to inhibit 5-HT-induced, but not eotaxin-induced migration. Intravital microscopy studies revealed that eosinophils roll in response to 5-HT in venules under conditions of physiological shear stress, which could be blocked by pretreating eosinophils with CYP. OVA-induced pulmonary eosinophilia in wild-type mice was significantly inhibited using CYP alone and maximally in combination with a CCR3 receptor antagonist. Interestingly, OVA-induced pulmonary eosinophilia in eotaxin-knockout (Eot-/-) mice was inhibited by treatment with the 5-HT2A but not CCR3 receptor antagonist. These results suggest that 5-HT is a potent eosinophil-active chemoattractant that can function additively with eotaxin and a dual CCR3/5-HT2A receptor antagonist may be more effective in blocking allergen-induced eosinophil recruitment.     

Joint Russian—Finnish study of radioactive contamination in the NW part of Lake Ladoga

In August 1992 a joint Russian-Finnish expedition was arranged to the NW part of Lake Ladoga to study radioactive contamination in the region. Special attention was paid to the area surrounding the Heinämaa Islands, where the wreck of the former mine carrier ship Kit had been lying about 30 years before it was moved to Novaya Zemlya in 1991. During this period the wreck had been used as a store for radioactive waste containing principally ⁹⁰Sr, ¹³⁷Cs and ^239,24OPu. Lake water, bottom sediment and some biological samples were collected for strontium, plutonium and gammaspectrometric analyses. In all the samples the radioactivity concentrations were very low, indicating radioactive contamination of about the same level as caused by global fallout in the 1960's and the Chernobyl fallout in the area. Only in two water samples taken close to the former site of the wreck slightly elevated ^239,240Pu concentrations were detected. The great water volume of Lake Ladoga and effective water exchange at the wreck site may explain the very low levels of radioactive wastes detected in the aquatic environment.