From the beginning to the present state of molecular microbial pathogenesis—A tribute to Pascale Cossart

The universe of Molecular Microbial Pathogenesis is filled with many female and male stars. But there are two particularly bright shining supernovae-like stars: the late Stanley Falkow and the very lively and creative Pascale Cossart. These two outstanding luminaries, surrounded by numerous planets, do not only belong to different scientific generations but their splendor also comes from very different scientific concepts. Stanley Falkow, often referred to as the ‘Father of Molecular Microbial Pathogenesis’, made many groundbreaking contributions to this field by addressing almost all important bacterial pathogens. Pascale Cossart, who could be called in analogy the ‘Queen of Modern Molecular Microbial Pathogenesis’ by combining the Microbiology and Cell Biology, concentrates in her similarly impressive scientific work essentially on a single bacterial species which she studied and still studies in great depth: the facultative intracellular bacterial pathogen Listeria monocytogenes—and the vast majority of her most prominent publications deals with this pathogen in almost all facets. It is certainly not an exaggeration to say that she together with her co-workers and collaborators developed this model bacterium into a paradigm among the intracellular bacterial pathogens.     

Field Hypothesis on the Self-regulation of Gene Expression

The mechanism of the self-regulation of gene expression in living cells is generally explained by considering complicated networks of key-lock relationships, and in fact there is a large body of evidence on a hugenumber of key-lock relationships. However, in the present article we stress that with the network hypothesis alone it is impossible to fully explain the mechanism of self-regulation in life. Recently, it has been established that individual giant DNA molecules, larger than several tens of kilo base pairs, undergo a large discrete transition in their higher-order structure. It has become clear that nonspecific weak interactions with various chemicals, suchas polyamines, small salts, ATP and RNA, cause on/off switching in the higher-order structure of DNA. Thus, the field parameters of the cellular environment should play important roles in the mechanism of self-regulation, in addition to networks of key and locks. This conformational transition induced by field parameters may be related to rigid on/off regulation, whereas key-lock relationships may be involved in a more flexible control of gene expression.     

Pollen allergen reports help to understand preseason symptoms

Early symptoms of pollen allergies arefrequently reported before pollination periodof allergenic plant starts. At northernlatitudes the main concern is Betulaceae-trees(alders, hazel, birches). Pollen allergeninformation, based on the analysis of actualairborne allergen concentrations, beside thetraditional pollen reports, based on pollencounts, has been given in SW Finland since1998. 1–2 weeks before the onset of floweringpollen allergens are detected airborne inquantities high enough to provoke symptoms.Information is given on radio and in localnewspapers. During the first season of the newservice (1998) we carried out a questionnairestudy. The results showed that new informationservice, though not as frequently used as wehad hoped for, was useful to allergic personsfor starting their medication in time. Theyalso received explanation for their earlierinexplicable symptoms. We recommend bothinformation services to be run concurrently togive the best information to the public.     

Quantitative changes in cytoskeletal beta- and gamma-actin mRNAs and apparent absence of sarcomeric actin gene transcripts in early mouse embryos

Actin is known to be synthesized both during oogenesis and in cleavage-stage embryos in mice. Cytoskeletal beta-actin appears to be the major component, followed by gamma-actin, but the synthesis of alpha-actin has also been inferred from protein electrophoretic patterns. We have studied the expression of cytoskeletal (beta- and gamma-) and sarcomeric (alpha-cardiac and alpha-skeletal) actin genes at the level of the individual mRNAs in blot hybridization experiments using isoform-specific RNA probes. The results show that there are about 2 x 10(4) beta-actin mRNA molecules in the fully grown oocyte; this number drops to about one-half in the egg and less than one-tenth in the late two-cell embryo but increases rapidly during cleavage to about 3 x 10(5) molecules in the late blastocyst. The amount of gamma-actin mRNA is similar to that of beta-actin in oocytes and eggs but only about 40% as much in late blastocysts, indicating a differential accumulation of these mRNAs during cleavage. The developmental pattern of beta- and gamma-actin mRNA provides a striking example of the transition from maternal to embryonic control that occurs at the two-cell stage and involves the elimination of most or all of the maternal actin mRNA. There was no detectable alpha-cardiac or alpha-skeletal mRNA (i.e., less than 1,000 molecules per embryo) at any stage from oocyte to late blastocyst, suggesting that the sarcomeric actin genes are silent during preimplantation development.     

Island urbanization and its ecological consequences: A case study in the Zhoushan Island,East China

Islands, which provide multiple ecosystem services, are subject to increasing urbanization pressure due to the ongoing marine development, especially in developing countries. Insights into the island urbanization mechanism and its ecological consequences are essential to sustainable development. In the present paper, the satellite images, nighttime lights, and topographic data were integrated to characterize the spatially explicit urbanization process and mechanism during 1995–2011 in the Zhoushan Island, East China. Furthermore, the corresponding spatially explicit changes in ecosystem services, including net primary productivity (NPP), carbon sequestration and oxygen production (CSOP), nutrient cycling, crop production, and habitat quality, were quantified based on the Carnegie–Ames–Stanford Approach (CASA) and Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) models. The results showed that the Zhoushan Island had experienced a rapid urbanization over the years, with significant urban encroachment on the farmland and tidal flat. Moreover, the urban land expansion was positively correlated with that of the nighttime lights and negatively correlated with the elevation, slope, and the distance to shoreline. These indicated that the urban expansion was resulted from the enhancement of socioeconomic activities, and concentrated in the near-shore areas with low altitude and gentle slope. The urban encroachment on other land use types resulted in a decrease of 3.4 Gg C a⁻¹ NPP, 8.7 Gg a⁻¹ CSOP, 13.2 Gg a⁻¹ nutrient cycling, and 12.3 t a⁻¹ crop production, respectively. In addition, the habitat quality in 11% area of this island degraded substantially. Therefore, to achieve sustainable development of islands, it is urgent to implement more stringent policies, such as island spatial regulation, environmental impact assessment, intensive land use, and urban greening, etc.     

Control of the bifunctional O2-sensor kinase NreB of Staphylococcus carnosus by the nitrate sensor NreA: Switching from kinase to phosphatase state

The NreB–NreC two-component system of Staphylococcus carnosus for O₂ sensing cooperates with the accessory nitrate sensor NreA in the NreA–NreB–NreC system for coordinated sensing and regulation of nitrate respiration by O₂ and nitrate. ApoNreA (NreA in the absence of nitrate) interacts with NreB and inhibits NreB autophosphorylation (and activation). NreB contains the phosphatase motif DxxxQ. The present study shows that NreB on its own was inactive for the dephosphorylation of the phosphorylated response regulator NreC (NreC-P), but co-incubation with NreB and NreA stimulated NreC-P dephosphorylation. Either the presence of instead of apoNreA or mutation of the phosphatase motif (D160 or Q164) of NreB abrogated phosphatase activity of NreB. Phosphatase activity was observed for anoxic (active) NreB as well as oxic NreB, therefore the functional state of NreB is not relevant for phosphatase activity. Thus, NreB is a bifunctional sensor kinase with an integral cryptic phosphatase activity. Activation of phosphatase activity and dephosphorylation of NreC-P requires NreA as a cofactor. Accordingly, NreA and nitrate have major and dual roles in NreA–NreB–NreC regulation by (i) inhibiting NreB phosphorylation and (ii) triggering a kinase/phosphatase switch of NreB when present as apoNreA.     

The changing chromatome as a driver of disease: A panoramic view from different methodologies

Chromatin-bound proteins underlie several fundamental cellular functions, such as control of gene expression and the faithful transmission of genetic and epigenetic information. Components of the chromatin proteome (the “chromatome”) are essential in human life, and mutations in chromatin-bound proteins are frequently drivers of human diseases, such as cancer. Proteomic characterization of chromatin and de novo identification of chromatin interactors could, thus, reveal important and perhaps unexpected players implicated in human physiology and disease. Recently, intensive research efforts have focused on developing strategies to characterize the chromatome composition. In this review, we provide an overview of the dynamic composition of the chromatome, highlight the importance of its alterations as a driving force in human disease (and particularly in cancer), and discuss the different approaches to systematically characterize the chromatin-bound proteome in a global manner.     

Biotechnological applications of microbial bioconversions

Modern research has focused on the microbial transformation of a huge variety of organic compounds to obtain compounds of therapeutic and/or industrial interest. Microbial transformation is a useful tool for producing new compounds, as a consequence of the variety of reactions for natural products. This article describes the production of many important compounds by biotransformation. Emphasis is placed on reporting the metabolites that may be of special interest to the pharmaceutical and biotechnological industries, as well as the practical aspects of this work in the field of microbial transformations.