Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Eavesdropping on Plant Volatiles by a Specialist Moth: Significance of Ratio and Concentration

We investigated the role that the ratio and concentration of ubiquitous plant volatiles play in providing host specificity for the diet specialist grape berry moth Paralobesia viteana (Clemens) in the process of locating its primary host plant Vitis sp. In the first flight tunnel experiment, using a previously identified attractive blend with seven common but essential components (“optimized blend”), we found that doubling the amount of six compounds singly [(E)- & (Z)-linalool oxides, nonanal, decanal, β-caryophyllene, or germacrene-D], while keeping the concentration of other compounds constant, significantly reduced female attraction (average 76% full and 59% partial upwind flight reduction) to the synthetic blends. However, doubling (E)-4,8-dimethyl 1,3,7-nonatriene had no effect on female response. In the second experiment, we manipulated the volatile profile more naturally by exposing clonal grapevines to Japanese beetle feeding. In the flight tunnel, foliar damage significantly reduced female landing on grape shoots by 72% and full upwind flight by 24%. The reduction was associated with two changes: (1) more than a two-fold increase in total amount of the seven essential volatile compounds, and (2) changes in their relative ratios. Compared to the optimized blend, synthetic blends mimicking the volatile ratio emitted by damaged grapevines resulted in an average of 87% and 32% reduction in full and partial upwind orientation, respectively, and the level of reduction was similar at both high and low doses. Taken together, these results demonstrate that the specificity of a ubiquitous volatile blend is determined, in part, by the ratio of key volatile compounds for this diet specialist. However, P. viteana was also able to accommodate significant variation in the ratio of some compounds as well as the concentration of the overall mixture. Such plasticity may be critical for phytophagous insects to successfully eavesdrop on variable host plant volatile signals

A Dialogue between the Hypoxia-Inducible Factor and the Tumor Microenvironment

The hypoxia-inducible factor is the key protein responsible for the cellular adaptation to low oxygen tension. This transcription factor becomes activated as a result of a drop in the partial pressure of oxygen, to hypoxic levels below 5% oxygen, and targets a panel of genes involved in maintenance of oxygen homeostasis. Hypoxia is a common characteristic of the microenvironment of solid tumors and, through activation of the hypoxia-inducible factor, is at the center of the growth dynamics of tumor cells. Not only does the microenvironment impact on the hypoxia-inducible factor but this factor impacts on microenvironmental features, such as pH, nutrient availability, metabolism and the extracellular matrix. In this review we discuss the influence the tumor environment has on the hypoxia-inducible factor and outline the role of this factor as a modulator of the microenvironment and as a powerful actor in tumor remodeling. From a fundamental research point of view the hypoxia-inducible factor is at the center of a signaling pathway that must be deciphered to fully understand the dynamics of the tumor microenvironment. From a translational and pharmacological research point of view the hypoxia-inducible factor and its induced downstream gene products may provide information on patient prognosis and offer promising targets that open perspectives for novel “anti-microenvironment” directed therapies

Seroepidemiology of Varicella and value of self-reported history of Varicella infection in Iranian medical students

Objectives: We conducted this study to assess the seroprevalence of Varicella zoster virus (VZV) antibodies in a group of Iranian medical sciences students that were at risk of Varicella and the value of self-reported history as a predictor of immunity. Material and Methods: 255 medical, nursing and obstetrics students who had not entered as a student or worked in a hospital from 3 different schools were enrolled in the study in 2012 (Qazvin province, Iran). Demographics and other information as well as the history of Varicella were obtained through a self-administered questionnaire. Blood samples were collected to determine the Varicella IgG levels via an enzyme-linked immunosorbent assay. A statistical analysis was performed by calculating prevalences and their 95% confidence intervals. Sensitivity, specificity, positive and negative predictive values, Cohen's kappa and positive and negative likelihood ratios of recalled history were determined. p < 0.05 was considered statistically significant. Results: The mean age of participants was 21.3±4.3 years. Seropositivity rate was 74.5%. The relationships between marital status, number of family members, and acquired VZV history with immunity against the virus were statistically significant. The overall rate of reported history was 57%. The positive and negative predictive values of self-reported history of Varicella were 91% and 47.3%, respectively. Conclusions: Immunization of students of Iranian medical sciences seems logical in the near future. Also, they should be tested for Varicella immunity regardless of the history of previous infection

Distribuição espacial de doenças endêmicas no município de Ribeirão Preto (SP) Spatial distribution of endemic diseases in Ribeirão Preto, São Paulo State

A percepção de que algumas doenças acontecem em determinados lugares é antiga. A preocupação em estudar as relações entre o homem e o meio resultou em diversos trabalhos de geografia médica, voltados à análise da distribuição espacial das doenças. Este estudo seccional foi desenvolvido no município de Ribeirão Preto (SP) e teve como objetivo ilustrar, por meio de agravos de saúde (dengue, hanseníase e tuberculose), de que forma uma ferramenta de um sistema de informação geográfica permite a identificação de áreas heterogêneas, fornecendo subsídios para a escolha de estratégias e intervenções específicas de acordo com a necessidade dos moradores, bem como a priorização de recursos para grupos mais vulneráveis. A população compreendeu os casos de dengue, hanseníase e tuberculose notificados no ano 2000 em Ribeirão Preto. Os dados foram coletados na Vigilância Epidemiológica da Secretaria Municipal de Saúde do município. Para a obtenção dos mapas temáticos, os dados foram geocodificados com auxílio do software MapInfo 7.8 e Spring 4.3. Os mapas temáticos ilustraram a distribuição da densidade de casos de dengue, hanseníase e tuberculose no município como uma maneira complementar de análise de informações de saúde, apontando as áreas prioritárias para o controle destas doenças.<br>The perception that some diseases happen in certain places is old. The concern in studying the relation between the human being and the environment resulted in several studies of medical geography, directed to the analysis of diseases spatial distribution. This sectional study was carried out in Ribeirão Preto, São Paulo State, and aimed to illustrate, through health problems (dengue, leprosy and tuberculosis), how a Geographic Information System tool allows the identification of heterogeneous areas, providing support for the choice of strategies and specific interventions according to the need of residents, as well as, priority of resources to more vulnerable groups. The population comprised cases of dengue, leprosy and tuberculosis notified in Ribeirão Preto in 2000. Data were collected in the Health Secretary Epidemiological Surveillance of the city. In order to obtain the thematic maps, data were geo-codified with the software MapInfo 7.8 e Spring 4.3. The thematic maps showed the density distribution of dengue, leprosy and tuberculosis cases in the city as a way to complement the analysis of health information, pointing priority areas for the control of these diseases