Coevolution between male and female genitalia in Belostoma angustum Lauck, 1964 (Insecta, Heteroptera, Belostomatidae): disentangling size and shape.

Sexual and natural selection mechanisms might drive variation in the genitalia of male animals. All aforementioned mechanisms are known to predict the coevolution of male and female genital morphology. Belostoma angustum is known to have subtle variation in the male and female genitalia of its members. In this species, phallosoma with dorsal arms and ventral diverticulum are assumed to be intromittent male genital traits that interact with the female genital chamber. We thus evaluated the existence of variation after disentangling the size from the shape of male genitalia in B. angustum. Body and genitalia dimensions and photographs of phallosoma with dorsal arms, ventral diverticulum and lateral views of the right paramere (the non-intromittent part) were obtained. Semi-landmarks and landmarks were used to capture phenotypic variation, by eliminating all non-shape variation with a Procrustes superimposition. Male and female specimens collected from the same location or immediate vicinity were grouped, and 12 groups originating from 12 locations were used to conduct two block-Partial Least Squares analyses (PLS). Group structures were also taken into account by adopting a multilevel approach. The male and female genital traits had similarly shallow static allometry slopes, as well as the dispersion values around the mean (i.e. coefficient of variation) and the standard error of the estimate. The correlation between the pooled within-locality covariance matrix of the symmetric component of phallosoma with dorsal arms and the female genital chamber was significant (r-PLS=0.37), as well as that with male body dimensions (r-PLS=0.36), even after controlling for allometry. Specimens with lower PLS shape scores had narrower phallosoma with dorsal arms, with poorly curved outer margins of the dorsal arms, whereas specimens with higher PLS shape scores had slightly shorter dorsal arms, with strongly curved outer margins. Lower shape scores were associated with narrower and especially shorter and narrower female genital chambers. Similar shallow allometric curves among sexes and the correlation between intromittent male parts and the female genital chamber, as well as male dimensions, suggest the coevolution of these contact structures in size and in shape.

A Model for p38MAPK-Induced Astrocyte Senescence.

Experimental evidence indicates that aging leads to accumulation of senescent cells in tissues and they develop a secretory phenotype (also known as SASP, for senescence-associated secretory phenotype) that can contribute to chronic inflammation and diseases. Recent results have showed that markers of senescence in astrocytes from aged brains are increased in brains with Alzheimer's disease. These studies strongly involved the stress kinase p38MAPK in the regulation of the secretory phenotype of astrocytes, yet the molecular mechanisms underlying the onset of senescence and SASP activation remain unclear. In this work, we propose a discrete logical model for astrocyte senescence determined by the level of DNA damage (reparable or irreparable DNA strand breaks) where the kinase p38MAPK plays a central role in the regulation of senescence and SASP. The model produces four alternative stable states: proliferation, transient cycle arrest, apoptosis and senescence (and SASP) computed from its inputs representing DNA damages. Perturbations of the model were performed through gene gain or loss of functions and compared with results concerning cultures of normal and mutant astrocytes showing agreement in most cases. Moreover, the model allows some predictions that remain to be tested experimentally.

Modelling the onset of senescence at the G1/S cell cycle checkpoint.

BACKGROUND: DNA damage (single or double-strand breaks) triggers adapted cellular responses. These responses are elicited through signalling pathways, which activate cell cycle checkpoints and basically lead to three cellular fates: cycle arrest promoting DNA repair, senescence (permanent arrest) or cell death. Cellular senescence is known for having a tumour-suppressive function and its regulation arouses a growing scientific interest. Here, we advance a qualitative model covering DNA damage response pathways, focusing on G1/S checkpoint enforcement, supposedly more sensitive to arrest than G2/M checkpoint. RESULTS: We define a discrete, logical model encompassing ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) pathways activation upon DNA damage, as well as G1/S checkpoint main components. It also includes the stress responsive protein p38MAPK (mitogen-activated protein kinase 14) known to be involved in the regulation of senescence. The model has four outcomes that convey alternative cell fates: proliferation, (transient) cell cycle arrest, apoptosis and senescence. Different levels of DNA damage are considered, defined by distinct combinations of single and double-strand breaks. Each leads to a single stable state denoting the cell fate adopted upon this specific damage. A range of model perturbations corresponding to gene loss-of-function or gain-of-function is compared to experimental mutations. CONCLUSIONS: As a step towards an integrative model of DNA-damage response pathways to better cover the onset of senescence, our model focuses on G1/S checkpoint enforcement. This model qualitatively agrees with most experimental observations, including experiments involving mutations. Furthermore, it provides some predictions.

Induced genome maintenance pathways in pre-cancer tissues describe an anti-cancer barrier in tumor development.

A recent model proposing that a barrier is raised against tumor evolution in pre-cancer tissues is investigated. For that we quantify expression alterations in genome maintenance pathways: DNA damage response, death pathways and cell cycle and also differentially expressed genes in transcriptomes of pre-cancerous and cancerous lesions deposited in the GEO database. We find that the main alterations in pre-cancer samples comprising the barrier are: (1) DNA double strand-breaks signaling and repair pathways induction, (2) upregulation of cyclin-dependent kinases, (3) p53 dependent (and independent) repair and apoptosis pathways induction and (4) replicative senescence induction early in tissue transformation. In the cancer samples we find that the induced pathways in pre-cancer are systematically inhibited and the only remaining induced pathway is p53, whereas the retinoblastoma pathway arises induced in most samples. The results give support to the model, furthermore they reveal the involvement of additional mechanisms in pre-cancer, including the early induction of replicative senescence and of p53 independent apoptosis.

A method to identify important dynamical states in Boolean models of regulatory networks: application to regulation of stomata closure by ABA in A. thaliana.

BACKGROUND: We introduce a method to analyze the states of regulatory Boolean models that identifies important network states and their biological influence on the global network dynamics. It consists in (1) finding the states of the network that are most frequently visited and (2) the identification of variable and frozen nodes of the network. The method, along with a simulation that includes random features, is applied to the study of stomata closure by abscisic acid (ABA) in A. thaliana proposed by Albert and coworkers. RESULTS: We find that for the case of study, that the dynamics of wild and mutant networks have just two states that are highly visited in their space of states and about a third of all nodes of the wild network are variable while the rest remain frozen in True or False states. This high number of frozen elements explains the low cardinality of the space of states of the wild network. Similar results are observed in the mutant networks. The application of the method allowed us to explain how wild and mutants behave dynamically in the SS and determined an essential feature of the activation of the closure node (representing stomata closure), i.e. its synchronization with the AnionEm node (representing anion efflux at the plasma membrane). The dynamics of this synchronization explains the efficiency reached by the wild and each of the mutant networks. CONCLUSIONS: For the biological problem analyzed, our method allows determining how wild and mutant networks differ 'phenotypically'. It shows that the different efficiencies of stomata closure reached among the simulated wild and mutant networks follow from a dynamical behavior of two nodes that are always synchronized. Additionally, we predict that the involvement of the anion efflux at the plasma membrane is crucial for the plant response to ABA. AVAILABILITY: The algorithm used in the simulations is available upon request.