Dynamic simulation of regulatory networks using SQUAD.

BACKGROUND: The ambition of most molecular biologists is the understanding of the intricate network of molecular interactions that control biological systems. As scientists uncover the components and the connectivity of these networks, it becomes possible to study their dynamical behavior as a whole and discover what is the specific role of each of their components. Since the behavior of a network is by no means intuitive, it becomes necessary to use computational models to understand its behavior and to be able to make predictions about it. Unfortunately, most current computational models describe small networks due to the scarcity of kinetic data available. To overcome this problem, we previously published a methodology to convert a signaling network into a dynamical system, even in the total absence of kinetic information. In this paper we present a software implementation of such methodology. RESULTS: We developed SQUAD, a software for the dynamic simulation of signaling networks using the standardized qualitative dynamical systems approach. SQUAD converts the network into a discrete dynamical system, and it uses a binary decision diagram algorithm to identify all the steady states of the system. Then, the software creates a continuous dynamical system and localizes its steady states which are located near the steady states of the discrete system. The software permits to make simulations on the continuous system, allowing for the modification of several parameters. Importantly, SQUAD includes a framework for perturbing networks in a manner similar to what is performed in experimental laboratory protocols, for example by activating receptors or knocking out molecular components. Using this software we have been able to successfully reproduce the behavior of the regulatory network implicated in T-helper cell differentiation. CONCLUSION: The simulation of regulatory networks aims at predicting the behavior of a whole system when subject to stimuli, such as drugs, or determine the role of specific components within the network. The predictions can then be used to interpret and/or drive laboratory experiments. SQUAD provides a user-friendly graphical interface, accessible to both computational and experimental biologists for the fast qualitative simulation of large regulatory networks for which kinetic data is not necessarily available.

Coevolutionary networks: a novel approach to understanding the relationships of humans with the infectious agents

Human organism is interpenetrated by the world of microorganisms, from the conception until the death. This interpenetration involves different levels of interactions between the partners including trophic exchanges, bi-directional cell signaling and gene activation, besides genetic and epigenetic phenomena, and tends towards mutual adaptation and coevolution. Since these processes are critical for the survival of individuals and species, they rely on the existence of a complex organization of adaptive systems aiming at two apparently conflicting purposes: the maintenance of the internal coherence of each partner, and a mutually advantageous coexistence and progressive adaptation between them. Humans possess three adaptive systems: the nervous, the endocrine and the immune system, each internally organized into subsystems functionally connected by intraconnections, to maintain the internal coherence of the system. The three adaptive systems aim at the maintenance of the internal coherence of the organism and are functionally linked by interconnections, in such way that what happens to one is immediately sensed by the others. The different communities of infectious agents that live within the organism are also organized into functional networks. The members of each community are linked by intraconnections, represented by the mutual trophic, metabolic and other influences, while the different infectious communities affect each other through interconnections. Furthermore, by means of its adaptive systems, the organism influences and is influenced by the microbial communities through the existence of transconnections. It is proposed that these highly complex and dynamic networks, involving gene exchange and epigenetic phenomena, represent major coevolutionary forces for humans and microorganisms.

Entomological and ecological aspects of six sylvatic species of triatomines (Hemiptera, Reduviidae) from the collection of the National Biodiversity Institute of Costa Rica, Central America

A total of 797 specimens of wild adult triatomines, belonging to six species from the entomological collections of the Costa Rican National Biodiversity Institute, was studied from the standpoint of their relative abundance, as reflected by light traps, distribution in the country, seasonal variations and climatic and altitudinal preferences. Triatoma dimidiata was the most abundant species (32.9% of the total specimens), with a very extensive distribution in different ecological zones, being more common between 100 to 400 m above sea level mainly at the end of the dry season. T. dispar was the third in frequency (21.5%), with narrower distribution, more abundant between 600 to 800 m and scarce during the dry season. Panstrongylus geniculatus and P. rufotuberculatus, second and fourth in frequency (22.1% and 15.1%, respectively), were widely distributed on both the Pacific and Caribbean basins, the former being more common between 80 to 270 m all year round and the latter below 800 m mainly during the first semester. Eratyrus cuspidatus which represented only 4.9% of the insects, was also present on both basins mainly below 200 m with a tendency to be scarce during certain months of the year, and was found in all types of ecological zones. Finally, Rhodnius pallescens, the least abundant species (3.6%) was restricted to very humid areas below 20 m, on the north side and Caribbean basin. With the exception of R. pallescens, males were more commonly found than females. Some epidemiological implications related to the six species are discussed.

Information Mobility: Information Dissemination in Mobile Networks

En el nostre projecte, considerem un escenari urbà o interurbà on persones amb dispositius mòbils (smartphones) o vehicles equipats amb interfícies de comunicació, estan interessats en compartir fitxers entre ells o descarregar-los al creuar Punts d’Accés (APs) propers a la carretera. Estudiem la possibilitat d’utilizar la cooperació en les trobades casuals entre nodes per augmentar la velocitat de descàrrega global. Amb aquest objectiu, plantejem algoritmes per a la selecció de quins paquets, per a quins destins i quins transportistes s’escullen en cada moment. Mitjançant extenses simulacions, mostrem com les cooperacions carry&forward dels nodes augmenten significativament la velocitat de descàrrega dels usuaris, i com aquest resultat es manté per a diversos patrons de mobilitat, col•locacions d'AP i càrregues de la xarxa. Per altra banda, aparells com els smartphones, on la targeta de WiFi està encesa contínuament, consumeixen l'energia de la bateria en poques hores. En molts escenaris, una targeta WiFi sempre activa és poc útil, perque sovint no hi ha necessitat de transmissió o recepció. Aquest fet es veu agreujat en les Delay Tolerant Networks (DTN), on els nodes intercanvien dades quan es creuen i en tenen l’oportunitat. Les tècniques de gestió de l’estalvi d’energia permeten extendre la duració de les bateries. El nostre projecte analitza els avantatges i inconvenients que apareixen quan els nodes apaguen períodicament la seva targeta wireless per a estalviar energia en escenaris DTN. Els nostres resultats mostren les condicions en que un node pot desconnectar la bateria sense afectar la probabilitat de contacte amb altres nodes, i les condicions en que aquesta disminueix. Per exemple, es demostra que la vida del node pot ser duplicada mantenint la probabilitat de contacte a 1. I que aquesta disminueix ràpidament en intentar augmentar més la vida útil.

Ecological Data of Travassosnema travassosi travassosi (Dracunculoidea: Guyanemidae) from the Humour of the Eyes of Acestrorhynchus lacustris from Tibagi River, Paraná, Brazil

Data obtained between 1990 and 1995 provide, for the first time, ecological information of the parasitic nematode Travassosnema travassosi travassosi Costa, Moreira & Oliveira, 1991 from Acestrorhynchus lacustris (Characiformes: Acestrorhynchidae) collected in the Tibagi River, Sertanópolis, Paraná, Brazil. These nematode occurred with low prevalences (7.7% to 28.6%) and intensities (1 to 3) during almost the whole year. The observation of mature females throughout the year indicate that liberation of larvae can occur during all the year around. This is the first report on the occurrence of T. travassosi travassosi inside the eyes. These nematodes were mostly located in humour of the eyes (87% of cases), being less frequently detected in tissues behind the eyes (13% of cases).

Ecological Aspects of Phebotomine (Diptera, Psychodidae) in an Endemic Area of Tegumentary Leishmaniasis in the Northeastern Argentina, 1993-1998

The first epidemic tegumentary leishmaniasis´ outbreak in the province of Misiones was recorded in 1998, in the locality of Puerto Esperanza. Phlebotominae collected in the region, previously or simultaneously to the outbreak (September 1993-December 1998) showed that the species Lutzomyia intermedia s. l. was prevalent (94%, n 6,150) at all the sites sampled with miniature light trap (10) and Shannon trap (3). L. pessoai, L. whitmani, L. migonei, L. shannoni, L. fischeri, L. misionensis, Brumptomyia avellari and B. guimaraesi were also captured. Sand fly distribution in time and space suggests that in the province of Misiones (1) the species already present before 1990 could give rise to the epidemic by the density/dispersion fluctuation of their local populations; (2) the abundance of L. intermedia s. l. was associated with environments with ecotones of primary-secondary vegetation, close to water bodies and with moderate human disturbance; (3) this species showed, towards the end of 1997, peaks of exceptional abundance, subsequent to rainfall peaks in 1996. This increase in abundance of potential vector sand fly populations close to houses with colonizable surroundings could have generated the 1998 epidemic outbreak.

Parasitic arthropods of some wild rodents from Juréia-Itatins Ecological Station, State of São Paulo, Brazil

A study of the associations between three species of rodents in the Atlantic forest and their parasitic arthropods was undertaken at the Juréia-Itatins Ecological Station, located in the State of São Paulo, Southeastern Brazil, from March 1989 to February 1990. Individuals of three species, Oryzomys russatus, Proechimys iheringi and Nectomys squamipes were captured and examined for ectoparasites. Eleven species of parasitic arthropods were found, including four species of insects and seven of Acari. Parasitism intensity, phenology, and rainfall were positively correlated with the abundance of the ectoparasites and their hosts. The most abundant host was O. russatus (Muridae: Sigmodontinae), and the most common parasite on it was the laelapid mite Gigantolaelaps oudemansi. The cuterebrid Metacuterebra apicalis caused myiasis in O. russatus. A mutualistic association between the staphylinid beetle Amblyopinus sp. and its host P. iheringi (Echimyidae) was observed. The few N. squamipes captured had small numbers of ectoparasites.

Triatoma rubrovaria (Blanchard, 1843) (Hemiptera, Reduviidae, Triatominae) II: trophic resources and ecological observations of five populations collected in the State of Rio Grande do Sul, Brazil

Triatoma rubrovaria has become the most frequently captured triatomine species after the control of T. infestans in the State of Rio Grande do Sul (RS), Brazil. Isoenzymatic and chromatic studies indicate the existence of, at least, two distinct phenotypic patterns of T. rubrovaria in RS. The geographic variation noted through molecular tools may also result in distinct profiles of vectorial potentiality. In order to enhance our understanding of the bionomic knowledge of T. rubrovaria separate batches of the species were collected from different municipalities of RS distant from 72 to 332 km: Santana do Livramento (natural ecotope), Santana do Livramento (artificial ecotope), Santiago (natural ecotope), Canguçu (peridomicile) and Encruzilhada do Sul (natural ecotope). A total of 285 specimens were collected, 85 specimens kept sufficient fecal material in their guts for the precipitin analysis. The results indicated the food eclecticism for this species and the anti-rodent serum showed the highest positivity in most localities. From the total of analyzed samples, only 1.3% of unique positivity for human blood was registered, all of them for Santiago population. This reactivity to human blood may be associated to pastures activities in the field.

Experimental evidence and ecological perspectives for the adaptation of Schistosoma mansoni Sambon, 1907 (Digenea: Schistosomatidae) to a wild host, the water-rat, Nectomys squamipes Brants, 1827 (Rodentia: Sigmodontinae)

Due to the semi aquatic habits and the overlap of the geographical distribution of the water-rat, Nectomys spp., with schistosomiasis endemic areas, these wild rodents are very likely to acquire Schistosoma mansoni infection in their daily activities. The role of the water-rat in the S. mansoni cycle would be substantiated if one could prove that these rodents acquire the parasite during their own activity time, a completely independent time schedule of human activities. To pursue this goal, we performed two field experiments in the municipality of Sumidouro, State of Rio de Janeiro, Brazil, a schistosomiasis endemic area where N. squamipes is found naturally infected. One experiment was devised as a series of observations of activity time of the water-rat. The other experiment was a test of the occurrence of late transmission of S. mansoni to the water-rat. The daily activity pattern showed that the water-rat is active chiefly just after sunset. At both diurnal and late exposition essays the water-rat sentinels got infected by S. mansoni. These findings clarify ecological and behavioral components necessary to the adaptation of S. mansoni to the water-rat as a non human definitive host and the existence of a transmission cycle involving this animals as a reservoir.

Ecological characteristics of Triatoma patagonica at the Southern limit of its distribution (Chubut, Argentina)

This study aimed at identifying the ecological characteristics of Triatoma patagonica Del Ponte 1929 (Hemiptera: Reduviidae) and evaluating the epidemiological importance of this species at its southernmost distribution limit. We carried out two surveys in the Province of Chubut, in summer and in spring, 1998. In each survey, we interviewed local health care agents for triatomine recognition and reports of the bugs, followed by entomological searches in houses and peridomestic and silvatic biotopes. The presence of T. patagonica was confirmed in two of the five localities indicated by interview. In agreement with previous studies, all these positive localities were east of the 11°C isotherm, within the Monte phytogeographic province. Triatomine abundance and infestation levels (in peridomiciles and peridomestic biotopes) were higher in summer than in spring, possibly reflecting adverse environmental conditions such as flood and cold winter weather. In the silvatic environment, we found three adult bugs under rocks in summer. In peridomestic sites bugs were only found associated with chickens, which were also the only blood meal source identified. Infection by Trypanosoma cruzi was not detected. We conclude that T. patagonica at its southernmost distribution limit does not represent a risk to public health due to its low abundance, lack of association with humans, and absence of T. cruzi infection.

Ecological analysis of Acari recovered from coprolites from archaeological site of Northeast Brazil

Coprolite samples of human and animal origin from the excavations performed at the archaeological site of Furna do Estrago, at Brejo da Madre de Deus in the state of Pernambuco, Brazil and sent to the Paleoparasitology Laboratory at Escola Nacional de Saúde Pública-Fiocruz, Rio de Janeiro, were analyzed for mites. After rehydratation and sedimentation of the coprolites, the alimentary contents and the sediments were examined and the mites collected and prepared in definitive whole mounts, using Hoyer's medium. Mites of the following suborders and orders were recovered: suborder Acaridia; order Gamasida; order Ixodida with the familiy Ixodidae (Ixodes sp. and Amblyomma sp. larvae, scutum, idiosoma, gnathosoma); order Oribatida (Aphelacarus sp., Apolohmannia sp., Eophypochthonius sp., Cosmochthonius sp., Pterobates sp., Poronoticae with pteromorphae not auriculate); order Astigmata with the families Atopomelidae (Chirodiscoides caviae), Anoetidae hypopus, Acaridae (Suidasia pontifica), Glycyphagidae (Blomia tropicalis), Pyroglyphidae (Hirstia passericola); order Actinedida with the family Tarsonemidae (Iponemus radiatae). The present work discusses the possibility of the preservation of the mite groups found up to the present day. We also discuss their relationship with the environment and their importance to present populations.