On the effects of the modularity of gene regulatory networks on phenotypic variability and its association with robustness.

Biological adaptations depend on natural selection sorting out those individuals that exhibit characters fit to their environment. Selection, in turn, depends on the phenotypic variation present in a population. Thus, evolutionary outcomes depend, to a certain extent, on the kind of variation that organisms can produce through random genetic perturbation, that is, their phenotypic variability. Moreover, the properties of developmental mechanisms that produce the organisms affect their phenotypic variability. Two of these properties are modularity and robustness. Modularity is the degree to which interactions occur mostly within groups of the system's elements and scarcely between elements in different groups. Robustness is the propensity of a system to endure perturbations while preserving its phenotype. In this paper, we used a model of gene regulatory networks (GRNs) to study the relationship between modularity and robustness in developmental processes and how modularity affects the variation that random genetic mutations produce in the expression patterns of GRNs. Our results show that modularity and robustness are correlated in multifunctional GRNs and that selection for one of these properties affects the other as well. We contend that these observations may help to understand why modularity and robustness are widespread in biological systems. Additionally, we found that modular networks tend to produce new expression patterns with subtle changes localized in the expression of a few groups of genes. This effect in the phenotypic variability of modular GRNs may bear important consequences for adaptive evolution: it may help to adjust the expression of one group of genes at a time, with few alterations on other previously evolved expression patterns.

Single-bubble and multibubble cavitation in water triggered by laser-driven focusing shock waves.

In this study a single laser pulse spatially shaped into a ring is focused into a thin water layer, creating an annular cavitation bubble and cylindrical shock waves: an outer shock that diverges away from the excitation laser ring and an inner shock that focuses towards the center. A few nanoseconds after the converging shock reaches the focus and diverges away from the center, a single bubble nucleates at the center. The inner diverging shock then reaches the surface of the annular laser-induced bubble and reflects at the boundary, initiating nucleation of a tertiary bubble cloud. In the present experiments, we have performed time-resolved imaging of shock propagation and bubble wall motion. Our experimental observations of single-bubble cavitation and collapse and appearance of ring-shaped bubble clouds are consistent with our numerical simulations that solve a one-dimensional Euler equation in cylindrical coordinates. The numerical results agree qualitatively with the experimental observations of the appearance and growth of large bubble clouds at the smallest laser excitation rings. Our technique of shock-driven bubble cavitation opens interesting perspectives for the investigation of shock-induced single-bubble or multibubble cavitation phenomena in thin liquids.

Situación de la tuberculosis multirresistente en Perú / Situation of multi-drug-resistant tuberculosis in Peru

La historia de las intervenciones y de la evolución epidemiológica de la hiperendemia de la tuberculosis multirresistente (TBMDR) comprende el periodo 1987-2016 y continúa. Un primer problema consistió en admitir su transmisibilidad y la necesidad de medir la magnitud. Durante los años 1990 una subestimación de la magnitud permitió su expansión. Durante los años 2000 se universalizaron las pruebas de sensibilidad, alentadas por la Unidad Técnica de TBMDR del ex-Programa Nacional de tuberculosis del Ministerio de Salud peruano. Durante todo ese lapso se han ensayado diferentes esquemas de tratamiento, con resultados dispares, mostrando persistente eficacia únicamente los esquemas individualizados basados en por lo menos tres drogas nuevas. Gracias al apoyo del Fondo Mundial, los pacientes tuvieron acceso universal al tratamiento. Ambas intervenciones impactaron sobre la tendencia de la hiperendemia, deteniendo su expansión. Limitaciones en los últimos años, incluyendo nuevamente una subestimación del mismo ha permitido su rebrote. Así, Perú es el país con mayor severidad de TBMDR y tuberculosis extensamente resistente en América

The history of interventions and the epidemiological history of the hyperendemicity of multi-drugresistant tuberculosis (MDRTB) encompasses the 1987-2016 period, and it still continues. The first problem was to recognize its transmissibility and the need to measure its real magnitude. During the 90s, the condition expanded because its extent was underestimated. During the first decade of the new millennium, universal access for susceptibility testing was granted, with the support of the Technical Unit of the former National Tuberculosis Control Program of the Peruvian Ministry of Health. During the whole period, different therapy schedules have been tested, with dissimilar results, and only individualized regimens with at least three new drugs were shown to be persistently efficacious. Thanks to the support of the World Fund, patients were able to get universal access to therapy. Both interventions had an impact upon the hyperendemic trend, and the expansion of this was stopped. However, some limitations occurring in the latter years, including an underestimation of the real magnitude of the problem, have led to a rebound in this condition. Consequently, Peru is the country with the most severe cases of MDR TB and extremely resistant tuberculosis in the Americas

Chlorpyrifos and neurodevelopmental effects: a literature review and expert elicitation on research and policy

Organophosphate pesticides are widely used on food crops grown in the EU. While they have been banned from indoor use in the US for a decade due to adverse health effects, they are still the most prevalent pesticides in the EU, with Chlorpyrifos (CPF) being the most commonly applied. It has been suggested CPF affects neurodevelopment even at levels below toxicity guidelines. Younger individuals may be more susceptible than adults due to biological factors and exposure settings.

Evolucionista ddarinn / Evolutionary Economics and Darwin

A partir del siglo XIX, se tomaron dos caminos distintos en la historia de la ciencia económica. Casi simultáneamente, la revolución darwiniana y la revolución marginalista tuvieron lugar pero sus intenciones ulteriores no pudieron ser más opuestas. La teoría de Darwin de la evolución de las especies por medio de la selección natural, se convirtió en un desafío a la visión del mundo dominante: la newtoniana (Witt, 1999). Este desafío al ideal newtoniano, fue influido, paradójicamente, por estímulos intelectuales proveniente de pensadores fuera de la biología. Estas influencias emanaron de la filosofía liberal del -dejar pasar, dejar hacer- de los siglos XVIII y de principios del siglo XIX. De los diarios de Darwin se destaca la correspondencia con Herbert Spencer, en donde se denota una clara influencia del trabajo de economistas-filósofos como Adam Smith, de la llamada escuela de Edimburgo, y Robert Malthus. Lo paradójico de esta situación es que ahora es Darwin quien, de vuelta, influye sobre los economistas modernos. La revolución darwiniana en la economía moderna consiste en mostrar al capitalismo como un proceso evolucionario explicado por procesos del cambio de patrones en las relaciones entre entidades. Pero gran parte de este estudio de influencia darwiniana no tiene que ver en sí con el estudio de la biología. Está relacionado con los principios y conceptos que definen el mecanismo evolucionario que es fundamento del desarrollo de la teoría evolucionista moderna. Desde el estudio del sistema natural, y sus disciplinas ¿qué podemos aprender en el campo de lo social en los temas de adaptabilidad, ante la adversidad y bio y sociodiversidad? El alto de emprenderismo en regiones y países latinoamericanos es síntoma de resiliencia social y adaptabilidad. Es en la adversidad donde se encuentra más variedad de comportamientos y hay más condiciones ante desafíos estresantes. Dado que la teoría convencional de disyuntivas racionales es insuficiente, esto plantea un reto para que futuras investigaciones consideren al pensamiento evolucionista como una alternativa a la hora de estudiar sistemas con altos niveles de emprenderismo por necesidad, alta desigualdad y alta felicidad. Es seguramente un terreno fructífero e interesante.

From the XIXth century onwards, two different paths were taken in the history of economic science. Almost simultaneously, the darwinian and the marginalist revolution took place but their respective -ulterior motif - could not be more opposited one from the other. The theory of Darwin about the evolution of the species by means of the natural selection, became a challenge to the dominant vision of the world: the Newtonian one (Witt, 1999). This challenge to the Newtonian ideal, was influenced, paradoxically, by intellectual stimuli coming from thinkers outside biology. These influences emanated from the liberal social philosophy of -laissez faire, laissez passer- during the XVIII century and beginning of the XIX century. In Darwin's correspondence with Herbert Spencer, stands out the clear influence of economists-philosophers like Adam Smith, from the so-called School of Edinburgh, and Robert Malthus. The paradox is that nowadays Darwin, in return, influences modern economists. The Darwinian revolution in the modern economy consists in showing capitalism as a evolutionary process explained by processes of change of patterns in the relations between entities. But great part of this study of Darwinian influence does not have to do with the study of Biology itself. It is related to the principles and concepts that define the evolutionary mechanism that is the foundation of the development of the modern evolutionary theory. What can we learn from the study of the natural system and its related disciplines in the field of social thinking in the adaptability of agents, in the face of adversity and bio- and sociodiversity? The high degree of entrepreneurship in Latin American countries is symptom of social resilience and adaptability. It is in adversity where more variety of behavior is present as well as higher conditions for stressing challenges. Since conventional theory of rational tradeoffs is insufficient, this raises a challenge to future research considering evolutionary thought as an alternative to studying systems with high levels of necessity-based entrepreneurship, high inequality but high degrees of happiness. It is surely a fruitful and interesting land.

Markers that predict serious bacterial infection in infants under 3 months of age presenting with fever of unknown origin.

OBJECTIVE: To evaluate potential markers of serious bacterial infection (SBI) in infants under 3 months of age presenting with fever of unknown origin. MATERIAL AND METHODS: We retrospectively studied all infants under 3 months of age seen in the emergency department between January 2004 and December 2006 for a febrile syndrome with no identifiable focus. Clinical data, procalcitonin (PCT), C reactive protein (CRP) and leucocyte count were evaluated for their ability to discriminate between SBI and non-SBI; receiver operating characteristic (ROC) curves were constructed for the laboratory markers and analysis was performed by multivariate logistic regression. RESULTS: The sample comprised 347 patients (23.63% with SBI). Mean PCT, CRP, leucocyte and neutrophil count were significantly higher in the group with SBI unlike the other criteria studied. The area under the ROC curve (AUC) for PCT was 0.77 (95% CI 0.72 to 0.81) and 0.79 for CRP (95% CI 0.75 to 0.84); both these variables were stronger predictors than leucocyte count (0.67, 95% CI 0.63 to 0.73). In the 15 infants with more invasive bacterial infections (sepsis, bacteraemia, bacterial meningitis), the diagnostic value of PCT (AUC 0.84, 95% CI 0.79 to 0.88) was higher than CRP (AUC 0.68, 95% CI 0.63 to 0.73). In infants who had been febrile for under 12 h, the differences between PCT, CRP and leucocyte count were statistically significant in both SBI and non-SBI groups, with increasing predictive value of PCT and decreasing value of CRP. CONCLUSIONS: PCT, CRP, and leucocyte count have intrinsic predictive value for SBI in febrile infants under 3 months of age. The diagnostic value of PCT is greater than CRP for more invasive bacterial infections and for fever of short duration.

Lesiones osteolíticas como forma de presentación de linfoma no Hodgkin / Osteolitic lesions as non-Hodgkin lymphoma presentation form

No disponible

Enteroaggregative Escherichia coli an emergent pathogen with different virulence properties.

Enteroaggregative Escherichia coli (EAEC) is an emergent bacterial pathogen. The first studies in developing countries with EAEC strains, showed that this bacterium was associated with persistent diarrhea. However, new studies showed that EAEC may be associated also with acute diarrhea, with both nosocomial and community outbreaks worldwide, and as an important pathogen of diarrheal disease in human immunodeficiency virus-infected adults. EAEC strains are recognized by their characteristic aggregative adherence or "stacked-brick" pattern to epithelial cells. Although the pathogenesis of EAEC infection is not well understood, cellular changes observed in animal models and in vitro assays, suggested that the alterations in the intestinal mucosa during EAEC infection are associated with adherence factors and toxins production. The damage has been associated with the release of inflammatory mediators, which may contribute also to the intestinal illness. The dissemination of the high pathogenicity island from Yersinia pestis evolutionary group to EAEC has been show; different studies suggest that it may contribute to the virulence of EAEC strains. Molecular methods to investigate the presence of plasmid and chromosomal EAEC-associated virulence markers, have been used for the characterization and epidemiological studies of EAEC strains. Although the clinical and epidemiological importance of EAEC have been demonstrated in different studies, Escherichia coli strains with adherent agreggative phenotype are commonly isolated from healthy children and environmental sources. This support the necessity to study virulence factors no related with the cells adherence pattern, that show the specific EAEC pathogenic clones associated whit intestinal disease.

Carrier detection and prenatal molecular diagnosis in a Duchenne muscular dystrophy family without any affected relative available.

In this paper we report a family where the affected DMD patients were not available for study and a molecular strategy was used for female carriers detection and for prenatal diagnosis. Linkage analysis was performed with two markers within the DMD gene, in all family members screened. DMD markers used (pERT87.8/Taq1 and pERT87.15/Xmn1) seemed not to be informative because the propositas mother (II-2) was homozygous for the minor allele at each marker (T2 and X2), however, the proposita and one sister carried only the major allele, which was inherited from the father. These results suggested that a deletion involving both markers could be present, and was inherited from the mother to both daughters. Quantitative multiplex PCR confirmed the deletion in female carriers, involving at least exons 12 to 17. DNA studies of cultured amniotic fluid cells at 14 weeks gestation, by amplification of specific Y-chromosome sequences, followed by multiplex PCR, lead to the diagnosis of a male fetus affected by DMD.

Charge interactions in sperm-egg recognition.

A novel method using derivatized agarose beads for investigating the types of molecules, when isolated from all others, that can form stable adhesive bonds, was recently described by Roque et al. (1996). The findings from this study were extended to living sea urchin cell systems. Both the bead results and the experiments with sea urchin cells suggested that phosphorylated amino acids can form stable adhesive bonds with positively charged peptides (Roque et al., 1996). As these experiments only examined phosphorylated amino acids, the validity of the hypotheses developed in the earlier study was dependent on extending the experiments to additional phosphorylated molecules. In this study, effects of D-mannose, D-mannose-1-phosphate, D-fructose, D-fructose-1-phosphate, maltose and maltose-1-phosphate on embryo cell reaggregation and sperm-egg interaction using untreated, jelly coat-free and vitelline layer disrupted Strongylocentrotus purpuratus sea urchin eggs were examined. The phosphorylated sugars (50 mM), and not their non-phosphorylated counterparts, strongly inhibited fertilization of the 3 types of eggs. ATP, at concentrations as low as 0.8 mM also completely inhibited fertilization. The phosphorylated sugars had little or no effect on reaggregating sea urchin blastula cells. A likely explanation of these results is that sperm-egg interaction in the sea urchin involves positively and negatively charged receptors; the positively charged receptors are blocked by exogenously added phosphorylated molecules. These and earlier studies indicate that by extending results from bead modeling studies to living systems, interesting information can be obtained regarding bonding mechanisms that may modulate adhesive interactions.

Electrotonic coupling between neurosecretory cells in the crayfish eyestalk.

Electrical coupling is described among neurosecretory cells in the crayfish X organ. By simultaneous impalements from pairs of neurons, only 30% were found to be coupled. All of them showed non-rectifying junctions. In all cases, electrical coupling corresponded to dye-coupling, as explored with intracellular injection of Lucifer yellow to one of the recorded cells. Some neurons were coupled to more than one neighbour. From dye fills it was apparent that the coupling site could be located far away from the cell body, immediately before the axonal branchings in the neuropile. The input resistance of the coupled neurons was consistently lower (24 +/- 16 M omega) than that of the non-coupled neurons (58 +/- 18 M omega). Synchronous synaptic activity was commonly recorded from coupled neurons, thus suggesting a functional significance of coupling in the integration of neurosecretory activity.

Growth and synapse formation by identified leech neurones in culture: a review.

Within hours after identified neurones have been isolated from the CNS of the leech, they begin to sprout and to form synapses. Electrical recordings made by loose-patch clamp show that the tip of the isolated neurone has distinct properties with a high density of sodium channels. Neurites grow out from this tip after about 30 min and continue to grow for the next few days. The extent of growth, the branching pattern and the distribution of calcium channels all depend critically upon the molecular composition of the substrate. The tip of the neurone also represents a preferred region for synapse formation. For example when the tips of two serotonin-containing neuromodulatory neurones, the Retzius cells, are placed in contact, chemical synapses develop within about 6 h. These chemical synapses are bidirectional and become stronger over the next 2 days. Electrical synapses between the two Retzius cells develop more slowly and appear only after about 20 h. When the tip of one Retzius cell is apposed to the soma of another, chemical transmission develops more slowly. When other regions of these same cells are placed in contact, electrical transmission can appear before chemical. Together these results show that specialized areas of neuronal membrane are involved in neurite extension and in the formation of specific synaptic connections.