Isolation and Mechanical Measurements of Myofibrils from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Summary: Tension production and contractile properties are poorly characterized aspects of excitation-contraction coupling of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Previous approaches have been limited due to the small size and structural immaturity of early-stage hiPSC-CMs. We developed a substrate nanopatterning approach to produce hiPSC-CMs in culture with adult-like dimensions, T-tubule-like structures, and aligned myofibrils. We then isolated myofibrils from hiPSC-CMs and measured the tension and kinetics of activation and relaxation using a custom-built apparatus with fast solution switching. The contractile properties and ultrastructure of myofibrils more closely resembled human fetal myofibrils of similar gestational age than adult preparations. We also demonstrated the ability to study the development of contractile dysfunction of myofibrils from a patient-derived hiPSC-CM cell line carrying the familial cardiomyopathy MYH7 mutation (E848G). These methods can bring new insights to understanding cardiomyocyte maturation and developmental mechanical dysfunction of hiPSC-CMs with cardiomyopathic mutations. : In this article, Pioner and colleagues reported contractile properties of isolated myofibrils from hiPSC-CMs with highly mature morphology. This approach permits quantitative assessment of maturation and contractile properties of hiPSC-CMs and can be used to study the development of contractile dysfunction in genetically based cardiac diseases. The authors present a patient-derived cell line carrying a novel familial cardiomyopathy MYH7 mutation (E848G)

Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

The Effect of Diet and Opponent Size on Aggressive Interactions Involving Caribbean Crazy Ants (Nylanderia fulva)

Biotic interactions are often important in the establishment and spread of invasive species. In particular, competition between introduced and native species can strongly influence the distribution and spread of exotic species and in some cases competition among introduced species can be important. The Caribbean crazy ant, Nylanderia fulva, was recently introduced to the Gulf Coast of Texas, and appears to be spreading inland. It has been hypothesized that competition with the red imported fire ant, Solenopsis invicta, may be an important factor in the spread of crazy ants. We investigated the potential of interspecific competition among these two introduced ants by measuring interspecific aggression between Caribbean crazy ant workers and workers of Solenopsis invicta. Specifically, we examined the effect of body size and diet on individual-level aggressive interactions among crazy ant workers and fire ants. We found that differences in diet did not alter interactions between crazy ant workers from different nests, but carbohydrate level did play an important role in antagonistic interactions with fire ants: crazy ants on low sugar diets were more aggressive and less likely to be killed in aggressive encounters with fire ants. We found that large fire ants engaged in fewer fights with crazy ants than small fire ants, but fire ant size affected neither fire ant nor crazy ant mortality. Overall, crazy ants experienced higher mortality than fire ants after aggressive encounters. Our findings suggest that fire ant workers might outcompete crazy ant workers on an individual level, providing some biotic resistance to crazy ant range expansion. However, this resistance may be overcome by crazy ants that have a restricted sugar intake, which may occur when crazy ants are excluded from resources by fire ants

Using Mitochondrial and Nuclear Sequence Data for Disentangling Population Structure in Complex Pest Species: A Case Study with Dermanyssus gallinae

Among global changes induced by human activities, association of breakdown of geographical barriers and impoverishered biodiversity of agroecosystems may have a strong evolutionary impact on pest species. As a consequence of trade networks' expansion, secondary contacts between incipient species, if hybrid incompatibility is not yet reached, may result in hybrid swarms, even more when empty niches are available as usual in crop fields and farms. By providing important sources of genetic novelty for organisms to adapt in changing environments, hybridization may be strongly involved in the emergence of invasive populations

Early Geometrical Thinking in the Environment of Patterns, Mosaics and Isometries

This book discusses the learning and teaching of geometry, with a special focus on kindergarten and primary education. It examines important new trends and developments in research and practice, and emphasizes theoretical, empirical and developmental issues. Further, it discusses various topics, including curriculum studies and implementation, spatial abilities and geometric reasoning, as well as the psychological roots of geometrical thinking and teacher preparation in geometry education. It considers these issues from historical, epistemological, cognitive semiotic and educational points of view in the context of students' difficulties and the design of teaching and curricula

Methylated HBHA Produced in M. smegmatis Discriminates between Active and Non-Active Tuberculosis Disease among RD1-Responders

A challenge in tuberculosis (TB) research is to develop a new immunological test that can help distinguish, among subjects responsive to QuantiFERON TB Gold In tube (QFT-IT), those who are able to control Mtb replication (remote LTBI, recent infection and past TB) from those who cannot (active TB disease). IFN-\u3b3 response to the Heparin-binding-hemagglutinin (HBHA) of Mtb has been associated with LTBI, but the cumbersome procedures of purifying the methylated and immunological active form of the protein from Mtb or M. bovis Bacillus Calmette et Guerin (BCG) have prevented its implementation in a diagnostic test. Therefore, the aim of the present study was to evaluate the IFN-\u3b3 response to methylated HBHA of Mtb produced in M. smegmatis (rHBHAms) in individuals at different stages of TB who scored positive to QFT-IT

Differences in stress tolerance and brood size between a non-indigenous and an indigenous gammarid in the northern Baltic Sea

Differences in stress tolerance and reproductive traits may drive the competitive hierarchy between nonindigenous and indigenous species and turn the former ones into successful invaders. In the northern Baltic Sea, the non-indigenous Gammarus tigrinus is a recent invader of littoral ecosystems and now occupies comparable ecological niches as the indigenous G. zaddachi. In laboratory experiments on specimens collected between June and August 2009 around Tva¨rminne in southern Finland (59°500N/23°150E), the tolerances towards heat stress and hypoxia were determined for the two species using lethal time, LT50, as response variable. The brood size of the two species was also studied and some observations were made on maturation of juveniles. Gammarus tigrinus was more resistant to hypoxia and survived at higher temperatures than G. zaddachi. Brood size was also greater in G. tigrinus than in G. zaddachi and G. tigrinus matured at a smaller size and earlier than G. zaddachi. Hence, there are clear competitive advantages for the non-indigenous G. tigrinus compared to the indigenous G. zaddachi, and these may be further strengthened through ongoing environmental changes related to increased eutrophication and a warming climate in the Baltic Sea region

Extracting key information from historical data to quantify the transmission dynamics of smallpox

<p>Abstract</p> <p>Background</p> <p>Quantification of the transmission dynamics of smallpox is crucial for optimizing intervention strategies in the event of a bioterrorist attack. This article reviews basic methods and findings in mathematical and statistical studies of smallpox which estimate key transmission parameters from historical data.</p> <p>Main findings</p> <p>First, critically important aspects in extracting key information from historical data are briefly summarized. We mention different sources of heterogeneity and potential pitfalls in utilizing historical records. Second, we discuss how smallpox spreads in the absence of interventions and how the optimal timing of quarantine and isolation measures can be determined. Case studies demonstrate the following. (1) The upper confidence limit of the 99th percentile of the incubation period is 22.2 days, suggesting that quarantine should last 23 days. (2) The highest frequency (61.8%) of secondary transmissions occurs 3–5 days after onset of fever so that infected individuals should be isolated before the appearance of rash. (3) The U-shaped age-specific case fatality implies a vulnerability of infants and elderly among non-immune individuals. Estimates of the transmission potential are subsequently reviewed, followed by an assessment of vaccination effects and of the expected effectiveness of interventions.</p> <p>Conclusion</p> <p>Current debates on bio-terrorism preparedness indicate that public health decision making must account for the complex interplay and balance between vaccination strategies and other public health measures (e.g. case isolation and contact tracing) taking into account the frequency of adverse events to vaccination. In this review, we summarize what has already been clarified and point out needs to analyze previous smallpox outbreaks systematically.</p

Facilitation and Competition among Invasive Plants: A Field Experiment with Alligatorweed and Water Hyacinth

Ecosystems that are heavily invaded by an exotic species often contain abundant populations of other invasive species. This may reflect shared responses to a common factor, but may also reflect positive interactions among these exotic species. Armand Bayou (Pasadena, TX) is one such ecosystem where multiple species of invasive aquatic plants are common. We used this system to investigate whether presence of one exotic species made subsequent invasions by other exotic species more likely, less likely, or if it had no effect. We performed an experiment in which we selectively removed exotic rooted and/or floating aquatic plant species and tracked subsequent colonization and growth of native and invasive species. This allowed us to quantify how presence or absence of one plant functional group influenced the likelihood of successful invasion by members of the other functional group. We found that presence of alligatorweed (rooted plant) decreased establishment of new water hyacinth (free-floating plant) patches but increased growth of hyacinth in established patches, with an overall net positive effect on success of water hyacinth. Water hyacinth presence had no effect on establishment of alligatorweed but decreased growth of existing alligatorweed patches, with an overall net negative effect on success of alligatorweed. Moreover, observational data showed positive correlations between hyacinth and alligatorweed with hyacinth, on average, more abundant. The negative effect of hyacinth on alligatorweed growth implies competition, not strong mutual facilitation (invasional meltdown), is occurring in this system. Removal of hyacinth may increase alligatorweed invasion through release from competition. However, removal of alligatorweed may have more complex effects on hyacinth patch dynamics because there were strong opposing effects on establishment versus growth. The mix of positive and negative interactions between floating and rooted aquatic plants may influence local population dynamics of each group and thus overall invasion pressure in this watershed