IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gamma(c)) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4(+) and CD8(+) T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R(-/-) mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R(-/-) T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.This work was supported by National Institutes of Health Grants R21 AI100766, R01 AI106725, and P01 AI073748

What Is a Group? : Young Children’s Perceptions of Different Types of Groups and Group Entitativity

To date, developmental research on groups has focused mainly on in-group biases and intergroup relations. However, little is known about children’s general understanding of social groups and their perceptions of different forms of group. In this study, 5- to 6-year-old children were asked to evaluate prototypes of four key types of groups: an intimacy group (friends), a task group (people who are collaborating), a social category (people who look alike), and a loose association (people who coincidently meet at a tram stop). In line with previous work with adults, the vast majority of children perceived the intimacy group, task group, and social category, but not the loose association, to possess entitativity, that is, to be a ‘real group.’ In addition, children evaluated group member properties, social relations, and social obligations differently in each type of group, demonstrating that young children are able to distinguish between different types of in-group relations. The origins of the general group typology used by adults thus appear early in development. These findings contribute to our knowledge about children's intuitive understanding of groups and group members' behavior

A Key Marine Diazotroph in a Changing Ocean: The Interacting Effects of Temperature, CO2 and Light on the Growth of Trichodesmium erythraeum IMS101

Trichodesmium is a globally important marine diazotroph that accounts for approximately 60-80% of marine biological N2 fixation and as such plays a key role in marine N and C cycles. We undertook a comprehensive assessment of how the growth rate of Trichodesmium erythraeum IMS101 was directly affected by the combined interactions of temperature, pCO2 and light intensity. Our key findings were: low pCO2 affected the lower temperature tolerance limit (Tmin) but had no effect on the optimum temperature (Topt) at which growth was maximal or the maximum temperature tolerance limit (Tmax); low pCO2 had a greater effect on the thermal niche width than low-light; the effect of pCO2 on growth rate was more pronounced at suboptimal temperatures than at supraoptimal temperatures; temperature and light had a stronger effect on the photosynthetic efficiency (Fv/Fm) than did CO2; and at Topt, the maximum growth rate increased with increasing CO2, but the initial slope of the growth-irradiance curve was not affected by CO2. In the context of environmental change, our results suggest that the (i) nutrient replete growth rate of Trichodesmium IMS101 would have been severely limited by low pCO2 at the last glacial maximum (LGM), (ii) future increases in pCO2 will increase growth rates in areas where temperature ranges between Tmin to Topt, but will have negligible effect at temperatures between Topt and Tmax, (iii) areal increase of warm surface waters (> 18°C) has allowed the geographic range to increase significantly from the LGM to present and that the range will continue to expand to higher latitudes with continued warming, but (iv) continued global warming may exclude Trichodesmium spp. from some tropical regions by 2100 where temperature exceeds Topt

Dusty Planetary Systems

Extensive photometric stellar surveys show that many main sequence stars show emission at infrared and longer wavelengths that is in excess of the stellar photosphere; this emission is thought to arise from circumstellar dust. The presence of dust disks is confirmed by spatially resolved imaging at infrared to millimeter wavelengths (tracing the dust thermal emission), and at optical to near infrared wavelengths (tracing the dust scattered light). Because the expected lifetime of these dust particles is much shorter than the age of the stars (>10 Myr), it is inferred that this solid material not primordial, i.e. the remaining from the placental cloud of gas and dust where the star was born, but instead is replenished by dust-producing planetesimals. These planetesimals are analogous to the asteroids, comets and Kuiper Belt objects (KBOs) in our Solar system that produce the interplanetary dust that gives rise to the zodiacal light (tracing the inner component of the Solar system debris disk). The presence of these "debris disks" around stars with a wide range of masses, luminosities, and metallicities, with and without binary companions, is evidence that planetesimal formation is a robust process that can take place under a wide range of conditions. This chapter is divided in two parts. Part I discusses how the study of the Solar system debris disk and the study of debris disks around other stars can help us learn about the formation, evolution and diversity of planetary systems by shedding light on the frequency and timing of planetesimal formation, the location and physical properties of the planetesimals, the presence of long-period planets, and the dynamical and collisional evolution of the system. Part II reviews the physical processes that affect dust particles in the gas-free environment of a debris disk and their effect on the dust particle size and spatial distribution.Comment: 68 pages, 25 figures. To be published in "Solar and Planetary Systems" (P. Kalas and L. French, Eds.), Volume 3 of the series "Planets, Stars and Stellar Systems" (T.D. Oswalt, Editor-in-chief), Springer 201

Gebiss: an ImageJ plugin for the specification of ground truth and the performance evaluation of 3D segmentation algorithms.

Background: Image segmentation is a crucial step in quantitative microscopy that helps to define regions of tissues, cells or subcellular compartments. Depending on the degree of user interactions, segmentation methods can be divided into manual, automated or semi-automated approaches. 3D image stacks usually require automated methods due to their large number of optical sections. However, certain applications benefit from manual or semi-automated approaches. Scenarios include the quantification of 3D images with poor signal-to-noise ratios or the generation of so-called ground truth segmentations that are used to evaluate the accuracy of automated segmentation methods. Results: We have developed Gebiss; an ImageJ plugin for the interactive segmentation, visualisation and quantification of 3D microscopic image stacks. We integrated a variety of existing plugins for threshold-based segmentation and volume visualisation. Conclusions: We demonstrate the application of Gebiss to the segmentation of nuclei in live Drosophila embryos and the quantification of neurodegeneration in Drosophila larval brains. Gebiss was developed as a cross-platform ImageJ plugin and is freely available on the web at http://imaging.bii.a-star.edu.sg/projects/gebiss

Planktonic events may cause polymictic-dimictic regime shifts in temperate lakes

Water transparency affects the thermal structure of lakes, and within certain lake depth ranges, it can determine whether a lake mixes regularly (polymictic regime) or stratifies continuously (dimictic regime) from spring through summer. Phytoplankton biomass can influence transparency but the effect of its seasonal pattern on stratification is unknown. Therefore we analysed long term field data from two lakes of similar depth, transparency and climate but one polymictic and one dimictic, and simulated a conceptual lake with a hydrodynamic model. Transparency in the study lakes was typically low during spring and summer blooms and high in between during the clear water phase (CWP), caused when zooplankton graze the spring bloom. The effect of variability of transparency on thermal structure was stronger at intermediate transparency and stronger during a critical window in spring when the rate of lake warming is highest. Whereas the spring bloom strengthened stratification in spring, the CWP weakened it in summer. The presence or absence of the CWP influenced stratification duration and under some conditions determined the mixing regime. Therefore seasonal plankton dynamics, including biotic interactions that suppress the CWP, can influence lake temperatures, stratification duration, and potentially also the mixing regime

Axelrod’s metanorm games on networks

Metanorms is a mechanism proposed to promote cooperation in social dilemmas. Recent experimental results show that network structures that underlie social interactions influence the emergence of norms that promote cooperation. We generalize Axelrod’s analysis of metanorms dynamics to interactions unfolding on networks through simulation and mathematical modeling. Network topology strongly influences the effectiveness of the metanorms mechanism in establishing cooperation. In particular, we find that average degree, clustering coefficient and the average number of triplets per node play key roles in sustaining or collapsing cooperationSpanish MICINN projects CSD2010-00034 (CONSOLIDER-INGENIO 2010) and DPI2010-16920, and by the Junta de Castilla y Leo´ n, references BU034A08 and GREX251-2009

TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells

TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR)

Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism

Defects in centrosome, centrosomal-associated and spindle-associated proteins are the most frequent cause of primary microcephaly (PM) and microcephalic primordial dwarfism (MPD) syndromes in humans. Mitotic progression and segregation defects, microtubule spindle abnormalities and impaired DNA damage-induced G2-M cell cycle checkpoint proficiency have been documented in cell lines from these patients. This suggests that impaired mitotic entry, progression and exit strongly contribute to PM and MPD. Considering the vast protein networks involved in coordinating this cell cycle stage, the list of potential target genes that could underlie novel developmental disorders is large. One such complex network, with a direct microtubule-mediated physical connection to the centrosome, is the kinetochore. This centromeric-associated structure nucleates microtubule attachments onto mitotic chromosomes. Here, we described novel compound heterozygous variants in CENPE in two siblings who exhibit a profound MPD associated with developmental delay, simplified gyri and other isolated abnormalities. CENPE encodes centromere-associated protein E (CENP-E), a core kinetochore component functioning to mediate chromosome congression initially of misaligned chromosomes and in subsequent spindle microtubule capture during mitosis. Firstly, we present a comprehensive clinical description of these patients. Then, using patient cells we document abnormalities in spindle microtubule organization, mitotic progression and segregation, before modeling the cellular pathogenicity of these variants in an independent cell system. Our cellular analysis shows that a pathogenic defect in CENP-E, a kinetochore-core protein, largely phenocopies PCNT-mutated microcephalic osteodysplastic primordial dwarfism-type II patient cells. PCNT encodes a centrosome-associated protein. These results highlight a common underlying pathomechanism. Our findings provide the first evidence for a kinetochore-based route to MPD in humans