Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Measurement of the Negative Muon Anomalous Magnetic Moment to 0.7 ppm

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 parts per million (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement of the negative muon. The result a_mu= 11 659 214(8)(3) \times 10^{-10} (0.7 ppm), where the first uncertainty is statistical and the second is sytematic, is consistend with previous measurements of the anomaly for the positive and negative muon. The average for the muon anomaly a_{mu}(exp) = 11 659 208(6) \times 10^{-10} (0.5ppm).Comment: 4 pages, 4 figures, submitted to Physical Review Letters, revised to reflect referee comments. Text further revised to reflect additional referee comments and a corrected Fig. 3 replaces the older versio

Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Sensitivity of Chaos Measures in Detecting Stress in the Focusing Control Mechanism of the Short-Sighted Eye

yesWhen fixating on a stationary object, the power of the eye’s lens fluctuates. Studies have suggested that changes in these so-called microfluctuations in accommodation may be a factor in the onset and progression of short-sightedness. Like many physiological signals, the fluctuations in the power of the lens exhibit chaotic behaviour. A breakdown or reduction in chaos in physiological systems indicates stress to the system or pathology. The purpose of this study was to determine whether the chaos in fluctuations of the power of the lens changes with refractive error, i.e. how short-sighted a subject is, and/or accommodative demand, i.e. the effective distance of the object that is being viewed. Six emmetropes (EMMs, non-short-sighted), six early-onset myopes (EOMs, onset of short-sightedness before the age of 15), and six late-onset myopes (LOMs, onset of short-sightedness after the age of 15) took part in the study. Accommodative microfluctuations were measured at 22 Hz using an SRW-5000 autorefractor at accommodative demands of 1 D (dioptres), 2 D, and 3 D. Chaos theory analysis was used to determine the embedding lag, embedding dimension, limit of predictability, and Lyapunov exponent. Topological transitivity was also tested for. For comparison, the power spectrum and standard deviation were calculated for each time record. The EMMs had a statistically significant higher Lyapunov exponent than the LOMs ( 0.64±0.330.64±0.33 vs. 0.39±0.20 D/s0.39±0.20 D/s ) and a lower embedding dimension than the LOMs ( 3.28±0.463.28±0.46 vs. 3.67±0.493.67±0.49 ). There was insufficient evidence (non-significant p value) of a difference between EOMs and EMMs or EOMs and LOMs. The majority of time records were topologically transitive. There was insufficient evidence of accommodative demand having an effect. Power spectrum analysis and assessment of the standard deviation of the fluctuations failed to discern differences based on refractive error. Chaos differences in accommodation microfluctuations indicate that the control system for LOMs is under stress in comparison to EMMs. Chaos theory analysis is a more sensitive marker of changes in accommodation microfluctuations than traditional analysis methods

New MACRO results on atmospheric neutrino oscillations

The final results of the MACRO experiment on atmospheric neutrino oscillations are presented and discussed. The data concern different event topologies with average neutrino energies of ~3 and ~50 GeV. Multiple Coulomb Scattering of the high energy muons in absorbers was used to estimate the neutrino energy of each event. The angular distributions, the L/E_nu distribution, the particle ratios and the absolute fluxes all favour nu_mu --> nu_tau oscillations with maximal mixing and Delta m^2 =0.0023 eV^2. A discussion is made on the Monte Carlos used for the atmospheric neutrino flux. Some results on neutrino astrophysics are also briefly discussed.Comment: Invited Paper at the NANP03 Int. Conf., Dubna, 200

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199

The Observation of Up-going Charged Particles Produced by High Energy Muons in Underground Detectors

An experimental study of the production of up-going charged particles in inelastic interactions of down-going underground muons is reported, using data obtained from the MACRO detector at the Gran Sasso Laboratory. In a sample of 12.2 10^6 single muons, corresponding to a detector livetime of 1.55 y, 243 events are observed having an up-going particle associated with a down-going muon. These events are analysed to determine the range and emission angle distributions of the up-going particle, corrected for detection and reconstruction efficiency. Measurements of the muon neutrino flux by underground detectors are often based on the observation of through-going and stopping muons produced in $\nu_\mu$ interactions in the rock below the detector. Up-going particles produced by an undetected down-going muon are a potential background source in these measurements. The implications of this background for neutrino studies using MACRO are discussed.Comment: 18 pages, 9 figures. Accepted by Astrop. Physic

Nuclearite search with the MACRO detector at Gran Sasso

In this paper we present the results of a search for nuclearites in the penetrating cosmic radiation using the scintillator and track-etch subdetectors of the MACRO apparatus. The analyses cover the beta =v/c range at the detector depth (3700 hg/cm^2) 10^-5 < beta < 1; for beta = 2 x 10^-3 the flux limit is 2.7 x 10^-16 cm^-2 s^-1 sr^-1 for an isotropic flux of nuclearites, and twice this value for a flux of downgoing nuclearites.Comment: 16 pages, 4 Encapsulated Postscript figures, uses article.sty. Submitted to The European Physical Journal