Host lifestyle affects human microbiota on daily timescales

Background: Disturbance to human microbiota may underlie several pathologies. Yet, we lack a comprehensive understanding of how lifestyle affects the dynamics of human-associated microbial communities. Results: Here, we link over 10,000 longitudinal measurements of human wellness and action to the daily gut and salivary microbiota dynamics of two individuals over the course of one year. These time series show overall microbial communities to be stable for months. However, rare events in each subjects’ life rapidly and broadly impacted microbiota dynamics. Travel from the developed to the developing world in one subject led to a nearly two-fold increase in the Bacteroidetes to Firmicutes ratio, which reversed upon return. Enteric infection in the other subject resulted in the permanent decline of most gut bacterial taxa, which were replaced by genetically similar species. Still, even during periods of overall community stability, the dynamics of select microbial taxa could be associated with specific host behaviors. Most prominently, changes in host fiber intake positively correlated with next-day abundance changes among 15% of gut microbiota members. Conclusions: Our findings suggest that although human-associated microbial communities are generally stable, they can be quickly and profoundly altered by common human actions and experiences.National Science Foundation (U.S.) (Grant 0821391

‘Hygienic’ Lymphocytes Convey Increased Cancer Risk

Risk of developing inflammation-associated cancers has increased in industrialized countries during the past 30 years. One possible explanation is societal hygiene practices with use of antibiotics and Caesarian births that provide too few early life exposures of beneficial microbes. Building upon a ‘hygiene hypothesis’ model whereby prior microbial exposures lead to beneficial changes in CD4+ lymphocytes, here we use an adoptive cell transfer model and find that too few prior microbe exposures alternatively result in increased inflammation-associated cancer growth in susceptible recipient mice. Specifically, purified CD4+ lymphocytes collected from ‘restricted flora’ donors increases multiplicity and features of malignancy in intestinal polyps of recipient Apc[superscript Min/+] mice, coincident with increased inflammatory cell infiltrates and instability of the intestinal microbiota. We conclude that while a competent immune system serves to maintain intestinal homeostasis and good health, under hygienic rearing conditions CD4+ lymphocytes instead exacerbate inflammation-associated tumorigenesis, subsequently contributing to more frequent cancers in industrialized societies.National Institutes of Health (U.S.) (Grant P30-ES002109)National Institutes of Health (U.S.) (Grant U01 CA164337)National Institutes of Health (U.S.) (Grant RO1CA108854

Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria.

Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.)

Planck Intermediate Results II: Comparison of Sunyaev-Zeldovich measurements from Planck and from the Arcminute Microkelvin Imager for 11 galaxy clusters

A comparison is presented of Sunyaev-Zeldovich measurements for 11 galaxy clusters as obtained by Planck and by the ground-based interferometer, the Arcminute Microkelvin Imager. Assuming a universal spherically-symmetric Generalised Navarro, Frenk & White (GNFW) model for the cluster gas pressure profile, we jointly constrain the integrated Compton-Y parameter (Y_500) and the scale radius (theta_500) of each cluster. Our resulting constraints in the Y_500-theta_500 2D parameter space derived from the two instruments overlap significantly for eight of the clusters, although, overall, there is a tendency for AMI to find the Sunyaev-Zeldovich signal to be smaller in angular size and fainter than Planck. Significant discrepancies exist for the three remaining clusters in the sample, namely A1413, A1914, and the newly-discovered Planck cluster PLCKESZ G139.59+24.18. The robustness of the analysis of both the Planck and AMI data is demonstrated through the use of detailed simulations, which also discount confusion from residual point (radio) sources and from diffuse astrophysical foregrounds as possible explanations for the discrepancies found. For a subset of our cluster sample, we have investigated the dependence of our results on the assumed pressure profile by repeating the analysis adopting the best-fitting GNFW profile shape which best matches X-ray observations. Adopting the best-fitting profile shape from the X-ray data does not, in general, resolve the discrepancies found in this subset of five clusters. Though based on a small sample, our results suggest that the adopted GNFW model may not be sufficiently flexible to describe clusters universally.Comment: update to metadata author list onl

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis