Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online

Precision Measurement of the Ds∗+−Ds+D_s^{*+}- D_s^+ Mass Difference

We have measured the vector-pseudoscalar mass splitting $M(D_s^{*+})-M(D_s^+) = 144.22\pm 0.47\pm 0.37 MeV$, significantly more precise than the previous world average. We minimize the systematic errors by also measuring the vector-pseudoscalar mass difference $M(D^{*0})-M(D^0)$ using the radiative decay $D^{*0}\rightarrow D^0\gamma$, obtaining $[M(D_s^{*+})-M(D_s^+)]-[M(D^{*0})-M(D^0)] = 2.09\pm 0.47\pm 0.37 MeV$. This is then combined with our previous high-precision measurement of $M(D^{*0})-M(D^0)$, which used the decay $D^{*0}\rightarrow D^0\pi^0$. We also measure the mass difference $M(D_s^+)-M(D^+)=99.5\pm 0.6\pm 0.3$ MeV, using the $\phi\pi^+$ decay modes of the $D_s^+$ and $D^+$ mesons.Comment: 18 pages uuencoded compressed postscript (process with uudecode then gunzip). hardcopies with figures can be obtained by sending mail to: [email protected]

Observation of a New Charmed Strange Meson

Using the CLEO-II detector, we have obtained evidence for a new meson decaying to $D^0 K^+$. Its mass is $2573.2^{+1.7}_{-1.6}\pm 0.8\pm 0.5$ {}~MeV/$c^2$ and its width is $16^{+5}_{-4}\pm 3$~MeV/$c^2$. Although we do not establish its spin and parity, the new meson is consistent with predictions for an $L=1$, $S=1$, $J_P=2^+$ charmed strange state.Comment: 9 pages uuencoded compressed postscript (process with uudecode then gunzip). hardcopies with figures can be obtained by sending mail to: [email protected]

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

Measurement of the branching fraction for Υ(1S)→τ+τ−\Upsilon (1S) \to \tau^+ \tau^-

We have studied the leptonic decay of the $\Upsilon (1S)$ resonance into tau pairs using the CLEO II detector. A clean sample of tau pair events is identified via events containing two charged particles where exactly one of the particles is an identified electron. We find $B(\Upsilon(1S) \to \tau^+ \tau^-) = (2.61~\pm~0.12~{+0.09\atop{-0.13}})$. The result is consistent with expectations from lepton universality.Comment: 9 pages, RevTeX, two Postscript figures available upon request, CLNS 94/1297, CLEO 94-20 (submitted to Physics Letters B

Measurement of the Decay Asymmetry Parameters in Λc+→Λπ+\Lambda_c^+ \to \Lambda\pi^+ and Λc+→Σ+π0\Lambda_c^+ \to \Sigma^+\pi^0

We have measured the weak decay asymmetry parameters (\aLC ) for two \LC\ decay modes. Our measurements are \aLC = -0.94^{+0.21+0.12}_{-0.06-0.06} for the decay mode $\Lambda_c^+ \to \Lambda\pi^+$ and \aLC = -0.45\pm 0.31 \pm 0.06 for the decay mode $\Lambda_c \to \Sigma^+\pi^0$. By combining these measurements with the previously measured decay rates, we have extracted the parity-violating and parity-conserving amplitudes. These amplitudes are used to test models of nonleptonic charmed baryon decay.Comment: 11 pages including the figures. Uses REVTEX and psfig macros. Figures as uuencoded postscript. Also available as http://w4.lns.cornell.edu/public/CLNS/1995/CLNS95-1319.p

Spatio-Temporal Variation in Length-Weight Relationships and Condition of the Ribbonfish Trichiurus lepturus (Linnaeus, 1758): Implications for Fisheries Management

Knowledge of length-weight relationships for commercially exploited fish is an important tool for assessing and managing of fish stocks. However, analyses of length-weight relationship fisheries data typically do not consider the inherent differences in length-weight relationships for fish caught from different habitats, seasons, or years, and this can affect the utility of these data for developing condition indices or calculating fisheries biomass. Here, we investigated length-weight relationships for ribbonfish Trichiurus lepturus in the waters of the Arabian Sea off Oman collected during three periods (2001-02, 2007-08, and 2014-15) and showed that a multivariate modelling approach that considers the areas and seasons in which ribbonfish were caught improved estimation of length-weight relationships. We used the outputs of these models to explore spatio-temporal variations in condition indices and relative weights among ribbonfish, revealing fish of 85-125 cm were in the best overall condition. We also found that condition differed according to where and when fish were caught, with condition lowest during spring and pre-south-west monsoon periods and highest during and after the south-west monsoons. We interpret these differences to be a consequence of variability in temperature and food availability. Based on our findings, we suggest fishing during seasons that have the lowest impact on fish condition and which are commercially most viable; such fishery management would enhance fisheries conservation and economic revenue in the region

Production and Decay of D_1(2420)^0 and D_2^*(2460)^0

We have investigated $D^{+}\pi^{-}$ and $D^{*+}\pi^{-}$ final states and observed the two established $L=1$ charmed mesons, the $D_1(2420)^0$ with mass $2421^{+1+2}_{-2-2}$ MeV/c$^{2}$ and width $20^{+6+3}_{-5-3}$ MeV/c$^{2}$ and the $D_2^*(2460)^0$ with mass $2465 \pm 3 \pm 3$ MeV/c$^{2}$ and width $28^{+8+6}_{-7-6}$ MeV/c$^{2}$. Properties of these final states, including their decay angular distributions and spin-parity assignments, have been studied. We identify these two mesons as the $j_{light}=3/2$ doublet predicted by HQET. We also obtain constraints on {\footnotesize $\Gamma_S/(\Gamma_S + \Gamma_D)$} as a function of the cosine of the relative phase of the two amplitudes in the $D_1(2420)^0$ decay.Comment: 15 pages in REVTEX format. hardcopies with figures can be obtained by sending mail to: [email protected]

Matching isotopic distributions from metabolically labeled samples

Motivation: In recent years stable isotopic labeling has become a standard approach for quantitative proteomic analyses. Among the many available isotopic labeling strategies, metabolic labeling is attractive for the excellent internal control it provides. However, analysis of data from metabolic labeling experiments can be complicated because the spacing between labeled and unlabeled forms of each peptide depends on its sequence, and is thus variable from analyte to analyte. As a result, one generally needs to know the sequence of a peptide to identify its matching isotopic distributions in an automated fashion. In some experimental situations it would be necessary or desirable to match pairs of labeled and unlabeled peaks from peptides of unknown sequence. This article addresses this largely overlooked problem in the analysis of quantitative mass spectrometry data by presenting an algorithm that not only identifies isotopic distributions within a mass spectrum, but also annotates matches between natural abundance light isotopic distributions and their metabolically labeled counterparts. This algorithm is designed in two stages: first we annotate the isotopic peaks using a modified version of the IDM algorithm described last year; then we use a probabilistic classifier that is supplemented by dynamic programming to find the metabolically labeled matched isotopic pairs. Such a method is needed for high-throughput quantitative proteomic metabolomic experiments measured via mass spectrometry