The Gut Microbiome and Substance Use Disorder.

Substance use disorders (SUDs) remain a significant public health challenge, affecting tens of millions of individuals worldwide each year. Often comorbid with other psychiatric disorders, SUD can be poly-drug and involve several different substances including cocaine, opiates, nicotine, and alcohol. SUD has a strong genetic component. Much of SUD research has focused on the neurologic and genetic facets of consumption behavior. There is now interest in the role of the gut microbiome in the pathogenesis of SUD. In this review, we summarize current animal and clinical evidence that the gut microbiome is involved in SUD, then address the underlying mechanisms by which the gut microbiome interacts with SUD through metabolomic, immune, neurological, and epigenetic mechanisms. Lastly, we discuss methods using various inbred and outbred mice models to gain an integrative understanding of the microbiome and host genetic controls in SUD

Validation of the Harvard Lyman-α in situ water vapor instrument: Implications for the mechanisms that control stratospheric water vapor

Building on previously published details of the laboratory calibrations of the Harvard Lyman-α photofragment fluorescence hygrometer (HWV) on the NASA ER-2 and WB-57 aircraft, we describe here the validation process for HWV, which includes laboratory calibrations and intercomparisons with other Harvard water vapor instruments at water vapor mixing ratios from 0 to 10 ppmv, followed by in-flight intercomparisons with the same Harvard hygrometers. The observed agreement exhibited in the laboratory and during intercomparisons helps corroborate the accuracy of HWV. In light of the validated accuracy of HWV, we present and evaluate a series of intercomparisons with satellite and balloon borne water vapor instruments made from the upper troposphere to the lower stratosphere in the tropics and midlatitudes. Whether on the NASA ER-2 or WB-57 aircraft, HWV has consistently measured about 1–1.5 ppmv higher than the balloon-borne NOAA/ESRL/GMD frost point hygrometer (CMDL), the NOAA Cryogenic Frost point Hygrometer (CFH), and the Microwave Limb Sounder (MLS) on the Aura satellite in regions of the atmosphere where water vapor is <10 ppmv. Comparisons in the tropics with the Halogen Occultation Experiment (HALOE) on the Upper Atmosphere Research Satellite show large variable differences near the tropopause that converge to ~10% above 460 K, with HWV higher. Results we show from the Aqua Validation and Intercomparison Experiment (AquaVIT) at the AIDA chamber in Karlsruhe do not reflect the observed in-flight differences. We illustrate that the interpretation of the results of comparisons between modeled and measured representations of the seasonal cycle of water entering the lower tropical stratosphere is dictated by which data set is used

Creating a honey bee consensus gene set

BACKGROUND: We wished to produce a single reference gene set for honey bee (Apis mellifera). Our motivation was twofold. First, we wished to obtain an improved set of gene models with increased coverage of known genes, while maintaining gene model quality. Second, we wished to provide a single official gene list that the research community could further utilize for consistent and comparable analyses and functional annotation. RESULTS: We created a consensus gene set for honey bee (Apis mellifera) using GLEAN, a new algorithm that uses latent class analysis to automatically combine disparate gene prediction evidence in the absence of known genes. The consensus gene models had increased representation of honey bee genes without sacrificing quality compared with any one of the input gene predictions. When compared with manually annotated gold standards, the consensus set of gene models was similar or superior in quality to each of the input sets. CONCLUSION: Most eukaryotic genome projects produce multiple gene sets because of the variety of gene prediction programs. Each of the gene prediction programs has strengths and weaknesses, and so the multiplicity of gene sets offers users a more comprehensive collection of genes to use than is available from a single program. On the other hand, the availability of multiple gene sets is also a cause for uncertainty among users as regards which set they should use. GLEAN proved to be an effective method to combine gene lists into a single reference set

Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus

Background: In a murine model of inflammatory bowel disease (IBD), treatment of colitis in IL-10 gene-deficient mice with the parasitic helminth Heligmosomoides polygyrus ameliorates colonic inflammation. The cellular and molecular mechanisms driving this therapeutic host response are being studied vigorously. One proposed mechanism is that H. polygyrus infection favors the outgrowth or suppression of certain bacteria, which in turn help modulate host immunity. Methods: To quantify the effect of H. polygyrus infection on the composition of the gastrointestinal (GI) tract microbiota, we conducted two independent microbial ecology analyses of C57BL/6 mice. We obtained and analyzed 3,353 bacterial 16S rRNA encoding gene sequences from the ileum and cecum of infected and uninfected mice as well as incective H. polygyrus larvae at the outset of the second experiment and adult worms taken directly from the mouse duodenum at the end of the second experiment. Results: We found that a significant shift in the abundance and relative distribution of bacterial species in the ileum of mice is associated with H. polygyrus infection. Members of the bacterial family Lactobacillaceae significantly increased in abundance in the ileum of infected mice reproducibly in two independent experiments despite having different microbiotas present at the outset of each experiment. Conclusions: These data support the concept that helminth infection shifts the composition of intestinal bacteria. The clinical consequences of these shifts in intestinal flora are yet to be explored. (Inflamm Bowel Dis 2010)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78230/1/21299_ftp.pd

Space-time versus particle-hole symmetry in quantum Enskog equations

The non-local scattering-in and -out integrals of the Enskog equation have reversed displacements of colliding particles reflecting that the -in and -out processes are conjugated by the space and time inversions. Generalisations of the Enskog equation to Fermi liquid systems are hindered by a request of the particle-hole symmetry which contradicts the reversed displacements. We resolve this problem with the help of the optical theorem. It is found that space-time and particle-hole symmetry can only be fulfilled simultaneously for the Bruckner-type of internal Pauli-blocking while the Feynman-Galitskii form allows only for particle-hole symmetry but not for space-time symmetry due to a stimulated emission of Bosons

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

ObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis.MethodsGWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes.ResultsMIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility

Relativity principles in 1+1 dimensions and differential aging reversal

We study the behavior of clocks in 1+1 spacetime assuming the relativity principle, the principle of constancy of the speed of light and the clock hypothesis. These requirements are satisfied by a class of Finslerian theories parametrized by a real coefficient $\beta$, special relativity being recovered for $\beta=0$. The effect of differential aging is studied for the different values of $\beta$. Below the critical values $|\beta| =1/c$ the differential aging has the usual direction - after a round trip the accelerated observer returns younger than the twin at rest in the inertial frame - while above the critical values the differential aging changes sign. The non-relativistic case is treated by introducing a formal analogy with thermodynamics.Comment: 12 pages, no figures. Previous title "Parity violating terms in clocks' behavior and differential aging reversal". v2: shortened introduction, some sections removed, pointed out the relation with Finsler metrics. Submitted to Found. Phys. Let

Superconducting Fluxon Pumps and Lenses

We study stochastic transport of fluxons in superconductors by alternating current (AC) rectification. Our simulated system provides a fluxon pump, "lens", or fluxon "rectifier" because the applied electrical AC is transformed into a net DC motion of fluxons. Thermal fluctuations and the asymmetry of the ratchet channel walls induce this "diode" effect, which can have important applications in devices, like SQUID magnetometers, and for fluxon optics, including convex and concave fluxon lenses. Certain features are unique to this novel two-dimensional (2D) geometric pump, and different from the previously studied 1D ratchets.Comment: Phys. Rev. Lett. 83, in press (1999); 4 pages, 5 .gif figures; figures also available at http://www-personal.engin.umich.edu/~nori/ratche

Deciphering functional redundancy in the human microbiome.

Although the taxonomic composition of the human microbiome varies tremendously across individuals, its gene composition or functional capacity is highly conserved - implying an ecological property known as functional redundancy. Such functional redundancy has been hypothesized to underlie the stability and resilience of the human microbiome, but this hypothesis has never been quantitatively tested. The origin of functional redundancy is still elusive. Here, we investigate the basis for functional redundancy in the human microbiome by analyzing its genomic content network - a bipartite graph that links microbes to the genes in their genomes. We find that this network exhibits several topological features that favor high functional redundancy. Furthermore, we develop a simple genome evolution model to generate genomic content network, finding that moderate selection pressure and high horizontal gene transfer rate are necessary to generate genomic content networks with key topological features that favor high functional redundancy. Finally, we analyze data from two published studies of fecal microbiota transplantation (FMT), finding that high functional redundancy of the recipient\u27s pre-FMT microbiota raises barriers to donor microbiota engraftment. This work elucidates the potential ecological and evolutionary processes that create and maintain functional redundancy in the human microbiome and contribute to its resilience