Phylogeny- and Abundance-Based Metrics Allow for the Consistent Comparison of Core Gut Microbiome Diversity Indices Across Host Species

The filtering of gut microbial datasets to retain high prevalence taxa is often performed to identify a common core gut microbiome that may be important for host biological functions. However, prevalence thresholds used to identify a common core are highly variable, and it remains unclear how they affect diversity estimates and whether insights stemming from core microbiomes are comparable across studies. We hypothesized that if macroecological patterns in gut microbiome prevalence and abundance are similar across host species, then we would expect that increasing prevalence thresholds would yield similar changes to alpha diversity and beta dissimilarity scores across host species datasets. We analyzed eight gut microbiome datasets based on 16S rRNA gene amplicon sequencing and collected from different host species to (1) compare macroecological patterns across datasets, including amplicon sequence variant (ASV) detection rate with sequencing depth and sample size, occupancy-abundance curves, and rank-abundance curves; (2) test whether increasing prevalence thresholds generate universal or host-species specific effects on alpha and beta diversity scores; and (3) test whether diversity scores from prevalence-filtered core communities correlate with unfiltered data. We found that gut microbiomes collected from diverse hosts demonstrated similar ASV detection rates with sequencing depth, yet required different sample sizes to sufficiently capture rare ASVs across the host population. This suggests that sample size rather than sequencing depth tends to limit the ability of studies to detect rare ASVs across the host population. Despite differences in the distribution and detection of rare ASVs, microbiomes exhibited similar occupancy-abundance and rank-abundance curves. Consequently, increasing prevalence thresholds generated remarkably similar trends in standardized alpha diversity and beta dissimilarity across species datasets until high thresholds above 70%. At this point, diversity scores tended to become unpredictable for some diversity measures. Moreover, high prevalence thresholds tended to generate diversity scores that correlated poorly with the original unfiltered data. Overall, we recommend that high prevalence thresholds over 70% are avoided, and promote the use of diversity measures that account for phylogeny and abundance (Balance-weighted phylogenetic diversity and Weighted Unifrac for alpha and beta diversity, respectively), because we show that these measures are insensitive to prevalence filtering and therefore allow for the consistent comparison of core gut microbiomes across studies without the need for prevalence filtering

Sex differences in condition dependence of natal dispersal in a large herbivore: dispersal propensity and distance are decoupled

International audienceEvolution should favour plasticity in dispersal decisions in response to spatial heterogeneity in social and environmental contexts. Sex differences in individual optimization of dispersal decisions are poorly documented in mammals, because species where both sexes commonly disperse are rare. To elucidate the sex-specific drivers governing dispersal, we investigated sex differences in condition dependence in the propensity and distance of natal dispersal in one such species, the roe deer, using fine-scale monitoring of 146 GPS-collared juveniles in an intensively monitored population in southwest France. Dispersal propensity increased with body mass in males such that 36% of light individuals dispersed, whereas 62% of heavy individuals did so, but there was no evidence for condition dependence in dispersal propensity among females. By contrast, dispersal distance increased with body mass at a similar rate in both sexes such that heavy dispersers travelled around twice as far as light dispersers. Sex differences in the strength of condition-dependent dispersal may result from different selection pressures acting on the behaviour of males and females. We suggest that females disperse prior to habitat saturation being reached, likely in relation to the risk of inbreeding. By contrast, natal dispersal in males is likely governed by competitive exclusion through male–male competition for breeding opportunities in this strongly territorial mammal. Our study is, to our knowledge, a first demonstration that condition dependence in dispersal propensity and dispersal distance may be decoupled, indicating contrasting selection pressures drive the behavioural decisions of whether or not to leave the natal range, and where to settle

Modeling transport through single-molecule junctions

Non-equilibrium Green's functions (NEGF) formalism combined with extended Huckel (EHT) and charging model are used to study electrical conduction through single-molecule junctions. Analyzed molecular complex is composed of asymmetric 1,4-Bis((2'-para-mercaptophenyl)-ethinyl)-2-acetyl-amino-5-nitro-benzene molecule symmetrically coupled to two gold electrodes [Reichert et al., Phys. Rev. Lett. Vol.88 (2002), pp. 176804]. Owing to this model, the accurate values of the current flowing through such junction can be obtained by utilizing basic fundamentals and coherently deriving model parameters. Furthermore, the influence of the charging effect on the transport characteristics is emphasized. In particular, charging-induced reduction of conductance gap, charging-induced rectification effect and charging-generated negative value of the second derivative of the current with respect to voltage are observed and examined for molecular complex.Comment: 8 pages, 3 figure

Phylogeny-and abundance-based metrics allow for the consistent comparison of core gut microbiome diversity indices across host species

The filtering of gut microbial datasets to retain high prevalence taxa is often performed to identify a common core gut microbiome that may be important for host biological functions. However, prevalence thresholds used to identify a common core are highly variable, and it remains unclear how they affect diversity estimates and whether insights stemming from core microbiomes are comparable across studies. We hypothesized that if macroecological patterns in gut microbiome prevalence and abundance are similar across host species, then we would expect that increasing prevalence thresholds would yield similar changes to alpha diversity and beta dissimilarity scores across host species datasets. We analyzed eight gut microbiome datasets based on 16S rRNA gene amplicon sequencing and collected from different host species to (1) compare macroecological patterns across datasets, including amplicon sequence variant (ASV) detection rate with sequencing depth and sample size, occupancy-abundance curves, and rank-abundance curves; (2) test whether increasing prevalence thresholds generate universal or host-species specific effects on alpha and beta diversity scores; and (3) test whether diversity scores from prevalence-filtered core communities correlate with unfiltered data. We found that gut microbiomes collected from diverse hosts demonstrated similar ASV detection rates with sequencing depth, required different sample sizes to sufficiently capture rare ASVs across the host population. This suggests that sample size rather than sequencing depth tends to limit the ability of studies to detect rare ASVs across the host population. Despite differences in the distribution and detection of rare ASVs, microbiomes exhibited similar occupancy-abundance and rank-abundance curves. Consequently, increasing prevalence thresholds generated remarkably similar trends in standardized alpha diversity and beta dissimilarity across species datasets until high thresholds above 70%. At this point, diversity scores tended to become unpredictable for some diversity measures. Moreover, high prevalence Frontiers in Microbiology. Filtering Effects on Core Microbiome thresholds tended to generate diversity scores that correlated poorly with the original unfiltered data. Overall, we recommend that high prevalence thresholds over 70% are avoided, and promote the use of diversity measures that account for phylogeny and abundance (Balance-weighted phylogenetic diversity and Weighted Unifrac for alpha and beta diversity, respectively), because we show that these measures are insensitive to prevalence filtering and therefore allow for the consistent comparison of core gut microbiomes across studies without the need for prevalence filtering.publishedVersio

The number of transmission channels through a single-molecule junction

We calculate transmission eigenvalue distributions for Pt-benzene-Pt and Pt-butadiene-Pt junctions using realistic state-of-the-art many-body techniques. An effective field theory of interacting $\pi$-electrons is used to include screening and van der Waals interactions with the metal electrodes. We find that the number of dominant transmission channels in a molecular junction is equal to the degeneracy of the molecular orbital closest to the metal Fermi level.Comment: 9 pages, 8 figure

Subharmonic Shapiro steps and assisted tunneling in superconducting point contacts

We analyze the current in a superconducting point contact of arbitrary transmission in the presence of a microwave radiation. The interplay between the ac Josephson current and the microwave signal gives rise to Shapiro steps at voltages V = (m/n) \hbar \omega_r/2e, where n,m are integer numbers and \omega_r is the radiation frequency. The subharmonic steps (n different from 1) are a consequence of the ocurrence of multiple Andreev reflections (MAR) and provide an unambiguous signature of the peculiar ac Josephson effect at high transmission. Moreover, the dc current exhibits a rich subgap structure due to photon-assisted MARs.Comment: Revtex, 4 pages, 4 figure

Day versus night use of forest by red and roe deer as determined by Corine Land Cover and Copernicus Tree Cover Density: assessing use of geographic layers in movement ecology

Diel use of forest and open habitats by large herbivores is linked to species-specific needs of multiple and heterogeneous resources. However, forest cover layers might deviate considerably for a given landscape, potentially affecting evaluations of animals’ habitat use. We assessed inconsistency in the estimates of diel forest use by red and roe deer at GPS location and home range (HR) levels, using two geographic layers: Tree Cover Density (TCD) and Corine Land Cover (CLC). We first measured the classification mismatch of red and roe deer GPS locations between TCD and CLC, also with respect to habitat units’ size. Then, we used generalized Least Squares models to assess the proportional use of forest at day and night at the GPS location and HR levels, both with TCD and CLC. About 20% of the GPS locations were inconsistently classified as forest or open habitat by the two layers, particularly within smaller habitat units. Overall proportion of forest and open habitat, though, was very similar for both layers. In all populations, both deer species used forest more at day than at night and this pattern was more evident with TCD than with CLC. However, at the HR level, forest use estimates were only marginally different between the two layers. When estimating animal habitat use, geographic layer choice requires careful evaluation with respect to ecological questions and target species. Habitat use analyses based on GPS locations are more sensitive to layer choice than those based on home ranges.publishedVersio

The molecular and structural bases for the association of complement C3 mutations with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) associates with complement dysregulation caused by muta-tions and polymorphisms in complement activators and regulators. However, the reasons why somemutations in complement proteins predispose to aHUS are poorly understood. Here, we have investigatedthe functional consequences of three aHUS-associated mutations in C3, R592W, R161W and I1157T. First,we provide evidence that penetrance and disease severity for these mutations is modulated by inheri-tance of documented “risk” haplotypes as has been observed with mutations in other complement genes.Next, we show that all three mutations markedly reduce the efficiency of factor I-mediated C3b cleavagewhen catalyzed by membrane cofactor protein (MCP), but not when catalyzed by factor H. Biacore anal-ysis showed that each mutant C3b bound sMCP (recombinant soluble MCP; CD46) at reduced affinity,providing a molecular basis for its reduced cofactor activity. Lastly, we show by electron microscopystructural analysis a displacement of the TED domain from the MG ring in C3b in two of the C3 mutantsthat explains these defects in regulation. As a whole our data suggest that aHUS-associated mutations inC3 selectively affect regulation of complement on surfaces and provide a structural framework to predictthe functional consequences of the C3 genetic variants found in patients

Evidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis.

Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins

Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence.

Importance: Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies. Objective: To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. Design, Setting, and Participants: This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. Data were analyzed from September 2018 to April 2020. Main Outcomes and Measures: In EU-GEI, transition status was assessed by the Comprehensive Assessment of At-Risk Mental States or contact with clinical services. In ALSPAC, PEs at age 18 years were assessed using the Psychosis-Like Symptoms Interview. Proteomic data were obtained from mass spectrometry of baseline plasma samples in EU-GEI and plasma samples at age 12 years in ALSPAC. Support vector machine learning algorithms were used to develop predictive models. Results: The EU-GEI subsample (133 participants at CHR (mean [SD] age, 22.6 [4.5] years; 68 [51.1%] male) comprised 49 (36.8%) who developed psychosis and 84 (63.2%) who did not. A model based on baseline clinical and proteomic data demonstrated excellent performance for prediction of transition outcome (area under the receiver operating characteristic curve [AUC], 0.95; positive predictive value [PPV], 75.0%; and negative predictive value [NPV], 98.6%). Functional analysis of differentially expressed proteins implicated the complement and coagulation cascade. A model based on the 10 most predictive proteins accurately predicted transition status in training (AUC, 0.99; PPV, 76.9%; and NPV, 100%) and test (AUC, 0.92; PPV, 81.8%; and NPV, 96.8%) data. The ALSPAC subsample (121 participants from the general population with plasma samples available at age 12 years (61 [50.4%] male) comprised 55 participants (45.5%) with PEs at age 18 years and 61 (50.4%) without PEs at age 18 years. A model using proteomic data at age 12 years predicted PEs at age 18 years, with an AUC of 0.74 (PPV, 67.8%; and NPV, 75.8%). Conclusions and Relevance: In individuals at risk of psychosis, proteomic biomarkers may contribute to individualized prognosis and stratification strategies. These findings implicate early dysregulation of the complement and coagulation cascade in the development of psychosis outcomes