Weighting Low-Intensity MS/MS Ions and m/z Frequency for Spectral Library Annotation.

Calculating spectral similarity is a fundamental step in MS/MS data analysis in untargeted metabolomics experiments, as it facilitates the identification of related spectra and the annotation of compounds. To improve matching accuracy when querying an experimental mass spectrum against a spectral library, previous approaches have proposed increasing peak intensities for high m/z ranges. These high m/z values tend to be smaller in magnitude, yet they offer more crucial information for identifying the chemical structure. Here, we evaluate the impact of using these weights for identifying structurally related compounds and mass spectral library searches. Additionally, we propose a weighting approach that (i) takes into account the frequency of the m/z values within a spectral library in order to assign higher importance to the most common peaks and (ii) increases the intensity of lower peaks, similar to previous approaches. To demonstrate our approach, we applied weighting preprocessing to modified cosine, entropy, and fidelity distance metrics and benchmarked it against previously reported weights. Our results demonstrate how weighting-based preprocessing can assist in annotating the structure of unknown spectra as well as identifying structurally similar compounds. Finally, we examined scenarios in which the utilization of weights resulted in diminished performance, pinpointing spectral features where the application of weights might be detrimental.

Characterizing Spatial Information Loss for Wastewater Surveillance Using crAssphage: Effect of Decay, Temperature, and Population Mobility.

Populations contribute information about their health status to wastewater. Characterizing how that information degrades in transit to wastewater sampling locations (e.g., wastewater treatment plants and pumping stations) is critical to interpret wastewater responses. In this work, we statistically estimate the loss of information about fecal contributions to wastewater from spatially distributed populations at the census block group resolution. This was accomplished with a hydrologically and hydraulically influenced spatial statistical approach applied to crAssphage (Carjivirus communis) load measured from the influent of four wastewater treatment plants in Hamilton County, Ohio. We find that we would expect to observe a 90% loss of information about fecal contributions from a given census block group over a travel time of 10.3 h. This work demonstrates that a challenge to interpreting wastewater responses (e.g., during wastewater surveillance) is distinguishing between a distal but large cluster of contributions and a near but small contribution. This work demonstrates new modeling approaches to improve measurement interpretation depending on sewer network and wastewater characteristics (e.g., geospatial layout, temperature variability, population distribution, and mobility). This modeling can be integrated into standard wastewater surveillance methods and help to optimize sewer sampling locations to ensure that different populations (e.g., vulnerable and susceptible) are appropriately represented.

On the correspondence between the transcriptomic response of a compound and its effects on its targets.

Better understanding the transcriptomic response produced by a compound perturbing its targets can shed light on the underlying biological processes regulated by the compound. However, establishing the relationship between the induced transcriptomic response and the target of a compound is non-trivial, partly because targets are rarely differentially expressed. Therefore, connecting both modalities requires orthogonal information (e.g., pathway or functional information). Here, we present a comprehensive study aimed at exploring this relationship by leveraging thousands of transcriptomic experiments and target data for over 2000 compounds. Firstly, we confirm that compound-target information does not correlate as expected with the transcriptomic signatures induced by a compound. However, we reveal how the concordance between both modalities increases by connecting pathway and target information. Additionally, we investigate whether compounds that target the same proteins induce a similar transcriptomic response and conversely, whether compounds with similar transcriptomic responses share the same target proteins. While our findings suggest that this is generally not the case, we did observe that compounds with similar transcriptomic profiles are more likely to share at least one protein target and common therapeutic applications. Finally, we demonstrate how to exploit the relationship between both modalities for mechanism of action deconvolution by presenting a case scenario involving a few compound pairs with high similarity.

Energetics of Acidianus ambivalens growth in response to oxygen availability.

All life requires energy to drive metabolic reactions such as growth and cell maintenance; therefore, fluctuations in energy availability can alter microbial activity. There is a gap in our knowledge concerning how energy availability affects the growth of extreme chemolithoautotrophs. Toward this end, we investigated the growth of thermoacidophile Acidianus ambivalens during sulfur oxidation under aerobic to microaerophilic conditions. Calorimetry was used to measure enthalpy (ΔHinc ) of microbial activity, and chemical changes in growth media were measured to calculate Gibbs energy change (ΔGinc ) during incubation. In all experiments, Gibbs energy was primarily dissipated through the release of heat, which suggests enthalpy-driven growth. In microaerophilic conditions, growth was significantly more efficient in terms of biomass yield (defined as C-mol biomass per mole sulfur consumed) and resulted in lower ΔGinc and ΔHinc . ΔGinc in oxygen-limited (OL) and oxygen- and CO2 -limited (OCL) microaerophilic growth conditions resulted in averages of -1.44 × 103  kJ/C-mol and -7.56 × 102  kJ/C-mol, respectively, and average ΔHinc values of -1.11 × 105  kJ/C-mol and -4.43 × 104  kJ/C-mol, respectively. High-oxygen experiments resulted in lower biomass yield values, an increase in ΔGinc to -1.71 × 104  kJ/C-mol, and more exothermic ΔHinc values of -4.71 × 105  kJ/C-mol. The observed inefficiency in high-oxygen conditions may suggest larger maintenance energy demands due to oxidative stresses and a preference for growth in microaerophilic environments.

Gender and Health: Beyond Binary Categorical Measurement.

This study leverages multiple measures of gender from a US national online survey (N = 1,508) to better assess how gender is related to self-rated health. In contrast to research linking feminine behaviors with good health and masculine behaviors with poor health, we find that masculinity is associated with better self-rated health for cisgender men, whereas femininity is associated with better self-rated health for cisgender women. The patterns are similar whether we consider self-identification or how people feel others perceive their gender, though reflected appraisals are most strongly associated with health for cisgender women. We also find that people who report they are seen as gender nonconforming report worse health, but only when this perception does not match their gender identification. Our results demonstrate that multiple measures of gender allow researchers to disentangle how health is not only shaped by gender enactments but also shapes perceptions of gender and gender difference.

Use of an alarm pheromone against ants for gaining access to aphid/scale prey by the red velvet mite Balaustium sp. (Erythraeidae) in a honeydew-rich environment.

This study shows that honeydew prompts arrestment and reduced activity, but not attraction, by the mite Balaustium sp. nr. putmani. When presented with short-range, two-choice bioassays, mites ceased their characteristic rapid crawling activity when they encountered honeydew-treated surfaces, resulting in them clustering around the honeydew. Approximately 80% of mites were retained by honeydew, with responses being independent of both mite life-history stage and source of honeydew (coccid scale insect or aphid). No obvious crawling movements or redirection of running path were made to the honeydew by the mites, implying the lack of any kind of attractant. Response of mites to single-sugar presentations of the main honeydew components--glucose, sucrose, fructose and trehalose--(0.001-0.1 mmol l(-1)) were inconsistent and failed to reproduce the arrestment/clustering associated with raw honeydew, suggesting that none of these sugars is an active arrestant ingredient. Formation of feeding clusters on honeydew does not contribute to enhancing water conservation by suppressing net transpiration (water loss) rates of individual mites as group size increases, indicating that the clustering is an artifact of arrestment. We hypothesize that release of neryl formate by the mites reduces negative interactions with the local ant species commonly associated with honeydew. We hypothesize that honeydew serves as: (1) a cue that facilitates discovery of scale/aphid prey; (2) a retainer on plants where these prey are present, signaling abundance and quality; and (3) an alternative and supplemental food source like that noted for other plant-inhabiting predatory mites. Neryl formate serves as an alarm pheromone and foul-tasting allomonal defense secretion that prevents predation of mites by ants that co-exist with aphid/scale insects in these honeydew-rich habitats.