Vulnerability to environmental and climatic health provocations among women and men hospitalized with chronic heart disease: insights from the RESILIENCE TRIAL cohort.

AIMS: We aimed to recruit a representative cohort of women and men with multi-morbid chronic heart disease as part of a trial testing an innovative, nurse-co-ordinated, multi-faceted intervention to lower rehospitalization and death by addressing areas of vulnerability to external challenges to their health. METHODS AND RESULTS: The prospective, randomized open, blinded end-point RESILIENCE Trial recruited 203 hospital inpatients (mean age 75.7 ± 10.2 years) of whom 51% were women and 94% had combined coronary artery disease, heart failure, and/or atrial fibrillation. Levels of concurrent multi-morbidity were high (mean Charlson Index of Comorbidity Score 6.5 ± 2.7), and 8.9% had at least mild frailty according to the Rockwood Clinical Frailty Scale. Including the index admission, 19-20% of women and men had a pre-existing pattern of seasonally linked hospitalization (seasonality). Detailed phenotyping revealed that 48% of women and 40% of men had ≥3 physiological factors, and 15% of women and 16% of men had ≥3 behavioural factors likely to increase their vulnerability to external provocations to their health. Overall, 61-62% of women and men had ≥4 combined factors indicative of such vulnerability. Additional factors such as reliance on the public health system (63 vs. 49%), lower education (30 vs. 14%), and living alone (48 vs. 29%) were more prevalent in women. CONCLUSION: We successfully recruited women and men with multi-morbid chronic heart disease and bio-behavioural indicators of vulnerability to external provocations to their health. Once completed, the RESILIENCE TRIAL will provide important insights on the impact of addressing such vulnerability (promoting resilience) on subsequent health outcomes. REGISTRATION: ClinicalTrials.org: NCT04614428.

Physiological Conditions Leading to Maternal Subclinical Ketosis in Holstein Dairy Cows Can Impair the Offspring's Postnatal Growth and Gut Microbiome Development.

Maternal metabolic disruptions, such as ketosis, can have adverse effects on fetal development and influence postnatal factors. Twelve Holstein calves were randomly enrolled in this study at birth and monitored until 8 weeks of age. The study was conducted from fall 2018 until spring 2019. After completing the data collection period, calves were classified according to their respective dams ketotic condition after parturition. This classification was based on dam blood ß-hydroxybutyrate < 1.4 mmol/L nonketotic (NONKET; n = 6 calves) or ≥1.4 mmol/L subclinical-ketotic (SK; n = 6 calves). SK calves had greater birth body weight (p = 0.05) but exhibited a slower growth rate compared to NONKET calves from 1 to 8 weeks (p = 0.02). At birth, SK calves had lower (p < 0.01) levels of non-esterified fatty acids and bilirubin compared to NONKET calves. Analysis of feces alpha diversity indicates that by 3 weeks, NONKET calves had greater diversity, richness, and evenness. Butyricicoccus pullicaecorum and Gallibacterium anatis were more abundant in SK calves (p < 0.05) at 3 weeks. In contrast, NONKET calves had a greater (p < 0.05) abundance of Sharpae azabuensis at 3 weeks. These findings suggest that subclinical ketosis in cows can impact the in-utero development, postnatal growth, and maturing gut microbiome of their offspring.

A Comparative Analysis of the Fecal Bacterial Communities of Light and Heavy Finishing Barrows Raised in a Commercial Swine Production Environment.

For commercial swine producers, the natural variation in body weight amongst pigs in a herd presents a challenge in meeting the standards of meat processors who incentivize target carcass weights by offering more favorable purchase prices. Body weight variation in a swine herd is evident as early as birth, and it is typically maintained throughout the entire production cycle. Amongst the various factors that can affect growth performance, the gut microbiome has emerged as an important factor that can affect efficiency, as it contributes to vital functions such as providing assimilable nutrients from feed ingredients that are inedible to the host, as well as resistance to infection by a pathogen. In this context, the objective of the study described in this report was to compare the fecal microbiomes of light and heavy barrows (castrated male finishing pigs) that were part of the same research herd that was raised under commercial conditions. Using high-throughput sequencing of amplicons generated from the V1-V3 regions of the 16S rRNA gene, two abundant candidate bacterial species identified as operational taxonomic units (OTUs), Ssd-1085 and Ssd-1144, were found to be in higher abundance in the light barrows group. Ssd-1085 was predicted to be a potential strain of Clostridium jeddahitimonense, a bacterial species capable of utilizing tagatose, a monosaccharide known to act as a prebiotic that can enhance the proliferation of beneficial microorganisms while inhibiting the growth of bacterial pathogens. OTU Ssd-1144 was identified as a candidate strain of C. beijerinckii, which would be expected to function as a starch utilizing symbiont in the swine gut. While it remains to be determined why putative strains of these beneficial bacterial species would be in higher abundance in lower weight pigs, their overall high levels in finishing pigs could be the result of including ingredients such as corn and soybean-based products in swine diets. Another contribution from this study was the determination that these two OTUs, along with five others that were also abundant in the fecal bacterial communities of the barrows that were analyzed, had been previously identified in weaned pigs, suggesting that these OTUs can become established as early as the nursery phase.

Sex-biased gene expression in nutrient-sensing pathways.

Differences in lifespan between males and females are found across many taxa and may be determined, at least in part, by differential responses to diet. Here we tested the hypothesis that the higher dietary sensitivity of female lifespan is mediated by higher and more dynamic expression in nutrient-sensing pathways in females. We first reanalysed existing RNA-seq data, focusing on 17 nutrient-sensing genes with reported lifespan effects. This revealed, consistent with the hypothesis, a dominant pattern of female-biased gene expression, and among sex-biased genes there tended to be a loss of female-bias after mating. We then tested directly the expression of these 17 nutrient-sensing genes in wild-type third instar larvae, once-mated 5- and 16-day-old adults. This confirmed sex-biased gene expression and showed that it was generally absent in larvae, but frequent and stable in adults. Overall, the findings suggest a proximate explanation for the sensitivity of female lifespan to dietary manipulations. We suggest that the contrasting selective pressures to which males and females are subject create differing nutritional demands and requirements, resulting in sex differences in lifespan. This underscores the potential importance of the health impacts of sex-specific dietary responses.

Assessing how Spirituality Affects Resiliency in the Pediatric Healthcare Practitioner.

A literature review was conducted to examine the role of spirituality with resiliency in the pediatric workplace. Two themes emerged from the literature review: healthcare practitioners desire to have a sense of belonging at work and the utilization of chaplains is helpful. This study aims to discover how practitioners experience spiritual health in the workplace and identify interventions that enhance resiliency with the challenges of pediatrics. Implications from this study are applied to chaplaincy and research.

Plastic responses of males and females interact to determine mating behavior.

Individuals can respond plastically to variation in their social environment. However, each sex may respond to different cues and contrasting aspects of competition. Theory suggests that the plastic phenotype expressed by one sex can influence evolutionary dynamics in the other, and that plasticity simultaneously expressed by both sexes can exert sex-specific effects on fitness. However, data are needed to test this theory base. Here, we examined whether the simultaneous expression of adaptive plasticity by both sexes of Drosophila melanogaster fruit flies in response to their respective social environments interacts to determine the value of key reproductive traits (mating latency, duration, and fecundity). To vary social environments, males were kept alone, or with same sex rivals, and females were kept alone, in same-sex, or mixed-sex groups. Matings were then conducted between individuals from all of these five social treatments in all combinations, and the resulting reproductive traits measured in both "choice" and "no-choice" assays. Mating latency was determined by an interaction between the plastic responses of both sexes to their social environments. Interestingly, the mating latency response occurred in opposing directions in the different assays. In females exposed to same-sex social treatments, mating latency was more rapid with rival treatment males in the choice assays, but slower with those same males in no-choice assays. In contrast, mating duration was determined purely by responses of males to their social environments, and fecundity purely by responses of females. Collectively, the results show that plastic responses represent an important and novel facet of sexual interactions.

An Investigation of Social Ecological Barriers to and Facilitators of WIC Farmers Market Nutrition Program Voucher Redemption.

In the United States, many communities lack sufficient access to fresh produce. To improve access to fresh fruits and vegetables, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides eligible participants vouchers through the Farmers Market Nutrition Program (FMNP) that can be redeemed directly from farmers at markets or farm stands. However, FMNP voucher redemption rates in New Jersey remain lower than those in neighboring states. This article used the social ecological model to examine differences between FMNP participants who redeem vouchers (Redeemers) and those who do not (non-Redeemers) in the areas of: produce procurement practices and consumption frequency, and barriers to and facilitators of FMNP voucher redemption. This cross-sectional study included WIC FMNP participants (N = 329) in northern New Jersey, USA. Analyses were conducted using descriptive statistics, independent sample t-tests, and one-way ANOVA. Compared to Redeemers, non-Redeemers consumed fewer average daily vegetable servings, were more likely to shop at small grocery/corner stores, and encountered significant barriers to FMNP redemption, e.g., difficulty finding time to redeem vouchers.

Evolutionary history of sexual selection affects microRNA profiles in Drosophila sperm.

The presence of small RNAs in sperm is a relatively recent discovery and little is currently known about their importance and functions. Environmental changes including social conditions and dietary manipulations are known to affect the composition and expression of some small RNAs in sperm and may elicit a physiological stress response resulting in an associated change in gamete miRNA profiles. Here, we tested how microRNA profiles in sperm are affected by variation in both sexual selection and dietary regimes in Drosophila melanogaster selection lines. The selection lines were exposed to standard versus low yeast diet treatments and three different population sex ratios (male-biased, female-biased, or equal sex) in a full-factorial design. After 38 generations of selection, all males were maintained on their selected diet and in a common garden male-only environment prior to sperm sampling. We performed transcriptome analyses on miRNAs in purified sperm samples. We found 11 differentially expressed miRNAs with the majority showing differences between male- and female-biased lines. Dietary treatment only had a significant effect on miRNA expression levels in interaction with sex ratio. Our findings suggest that long-term adaptation may affect miRNA profiles in sperm and that these may show varied interactions with short-term environmental changes.

Effects of a Bioprocessed Soybean Meal Ingredient on the Intestinal Microbiota of Hybrid Striped Bass, Morone chrysops x M. saxatilis.

The hybrid striped bass (Morone chrysops x M. saxatilis) is a carnivorous species and a major product of US aquaculture. To reduce costs and improve resource sustainability, traditional ingredients used in fish diets are becoming more broadly replaced by plant-based products; however, plant meals can be problematic for carnivorous fish. Bioprocessing has improved nutritional quality and allowed higher inclusions in fish diets, but these could potentially affect other systems such as the gut microbiome. In this context, the effects of bioprocessed soybean meal on the intestinal bacterial composition in hybrid striped bass were investigated. Using high-throughput sequencing of amplicons targeting the V1-V3 region of the 16S rRNA gene, no significant difference in bacterial composition was observed between fish fed a control diet, and fish fed a diet with the base bioprocessed soybean meal. The prominent Operational Taxonomic Unit (OTU) in these samples was predicted to be a novel species affiliated to Peptostreptococcaceae. In contrast, the intestinal bacterial communities of fish fed bioprocessed soybean meal that had been further modified after fermentation exhibited lower alpha diversity (p < 0.05), as well as distinct and more varied composition patterns, with OTUs predicted to be strains of Lactococcus lactis, Plesiomonas shigelloides, or Ralstonia pickettii being the most dominant. Together, these results suggest that compounds in bioprocessed soybean meal can affect intestinal bacterial communities in hybrid striped bass.

Divergence in Transcriptional and Regulatory Responses to Mating in Male and Female Fruitflies.

Mating induces extensive physiological, biochemical and behavioural changes in female animals of many taxa. In contrast, the overall phenotypic and transcriptomic consequences of mating for males, hence how they might differ from those of females, are poorly described. Post mating responses in each sex are rapidly initiated, predicting the existence of regulatory mechanisms in addition to transcriptional responses involving de novo gene expression. That post mating responses appear different for each sex also predicts that the genome-wide signatures of mating should show evidence of sex-specific specialisation. In this study, we used high resolution RNA sequencing to provide the first direct comparisons of the transcriptomic responses of male and female Drosophila to mating, and the first comparison of mating-responsive miRNAs in both sexes in any species. As predicted, the results revealed the existence of sex- and body part-specific mRNA and miRNA expression profiles. More genes were differentially expressed in the female head-thorax than the abdomen following mating, whereas the opposite was true in males. Indeed, the transcriptional profile of male head-thorax tissue was largely unaffected by mating, and no differentially expressed genes were detected at the most stringent significance threshold. A subset of ribosomal genes in females were differentially expressed in both body parts, but in opposite directions, consistent with the existence of body part-specific resource allocation switching. Novel, mating-responsive miRNAs in each sex were also identified, and a miRNA-mRNA interactions analysis revealed putative targets among mating-responsive genes. We show that the structure of genome-wide responses by each sex to mating is strongly divergent, and provide new insights into how shared genomes can achieve characteristic distinctiveness.

Genome-wide profiling of DNA methylome and transcriptome in peripheral blood monocytes for major depression: A Monozygotic Discordant Twin Study.

DNA methylation plays an important role in major depressive disorder (MDD), but the specific genes and genomic regions associated with MDD remain largely unknown. Here we conducted genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) and gene expression (RNA-seq) in peripheral blood monocytes from 79 monozygotic twin pairs (mean age 38.2 ± 15.6 years) discordant on lifetime history of MDD to identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with MDD, followed by replication in brain tissue samples. Integrative DNA methylome and transcriptome analysis and network analysis was performed to identify potential functional epigenetic determinants for MDD. We identified 39 DMRs and 30 DEGs associated with lifetime history of MDD. Some genes were replicated in postmortem brain tissue. Integrative DNA methylome and transcriptome analysis revealed both negative and positive correlations between DNA methylation and gene expression, but the correlation pattern varies greatly by genomic locations. Network analysis revealed distinct gene modules enriched in signaling pathways related to stress responses, neuron apoptosis, insulin receptor signaling, mTOR signaling, and nerve growth factor receptor signaling, suggesting potential functional relevance to MDD. These results demonstrated that altered DNA methylation and gene expression in peripheral blood monocytes are associated with MDD. Our results highlight the utility of using peripheral blood epigenetic markers and demonstrate that a monozygotic discordant co-twin control design can aid in the discovery of novel genes associated with MDD. If validated, the newly identified genes may serve as novel biomarkers or druggable targets for MDD and related disorders.

The role of mouse tumour models in the discovery and development of anticancer drugs.

Our understanding of cancer biology has increased substantially over the past 30 years. Despite this, and an increasing pharmaceutical company expenditure on research and development, the approval of novel oncology drugs during the past decade continues to be modest. In addition, the attrition of agents during clinical development remains high. This attrition can be attributed, at least in part, to the clinical development being underpinned by the demonstration of predictable efficacy in experimental models of human tumours. This review will focus on the range of models available for the discovery and development of anticancer drugs, from traditional subcutaneous injection of tumour cell lines to mice genetically engineered to spontaneously give rise to tumours. It will consider the best time to use the models, along with practical applications and shortcomings. Finally, and most importantly, it will describe how these models reflect the underlying cancer biology and how well they predict efficacy in the clinic. Developing a line of sight to the clinic early in a drug discovery project provides clear benefit, as it helps to guide the selection of appropriate preclinical models and facilitates the investigation of relevant biomarkers.

Study Design and Rationale for the Mood and Methylation Study: A Platform for Multi-Omics Investigation of Depression in Twins.

Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future 'multi-omic' analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other 'omic' factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

Control of seminal fluid protein expression via regulatory hubs in Drosophila melanogaster.

Highly precise, yet flexible and responsive coordination of expression across groups of genes underpins the integrity of many vital functions. However, our understanding of gene regulatory networks (GRNs) is often hampered by the lack of experimentally tractable systems, by significant computational challenges derived from the large number of genes involved or from difficulties in the accurate identification and characterization of gene interactions. Here we used a tractable experimental system in which to study GRNs: the genes encoding the seminal fluid proteins that are transferred along with sperm (the 'transferome') in Drosophila melanogaster fruit flies. The products of transferome genes are core determinants of reproductive success and, to date, only transcription factors have been implicated in the modulation of their expression. Hence, as yet, we know nothing about the post-transcriptional mechanisms underlying the tight, responsive and precise regulation of this important gene set. We investigated this omission in the current study. We first used bioinformatics to identify potential regulatory motifs that linked the transferome genes in a putative interaction network. This predicted the presence of putative microRNA (miRNA) 'hubs'. We then tested this prediction, that post-transcriptional regulation is important for the control of transferome genes, by knocking down miRNA expression in adult males. This abolished the ability of males to respond adaptively to the threat of sexual competition, indicating a regulatory role for miRNAs in the regulation of transferome function. Further bioinformatics analysis then identified candidate miRNAs as putative regulatory hubs and evidence for variation in the strength of miRNA regulation across the transferome gene set. The results revealed regulatory mechanisms that can underpin robust, precise and flexible regulation of multiple fitness-related genes. They also help to explain how males can adaptively modulate ejaculate composition.

Childhood Trauma, DNA Methylation of Stress-Related Genes, and Depression: Findings From Two Monozygotic Twin Studies.

OBJECTIVE: DNA methylation has been associated with both early life stress and depression. This study examined the combined association of DNA methylation at multiple CpG probes in five stress-related genes with depressive symptoms and tested whether these genes methylation mediated the association between childhood trauma and depression in two monozygotic (MZ) twin studies. METHODS: The current analysis comprised 119 MZ twin pairs (84 male pairs [mean = 55 years] and 35 female pairs [mean = 36 years]). Peripheral blood DNA methylation of five stress-related genes (BDNF, NR3C1, SLC6A4, MAOA, and MAOB) was quantified by bisulfite pyrosequencing or 450K BeadChip. We applied generalized Poisson linear-mixed models to examine the association between each single CpG methylation and depressive symptoms. The joint associations of multiple CpGs in a single gene or all five stress-related genes as a pathway were tested by weighted truncated product method. Mediation analysis was conducted to test the potential mediating effect of stress gene methylation on the relationship between childhood trauma and depressive symptoms. RESULTS: Multiple CpG probes showed nominal individual associations, but very few survived multiple testing. Gene-based or gene-set approach, however, revealed significant joint associations of DNA methylation in all five stress-related genes with depressive symptoms in both studies. Moreover, two CpG probes in the BDNF and NR3C1 mediated approximately 20% of the association between childhood trauma and depressive symptoms. CONCLUSIONS: DNA methylation at multiple CpG sites are jointly associated with depressive symptoms and partly mediates the association between childhood trauma and depression. Our results highlight the importance of testing the combined effects of multiple CpG loci on complex traits and may unravel a molecular mechanism through which adverse early life experiences are biologically embedded.

Small RNA populations revealed by blocking rRNA fragments in Drosophila melanogaster reproductive tissues.

RNA interference (RNAi) is a complex and highly conserved regulatory mechanism mediated via small RNAs (sRNAs). Recent technical advances in high throughput sequencing have enabled an increasingly detailed analysis of sRNA abundances and profiles in specific body parts and tissues. This enables investigations of the localized roles of microRNAs (miRNAs) and small interfering RNAs (siRNAs). However, variation in the proportions of non-coding RNAs in the samples being compared can hinder these analyses. Specific tissues may vary significantly in the proportions of fragments of longer non-coding RNAs (such as ribosomal RNA or transfer RNA) present, potentially reflecting tissue-specific differences in biological functions. For example, in Drosophila, some tissues contain a highly abundant 30nt rRNA fragment (the 2S rRNA) as well as abundant 5' and 3' terminal rRNA fragments. These can pose difficulties for the construction of sRNA libraries as they can swamp the sequencing space and obscure sRNA abundances. Here we addressed this problem and present a modified "rRNA blocking" protocol for the construction of high-definition (HD) adapter sRNA libraries, in D. melanogaster reproductive tissues. The results showed that 2S rRNAs targeted by blocking oligos were reduced from >80% to < 0.01% total reads. In addition, the use of multiple rRNA blocking oligos to bind the most abundant rRNA fragments allowed us to reveal the underlying sRNA populations at increased resolution. Side-by-side comparisons of sequencing libraries of blocked and non-blocked samples revealed that rRNA blocking did not change the miRNA populations present, but instead enhanced their abundances. We suggest that this rRNA blocking procedure offers the potential to improve the in-depth analysis of differentially expressed sRNAs within and across different tissues.

Comparison of alternative approaches for analysing multi-level RNA-seq data.

RNA sequencing (RNA-seq) is widely used for RNA quantification in the environmental, biological and medical sciences. It enables the description of genome-wide patterns of expression and the identification of regulatory interactions and networks. The aim of RNA-seq data analyses is to achieve rigorous quantification of genes/transcripts to allow a reliable prediction of differential expression (DE), despite variation in levels of noise and inherent biases in sequencing data. This can be especially challenging for datasets in which gene expression differences are subtle, as in the behavioural transcriptomics test dataset from D. melanogaster that we used here. We investigated the power of existing approaches for quality checking mRNA-seq data and explored additional, quantitative quality checks. To accommodate nested, multi-level experimental designs, we incorporated sample layout into our analyses. We employed a subsampling without replacement-based normalization and an identification of DE that accounted for the hierarchy and amplitude of effect sizes within samples, then evaluated the resulting differential expression call in comparison to existing approaches. In a final step to test for broader applicability, we applied our approaches to a published set of H. sapiens mRNA-seq samples, The dataset-tailored methods improved sample comparability and delivered a robust prediction of subtle gene expression changes. The proposed approaches have the potential to improve key steps in the analysis of RNA-seq data by incorporating the structure and characteristics of biological experiments.

Genomic responses to the socio-sexual environment in male Drosophila melanogaster exposed to conspecific rivals.

Socio-sexual environments have profound effects on fitness. Local sex ratios can alter the threat of sexual competition, to which males respond via plasticity in reproductive behaviors and ejaculate composition. In Drosophila melanogaster, males detect the presence of conspecific, same-sex mating rivals prior to mating using multiple, redundant sensory cues. Males that respond to rivals gain significant fitness benefits by altering mating duration and ejaculate composition. Here we investigated the underlying genome-wide changes involved. We used RNA-seq to analyze male transcriptomic responses 2, 26, and 50 h after exposure to rivals, a time period that was previously identified as encompassing the major facets of male responses to rivals. The results showed a strong early activation of multiple sensory genes in the head-thorax (HT), prior to the expression of any phenotypic differences. This gene expression response was reduced by 26 h, at the time of maximum phenotypic change, and shut off by 50 h. In the abdomen (A), fewer genes changed in expression and gene expression responses appeared to increase over time. The results also suggested that different sets of functionally equivalent genes might be activated in different replicates. This could represent a mechanism by which robustness is conferred upon highly plastic traits. Overall, our study reveals that mRNA-seq can identify subtle genomic signatures characteristic of flexible behavioral phenotypes.

The abundant marine bacterium Pelagibacter simultaneously catabolizes dimethylsulfoniopropionate to the gases dimethyl sulfide and methanethiol.

Marine phytoplankton produce ∼10(9) tonnes of dimethylsulfoniopropionate (DMSP) per year(1,2), an estimated 10% of which is catabolized by bacteria through the DMSP cleavage pathway to the climatically active gas dimethyl sulfide(3,4). SAR11 Alphaproteobacteria (order Pelagibacterales), the most abundant chemo-organotrophic bacteria in the oceans, have been shown to assimilate DMSP into biomass, thereby supplying this cell's unusual requirement for reduced sulfur(5,6). Here, we report that Pelagibacter HTCC1062 produces the gas methanethiol, and that a second DMSP catabolic pathway, mediated by a cupin-like DMSP lyase, DddK, simultaneously shunts as much as 59% of DMSP uptake to dimethyl sulfide production. We propose a model in which the allocation of DMSP between these pathways is kinetically controlled to release increasing amounts of dimethyl sulfide as the supply of DMSP exceeds cellular sulfur demands for biosynthesis.