Explore the vast range of titles available.

Marine microbes exhibit seasonal cycles in community composition, yet the key drivers of these patterns and microbial population fidelity to specific environmental conditions remain to be determined. To begin addressing these questions, we characterized microbial dynamics weekly for 3 years at a temperate, coastal site with dramatic environmental seasonality. This high-resolution time series reveals that changes in microbial community composition are not continuous; over the duration of the time series, the community instead resolves into distinct summer and winter profiles with rapid spring and fall transitions between these states. Here, we show that these community shifts involve switching between closely related strains that exhibit either summer or winter preferences. Moreover, taxa repeat this process annually in both this and another temperate coastal time series, suggesting that this phenomenon may be widespread in marine ecosystems. To address potential biogeochemical impacts of these community changes, PICRUSt-based metagenomes predict seasonality in transporters, photosynthetic proteins, peptidases and carbohydrate metabolic pathways in spite of closely related summer- and winter-associated taxa. Thus, even small temperature shifts, such as those predicted by climate change models, could affect both the structure and function of marine ecosystems.

Hyperthermia induced by phenethylamines, such as 3,4–methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia.

Deciphering dissolved organic matter (DOM) molecular complexity is crucial for understanding ecosystem function. Using the continental-scale Worldwide Hydrobiogeochemistry Observation Network for Dynamic Rivers Systems (WHONDRS) Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS) dataset, we reveal fundamental scaling patterns of DOM chemodiversity with watershed characteristics. Analysis of 54 river sites shows local and regional watershed features significantly influence DOM chemodiversity (2500–8718 unique formulae), exhibiting consistent scaling patterns across compound classes and a novel latitudinal gradient (decreasing diversity with increasing latitude). Scaling relationships for DOM composition vary by compound class. Crucially, the scaling parameters (B, baseline chemodiversity; Z, sensitivity) are linearly interrelated. This B–Z relationship is most robust for potentially bio-labile carbohydrates (coefficient of determination R 2 ≈ 0.85), diminishing for recalcitrant, plant-derived molecules (such as lignin), and indicates (potential) biolability-dependent coupling between baseline diversity and environmental responsiveness. These quantitative scaling relationships, with scaling exponents ranging from − 2.1 to 2.2 across compound classes, enable prediction of DOM composition across watersheds, offering a framework to understand ecosystem responses to environmental change. This research bridges biogeochemistry and ecology, providing tools to anticipate molecular transformations across scales.

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three vesicular glutamate transporters ( Slc17a7 (Vglut1), Slc17a6 (Vglut2), and Slc17a8 (Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA-derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.

Rett syndrome (RTT) is characterized by specific motor, cognitive, and behavioral deficits. Because several of these abnormalities occur in other disease states associated with alterations in aminergic neurotransmitters, we investigated the contribution of such alterations to RTT pathogenesis. We found that both individuals with RTT and Mecp2-null mice have lower-than-normal levels of aminergic metabolites and content. Deleting Mecp2 from either TH-positive dopaminergic and noradrenergic neurons or PET1-positive serotonergic neurons in mice decreased corresponding neurotransmitter concentration and specific phenotypes, likely through MeCP2 regulation of rate-limiting enzymes involved in aminergic neurotransmitter production. These data support a cell-autonomous, MeCP2-dependent mechanism for the regulation of aminergic neurotransmitter synthesis contributing to unique behavioral phenotypes.

Increasing atmospheric carbon dioxide (CO2) from anthropogenic sources is acidifying marine environments resulting in potentially dramatic consequences for the physical, chemical and biological functioning of these ecosystems. If current trends continue, mean ocean pH is expected to decrease by ~0.2 units over the next ~50 years. Yet, there is also substantial temporal variability in pH and other carbon system parameters in the ocean resulting in regions that already experience change that exceeds long-term projected trends in pH. This points to short-term dynamics as an important layer of complexity on top of long-term trends. Thus, in order to predict future climate change impacts, there is a critical need to characterize the natural range and dynamics of the marine carbonate system and the mechanisms responsible for observed variability. Here, we present pH and dissolved inorganic carbon (DIC) at time intervals spanning 1 hour to >1 year from a dynamic, coastal, temperate marine system (Beaufort Inlet, Beaufort NC USA) to characterize the carbonate system at multiple time scales. Daily and seasonal variation of the carbonate system is largely driven by temperature, alkalinity and the balance between primary production and respiration, but high frequency change (hours to days) is further influenced by water mass movement (e.g. tides) and stochastic events (e.g. storms). Both annual (~0.3 units) and diurnal (~0.1 units) variability in coastal ocean acidity are similar in magnitude to 50 year projections of ocean acidity associated with increasing atmospheric CO2. The environmental variables driving these changes highlight the importance of characterizing the complete carbonate system rather than just pH. Short-term dynamics of ocean carbon parameters may already exert significant pressure on some coastal marine ecosystems with implications for ecology, biogeochemistry and evolution and this shorter term variability layers additive effects and complexity, including extreme values, on top of long-term trends in ocean acidification.

Plastics of various chemistries pollute global water bodies. Toxic chemicals leach with detrimental and often unpredictable impacts on the surrounding ecosystems. We found that seawater leachates of plastic pre-production pellets from 7 recycle categories are acutely toxic to stage II barnacle nauplii; lethal concentration 50 (LC50s) were observed in 24-h leachates from dilutions ranging from 0.007 to 2.1 mg/mL of seawater. Based on previous observations that macro-organismal settlement on fouling management coatings of various toxicities can be used to predict the toxicity of the coating, we hypothesized that interaction of plastic pre-production pellets with emerging microbiomes would exhibit patterns indicative of the chemistry at the pellet surface. We used amplicon sequencing of bacterial 16S ribosomal RNA genes to characterize the microbiomes that developed from 8 through 70 days on pellets exposed to the same flowing ambient seawater. Diversity and composition of the microbiomes colonizing plastic pellets changed over time and varied with plastic type. Microbial taxa belong to taxonomic groups known to consume hydrocarbons, to be prevalent following marine oil spills, or to live on fouling management surfaces. Microbiomes were still distinct between plastic types at Day 70, suggesting that differences in the physicochemical characteristics of the underlying plastics continue to exert variable selection of surface microbial communities. A random forest-based sample classifier correctly predicted 93% of plastic types using microbiome compositions. Surface microbiomes have promise for use in forensically identifying plastic types and potential toxicities.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a CAG repeat encoding a polyglutamine tract in Ataxin-1 (ATXN1). Both WT and mutant ATXN1 interact with 14-3-3 proteins, and 14-3-3 overexpression stabilizes ATXN1 levels in cells and increases ATXN1 toxicity in flies. To determine whether reducing 14-3-3 levels might mitigate SCA1 pathogenesis, we bred Sca1¹⁵⁴Q/⁺ mice to mice lacking one allele of 14-3-3ε. 14-3-3ε haploinsufficiency rescued cerebellar pathology and motor phenotypes but, surprisingly, not weight loss, respiratory dysfunction, or premature lethality. Biochemical studies revealed that reducing 14-3-3ε levels exerted different effects in two brain regions especially vulnerable in SCA1: Although diminishing levels of both WT and mutant ATXN1 in the cerebellum, 14-3-3ε haploinsufficiency did not alter ATXN1 levels in the brainstem. Furthermore, 14-3-3ε haploinsufficiency decreased the incorporation of expanded ATXN1 into its large toxic complexes in the cerebellum but not in the brainstem, and the distribution of ATXN1's small and large native complexes differed significantly between the two regions. These data suggest that distinct pathogenic mechanisms operate in different vulnerable brain regions, adding another level of complexity to SCA1 pathogenesis.

Histone deacetylase (HDAC) inhibitors have emerged as effective antineoplastic agents in the clinic. Studies from our lab and others have reported that magnetic resonance spectroscopy (MRS)-detectable phosphocholine (PC) is elevated following SAHA treatment, providing a potential noninvasive biomarker of response. Typically, elevated PC is associated with cancer while a decrease in PC accompanies response to antineoplastic treatment. The goal of this study was therefore to elucidate the underlying biochemical mechanism by which HDAC inhibition leads to elevated PC. We investigated the effect of SAHA on MCF-7 breast cancer cells using (13)C MRS to monitor [1,2-(13)C] choline uptake and phosphorylation to PC. We found that PC synthesis was significantly higher in treated cells, representing 154±19% of control. This was within standard deviation of the increase in total PC levels detected by (31)P MRS (129±7% of control). Furthermore, cellular choline kinase activity was elevated (177±31%), while cytidylyltransferase activity was unchanged. Expression of the intermediate-affinity choline transporter SLC44A1 and choline kinase α increased (144% and 161%, respectively) relative to control, as determined by mRNA microarray analysis with protein-level confirmation by Western blotting. Taken together, our findings indicate that the increase in PC levels following SAHA treatment results from its elevated synthesis. Additionally, the concentration of glycerophosphocholine (GPC) increased significantly with treatment to 210±45%. This is likely due to the upregulated expression of several phospholipase A2 (PLA2) isoforms, resulting in increased PLA2 activity (162±18%) in SAHA-treated cells. Importantly, the levels of total choline (tCho)-containing metabolites, comprised of choline, PC and GPC, are readily detectable clinically using (1)H MRS. Our findings thus provide an important step in validating clinically translatable non-invasive imaging methods for follow-up diagnostics of HDAC inhibitor treatment.

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized.