Genome-inferred spatio-temporal resolution of an uncultivated Roizmanbacterium reveals its ecological preferences in groundwater

Subsurface ecosystems like groundwater harbour diverse microbial communities, including small-sized, putatively symbiotic organisms of the Candidate Phyla Radiation, yet little is known about their ecological preferences and potential microbial partners. Here, we investigated a member of the superphylum Microgenomates (Cand. Roizmanbacterium ADI133) from oligotrophic groundwater using mini-metagenomics and monitored its spatio-temporal distribution using 16S rRNA gene analyses. A Roizmanbacteria-specific quantitative PCR assay allowed us to track its abundance over the course of 1 year within eight groundwater wells along a 5.4 km hillslope transect, where Roizmanbacteria reached maximum relative abundances of 2.3%. In-depth genomic analyses suggested that Cand. Roizmanbacterium ADI133 is a lactic acid fermenter, potentially able to utilize a range of complex carbon substrates, including cellulose. We hypothesize that it attaches to host cells using a trimeric autotransporter adhesin and inhibits their cell wall biosynthesis using a toxin–antitoxin system. Network analyses based on correlating Cand. Roizmanbacterium ADI133 abundances with amplicon sequencing-derived microbial community profiles suggested one potential host organism, classified as a member of the class Thermodesulfovibrionia (Nitrospirae). By providing lactate as an electron donor Cand. Roizmanbacterium ADI133 potentially mediates the transfer of carbon to other microorganisms and thereby is an important connector in the microbial community.     

Impact of genetic variations in ADORA2A gene on depression and symptoms: a cross-sectional population-based study

Purinergic Signalling - Genetic variants involved in adenosine metabolism and its receptors were associated with increased risk for psychiatric disorders, including anxiety, depression, and...     

Reduced Serum Levels of Neuron Specific Enolase (NSE) in Drug-Naïve Subjects with Major Depression and Bipolar Disorder

Several biological factors have been recently related with major depression and bipolar disorder. The aim of our paper was to investigate the peripheral levels of the protein neuronal specific enolase (NSE), a putative marker of neuronal damage, comparing patients with major depressive disorder and bipolar disorder to control subjects. This is a case–control study nested in a cross-sectional population-based survey. Psychopathology screen was performed using the Mini-International Neuropsychiatric Interview 5.0 and blood samples were collected from 108 young adults. Three groups were selected, 36 healthy controls, 36 subjects with major depression disorder and 36 subjects with bipolar disorder. Serum levels of NSE significantly decreased (p = 0.002) in major depression disorder (2.19 ± 1.78 ng/mL) and bipolar disorder subjects (2.53 ± 2.61 ng/mL) compared to the control group (3.55 ± 2.19 ng/mL). In conclusion, peripheral neuronal specific enolase may be a useful marker drug-naïve major depression disorder and bipolar disorder, but its pathophysiological significance and response to treatment should be further investigated.     

Single‐cell genomics based on Raman sorting reveals novel carotenoid‐containing bacteria in the Red Sea

Cell sorting coupled with single‐cell genomics is a powerful tool to circumvent cultivation of microorganisms and reveal microbial ‘dark matter’. Single‐cell Raman spectra (SCRSs) are label‐free biochemical ‘fingerprints’ of individual cells, which can link the sorted cells to their phenotypic information and ecological functions. We employed a novel Raman‐activated cell ejection (RACE) approach to sort single bacterial cells from a water sample in the Red Sea based on SCRS. Carotenoids are highly diverse pigments and play an important role in phototrophic bacteria, giving strong and distinctive Raman spectra. Here, we showed that individual carotenoid‐containing cells from a Red Sea sample were isolated based on the characteristic SCRS. RACE‐based single‐cell genomics revealed putative novel functional genes related to carotenoid and isoprenoid biosynthesis, as well as previously unknown phototrophic microorganisms including an unculturable Cyanobacteria spp. The potential of Raman sorting coupled to single‐cell genomics has been demonstrated.     

Phylogenetic structure of Neotropical annual fish of the genus Cynopoecilus (Cyprinodontiformes: Rivulidae), with an assessment of taxonomic implications

The definition of species boundaries constitutes an important challenge in biodiversity studies. Cynopoecilus Regan, 1912 encompasses several endangered species of annual fish, occurring in temporary ponds in a restricted area of Southern Brazil and Uruguay. Divergences about the taxonomic status of Cynopoecilus species highlight the importance of species delimitation studies. Therefore, we address here the phylogenetic structure of Cynopoecilus, while assessing its taxonomic implications. For this, fragments of the mitochondrial COI and nuclear RAG1 genes were characterized and analyzed for a set of 275 and 280 specimens, respectively. DNA barcoding and phylogenetic analyses detected subdivision of these specimens in 8–10 clusters, which comprise the six previously described species, and suggest one invalid taxon and at least 3–5 putative new species. The phylogenetic structure also suggests that the Jacuí River and the Patos Lagoon historically acted as effective barriers to gene flow between populations, although some isolated dispersal events across these water bodies could be evidenced, especially for C. melanotaenia Regan, 1912. In general, the results highlight the need of independent conservation strategies within the distribution area of each of the endemic allopatric killifish clusters, while questioning several taxonomic boundaries and distribution data.     

Moderate long-term modulation of neuropeptide Y in hypothalamic arcuate nucleus induces energy balance alterations in adult rats

Neuropeptide Y (NPY) produced by arcuate nucleus (ARC) neurons has a strong orexigenic effect on target neurons. Hypothalamic NPY levels undergo wide-ranging oscillations during the circadian cycle and in response to fasting and peripheral hormones (from 0.25 to 10-fold change). The aim of the present study was to evaluate the impact of a moderate long-term modulation of NPY within the ARC neurons on food consumption, body weight gain and hypothalamic neuropeptides. We achieved a physiological overexpression (3.6-fold increase) and down-regulation (0.5-fold decrease) of NPY in the rat ARC by injection of AAV vectors expressing NPY and synthetic microRNA that target the NPY, respectively. Our work shows that a moderate overexpression of NPY was sufficient to induce diurnal over-feeding, sustained body weight gain and severe obesity in adult rats. Additionally, the circulating levels of leptin were elevated but the immunoreactivity (ir) of ARC neuropeptides was not in accordance (POMC-ir was unchanged and AGRP-ir increased), suggesting a disruption in the ability of ARC neurons to response to peripheral metabolic alterations. Furthermore, a dysfunction in adipocytes phenotype was observed in these obese rats. In addition, moderate down-regulation of NPY did not affect basal feeding or normal body weight gain but the response to food deprivation was compromised since fasting-induced hyperphagia was inhibited and fasting-induced decrease in locomotor activity was absent.These results highlight the importance of the physiological ARC NPY levels oscillations on feeding regulation, fasting response and body weight preservation, and are important for the design of therapeutic interventions for obesity that include the NPY.     

Model of Tryptophan Metabolism,Readily Scalable Using Tissue-specific Gene Expression Data

Tryptophan is utilized in various metabolic routes including protein synthesis, serotonin, and melatonin synthesis and the kynurenine pathway. Perturbations in these pathways have been associated with neurodegenerative diseases and cancer. Here we present a comprehensive kinetic model of the complex network of human tryptophan metabolism based upon existing kinetic data for all enzymatic conversions and transporters. By integrating tissue-specific expression data, modeling tryptophan metabolism in liver and brain returned intermediate metabolite concentrations in the physiological range. Sensitivity and metabolic control analyses identified expected key enzymes to govern fluxes in the branches of the network. Combining tissue-specific models revealed a considerable impact of the kynurenine pathway in liver on the concentrations of neuroactive derivatives in the brain. Moreover, using expression data from a cancer study predicted metabolite changes that resembled the experimental observations. We conclude that the combination of the kinetic model with expression data represents a powerful diagnostic tool to predict alterations in tryptophan metabolism. The model is readily scalable to include more tissues, thereby enabling assessment of organismal tryptophan metabolism in health and disease.