Increased serotonin (5-hydroxytryptamine, 5-HT) transporter activity has been observed in human familial pulmonary hypertension.
We investigated pulmonary hemodynamics and the development of ...hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in mice overexpressing the gene for the 5-HT transporter (5-HTT+ mice). Right ventricular pressure was elevated 3-fold in normoxic 5-HTT+ mice compared with their wild-type controls. Hypoxia-induced increases in right ventricular hypertrophy and pulmonary vascular remodeling were also potentiated in the 5-HTT+ mice. 5-HTT-like immunoreactivity, protein, and binding sites were markedly increased in the lungs from the 5-HTT+ mice. Hypoxia, however, decreased 5-HT transporter immunoreactivity, mRNA transcription, protein, and binding sites in both wild-type and 5-HTT+ mice.
Increased 5-HT transporter expression causes elevated right ventricular pressures, and this occurs before the onset of right ventricular hypertrophy or pulmonary arterial remodeling. Hypoxia-induced remodeling is, however, increased in 5-HTT+ mice, whereas hypoxia inhibits 5-HTT expression. This provides a unique model that demonstrates differential mechanisms for familial pulmonary arterial hypertension and pulmonary arterial hypertension with hypoxemia.
Although phenylpropanoids and flavonoids are common plant natural products, these major classes of biologically active secondary metabolites are largely absent from bacteria. The ubiquitous plant ...enzymes phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) are key biosynthetic catalysts in phenylpropanoid and flavonoid assembly, respectively. Until recently, few bacterial counterparts were known, thus reflecting the dearth of these plant natural products in bacteria. This review highlights our progress on the biochemical and genetic characterization of recently identified streptomycete biosynthetic pathways to benzoic acid and type III polyketide synthase (PKS)-derived products. The sediment-derived bacterium “Streptomyces maritimus” produces benzoyl-CoA in a plant-like manner from phenylalanine involving a PAL-mediated reaction through cinnamic acid during the biosynthesis of the polyketide antibiotic enterocin. All but one of the genes encoding benzoyl-CoA biosynthesis in “S. maritimus” have been cloned, sequenced, and inactivated, providing a model for benzoate biosynthesis not only in this bacterium, but in plants where benzoic acid is an important constituent of many products. The recent discovery that bacteria harbor homodimeric PKSs belonging to the plant CHS superfamily of condensing enzymes has further linked the biosynthetic capabilities of plants and bacteria. A bioinformatics approach led to the prediction that the model actinomycete Streptomyces coelicolor A3(2) contains up to three type III PKSs. Biochemical analysis of one of the recombinant type III PKSs from S. coelicolor demonstrated activity as a 1,3,6,8-tetrahydroxynaphthalene synthase (THNS). A homology model of THNS based upon the known three-dimensional structure of CHS was constructed to explore the structural and mechanistic details of this new subclass of bacterial PKSs.
The biosynthesis of the meroterpenoid neomarinone from a marine actinomycete was probed through feeding experiments with 13C-labeled precursors. NMR characterization of U-13C6glucose-enriched ...neomarinone led to the structural revision of structure 4a to 4b, which was confirmed by extensive 2D NMR spectrometry with unlabeled compound.
Rewriting results sections in the language of evidence Muff, Stefanie; Nilsen, Erlend B.; O’Hara, Robert B. ...
Trends in ecology & evolution (Amsterdam),
March 2022, 2022-03-00, 20220301, Letnik:
37, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Despite much criticism, black-or-white null-hypothesis significance testing with an arbitrary P-value cutoff still is the standard way to report scientific findings. One obstacle to progress is ...likely a lack of knowledge about suitable alternatives. Here, we suggest language of evidence that allows for a more nuanced approach to communicate scientific findings as a simple and intuitive alternative to statistical significance testing. We provide examples for rewriting results sections in research papers accordingly. Language of evidence has previously been suggested in medical statistics, and it is consistent with reporting approaches of international research networks, like the Intergovernmental Panel on Climate Change, for example. Instead of re-inventing the wheel, ecology and evolution might benefit from adopting some of the ‘good practices’ that exist in other fields.
It has been known for decades that there are severe problems associated with null-hypothesis significance testing (NHST) based on arbitrary P-value thresholds (e.g., P = 0.05).A small literature review indicates that much of the current research in ecology and evolution is still disregarding the warnings and frequently relies on binary decisions based on P-values to report statistical significance.While the P-value itself is a sound mathematical concept that does not have to be banned when used correctly, we should stop using the term ‘statistical significance’ and replace it with a gradual notion of evidence.Language matters and ‘evidence’ is an intuitive concept that honestly reflects what the data really tell us.To facilitate rewriting scientific results, we offer generic examples of how to translate (binary) significance language into a gradual language of evidence.
Protocols for testing conditioned pain modulation (CPM) vary between different labs/clinics. In order to promote research and clinical application of this tool, we summarize the recommendations of ...interested researchers consensus meeting regarding the practice of CPM and report of its results.
A mutational analysis of the enterocin biosynthesis genes revealed that the putative oxygenase and the methyltransferase gene products EncM and EncK, respectively, jointly catalyze a biosynthetic ...Favorskii-like rearrangement. Inactivation of either gene terminated enterocin production and caused the accumulation of four nonrearranged, nonmethylated polyketides. The structure elucidation of the new wailupemycins E−G is reported.
Dopant fluctuations in silicon wafers are responsible for systematic errors in the determination of the particle crossing point in silicon drift detectors. In this paper, we report on the first ...large-scale measurement of this effect by means of a particle beam. A significant improvement of the anodic resolution has been obtained by correcting for these systematic deviations.
An isopycnic coordinate ocean model has been used to investigate the importance of different mechanisms on the Barents Sea climate variability for the period 1948–2006 Observed and simulated time ...series from the Kola Section are used to evaluate the model, and the model captures both the temperature and its variability. Based on lagged correlations between different climatological time series, it is shown here that heat transport through the Barents Sea Opening and solar heat flux are about equally important to the climate variability in the Barents Sea. The heat transport has greater potential of predictability due to a relatively long time lag. Furthermore, the non‐solar and the net heat flux variability is governed by fluctuations in the oceanic heat content. All time series considered important for the Barents Sea climate variability show significant correlation to the North Atlantic Oscillation (NAO) pattern on a decadal time scale. As the associated low pressure system in the Nordic Seas moves eastward from 1948–1977 to 1978–2006, the correlation between NAO and heat transports into the Barents Sea becomes higher.
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