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Over the last decade, hydrogen sulfide (H2S) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide,H2S is p...
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Over the last decade, hydrogen sulfide (H2S) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide,H2S is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. H2S levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of H2S, either based on H2S donation or inhibition ofH2S biosynthesis.H2S donation can be achieved through the inhalation of H2S gas and/or the parenteral or enteral administration of so-called fast-releasing H2S donors (salts of H2S such as NaHS and Na2S) or slow-releasingH2S donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated H2S release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with H2S-donating groups (the most advanced compound in clinical trials is ATB-346, anH2S-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition ofH2S synthesis, there are now several small molecule compounds targeting each of the three H2S-producing enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), thesemolecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous H2S production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known H2S donors and H2S biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.
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Digenic inheritance of resistance to barley powdery mildew is common. Thus Weihenstephan CP 127422 has a second gene, linked to Ml-g (p = 0.277–0.379), conditioning resistance to race K1. Several varieties (e.g. Gopal, Mian wali a...
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Digenic inheritance of resistance to barley powdery mildew is common. Thus Weihenstephan CP 127422 has a second gene, linked to Ml-g (p = 0.277–0.379), conditioning resistance to race K1. Several varieties (e.g. Gopal, Mian wali and Monte Cristo) with resistance at Ml-a locus carry a second closely linked (p = 0.06–0.08) gene with a spectrum of resistance similar to that of HOR 1063. Concerning Monte Cristo the additional factor is weakly linked to Ml-at. In other varieties such as Sv 57/510–44 and C.I. 8503 the distance is greater between the main Ml-a allele and the corresponding additional factor. Almost similar expressions but different spectra of resistance characterize the two genes present in HOR 1104, with indicated locations at Ml-at and Ml-h, respectively. No indications of linkage were obtained between potential alleles in the following pairs of loci: Ml-a — Ml-at, Ml-a — Ml-p, Ml-a — Ml-h, Ml-a — Ml-n, Ml-at — Ml-p, Ml-at — Ml-h, and Ml-at — Ml-n. On chromosome 5 there is no, or only weak, linkage between translocations and markers, and Ml-genes. This fits a proximal position of the translocation breakpoints and a distal localization of markers and Ml-loci. Strong linkage in the crosses T2–5a x Cebada Negra (BB) and T2–5e x Atat indicates a distal position of the breakpoints versus the marker genes.
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The European Space Agency’s Planck satellite, dedicated to studying the early Universe and its subsequent evolution, was launched 14 May 2009 and has been scanning the microwave and submillimetre sky continuously since 12 August ...
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The European Space Agency’s Planck satellite, dedicated to studying the early Universe and its subsequent evolution, was launched 14 May 2009 and has been scanning the microwave and submillimetre sky continuously since 12 August 2009. In March 2013, ESA and the Planck Collaboration released the initial cosmology products based on the first 15.5?months of Planck data, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the mission and its performance, the processing, analysis, and characteristics of the data, the scientific results, and the science data products and papers in the release. The science products include maps of the cosmic microwave background (CMB) and diffuse extragalactic foregrounds, a catalogue of compact Galactic and extragalactic sources, and a list of sources detected through the Sunyaev-Zeldovich effect. The likelihood code used to assess cosmological models against the Planck data and a lensing likelihood are described. Scientific results include robust support for the standard six-parameter ΛCDM model of cosmology and improved measurements of its parameters, including a highly significant deviation from scale invariance of the primordial power spectrum. The Planck values for these parameters and others derived from them are significantly different from those previously determined. Several large-scale anomalies in the temperature distribution of the CMB, first detected by WMAP, are confirmed with higher confidence. Planck sets new limits on the number and mass of neutrinos, and has measured gravitational lensing of CMB anisotropies at greater than 25σ. Planck finds no evidence for non-Gaussianity in the CMB. Planck’s results agree well with results from the measurements of baryon acoustic oscillations. Planck finds a lower Hubble constant than found in some more local measures. Some tension is also present between the amplitude of matter fluctuations (σ8) derived from CMB data and that derived from Sunyaev-Zeldovich data. The Planck and WMAP power spectra are offset from each other by an average level of about 2% around the first acoustic peak. Analysis of Planck polarization data is not yet mature, therefore polarization results are not released, although the robust detection of E-mode polarization around CMB hot and cold spots is shown graphically.
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The study of over 700 species, from algae to humans, reveals that specific DNA sequences, have an optimal territory within the centromere-telomere field. These DNA sequences have maintained their territory within the chromosome fi...
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The study of over 700 species, from algae to humans, reveals that specific DNA sequences, have an optimal territory within the centromere-telomere field. These DNA sequences have maintained their territory within the chromosome field for millions of years irrespective of variation in arm length, of change in chromosome type and of species evolution. Some of these DNA sequences have been isolated biochemically or analysed at the molecular level. They include, e.g., the proximal heterochromatic segments, the genes for ribosomal RNA, and the telomeric heterochromatin. Order prevails in the eukaryotic chromosome.This order allows classification of genes, rearrangements and chromosomes on a genetic basis. Genes are classified as centrons, medons and telons. Rearrangements are classified as: conservative, discordant, disruptive, destructive and incompatible. Chromosomes are also classified depending on their length, arm size and number. These chromosome properties and features now acquire an organizatory meaning which they lacked previously.The available molecular information supports the evidence from the field. The study of the split gene reveals that it is the relative position of the DNA sequences which determines their function.On the basis of the chromosome field, predictions can be made concerning gene organization, gene function and chromosome evolution.
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