Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O₂ saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O₂-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.     

Beh?et's: A Disease or a Syndrome? Answer from an Expression Profiling Study

Behçet’s disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet’s is “a disease or a syndrome”. To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection “MB vs C” ∩ “OB vs C” ∩ “VB vs C”. Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as “Behçet’s syndrome” (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.     

Marqueurs Á spin construits directement sur le squelette carboné de sucres

Treatment of aldehydo-sugars with 2,3-bis(hydroxyamino)-2,3-dimethylbutane gave the corresponding 1,3-dihydroxyimidazolidines. Oxidation of these compounds gave, successively, unstable, free radicals having a 3-hydroxyimidazolidine 1-oxyl structure, then stable, free radicals having a 2-glycosyl-2-imidazoline 3-oxide 1-oxyl structure, which were reduced to stable 2-glycosyl-2-imidazoline 1-oxyl compounds. The orientation of the two last-named series of compounds around the σ bond between carbohydrate and heterocyclic residues that bears the radical centre is indicated by the value of the hyperfine coupling aH of the carbohydrate proton nearest to the nitrogenous heterocyclic residue. The study of numerous compounds of both series shows that the value of the hyperfine coupling depends greatly on the structure of the carbohydrate residue. A general explanation based on the preponderance of eclipsed forms and on the primary influence of steric hindrance due to the substituents of the carbohydrate residue is proposed. This study also gives some indirect information on the conformation of diamagnetic compounds that show little sterical difference, and about which ¹H-n.m.r. spectroscopy does not provide useful information.     

The Application of Reverse Genetics to Polyploid Plant Species

Polyploidy events (polyploidization) followed by progressive loss of redundant genome components are a major feature of plant evolution, with new evidence suggesting that all flowering plants possess ancestral genome duplications. Furthermore, many of our most important crop plants have undergone additional, relatively recent, genome duplication events. Recent advances in DNA sequencing have made vast amounts of new genomic data available for many plants, including a range of important crop species with highly duplicated genomes. Along with assisting traditional forward genetics approaches to study gene function, this wealth of new sequence data facilitates extensive reverse genetics-based functional analyses. However, plants featuring high levels of genome duplication as a result of recent polyploidization pose additional challenges for reverse genetic analysis. Here we review reverse genetic analysis in such polyploid plants and highlight key challenges.     

Top‐down regulation of filamentous cyanobacteria varies among a raptorial versus current feeding copepod across multiple prey generations

1. Although considered a key functional trait, little is known about how zooplankton feeding mode affects top‐down regulation of phytoplankton communities. Indeed, copepods are expected to promote the dominance of toxic phytoplankton by selective removal of their edible competitors; however, empirical evidence comparing the effect among calanoid and cyclopoid copepods is lacking.
2. We compared the top‐down effects of two copepods with contrasting feeding modes—the calanoid Notodiaptomus iheringi (current feeder) and the cyclopoid Thermocyclops decipiens (ambush feeder) — on the relative and absolute biomass of the filamentous cyanobacterium Raphidiopsis raciborskii co‐cultured with the nutritious eukaryotic phytoplankton Cryptomonas obovata in a week‐long laboratory assay.
3. The current feeder had a stronger top‐down effect on the biomass of both prey throughout the experiment, with mass‐specific clearance rates 3–5× higher than ambush feeder. By the end of the experiment, the current feeder significantly reduced cyanobacteria biomass compared to controls while the ambush feeder did not. During the week‐long experiment, the current feeder switched from grazing on edible prey to cyanobacteria as the former became less abundant.
4. Contrary to expectation, neither of the copepod species promoted cyanobacterial dominance by the end of the experiment. This is because both grazers, but especially the current feeder, initially increased but subsequently decreased the relative contribution of cyanobacteria to total phytoplankton biomass. Moreover, both copepods decreased the length of cyanobacteria filaments by c. 70%
5. Current feeders can switch from edible prey to cyanobacteria when the abundance of shortened filaments surpasses the abundance of edible prey. While top‐down regulation of phytoplankton can be stronger for current feeding copepods, ambush feeding copepods can have a significant role during blooms by shortening cyanobacterial filaments. Hence, the broader role of contrasting copepod feeding traits on phytoplankton communities merits further study.

     

Direct and indirect regeneration of plants from internodal and leaf expiants of<Emphasis Type="Italic">Hypencum bupleuroides</Emphasis> gris

Species of the genusHypencum are of considerable interest worldwide because of their medicinal properties.In- vitro culture is a useful tool for both multiplication of the genus and studying its economically important secondary metabolites. Here, we present an effectivein- vitro propagation method forH. bupleuroides. Leaf and internodal expiants excised from 9-week-old,in vitro-germinated seedlings were cultured on a Murashige and Skoog (MS) medium supplemented with benzyladenine (BA; 1.0 or 0.1 mg L^-1) and 2,4-dichlorophenoxyacetic acid (2,4-D; 1.0 or 0.1 mg L¹). Depending on the BA and 2,4-D combination used, these cultures produced adventitious shoot buds directly on the surfaces of both types of explants as well as excessive calli. Numerous shoots were obtained when the calli from both expiant types were cultured on an MS medium supplemented with 2 mg L^-1 BA. Internodal expiants were more responsive than leaf tissues to direct and indirect plant regeneration. After shoots that regenerated from either the calli or the expiant surface were excised, rooting was best on an MS medium lacking any growth hormones. These rooted plants were then acclimatized under greenhouse conditions, and 90% of regenerants had survived. Ours is the first report ofin- vitro plant regeneration fromH. bupleuroides.     

High-resolution preparative separation of glycosaminoglycan oligosaccharides by polyacrylamide gel electrophoresis

Separation of milligram amounts of heparin oligosaccharides ranging in degree of polymerization from 4 to 32 is achieved within 6 h using continuous elution polyacrylamide gel electrophoresis (CE-PAGE) on commercially available equipment. The purity and structural integrity of CE-PAGE-separated oligosaccharides are confirmed by strong anion exchange high-pressure liquid chromatography, electrospray ionization Fourier transform mass spectrometry, and two-dimensional nuclear magnetic resonance spectroscopy. The described method is straightforward and time-efficient, affording size-homogeneous oligosaccharides that can be used in sequencing, protein binding, and other structure-function relationship studies.     

A high-throughput method for the detection of homoeologous gene deletions in hexaploid wheat

Background  

Mutational inactivation of plant genes is an essential tool in gene function studies. Plants with inactivated or deleted genes may also be exploited for crop improvement if such mutations/deletions produce a desirable agronomical and/or quality phenotype. However, the use of mutational gene inactivation/deletion has been impeded in polyploid plant species by genetic redundancy, as polyploids contain multiple copies of the same genes (homoeologous genes) encoded by each of the ancestral genomes. Similar to many other crop plants, bread wheat (Triticum aestivum L.) is polyploid; specifically allohexaploid possessing three progenitor genomes designated as 'A', 'B', and 'D'. Recently modified TILLING protocols have been developed specifically for mutation detection in wheat. Whilst extremely powerful in detecting single nucleotide changes and small deletions, these methods are not suitable for detecting whole gene deletions. Therefore, high-throughput methods for screening of candidate homoeologous gene deletions are needed for application to wheat populations generated by the use of certain mutagenic agents (e.g. heavy ion irradiation) that frequently generate whole-gene deletions.