Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study

Detecting left ventricular (LV) dysfunction at an early stage is key in addressing the heart failure epidemic. In proteome profiling experiments in mice subjected either to aortic banding or sham, the circulating CXCR3 ligands monokine induced by interferon-γ (MIG) and interferon-γ inducible protein 10 (IP10) were 5 to 40 fold up-regulated at eight weeks. We assessed the diagnostic value of circulating NT-pro BNP and CXCR3 ligands (MIG, IP10, Interferon-inducible T-cell alpha chemo-attractant [I–TAC]) in patients with hypertension (≥140/90 mm Hg) associated with subclinical (n = 19) or symptomatic (n = 16) diastolic LV dysfunction on echocardiography and healthy controls. NT–pro BNP, MIG, IP10, I–TAC all increased (p ≤ 0.014) across the categories of worsening left ventricular dysfunction. In patients with symptomatic disease, MIG, IP10, and I–TAC increased 210% (p = 0.015), 140% (p = 0.007) and 120% (p = 0.035) more than NT-pro BNP. The optimal discrimination limits, obtained by maximizing Youden’s index were 246 pmol/L, 65 pg/mL, 93 pg/mL, and 24 pg/mL, respectively. The odds ratios associated with the four biomarkers were significant (p ≤ 0.010), ranging from 4.00 for IP10 to 9.69 for MIG. With adjustment for NT–pro BNP, the CXCR3 ligands retained significance (p ≤ 0.028). Adding optimized thresholds for the CXCR3 ligands to NT–pro BNP enhanced (p ≤ 0.014) the integrated discrimination improvement and the net reclassification improvement. In conclusion, congruent with the concept that inflammation plays a key role in the pathogenesis of LV dysfunction, MIG, IP10 and I–TAC add diagnostic accuracy over and beyond NT–pro BNP.     

Anaphylactic reactions to cinoxacin.

During 1981 to mid-1988 three cases of anaphylactic shock after treatment with the quinolone derivative cinoxacin were reviewed by the Netherlands Centre for Monitoring of Adverse Reactions to Drugs and 17 cases of an anaphylactic type of reaction notified to the World Health Organisation Collaborating Centre for International Drug Monitoring. In five out of six patients for whom data were available the reaction began shortly after taking a single capsule of a second or next course of treatment. Cinoxacin is related to nalidixic acid, and one patient previously treated with that agent subsequently had an anaphylactoid reaction to cinoxacin and later developed a skin reaction to nalidixic acid. There were no deaths, and patients treated as an emergency with plasma expanders or with adrenaline and corticosteroids generally recovered promptly and uneventfully. In view of the potentially fatal consequences of anaphylactic reactions to cinoxacin and other quinolones doctors should take care when prescribing these drugs.     

Microbial community of predatory bugs of the genus <Emphasis Type="Italic">Macrolophus</Emphasis>(Hemiptera: Miridae)

BACKGROUND: The predatory mirids of the genus Macrolophus are key natural enemies of various economically important agricultural pests. Both M. caliginosus and M. pygmaeus are commercially available for the augmentative biological control of arthropod pests in European greenhouses. The latter species is known to be infected with Wolbachia -inducing cytoplasmic incompatibility in its host- but the presence of other endosymbionts has not been demonstrated. In the present study, the microbial diversity was examined in various populations of M. caliginosus and M. pygmaeus by 16S rRNA sequencing and denaturing gradient gel electrophoresis. RESULTS: Besides Wolbachia, a co-infection of 2 Rickettsia species was detected in all M. pygmaeus populations. Based on a concatenated alignment of the 16S rRNA gene, the gltA gene and the coxA gene, the first is phylogenetically related to Rickettsia bellii, whereas the other is closely related to Rickettsia limoniae. All M. caliginosus populations were infected with the same Wolbachia and limoniae-like Rickettsia strain as M. pygmaeus, but did not harbour the bellii-like Rickettsia strain. Interestingly, individuals with a single infection were not found. A PCR assay on the ovaries of M. pygmaeus and M. caliginosus indicated that all endosymbionts are vertically transmitted. The presence of Wolbachia and Rickettsia in oocytes was confirmed by a fluorescence in situ hybridisation. A bio-assay comparing an infected and an uninfected M. pygmaeus population suggested that the endosymbionts had minor effects on nymphal development of their insect host and did not influence its fecundity. CONCLUSION: Two species of the palaearctic mirid genus Macrolophus are infected with multiple endosymbionts, including Wolbachia and Rickettsia. Independent of the origin, all tested populations of both M. pygmaeus and M. caliginosus were infected with three and two endosymbionts, respectively. There was no indication that infection with endosymbiotic bacteria had a fitness cost in terms of development and fecundity of the predators.     

Is low pathogenic avian influenza virus virulent for wild waterbirds?

Although low pathogenic avian influenza virus (LPAIV) is traditionally considered to have adapted to its wild waterbird host to become avirulent, recent studies have suggested that LPAIV infection might after all have clinical effects. Therefore, I reviewed the literature on LPAIV infections in wild waterbirds. The virulence of LPAIV was assessed in 17 studies on experimental infections and nine studies on natural infections. Reported evidence for virulence were reductions in return rate, feeding rate, body weight, long-range movement and reproductive success, as well as pathological changes in infected organs. However, major caveats in studies of experimental infections were unnatural route of LPAIV inoculation, animal husbandry not simulating natural stressors and low sensitivity of clinical assessment. Major caveats in studies of natural infections were incomplete measurement of LPAIV infection burden, quasi-experimental design and potential misclassification of birds. After taking these caveats into account, the only remaining evidence for virulence was that presence and intensity of LPAIV infection were negatively correlated with body weight. Based on this correlation, together with the demonstrated LPAIV tropism for the intestinal tract, I hypothesize that LPAIV reduces digestive tract function, and suggest how future studies could be directed to test this hypothesis.     

Steady flow through a double converging-diverging tube model for mild coronary stenoses

Velocity profiles and the pressure drop across two mild (62 percent) coronary stenoses in series have been investigated numerically and experimentally in a perspex-tube model. The mean flow rate was varied to correspond to a Reynolds number range of 50-400. The pressure drop across two identical (62 percent) stenoses show that for low Reynolds numbers the total effect of two stenoses equals that of two single stenoses. A reduction of 10 percent is found for the higher Reynolds numbers investigated. Numerical and experimental results obtained for the velocity profiles agree very well. The effect of varying the converging angle of a single mild (62 percent) coronary stenosis on the fluid flow has been determined numerically using a finite element method. Pressure-flow relation, especially with respect to relative short stenoses, is discussed.     

Confident phylogenetic identification of uncultured prokaryotes through long read amplicon sequencing of the 16S-ITS-23S rRNA operon

Amplicon sequencing of the 16S rRNA gene is the predominant method to quantify microbial compositions and to discover novel lineages. However, traditional short amplicons often do not contain enough information to confidently resolve their phylogeny. Here we present a cost-effective protocol that amplifies a large part of the rRNA operon and sequences the amplicons with PacBio technology. We tested our method on a mock community and developed a read-curation pipeline that reduces the overall read error rate to 0.18%. Applying our method on four environmental samples, we captured near full-length rRNA operon amplicons from a large diversity of prokaryotes. The method operated at moderately high-throughput (22286–37,850 raw ccs reads) and generated a large amount of putative novel archaeal 23S rRNA gene sequences compared to the archaeal SILVA database. These long amplicons allowed for higher resolution during taxonomic classification by means of long (∼1000 bp) 16S rRNA gene fragments and for substantially more confident phylogenies by means of combined near full-length 16S and 23S rRNA gene sequences, compared to shorter traditional amplicons (250 bp of the 16S rRNA gene). We recommend our method to those who wish to cost-effectively and confidently estimate the phylogenetic diversity of prokaryotes in environmental samples at high throughput.     

Interdisciplinarity and Impact: Distinct Effects of Variety,Balance, and Disparity

Interdisciplinary research is increasingly recognized as the solution to today’s challenging scientific and societal problems, but the relationship between interdisciplinary research and scientific impact is still unclear. This paper studies the association between the degree of interdisciplinarity and the number of citations at the paper level. Different from previous studies compositing various aspects of interdisciplinarity into a single indicator, we use factor analysis to uncover distinct dimensions of interdisciplinarity corresponding to variety, balance, and disparity. We estimate Poisson models with journal fixed effects and robust standard errors to analyze the divergent relationships between these three factors and citations. We find that long-term (13-year) citations (1) increase at an increasing rate with variety, (2) decrease with balance, and (3) increase at a decreasing rate with disparity. Furthermore, interdisciplinarity also affects the process of citation accumulation: (1) although variety and disparity have positive effects on long-term citations, they have negative effects on short-term (3-year) citations, and (2) although balance has a negative effect on long-term citations, its negative effect is insignificant in the short run. These findings have important implications for interdisciplinary research and science policy.     

Development and preliminary evaluation of a 90?K Axiom? SNP array for the allo-octoploid cultivated strawberry Fragaria × ananassa

Background

A high-throughput genotyping platform is needed to enable marker-assisted breeding in the allo-octoploid cultivated strawberry Fragaria × ananassa. Short-read sequences from one diploid and 19 octoploid accessions were aligned to the diploid Fragaria vesca ‘Hawaii 4’ reference genome to identify single nucleotide polymorphisms (SNPs) and indels for incorporation into a 90 K Affymetrix® Axiom® array. We report the development and preliminary evaluation of this array.

Results

About 36 million sequence variants were identified in a 19 member, octoploid germplasm panel. Strategies and filtering pipelines were developed to identify and incorporate markers of several types: di-allelic SNPs (66.6%), multi-allelic SNPs (1.8%), indels (10.1%), and ploidy-reducing “haploSNPs” (11.7%). The remaining SNPs included those discovered in the diploid progenitor F. iinumae (3.9%), and speculative “codon-based” SNPs (5.9%). In genotyping 306 octoploid accessions, SNPs were assigned to six classes with Affymetrix’s “SNPolisher” R package. The highest quality classes, PolyHigh Resolution (PHR), No Minor Homozygote (NMH), and Off-Target Variant (OTV) comprised 25%, 38%, and 1% of array markers, respectively. These markers were suitable for genetic studies as demonstrated in the full-sib family ‘Holiday’ × ‘Korona’ with the generation of a genetic linkage map consisting of 6,594 PHR SNPs evenly distributed across 28 chromosomes with an average density of approximately one marker per 0.5 cM, thus exceeding our goal of one marker per cM.

Conclusions

The Affymetrix IStraw90 Axiom array is the first high-throughput genotyping platform for cultivated strawberry and is commercially available to the worldwide scientific community. The array’s high success rate is likely driven by the presence of naturally occurring variation in ploidy level within the nominally octoploid genome, and by effectiveness of the employed array design and ploidy-reducing strategies. This array enables genetic analyses including generation of high-density linkage maps, identification of quantitative trait loci for economically important traits, and genome-wide association studies, thus providing a basis for marker-assisted breeding in this high value crop.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1310-1) contains supplementary material, which is available to authorized users.