The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure.

BACKGROUND: Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into HF pathophysiology. OBJECTIVE: We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters, as well as with elevated left atrial pressure (LAP), in HFrEF patients, to provide insights into underlying mechanisms. METHODS: In 173 HFrEF patients, we performed six-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7(IQR:2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular (left ventricular ejection fraction[LVEF], global longitudinal strain[GLS]), and left atrial function (left atrial reservoir strain[LASr]) and elevated LAP(E/e' ratio >15), and used gene enrichment analyses to identify underlying pathophysiological processes. RESULTS: We found 723, 249, 792 and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix (ECM). Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: Cystatin-D, Fibulin-5 and HSP40. CONCLUSION: Circulating proteins show varying associations with different echocardiographic parameters in HFrEF patients. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

Prognostic value of temporal patterns of left atrial reservoir strain in patients with heart failure with reduced ejection fraction.

BACKGROUND: We investigated whether repeatedly measured left atrial reservoir strain (LASr) in heart failure with reduced ejection fraction (HFrEF) patients provides incremental prognostic value over a single baseline LASr value, and whether temporal patterns of LASr provide incremental prognostic value over temporal patterns of other echocardiographic markers and NT-proBNP. METHODS: In this prospective observational study, 153 patients underwent 6-monthly echocardiography, during a median follow-up of 2.5 years. Speckle tracking echocardiography was used to measure LASr. Hazard ratios (HRs) were calculated for LASr from Cox models (baseline) and joint models (repeated measurements). The primary endpoint (PEP) comprised HF hospitalization, left ventricular assist device, heart transplantation, and cardiovascular death. RESULTS: Mean age was 58 ± 11 years, 76% were men, 82% were in NYHA class I/II, mean LASr was 20.9% ± 11.3%, and mean LVEF was 29% ± 10%. PEP was reached by 50 patients. Baseline and repeated measurements of LASr (HR per SD change (95% CI) 0.20 (0.10-0.41) and (0.13 (0.10-0.29), respectively) were both significantly associated with the PEP, independent of both baseline and repeated measurements of other echo-parameters and NT-proBNP. Although LASr was persistently lower over time in patients with PEP, temporal trajectories did not diverge in patients with versus without the PEP as the PEP approached. CONCLUSION: LASr was associated with adverse events in HFrEF patients, independent of baseline and repeated other echo-parameters and NT-proBNP. Temporal trajectories of LASr showed decreased but stable values in patients with the PEP, and do not provide incremental prognostic value for clinical practice compared to single measurements of LASr.

Does a 5500-km swim trial stimulate early sexual maturation in the European eel (Anguilla anguilla L.)?

The catadromous European eel (Anguilla anguilla L.) undertakes a 6000-km spawning migration from its freshwater habitats to the Sargasso Sea. In large Blazka swim tunnels of 127 l, the physiological effect of such a prolonged swimming performance on sexual maturation in adult female eels was investigated. Two groups of eels were placed in swim tunnels for 173 days, one group was able to swim at 0.5 body lengths/second (Swim group) covering a distance of c. 5500-km over the experimental period, and one group kept in static (End Control group). A control group was sampled at the start of the experiment in order to determine the initial stage of reproductive development (Initial Control group). At the end of the swim trial, the maturation parameters 11-ketotestosterone, pituitary levels of LH and plasma levels of estradiol were higher (although not significantly) in the Swim compared to the End Control group. In addition, no significant differences were observed in most measured morphometric and reproductive parameters, including eye-index, gonadosomatic index, hepatosomatic index, and plasma levels of vitellogenin, cortisol and melanophore-stimulating hormone (MSH). Also, pituitary levels of both MSH, and adrenocorticotropic hormone (ACTH) were unaffected. In contrast, the oocyte diameter was found to be significantly higher in the Swim compared to the End Control group. Based on these observations we conclude that a period of prolonged swimming might be a physiological stimulus necessary for the onset of maturation in the European eel.

Genomic annotation and transcriptome analysis of the zebrafish (Danio rerio) hox complex with description of a novel member, hox b 13a.

The zebrafish (Danio rerio) is an important model in evolutionary developmental biology, and its study is being revolutionized by the zebrafish genome project. Sequencing is at an advanced stage, but annotation is largely the result of in silico analyses. We have performed genomic annotation, comparative genomics, and transcriptional analysis using microarrays of the hox homeobox-containing transcription factors. These genes have important roles in specifying the body plan. Candidate sequences were located in version Z v 4 of the Ensembl genome database by TBLASTN searching with Danio and other vertebrate published Hox protein sequences. Homologies were confirmed by alignment with reference sequences, and by the relative position of genes along each cluster. RT-PCR using adult Tübingen cDNA was used to confirm annotations, to check the genomic sequence and to confirm expression in vivo. Our RT-PCR and microarray data show that all 49 hox genes are expressed in adult zebrafish. Significant expression for all known hox genes could be detected in our microarray analysis. We also find significant expression of hox 8 paralogs and hox b 7 a in the anti-sense direction. A novel gene, D. rerio hox b 13 a, was identified, and a preliminary characterization by in situ hybridization showed expression at 24 hpf at the tip of the developing tail. We are currently characterizing this gene at the functional level. We argue that the oligo design for microarrays can be greatly enhanced by the availability of genomic sequences.

Phylogenetic relationships of finches and allies based on nuclear and mitochondrial DNA.

The complete mitochondrial gene cytochrome b in combination with a nuclear gene, beta-fibrinogen intron 7, is sequenced for different groups of mostly granivorous species in the superfamily Passeroidea, with a focus on the estrildids and fringillids. From our study we can conclude that within the group of granivorous finches two clades can be distinguished, the estrildid weaver clade and the cardueline, fringillid, emberizid, passerine sparrow clade. In contrast to many other studies the passerine sparrows are not placed within the weavers estrildid clade which is in agreement with other recent studies (e.g., ). Our study also shows that the estrildids do form a monophyletic group, but there is a division based on geographic origin: an African group and an Asian-Australian group. Within the Fringillidae the Fringilla species are the sister group of the carduelines.

The composition of trigeminal nerve branches in normal adult chickens and after debeaking at different ages.

The long term effects of amputation of the tip of the beak were studied in adult hens that were debeaked on the day of hatching, at the age of 8 d and at 6 wk, by EM analysis of fibre spectra of the medial branch of the ophthalmic nerve and of the intramandibular nerve. Three categories of fibre were distinguished for further analysis, i.e. unmyelinated axons, small myelinated fibres and large myelinated fibres. In normal birds the ophthalmic nerve contains relatively more large fibres than the intramandibular nerve. Amputation consistently results in a reduction of the number of large fibres and a substantial increase in the number of small myelinated fibres. The proportion of unmyelinated axons is rather variable, but is not affected by beak trimming. Age at debeaking has no effect. The observations are inconclusive concerning the possibility of heightened nociception.