Electrical excitation of the heart in a basal vertebrate, the european river lamprey (Lampetra fluviatilis)

Hagfishes and lampreys (order Cyclostomata) are living representatives of an ancient group of jawless vertebrates (class Agnatha). Studies on cyclostome hearts may provide insights into the evolution of the vertebrate heart and thereby increase our understanding of cardiac function in higher vertebrates, including mammals. To this end, electrical ex-citability of the heart in a basal vertebrate, the European river lamprey (Lampetra fluviatilis), was examined. Ion currents of cardiac myocytes, action potentials (APs) of atrial and ven-tricular muscle, and electrocardiogram (in vivo) were mea-sured using the patch-clamp method, intracellular micro-electrodes, and trailing wires, respectively. The characteristic features of fairly high heart rate (28.4 5 3 beats min−1) and short AP duration (550 ± 44 and 122.1 ± 28.5 for ventricle and atrium, respectively) at low ambient temperature (5°C) are shared with cold-active teleost fishes. However, the ion current basis of the ventricular AP differs from that of other fishes. For inward currents, sodium current density (INa) is lower and calcium current density (ICa) higher than in teleost ventricles, while the kinetics of INa is slow and that of ICa is fast in comparison. Among the ventricular repolarizing currents, the delayed rectifier K+ current is smaller than in myocytes of several teleost species. Unlike mammalian hearts, ATP-sensitive K+ channels are constitutively open under normoxic conditions, thus contributing to negative resting membrane potential and repolarization of APs. Upstroke velocity of AP (5.4± and 6.3±0.6 V s−1 for ventricular and atrial myocytes, respectively) is slower than in teleost hearts. Ex-citability of the lamprey heart seems to possess both primitive and advanced characteristics. Short APs are appropriate to support brief and vigorous contractions (in common with. higher vertebrates), while relatively low AP upstroke velocities enable only relatively slow propagation of contraction over the heart

Effects of prolonged anoxia on electrical activity of the heart in Crucian carp (Carassius carassius)

The effects of sustained anoxia on cardiac electrical excitability were examined in the anoxia-tolerant Crucian carp (Carassius carassius). The electrocardiogram (ECG) and expression of excitation-contraction coupling genes were studied in fish acclimatised to normoxia in summer (+18°C) or winter (+2°C), and in winter fish after 1, 3 and 6 weeks of anoxia. Anoxia induced a sustained bradycardia from a heart rate of 10.3±0.77 to 4.1±0.29 bpm (P<0.05) after 5 weeks, and heart rate slowly recovered to control levels when oxygen was restored. Heart rate variability greatly increased under anoxia, and completely recovered under re-oxygenation. The RT interval increased from 2.8±0.34 s in normoxia to 5.8±0.44 s under anoxia (P<0.05), which reflects a doubling of the ventricular action potential (AP) duration. Acclimatisation to winter induced extensive changes in gene expression relative to summer-acclimatised fish, including depression in those coding for the sarcoplasmic reticulum calcium pump (Serca2-q2) and ATP-sensitive K(+) channels (Kir6.2) (P<0.05). Genes of delayed rectifier K(+) (kcnh6) and Ca(2+) channels (cacna1c) were up-regulated in winter fish (P<0.05). In contrast, the additional challenge of anoxia caused only minor changes in gene expression, e.g. depressed expression of Kir2.2b K(+) channel gene (kcnj12b), whereas expression of Ca(2+) (cacna1a, -c and -g) and Na(+) channel genes (scn4a and scn5a) were not affected. These data suggest that low temperature pre-conditions the Crucian carp heart for winter anoxia, whereas sustained anoxic bradycardia and prolongation of AP duration are directly induced by oxygen shortage without major changes in gene expression

Transcript expression of inward rectifier potassium channels of Kir2 subfamily in Arctic marine and freshwater fish species

Inward rectifier K+ (Kir2) channels are critical for electrical excitability of cardiac myocytes. Here, we examine expression of Kir2 channels in the heart of three Gadiformes species, polar cod (Boreogadus saida) and navaga (Eleginus nawaga) of the Arctic Ocean and burbot (Lota lota) of the temperate lakes to find out the role of Kir2 channels in cardiac adaptation to cold. Five boreal freshwater species: brown trout (Salmo trutta fario), arctic char (Salvelinus alpinus), roach (Rutilus rutilus), perch (Perca fluviatilis) and pike (Esox lucius), and zebrafish (Danio rerio), were included for comparison. Transcript expression of genes encoding Kir2.1a, − 2.1b, − 2.2a, − 2.2b and − 2.4 was studied from atrium and ventricle of thermally acclimated or acclimatized fish by quantitative PCR. Kir2 composition in the polar cod was more diverse than in other species in that all Kir2 isoforms were relatively highly expressed. Kir2 composition of navaga and burbot differed from that of the polar cod as well as from those of other species. The relative expression of Kir2.2 transcripts, especially Kir2.2b, was higher in both atrium and ventricle of navaga and burbot (56–89% from the total Kir2 pool) than in other species (0.1–11%). Thermal acclimation induced only small changes in cardiac Kir2 transcript expression in Gadiformes species. However, Kir2.2b transcripts were upregulated in cold-acclimated navaga and burbot hearts. All in all, the cardiac Kir2 composition seems to be dependent on both phylogenetic position and thermal preference of the fish. © 2019, The Author(s).Academy of Finland: 14955Open access funding provided by University of Eastern Finland (UEF) including Kuopio University Hospital. The authors thank Anita Kervinen for her assistance with the fish. This work was supported by the Academy of Finland (grant number 14955)

V405 Aurigae: A High Magnetic Field Intermediate Polar

Our simultaneous multicolor (UBVRI) circular polarimetry has revealed nearly sinusoidal variation over the WD spin cycle, and almost symmetric positive and negative polarization excursions. Maximum amplitudes are observed in the B and V bands (+-3 %). This is the first time that polarization peaking in the blue has been discovered in an IP, and suggests that V405 Aur is the highest magnetic field IP found so far. The polarized flux spectrum is similar to those found in polars with magnetic fields in the range B ~ 25-50 MG. Our low resolution circular spectropolarimetry has given evidence of transient features which can be fitted by cyclotron harmonics n = 6, 7, and 8, at a field of B = 31.5 +- 0.8 MG, consistent with the broad-band polarized flux spectrum. Timings of the circular polarization zero crossovers put strict upper limits on WD spin period changes and indicate that the WD in V405 Aur is currently accreting closely at the spin equilibrium rate, with very long synchronization timescales, T_s > 10^9 yr. For the observed spin to orbital period ratio, P_{spin}/P_{orb} = 0.0365, and P_{orb} ~ 4.15 hr, existing numerical accretion models predict spin equilibrium condition with B ~ 30 MG if the mass ratio of the binary components is q_1 ~ 0.4. The high magnetic field makes V405 Aur a likely candidate as a progenitor of a polar.Comment: To appear in The Astrophysical Journal, September 1 Issue (2008), 9 pages, 10 figure

Tobacco smoking, alcohol drinking and Hodgkin's lymphoma: a European multi-centre case–control study (EPILYMPH)

We analysed the effects of tobacco and alcohol in the aetiology of Hodgkin's lymphoma (HL), based on 340 cases and 2465 controls enrolled in Spain, France, Italy, Germany, Ireland and Czech Republic, between 1998 and 2004. Current smokers showed a significantly increased odds ratio (OR) of HL of 1.39 (95% confidence interval (CI)=1.04–1.87). Analyses were also conducted separately for subjects younger than 35 years (179 cases) and for older subjects (161 cases). For subjects below age 35, no association was observed between tobacco and HL, whereas for older subjects, ever-smokers experienced a doubled risk of HL as compared to never smokers and the OR of HL for current smoking was 2.35 (95% CI=1.52–3.61), with suggestion of a dose–response relationship. A protective effect of alcohol was observed in both age groups. The OR for ever-regular drinking was 0.58 (95% CI=0.38–0.89) for younger subjects and 0.50 (95% CI=0.34–0.74) for older subjects. There was no evidence of interaction between tobacco and alcohol. Our results are consistent with previous studies, suggesting a protective effect of alcohol on HL. An effect of tobacco was suggested for HL occurring in middle and late age, although this finding might have occurred by chance

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta' (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD &lt;sup&gt;+&lt;/sup&gt; LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD &lt;sup&gt;+&lt;/sup&gt; B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD &lt;sup&gt;+&lt;/sup&gt; DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD &lt;sup&gt;+&lt;/sup&gt; BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies

Lay Perspectives on Receiving Different Types of Genomic Secondary Findings : a Qualitative Vignette Study

available at: https://rdcu.be/4BhDGenome-wide sequencing may generate secondary findings (SFs). It is recommended that validated, clinically actionable SFs are reported back to patients/research participants. To explore publics’ perspectives on the best ways to do this, we performed a vignette study among Finnish adults. Our aim was to explore how lay people react to different types of hypothetical genomic SFs. Participants received a hypothetical letter revealing a SF predisposing to a severe but actionable disease - cardiovascular disease (familial hypercholesterolemia, long QT syndrome) or cancer (Lynch syndrome, Li–Fraumeni syndrome). Participants (N=29) wrote down their initial reactions, and discussed (N=23) these in focus groups. Data were analyzed using inductive thematic analysis. Reactions to hypothetical SFs varied according to perceived severity and familiarity of the diseases. SFs for cancer were perceived as more threatening than for cardiovascular diseases, but less distressing than risk for psychiatric or neurological disorders, which participants spontaneously brought up. Illness severity in terms of lived experience, availability of treatment, stigma, and individual’s responsibility to control risk were perceived to vary across these disease types. In addition to clinical validity and utility, SF reporting practices need to take into account potential familiarity and lay illness representations of different diseases. Illness representations may influence willingness to receive SFs, and individuals’ reactions to this information.Peer reviewe