Heritability of eleven metabolic phenotypes in Danish and Chinese twins: A cross‐population comparison

Objectives : A twin‐based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. Design and Methods : Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18‐67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18‐69). Twin modeling was performed on full and nested models with the best fitting models selected. Results : Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure was more genetically controlled in Danish than in Chinese twins. Conclusions : Metabolic endophenotypes show disparity in their genetic determinants in populations under distinct environmental conditions.     

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.     

Urinary nucleic acid oxidation product levels show differential associations with pharmacological treatment in patients with type 2 diabetes

The relationship between RNA and DNA oxidation and pharmacological treatment has not been systematically investigated in patients with type 2 diabetes (T2D). We aimed to investigate the association between pharmacological treatments and levels of urinary markers of nucleic acid oxidation in T2D patients. Vejle Diabetes Biobank cohort data was nested into nationwide registry data. Multiple logistic regression was used to associate drug usage with risk of high (above median) RNA and DNA oxidation. Data from 2664 T2D patients (64% male, age range: 25–75) were included. Questionnaire-validated lipid lowering drug use was associated with low RNA oxidation (Odds ratio, OR 0.71, 95% CI: [0.59–0.87]). Insulin and non-specific antidiabetic drugs were associated with low DNA oxidation (insulin: OR 0.60, 95% CI [0.49–0.73]). Oral antidiabetics were associated with high DNA oxidation and RNA oxidation (OR 1.30, 95% CI [1.10–1.53] and OR 1.26, 95% CI [1.07–1.29]). Our findings indicate that diabetes-related drugs are associated with RNA and DNA oxidation and further studies are required to determine causality in T2D patients.     

Serum cytokines of the 20 Krad-irradiated S. mansoni cercariae vaccinated, primary and superinfected Cercopethicus aethiops aethiops

Appropriate animal models are necessary to better understand the immune response in schistosomiasis. Schistosoma mansoni infection was established using irradiated cercariae in Cercopithecus aethiops aethiops (Grivet monkey) to describe immune responses of the serum cytokines, IL-4, IL-10, IL-12, IFN- gamma, and TNF-alpha. Intraperitoneal irradiated cercariae immunization on three occasions resulted in some differences of cytokine production. In primary infection, IL-4 was significantly raised (p=0.03) in the immunized monkeys, and there was an insignificant increase (p>0.05) in IL-10. However, ova excretion did not influence the cytokines, except in the controls where both IL-4 and IL-10 were significantly increased (p<0.05). In the controls, IL-12 and INF-gamma levels were lower after ova excretion, but the inflammatory TNF-alpha increased (p=0.049) and these findings can be associated with more liver pathogenesis in the group. Thus, this work has indicated the potential importance of anti-schistosome vaccine studies on the grivet monkeys.     

Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity

Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory, and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and, in particular, whether stimulus-driven high-frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that 3 key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: Odor induces theta, beta, and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting that they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low-frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.

Intracranial recordings from human olfactory cortex reveal a characteristic spectrotemporal response to odors, including theta, beta and gamma oscillations, and show that high-frequency responses are critical for accurate perception of odors.     

Dawn song of male blue tits as a predictor of competitiveness in midmorning singing interactions

During the dawn chorus, territorial male songbirds vocalise intensively within signalling range of several conspecific males and can therefore be considered members of a busy communication network. The more or less continuous singing over a long period of time under standardised stimulus conditions makes the dawn song a potentially important information source both for simple receivers and for eavesdroppers. Male blue tits (Parus caeruleus) vary in features of their dawn song, e.g. older males sing longer strophes, and females choose males that sing longer strophes as extra-pair partners. However, so far, dawn song in the blue tit has been investigated separately from other singing behaviour of the same males. In this study, we investigate aspects of blue tit male quality, reflected in dawn song characteristics, and their predictive value for how males behave during singing interactions later in the morning. We acted as simple receivers by recording the singing activity of one male at a time at dawn and compared features of its dawn song, such as onset before sunrise, repertoire size, mean bout length, strophe length and percentage performance time to responses of the same male to a territory intrusion simulated by playback of synthesised songs later during the same morning. We assume that an aggressive response towards an intruder will involve a fast approach to the loudspeaker broadcasting strophes of blue tit song, searching for the intruder (flying around), and a high amount of counter singing and overlapping of the intruders songs. Aspects of vigour of response to the simulated intrusion could be predicted from all five investigated dawn song parameters as well as male age. This is, to our knowledge, the first indication that a simple receiver could extract reliable information from a males dawn singing behaviour about its competitiveness later in the day.Communicated by P.K. McGregor     

Moisture Effects on Temperature Sensitivity of CO<Subscript>2</Subscript> Exchange in a Subarctic Heath Ecosystem

Carbon fluxes between natural ecosystems and the atmosphere have received increased attention in recent years due to the impact they have on climate. In order to investigate independently how soil moisture and temperature control carbon fluxes into and out of a dry subarctic dwarf shrub dominated heath, monoliths containing soil and plants were incubated at three different moisture levels and subjected to four different temperature levels between 7 and 20 °C. Ecosystem CO₂ exchange was monitored continuously day and night during the 16 to 18 days that each of three experiments lasted. Additionally, the carbon allocation pattern of the plants was investigated by labelling monoliths with ¹⁴CO₂ followed by harvest of above and below ground plant parts. The results revealed that the three different soil moisture levels caused distinctly differing levels of CO₂ fluxes. Also, both carbon fixation calculated as gross ecosystem production (GEP) and carbon release measured as ecosystem respiration (ER) increased with increasing temperatures, with ER increasing faster than GEP. Hence, short term carbon loss from the ecosystem accelerated with raised temperatures. Temperature sensitivity of the ecosystem was dependent on the soil moisture level, shown by differing Q10 values of both GEP and ER at different soil moisture levels. It is therefore highly important to take soil moisture levels into consideration when evaluating responses of ecosystem carbon balance to changes in temperature. The greatest C fixation took place via the two most dominant species of the ecosystem, Vaccinium uliginosum and Empetrum hermaphroditum, with the former being responsible for the different size of C fixation at the three moisture levels.     

Identification of a core set of genes that signifies pathways underlying cardiac hypertrophy

Although the molecular signals underlying cardiac hypertrophy have been the subject of intense investigation, the extent of common and distinct gene regulation between different forms of cardiac hypertrophy remains unclear. We hypothesized that a general and comparative analysis of hypertrophic gene expression, using microarray technology in multiple models of cardiac hypertrophy, including aortic banding, myocardial infarction, an arteriovenous shunt and pharmacologically induced hypertrophy, would uncover networks of conserved hypertrophy-specific genes and identify novel genes involved in hypertrophic signalling. From gene expression analyses (8740 probe sets, n = 46) of rat ventricular RNA, we identified a core set of 139 genes with consistent differential expression in all hypertrophy models as compared to their controls, including 78 genes not previously associated with hypertrophy and 61 genes whose altered expression had previously been reported. We identified a single common gene program underlying hypertrophic remodelling, regardless of how the hypertrophy was induced. These genes constitute the molecular basis for the existence of one main form of cardiac hypertrophy and may be useful for prediction of a common therapeutic approach. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat.