Cardiac MIBG imaging at the edge of clinical application in heart failure

Neuronal innervation plays a crucial role in cardiac function. The heart is richly innervated with sympathetic and parasympathetic fibers that work in conjunction with circulating catecholamine mediators, such as norepinephrine (NE), to tightly regulate cardiac output at rest and during periods of increased cardiac demand. An impairment of cardiac autonomic function, most often the result of cardiac disease (ischemic or nonischemic cardiomyopathy), can reflect the severity of the condition, and in many cases is associated with and likely contributing to worsening of the clinical condition, increasing the potential for life-threatening cardiac arrhythmias and death. Because cardiac autonomic function involves numerous molecular processes, use of radiotracers for imaging is an ideal method of assessment.     

Carcinosarcoma of the gallbladder

The case of a 60-year-old woman with a five-year history of abdominal pain, jaundice, and weight loss is presented. On physical examination a hard mass on her right flank was evident. She died under unknown circumstances while she was waiting to be examined. At post-mortem examination the gallbladder was replaced by a neoplasm and there were gallstones within its lumen. Histologically, the tumour was constituted by a mixture of adenocarcinoma, squamous cell carcinoma and undifferentiated sarcoma. The diagnosis of carcinosarcoma of the gallbladder was established. A review of previously reported cases is presented too.     

Genome sequence of M6, a diploid inbred clone of the high‐glycoalkaloid‐producing tuber‐bearing potato species Solanum chacoense,reveals residual heterozygosity

Cultivated potato (Solanum tuberosum L.) is a highly heterozygous autotetraploid that presents challenges in genome analyses and breeding. Wild potato species serve as a resource for the introgression of important agronomic traits into cultivated potato. One key species is Solanum chacoense and the diploid, inbred clone M6, which is self‐compatible and has desirable tuber market quality and disease resistance traits. Sequencing and assembly of the genome of the M6 clone of S. chacoense generated an assembly of 825 767 562 bp in 8260 scaffolds with an N50 scaffold size of 713 602 bp. Pseudomolecule construction anchored 508 Mb of the genome assembly into 12 chromosomes. Genome annotation yielded 49 124 high‐confidence gene models representing 37 740 genes. Comparative analyses of the M6 genome with six other Solanaceae species revealed a core set of 158 367 Solanaceae genes and 1897 genes unique to three potato species. Analysis of single nucleotide polymorphisms across the M6 genome revealed enhanced residual heterozygosity on chromosomes 4, 8 and 9 relative to the other chromosomes. Access to the M6 genome provides a resource for identification of key genes for important agronomic traits and aids in genome‐enabled development of inbred diploid potatoes with the potential to accelerate potato breeding.     

Benzoate effect on a benzoate-resistant strain ofZygosaccharomyces bailii

Summary Benzoic acid inZ. bailii decreases cell yield and increases sugar uptake rate in a similar way as inS. cerevisiae. The final catabolic destiny of pyruvate, however, is a function of the respiratory capacity of each strain. On the other hand, benzoic acid inhibits oxidative metabolism inZ. bailii. This work was supported byEC project AIR2-CT-92-CO-2.     

Long-term responses of the green-algal lichen Parmelia caperata to natural CO2 enrichment

Acclimation to elevated CO₂ was investigated in Parmelia caperata originating from the vicinity of a natural CO₂ spring, where the average daytime CO₂ concentration was 729 ± 39 μmol mol⁻¹ dry air. Thalli showed no evidence of a down-regulation in photosynthetic capacity following long-term exposure to CO₂ enrichment in the field; carboxylation efficiency, total Ribulose bisphosphate carboxylase/oxygenase (Rubisco) content, apparent quantum yield of CO₂ assimilation, and the light-saturated rate of CO₂ assimilation (measured under ambient and saturating CO₂ concentrations) were similar in thalli from the naturally CO₂ enriched site and an adjacent control site where the average long-term CO₂ concentration was about 355 μmol mol⁻¹. Thalli from both CO₂ environments exhibited low CO₂ compensation points and early saturation of CO₂ uptake kinetics in response to increasing external CO₂ concentrations, suggesting the presence of an active carbon-concentrating mechanism. Consistent with the lack of significant effects on photosynthetic metabolism, no changes were found in the nitrogen content of thalli following prolonged exposure to elevated CO₂. Detailed intrathalline analysis revealed a decreased investment of nitrogen in Rubisco in the pyrenoid of algae located in the elongation zone of thalli originating from elevated CO₂, an effect associated with a reduction in the percentage of the cell volume occupied by lipid bodies and starch grains. Although these differences did not affect the photosynthetic capacity of thalli, there was evidence of enhanced limitations to CO₂ assimilation in lichens originating from the CO₂-enriched site. The light-saturated rate of CO₂ assimilation measured at the average growth CO₂ concentration was found to be significantly lower in thalli originating from a CO₂-enriched atmosphere compared with that of thalli originating and measured at ambient CO₂. At lower photosynthetic photon flux densities, the light compensation point of net CO₂ assimilation was significantly higher in thalli originating from elevated CO₂, and this effect was associated with higher usnic acid content. Received: 8 May 1998 / Accepted: 22 January 1999     

Nitrogen fixation persists under conditions of salt stress in transgenic Medicago truncatula plants expressing a cyanobacterial flavodoxin

Several recent studies have demonstrated that the expression of a cyanobacterial flavodoxin in plants can provide tolerance to a wide range of environmental stresses. Indeed, this strategy has been proposed as a potentially powerful biotechnological tool to generate multiple‐tolerant crops. To determine whether flavodoxin expression specifically increased tolerance to salt stress and whether it might also preserve legume nitrogen fixation under saline conditions, the flavodoxin gene was introduced into the model legume Medicago truncatula. Expression of flavodoxin did not confer saline tolerance to the whole plant, although the sensitive nitrogen‐fixing activity was maintained under salt stress in flavodoxin‐expressing plants. Our results indicate that flavodoxin induced small but significant changes in the enzymatic activities involved in the nodule redox balance that might be responsible for the positive effect on nitrogen fixation. Expression of flavodoxin can be regarded as a potential tool to improve legume symbiotic performance under salt stress, and possibly other environmental stresses.     

Compounds released by disturbed adults of the haematophagous bug Triatoma infestans (Hemiptera: Reduviidae): behavioural effects of single compounds and binary mixtures

Adults of the Chagas disease vector Triatoma infestans Klug (Hemiptera: Reduviidae: Triatominae), possess paired exocrine glands: the metasternal and Brindley's glands. Both glands are discharged by disturbed adults, releasing an alarm pheromone that elicits an escape response of larvae. The present study analyzes the individual (or combined) effects of some of the volatiles of the whole pheromone blend released under disturbance, searching for active compounds and for possible interactions (e.g. synergism, additive effects) between them. Using an experimental arena, different doses of components emitted by disturbed adults are tested against larvae. Larvae show escape responses to some of the acids, as well as to one alcohol, but no response to ketones. This is observed with certain doses of compounds from Brindley's glands (isobutyric, butyric and acetic acid; 2‐methyl‐1‐butanol), although the compounds tested in the present study that are produced by metasternal glands are shown to evoke random responses, suggesting that mainly Brindley's glands are involved in the alarm context. Two combinations of two individually repellent compounds (2‐methyl‐1‐butanol with acetic or isobutyric acid) evoke escape responses, although other combinations make the individual effect disappear. A different mixture of two individually repellent compounds (butyric and isobutyric acid) evokes attraction, although these are also host odours. The potential use of the active compounds released by disturbed adults to monitor triatomine populations is discussed.     

Low-dose spironolactone reduces reactive oxygen species generation and improves insulin-stimulated glucose transport in skeletal muscle in the TG(mRen2)27 rat

Renin-angiotensin-aldosterone system (RAAS) activation mediates increases in reactive oxygen species (ROS) and impaired insulin signaling. The transgenic Ren2 rat manifests increased tissue renin-angiotensin system activity, elevated serum aldosterone, hypertension, and insulin resistance. To explore the role of aldosterone in the pathogenesis of insulin resistance, we investigated the impact of in vivo treatment with a mineralocorticoid receptor (MR) antagonist on insulin sensitivity in Ren2 and aged-matched Sprague-Dawley (SD) control rats. Both groups (age 6-8 wk) were implanted with subcutaneous time-release pellets containing spironolactone (0.24 mg/day) or placebo over 21 days. Systolic blood pressure (SBP) and intraperitoneal glucose tolerance test were determined. Soleus muscle insulin receptor substrate-1 (IRS-1), tyrosine phosphorylated IRS-1, protein kinase B (Akt) phosphorylation, GLUT4 levels, and insulin-stimulated 2-deoxyglucose uptake were evaluated in relation to NADPH subunit expression/oxidase activity and ROS production (chemiluminescence and 4-hydroxy-2-nonenal immunostaining). Along with increased soleus muscle NADPH oxidase activity and ROS, there was systemic insulin resistance and reduced muscle IRS-1 tyrosine phosphorylation, Akt phosphorylation/activation, and GLUT4 expression in the Ren2 group (each P < 0.05). Despite not decreasing blood pressure, low-dose spironolactone treatment improved soleus muscle insulin signaling parameters and systemic insulin sensitivity in concert with reductions in NADPH oxidase subunit expression/activity and ROS production (each P < 0.05). Our findings suggest that aldosterone contributes to insulin resistance in the transgenic Ren2, in part, by increasing NADPH oxidase activity in skeletal muscle tissue.     

Influence of Mismatch of Env Sequences on Vaccine Protection by Live Attenuated Simian Immunodeficiency Virus

Vaccine/challenge experiments that utilize live attenuated strains of simian immunodeficiency virus (SIV) in monkeys may be useful for elucidating what is needed from a vaccine in order to achieve protective immunity. Derivatives of SIVmac239 and SIVmac239Δnef were constructed in which env sequences were replaced with those of the heterologous strain E543; these were then used in vaccine/challenge experiments. When challenge occurred at 22 weeks, 10 of 12 monkeys exhibited apparent sterilizing immunity despite a mismatch of Env sequences, compared to 12 of 12 monkeys with apparent sterilizing immunity when challenge virus was matched in its Env sequence. However, when challenge occurred at 6 weeks, 6 of 6 SIV239Δnef-immunized monkeys became superinfected by challenge virus mismatched in its Env sequence (SIV239/EnvE543). These results contrast markedly not only with the results of the week 22 challenge but also with the sterilizing immunity observed in 5 of 5 SIV239Δnef-immunized rhesus monkeys challenged at 5 weeks with SIV239, i.e., with no mismatch of Env sequences. We conclude from these studies that a mismatch of Env sequences in the challenge virus can have a dramatic effect on the extent of apparent sterilizing immunity when challenge occurs relatively early, 5 to 6 weeks after the nef-deleted SIV administration. However, by 22 weeks, mismatch of Env sequences has little or no influence on the degree of protection against challenge virus. Our findings suggest that anti-Env immune responses are a key component of the protective immunity elicited by live attenuated, nef-deleted SIV.