Decrease in manganese superoxide dismutase leads to reduced root growth and affects tricarboxylic acid cycle flux and mitochondrial redox homeostasis

Superoxide dismutases (SODs) are key components of the plant antioxidant defense system. While plastidic and cytosolic isoforms have been extensively studied, the importance of mitochondrial SOD at a cellular and whole-plant level has not been established. To address this, transgenic Arabidopsis (Arabidopsis thaliana) plants were generated in which expression of AtMSD1, encoding the mitochondrial manganese (Mn)SOD, was suppressed by antisense. The strongest antisense line showed retarded root growth even under control growth conditions. There was evidence for a specific disturbance of mitochondrial redox homeostasis in seedlings grown in liquid culture: a mitochondrially targeted redox-sensitive green fluorescent protein was significantly more oxidized in the MnSOD-antisense background. In contrast, there was no substantial change in oxidation of cytosolically targeted redox-sensitive green fluorescent protein, nor changes in antioxidant defense components. The consequences of altered mitochondrial redox status of seedlings were subtle with no widespread increase of mitochondrial protein carbonyls or inhibition of mitochondrial respiratory complexes. However, there were specific inhibitions of tricarboxylic acid (TCA) cycle enzymes (aconitase and isocitrate dehydrogenase) and an inhibition of TCA cycle flux in isolated mitochondria. Nevertheless, total respiratory CO2 output of seedlings was not decreased, suggesting that the inhibited TCA cycle enzymes can be bypassed. In older, soil-grown plants, redox perturbation was more pronounced with changes in the amount and/or redox poise of ascorbate and glutathione. Overall, the results demonstrate that reduced MnSOD affects mitochondrial redox balance and plant growth. The data also highlight the flexibility of plant metabolism with TCA cycle inhibition having little effect on overall respiratory rates.     

Effects of Aminoguanidine on Glomerular Basement Membrane Thickness and Anionic Charge in a Diabetic Rat Model

We investigated the effect of aminoguanidine (AG) administration on GBM thickness, glomerular heparan sulfate (HS) content, and urinary albumin and HS excretion in diabetic rats. After induction of diabetes, female Wistar rats were divided into 2 groups: Group AGDM (n=11) received 1g/L aminoguanidine bicarbonate in drinking water, group DC (n=12) was given only tap water. Control rats received AG (group AGH, n=8) or tap water (group HC, n=8). At the end of a period of 8 weeks, urinary albumin and glycosaminoglycan (GAG) excretion was detected. GBM heparan sulfate distribution and count was determined under the electron microscope. The AGDM group had lower urinary albumin and GAG excretion than diabetic controls. GBM thickness was increased in diabetic rats compared to groups of AGDM and HC. In AGDM group alcian blue stained particle distribution and count in the GBM was similar to healthy controls. In conclusion AG prevents the decrease of anionic charged molecules in the GBM and GBM thickening. This can be one of the mechanisms by which AG decreases albuminuria in diabetic rats.     

Biological control of weeds: an analysis of introductions,rates of establishment and estimates of success,worldwide

The foremost document that comprehensively reports on biological control introductions against weeds—‘Biological control of weeds: a world catalogue of agents and their target weeds’—has been updated and now includes all deliberate releases made through 2012. It includes data on 1555 intentional releases of 468 biological control agent species used against 175 species of target weeds in 48 plant families, in 90 countries. For 55 (31.4%) of the target weed species, only one biocontrol agent was introduced. The largest number of agent species (44) was introduced for the biological control of Lantana camara (Verbenaceae). Three insect orders (Coleoptera, Lepidoptera and Diptera) comprised about 80% of all biocontrol agent species released and releases made. Of the 468 biocontrol agent species introduced, 332 (70.9%) established in at least one instance. Of the 313 species, for which impact could be categorized, 172 (55.0%) caused medium, variable or heavy levels of damage (impacts). Of all releases made through 2012, 982 (63.2%) led to establishment. Forty-two releases were judged too early post-release to categorize impact, leaving 940 releases for which impact analyses were conducted. Similar to agent species, approximately half of the established releases (503 or 53.5%) caused medium, variable or heavy levels of damage on the target weeds, and almost a quarter of releases (225 or 23.9%) caused heavy impact. Across all countries and regions, 65.7% of the weeds targeted for biological control experienced some level of control. These data indicate the value of this practice, on its own, or as a supplement to other methods, in the management of invasive plants.     

Intra-pericardial thrombin injection as bailout strategy in iatrogenic pericardial tamponade

BackgroundCardiac tamponade is a rare but life-threatening complication of cardiac interventions. Despite prompt pericardiocentesis, clinical management can be challenging and sometimes haemodynamic stabilisation is difficult to achieve. Intra-pericardial thrombin injection after pericardiocentesis promotes haemostasis and acts as a sealing agent, as previously described for left ventricular free-wall rupture. We aimed to evaluate intra-pericardial thrombin injection as a bailout strategy for pericardial tamponade following percutaneous cardiac interventions.MethodsIn a 5-year single-centre retrospective analysis we identified 31 patients with cardiac tamponade due to percutaneous intracardiac procedures. Intra-pericardial thrombin injection as a bailout strategy was administered in 5 of 31 patients (16.1%).ResultsPatients receiving intra-pericardial thrombin were in a more critical state when thrombin was applied, as demonstrated by a higher rate of resuscitation (40% versus 26.9%) and a trend toward a prolonged stay in the intensive care unit (177.6 ± 84.0 vs 98.0 ± 31.4 h). None of the patients with pericardial tamponades treated with intra-pericardial thrombin needed cardiothoracic surgery. Mortality after 30 days was lower with intra-pericardial thrombin injection than with standard treatment (0% vs 15.4%). We observed no complications using intra-pericardial thrombin.ConclusionIntra-pericardial thrombin injection could be considered as a bailout strategy for patients with iatrogenic pericardial tamponade due to percutaneous procedures. We recommend further evaluation of this technique in the clinical management of refractory pericardial tamponade.Supplementary InformationThe online version of this article (10.1007/s12471-022-01701-y) contains supplementary material, which is available to authorized users.     

The influence of intercalator binding on DNA triplex stability: correlation with effects on A-tract duplex structure

The triplex form of DNA is of interest because of a possible biological role as well as the potential therapeutic use of this structure. In this paper the stabilizing effects of two intercalating drugs, ethidium and the quinoxaline derivative 9-OH-B220, on DNA triplexes have been studied by thermal denaturation measurements. The corresponding duplex structures of the DNA triplex systems investigated are either A-tract or normal B-DNA. The largest increases in the triplex melting temperatures caused by the intercalators were found for sequences having A-tract duplex structures. Inserting a single base pair with an N2-amino group in the minor groove, e.g. a G-C pair, breaks up the A-tract duplex structure and also reduces the stabilizing effect of the drugs on the triplex melting temperatures. The large drug-induced increase in triplex melting temperature for complexes having an original duplex A-tract structure is correlated with a low initial melting point of the triplex, not with the triplex being unusually stable in the presence of the drug. Hence, we conclude that the large thermal stabilizing effect exhibited by ethidium and 9-OH-B220 on dTn.dAn-dTn triplexes is partly caused by the intercalators breaking up the intrinsic A-tract structure of the underlying duplex.     

The virtual eco-costs ‘99 A single LCA-based indicator for sustainability and the eco-costs-value ratio (EVR) model for economic allocation

In literature, many models (qualitatively as well as quantitatively) can be found to cope with the problem of communicating results of LCA analyses with decision takers. In a previous article of this Journal, an LCA-based single indicator for emissions is proposed: the ‘virtual pollution prevention costs ‘99’ (Vogtländer et al. 2000a). In this article, a single LCA-based indicator for sustainability is proposed. It builds on the virtual pollution prevention costs ‘99 for emissions, and adds the other two main aspects of sustainability: material depletion and energy consumption. This single indicator, the ‘virtual eco-costs ‘99’, is the sum of the marginal prevention costs of:

Material depletion, applying ‘material depletion costs’, to be reduced by recycling

Energy consumption, applying ‘eco-costs of energy’ being the price of renewable energy

Toxic emissions, applying the ‘virtual pollution prevention costs ‘99’

The calculation model includes ‘direct’ as well as ‘indirect’ environmental impacts. The main groups of ‘indirect’ components in the life cycle of products and services are:

Labour (the environmental impacts of office heating, lighting, computers, commuting, etc.)

production assets (equipment, buildings, transport vehicles, etc.)

To overcome allocation problems of the indirect components of complex product-service systems, a methodology of economic allocation has been developed, based on the so called Eco-costs/ Value Ratio (EVR) model. This EVR calculation model appears to be a practical and powerful tool to assess the sustainability of a product, a service, or a product-service combination.     

Postnatal development and thermoregulation in the precocial European hare (<Emphasis Type="Italic">Lepus europaeus</Emphasis>)

We investigated postnatal development of captive juvenile European hares (Lepus europaeus) with respect to growth, food intake and thermoregulation. Leverets increased their body weight on average 8.5-fold within 35 days, with a peak in relative growth rate on day 8. Although leverets started to take up solid food in the 2nd week of lactation, milk was the main energy source. Leverets of larger litters (two or three young) had less energy supply via milk than those of smaller litters (one young), and digested more energy in form of solid food. Weaning weight was positively correlated with body weight at birth and decreased with increasing litter size. Metabolic rates were largely determined by ambient temperature (Ta) and the increasing body weights. Leverets were able to maintain normothermic body temperatures from the Ist day of life during cold exposure down to Ta -8 degrees C. In their 1st week of life leverets showed reduced rates of heat loss in the cold, possibly by using peripheral vasoconstriction. Our results suggest that the precocial development of leverets is characterised by high maintenance costs due to rapid growth and thermoregulation, which may lead to negative energy balances when food supply is inadequate and T(a)s are low. We hypothesise that these physiological characteristics have played an important role in the recent decline of European hare populations.     

Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis

T cell-mediated loss of insulin-secreting beta cells in the islets of Langerhans is the hallmark of type 1 diabetes. The molecular basis for the directed migration of autoreactive T cells leading to insulitis is presently unknown. Here we demonstrate that in response to inflammation, beta cells secrete the chemokines CXC ligand 10 and CXC ligand 9, which specifically attract T-effector cells via the CXC chemokine receptor 3. In mice deficient for this receptor, the onset of type 1 diabetes is substantially delayed. Thus, in the absence of known etiological agents, CXC receptor 3 represents a novel target for therapeutic interference early in type 1 diabetes.     

A new subunit of the epithelial Na+ channel identifies regions involved in Na+ self-inhibition

The epithelial Na+ channel (ENaC) is the apical entry pathway for Na+ in many Na+-reabsorbing epithelia. ENaC is a heterotetrameric protein composed of homologous alpha, beta, and gamma subunits. Mutations in ENaC cause severe hypertension or salt wasting in humans; and consequently, ENaC activity is tightly controlled. According to the concept of Na+ self-inhibition, the extracellular Na+ ion itself can reduce ENaC activity. The molecular basis for Na+ self-inhibition is unknown. Here, we describe cloning of a new ENaC subunit from Xenopus laevis (epsilonxENaC). epsilonxENaC can replace alphaxENaC and formed functional, highly selective, amiloride-sensitive Na+ channels when coexpressed with betaxENaC and gammaxENaC. Channels containing epsilonxENaC showed strong inhibition by extracellular Na+. This Na+ self-inhibition was significantly slower than for alphaxENaC-containing channels. Using site-directed mutagenesis, we show that the proximal part of the large extracellular domain controls the speed of self-inhibition. This suggests that this region is involved in conformational changes during Na+ self-inhibition.