Periplasmic expression of soluble single chain T cell receptors is rescued by the chaperone FkpA

Background  

Efficient expression systems exist for antibody (Ab) molecules, which allow for characterization of large numbers of individual Ab variants. In contrast, such expression systems have been lacking for soluble T cell receptors (TCRs). Attempts to generate bacterial systems have generally resulted in low yields and material which is prone to aggregation and proteolysis. Here we present an optimized periplasmic bacterial expression system for soluble single chain (sc) TCRs.     

Hormone,vitamin and contaminant status during the moulting/fasting period in ringed seals (Pusa [Phoca] hispida) from Svalbard

This study investigates the potential effects of moulting, and the concomitant period of fasting undertaken by ringed seals, on hormone, vitamin and contaminant status in adult animals in a population from Svalbard, Norway, which has relatively low contaminant levels. Concentrations of circulating total and free thyroxine and triiodothyronine, circulating and hepatic vitamin A, hepatic persistent organic pollutants and their circulating hydroxyl metabolites were higher in moulting seals compared to pre-moulting seals. The opposite trend was observed for body condition, circulating calcitriol levels and hepatic mRNA expression of thyroid hormone receptor β. No differences were observed for circulating or hepatic vitamin E levels or hepatic mRNA expressions for deioidinase 1 or 2, or retinoic acid receptor α between the two seal groups. The observed differences are likely the result of increased metabolic rates required during moulting to maintain thermal balance and replace the pelage, in combination with mobilization of lipid soluble compounds from blubber stores during the fasting period that is associated with moulting. The present study shows that contaminant levels and their relationships with physiological or endogenous variables can be highly confounded by moulting/fasting status. Thus, moulting status and body condition should be taken into consideration when using variables related to thyroid, calcium or vitamin A homeostasis as biomarkers for contaminant effects.     

Quercetin Might Promote Autophagy in a Middle Cerebral Artery Occlusion-Mediated Ischemia Model: Comments on Fawad-Ali Shah et al.

Neurochemical Research -     

Treatment strategies in Alzheimer’s disease: a review with focus on selenium supplementation

Alzheimer’s disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aβ) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aβ production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aβ plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.     

Quantifying the ocean, freshwater and human effects on year-to-year variability of one-sea-winter Atlantic salmon angled in multiple Norwegian rivers

Many Atlantic salmon, Salmo salar, populations are decreasing throughout the species' distributional range probably due to several factors acting in concert. A number of studies have documented the influence of freshwater and ocean conditions, climate variability and human impacts resulting from impoundment and aquaculture. However, most previous research has focused on analyzing single or only a few populations, and quantified isolated effects rather than handling multiple factors in conjunction. By using a multi-river mixed-effects model we estimated the effects of oceanic and river conditions, as well as human impacts, on year-to-year and between-river variability across 60 time series of recreational catch of one-sea-winter salmon (grilse) from Norwegian rivers over 29 years (1979-2007). Warm coastal temperatures at the time of smolt entrance into the sea and increased water discharge during upstream migration of mature fish were associated with higher rod catches of grilse. When hydropower stations were present in the course of the river systems the strength of the relationship with runoff was reduced. Catches of grilse in the river increased significantly following the reduction of the harvesting of this life-stage at sea. However, an average decreasing temporal trend was still detected and appeared to be stronger in the presence of salmon farms on the migration route of smolts in coastal/fjord areas. These results suggest that both ocean and freshwater conditions in conjunction with various human impacts contribute to shape interannual fluctuations and between-river variability of wild Atlantic salmon in Norwegian rivers. Current global change altering coastal temperature and water flow patterns might have implications for future grilse catches, moreover, positioning of aquaculture facilities as well as the implementation of hydropower schemes or other encroachments should be made with care when implementing management actions and searching for solutions to conserve this species.     

Evaluation of a new fiber-optic pressure recording system for cardiovascular measurements in mice

We have tested a new fiber-optic pressure recording system, Samba, with a thin fiber [outer diameter (OD) = 0.25 mm] and a pressure sensor (length and OD = 0.42 mm) attached to the end. The accuracy of the system tested in vitro was good, with a coefficient of variation of 2.54% at 100 mmHg. The drift was <0.45 mmHg/h, and the temperature sensitivity was approximately 0.07 mmHg/1 degrees C between 22 and 37 degrees C. The frequency response characteristics were similar to a 1.4-Fr Millar catheter (0-200 Hz). Introduction of the Samba sensor from the right carotid artery into the left ventricle in six mice caused no drop in mean aortic pressure, whereas introduction of a 1.4-Fr Millar catheter (OD = 0.47 mm; n = 6) caused a pressure drop from 91.6 +/- 9.2 to 65.1 +/- 6.2 mmHg; P < 0.05. Thus the Samba sensor system may represent a new alternative to assess hemodynamic variables in the murine cardiovascular system.     

Construction of vectors for inducible gene expression in Lactobacillus sakei and L plantarum

We have constructed vectors for inducible expression of genes in Lactobacillus sakei and Lactobacillus plantarum. The key elements of these vectors are a regulatable promoter involved in the production of the bacteriocins sakacin A and sakacin P and the genes encoding the cognate histidine protein kinase and response regulator that are necessary to activate this promoter upon induction by a peptide pheromone. The vectors are built up of cassettes that permit easy exchange of all parts through restriction enzyme digestion and ligation. Using beta-glucuronidase as a reporter enzyme, variants of these vectors were compared with each other, and with a corresponding system based on genes involved in the production of nisin. Several of the new vectors permitted tightly controlled and efficient expression of beta-glucuronidase in both L. sakei and L. plantarum.     

Sex,size, competition and escape—strategies of reproduction and dispersal in Lasallia pustulata (Umbilicariaceae,Ascomycetes)

The lichen Lasallia pustulata has a mixed strategy of asexual and sexual reproduction. Close-dispersed, asexual, symbiotic isidia are produced early, when the thalli are small. The asexual propagules are subsequently supplemented by far-dispersed, sexually generated ascospores when the thalli grow larger. This observation is consistent with evolutionary stable strategy (ESS) models of dispersal allocations in heterocarpic plants accordin to which the production of far-dispersed propagules should increase as clutch size and sibcompetition in the local habitat increases. The observation is also consistent with the tangled bank or elbow room hypothesis for the maintenance of sexuality, according to which sex, by generating genetic variation, represents an escape from competition in biologically saturated environments. Thus the advantage of sex is density dependent. L. pustulata grows in densely packed populations where intraspecific competition results in self-thining and the development of distinct sizehierarchies.     

Host density predicts presence of cuckoo parasitism in reed warblers

In some hosts of avian brood parasites, several populations apparently escape parasitism, while others are parasitized. Many migratory specialist brood parasites like common cuckoos, Cuculus canorus , experience a short breeding season, and in order to maintain local parasite populations host densities should be sufficiently high to allow efficient nest search. However, no studies have investigated the possible effect of host density on presence of cuckoo parasitism among populations of a single host species. Here, we investigated possible predictors of common cuckoo parasitism in 16 populations of reed warblers, Acrocephalus scirpaceus , across Europe. In more detail, we quantified the effect of host density, number of host breeding pairs, habitat type, mean distance to nearest cuckoo vantage point, predation rate and latitude on the presence of cuckoo parasitism while controlling for geographical distance among study populations. Host density was a powerful predictor of parasitism. We also found a less pronounced effect of habitat type on occurrence of parasitism, while the other variables did not explain why cuckoos utilize some reed warbler populations and not others. This is the first study focusing on patterns of common cuckoo-host interactions within a specific host species on a large geographic scale. The results indicate that if host density is below a specific threshold, cuckoo parasitism is absent regardless of the state of other potentially confounding variables.