Strong gene flow and lack of stable population structure in the face of rapid adaptation to local temperature in a spring-spawning salmonid, the European grayling (Thymallus thymallus)

Gene flow has the potential to both constrain and facilitate adaptation to local environmental conditions. The early stages of population divergence can be unstable because of fluctuating levels of gene flow. Investigating temporal variation in gene flow during the initial stages of population divergence can therefore provide insights to the role of gene flow in adaptive evolution. Since the recent colonization of Lake Lesjaskogsvatnet in Norway by European grayling (Thymallus thymallus), local populations have been established in over 20 tributaries. Multiple founder events appear to have resulted in reduced neutral variation. Nevertheless, there is evidence for local adaptation in early life-history traits to different temperature regimes. In this study, microsatellite data from almost a decade of sampling were assessed to infer population structuring and its temporal stability. Several alternative analyses indicated that spatial variation explained 2-3 times more of the divergence in the system than temporal variation. Over all samples and years, there was a significant correlation between genetic and geographic distance. However, decomposed pairwise regression analysis revealed differing patterns of genetic structure among local populations and indicated that migration outweighs genetic drift in the majority of populations. In addition, isolation by distance was observable in only three of the six years, and signals of population bottlenecks were observed in the majority of samples. Combined, the results suggest that habitat-specific adaptation in this system has preceded the development of consistent population substructuring in the face of high levels of gene flow from divergent environments.     

A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth

Screening a phage-display single-chain antibody library for binding to the breast cancer cell line PM-1 an antibody, scFv173, recognising activated leukocyte cell adhesion molecule (ALCAM, CD166) was isolated and its binding profile was characterized. Positive ALCAM immunohistochemical staining of frozen human tumour sections was observed. No ALCAM staining was observed in the majority of tested normal human tissues (nine of ten). Flow cytometry analyses revealed binding to 22 of 26 cancer cell lines of various origins and no binding to normal blood and bone marrow cells. Antibody binding inhibited invasion of the breast cancer cell line MDA-MB-231 by 50% in an in vitro Matrigel-coated membrane invasion assay. Reduced growth of tumours in nude mice was observed in an in vivo model in which the mice were injected subcutaneously with colorectal carcinoma HCT 116 cells and treated with scFv173 when compared to control. In summary, we have characterized a novel fully human scFv antibody recognising ALCAM on cancer cells and in tumour tissues that reduces cancer cell invasion and tumour growth in accordance with the hypothesised role for ALCAM in cell growth and migration control.     

Biomechanical analysis of rollator walking

Background  

The rollator is a very popular walking aid. However, knowledge about how a rollator affects the walking patterns is limited. Thus, the purpose of the study was to investigate the biomechanical effects of walking with and without a rollator on the walking pattern in healthy subjects.     

Mice with targeted disruption of the acyl-CoA binding protein display attenuated urine concentrating ability and diminished renal aquaporin-3 abundance

The acyl-CoA binding protein (ACBP) is a small intracellular protein that specifically binds and transports medium to long-chain acyl-CoA esters. Previous studies have shown that ACBP is ubiquitously expressed but found at particularly high levels in lipogenic cell types as well as in many epithelial cells. Here we show that ACBP is widely expressed in human and mouse kidney epithelium, with the highest expression in the proximal convoluted tubules. To elucidate the role of ACBP in the renal epithelium, mice with targeted disruption of the ACBP gene (ACBP(-/-)) were used to study water and NaCl balance as well as urine concentrating ability in metabolic cages. Food intake and urinary excretion of Na(+) and K(+) did not differ between ACBP(-/-) and (+/+) mice. Interestingly, however, water intake and diuresis were significantly higher at baseline in ACBP(-/-) mice compared with that of (+/+) mice. Subsequent to 20-h water deprivation, ACBP(-/-) mice exhibited increased diuresis, reduced urine osmolality, elevated hematocrit, and higher relative weight loss compared with (+/+) mice. There were no significant differences in plasma concentrations of renin, corticosterone, and aldosterone between mice of the two genotypes. After water deprivation, renal medullary interstitial fluid osmolality and concentrations of Na(+), K(+), and urea did not differ between genotypes and cAMP excretion was similar. Renal aquaporin-1 (AQP1), -2, and -4 protein abundances did not differ between water-deprived (+/+) and ACBP(-/-) mice; however, ACBP(-/-) mice displayed increased apical targeting of pS256-AQP2. AQP3 abundance was lower in ACBP(-/-) mice than in (+/+) control animals. Thus we conclude that ACBP is necessary for intact urine concentrating ability. Our data suggest that the deficiency in urine concentrating ability in the ACBP(-/-) may be caused by reduced AQP3, leading to impaired efflux over the basolateral membrane of the collecting duct.     

Triploidy alters brain morphology in pre‐smolt Atlantic salmon Salmo salar: possible implications for behaviour

Total brain mass and the volumes of five specific brain regions in diploid and triploid Atlantic salmon Salmo salar pre‐smolts were measured using digital images. There were no significant differences (P > 0·05) in total brain mass when corrected for fork length, or the volumes of the optic tecta or hypothalamus when corrected for brain mass, between diploids and triploids. There was a significant effect (P < 0·01) of ploidy on the volume of the olfactory bulb, with it being 9·0% larger in diploids compared with triploids. The cerebellum and telencephalon, however, were significantly larger, 17 and 8% respectively, in triploids compared with diploids. Sex had no significant effect (P > 0·05) on total brain mass or the volumes of any measured brain region. As the olfactory bulbs, cerebellum and telencephalon are implicated in a number of functions, including foraging ability, aggression and spatial cognition, these results may explain some of the behavioural differences previously reported between diploids and triploids.     

Characterization of human phosphodiesterase 12 and identification of a novel 2'-5' oligoadenylate nuclease - The ectonucleotide pyrophosphatase/phosphodiesterase 1

The vertebrate 2-5A system is part of the innate immune response and central to cellular antiviral activities. Upon activation by viral double-stranded RNA, 5′-triphosphorylated, 2′-5′-linked oligoadenylate polyribonucleotides (2-5As) are synthesized by one of several 2′-5′ oligoadenylate synthetases. The 2-5As bind and activate RNase L, an unspecific endoribonuclease, resulting in viral and cellular RNA decay. Given that most endogenous RNAs are degraded by RNase L, continued enzyme activity will eventually lead to cell growth arrest and cell death. This is averted, when 2-5As and their 5′-dephosphorylated forms, the so-called 2-5A core molecules, are cleaved and thus inactivated by 2′-5′-specific nuclease(s), e.g. phosphodiesterase 12, thereby turning RNase L into its latent form. In this study, we have characterized the human phosphodiesterase 12 in vitro focusing on its ability to degrade 2-5As and 2-5A core molecules. We have found that the enzyme activity is distributive and is influenced by temperature, pH and divalent cations. This allowed us to determine V_max and K_m kinetic parameters for the enzyme. We have also identified a novel 2′-5′-oligoadenylate nuclease; the human plasma membrane-bound ectonucleotide pyrophosphatase/phosphodiesterase 1, suggesting that 2-5A catabolism may be a multienzyme-regulated process.