Identification of glyoxalase 1 polymorphisms associated with enzyme activity

The glyoxalase system and its main enzyme, glyoxalase 1 (GLO1), protect cells from advanced glycation end products (AGEs), such as methylglyoxal (MG) and other reactive dicarbonyls, the formation of which is increased in diabetes patients as a result of excessive glycolysis. MG is partly responsible for harmful protein alterations in living cells, notably in neurons, leading to their dysfunction, and recent studies have shown a negative correlation between GLO1 expression and tissue damage. Neuronal dysfunction is a common diabetes complication due to elevated blood sugar levels, leading to high levels of AGEs. The aim of our study was to determine whether single nucleotide polymorphisms (SNPs) in the GLO1 gene influence activity of the enzyme. In total, 125 healthy controls, 101 type 1 diabetes, and 100 type 2 diabetes patients were genotyped for three common SNPs, rs2736654 (A111E), rs1130534 (G124G), and rs1049346 (5′-UTR), in GLO1. GLO1 activity was determined in whole blood lysates for all participants of the study.     

Multiparametric Functional MRI: A Tool to Uncover Subtle Changes following Allogeneic Renal Transplantation

PurposeTo investigate multiparametric functional MRI to characterize acute rejection in a murine allogeneic renal transplant model and evaluate the effect of novel therapeutics.ResultsDWI showed a significant diffusion restriction in allogeneic compared to syngeneic transplants (ADC: 0.63±0.08 vs. 1.29±0.12 mm²/s*10³) with decreasing diffusion restriction under therapy. DCE-MRI showed restored organ perfusion under Ciclosporin A alone and combination therapy (Plasma Flow: 43.43±12.49; 38.75±7.53ml/100ml/min) compared to syngeneic controls (51.03±12.49ml/100ml/min). Ex vivo analysis showed reduced monocytic infiltrates, attenuated levels of inflammatory cytokines under mNOX-E36 monotherapy with an additive effect of low dose Ciclosporin A. There was a significant (p<0.05) negative correlation between ADC and interstitial inflammation (r = -0.73) or macrophage infiltration (r = -0.81) and between organ perfusion and intimal arteritis (r = -0.63).ConclusionMultiparametric functional MRI is suited to detect renal allograft rejection in an experimental murine model and allows to characterize effects of immunosuppressive therapy alleviating acute rejection processes in allogeneic transplantation.     

North-South Differentiation and a Region of High Diversity in European Wolves (Canis lupus)

European wolves (Canis lupus) show population genetic structure in the absence of geographic barriers, and across relatively short distances for this highly mobile species. Additional information on the location of and divergence between population clusters is required, particularly because wolves are currently recolonizing parts of Europe. We evaluated genetic structure in 177 wolves from 11 countries using over 67K single nucleotide polymorphism (SNP) loci. The results supported previous findings of an isolated Italian population with lower genetic diversity than that observed across other areas of Europe. Wolves from the remaining countries were primarily structured in a north-south axis, with Croatia, Bulgaria, and Greece (Dinaric-Balkan) differentiated from northcentral wolves that included individuals from Finland, Latvia, Belarus, Poland and Russia. Carpathian Mountain wolves in central Europe had genotypes intermediate between those identified in northcentral Europe and the Dinaric-Balkan cluster. Overall, individual genotypes from northcentral Europe suggested high levels of admixture. We observed high diversity within Belarus, with wolves from western and northern Belarus representing the two most differentiated groups within northcentral Europe. Our results support the presence of at least three major clusters (Italy, Carpathians, Dinaric-Balkan) in southern and central Europe. Individuals from Croatia also appeared differentiated from wolves in Greece and Bulgaria. Expansion from glacial refugia, adaptation to local environments, and human-related factors such as landscape fragmentation and frequent killing of wolves in some areas may have contributed to the observed patterns. Our findings can help inform conservation management of these apex predators and the ecosystems of which they are part.     

Characterisation of tumour-associated antigens in colon cancer

In order to search for clinically relevant cancer-associated genes and to define further the spectrum of immunogenic proteins, we applied SEREX (serological identification of antigens by recombinant expression cloning) to analyse genes expressed in colon adenocarcinoma. Eight different serum-reactive cDNA clones were isolated by immunoscreening from a colon cancer-derived cDNA expression library. mRNA expression studies showed that 2 of them, RHAMM and AD034, have a differential tissue distribution, and that 3 genes, NAP1L1, RHAMM and AD034, are overexpressed in tumours in comparison with the adjacent non-cancerous tissues. 5' RLM-RACE analysis of AD034, a sequence with a tyrosine kinase motif, revealed a frameshifting insertion of 32 bp, most likely generated by use of cryptic splice site in tumour-derived cDNA. Analysis of full-length RHAMM cDNA sequence revealed the presence of two splice variants, which are known to have a different sub-cellular localisation; expression of these splice variants is altered in colon cancer tissues. Serological responses to three antigens (C21ORF2, EPRS and NAP1L1) were found mainly in cancer patients' sera.     

Individual quality, survival variation and patterns of phenotypic selection on body condition and timing of nesting in birds

Questions about individual variation in quality and fitness are of great interest to evolutionary and population ecologists. Such variation can be investigated using either a random effects approach or an approach that relies on identifying observable traits that are themselves correlated with fitness components. We used the latter approach with data from 1,925 individual females of three species of ducks (tufted duck, Aythya fuligula; common pochard, Aythya ferina; northern shoveler, Anas clypeata) sampled on their breeding grounds at Engure Marsh, Latvia, for over 15 years. Based on associations with reproductive output, we selected two traits, one morphological (relative body condition) and one behavioral (relative time of nesting), that can be used to characterize individual females over their lifetimes. We then asked whether these traits were related to annual survival probabilities of nesting females. We hypothesized quadratic, rather than monotonic, relationships based loosely on ideas about the likely action of stabilizing selection on these two traits. Parameters of these relationships were estimated directly using ultrastructural models embedded within capture-recapture-band-recovery models. Results provided evidence that both traits were related to survival in the hypothesized manner. For all three species, females that tended to nest earlier than the norm exhibited the highest survival rates, but very early nesters experienced reduced survival and late nesters showed even lower survival. For shovelers, females in average body condition showed the highest survival, with lower survival rates exhibited by both heavy and light birds. For common pochard and tufted duck, the highest survival rates were associated with birds of slightly above-average condition, with somewhat lower survival for very heavy birds and much lower survival for birds in relatively poor condition. Based on results from this study and previous work on reproduction, we conclude that nest initiation date and body condition covary with both reproductive and survival components of fitness. These associations lead to a positive covariance of these two fitness components within individuals and to the conclusion that these two traits are indeed correlates of individual quality.     

Static magnetic field influence on rat brain function detected by heart rate monitoring

The aim of the present study was to identify the effects of a static magnetic field (SMF) on rat brain structures that control autonomic functions, specifically heart rate and heart rhythmicity. The experiments were carried out on 44 male Wistar rats under ketamine-xylazine anesthesia. SMF was induced using samarium-cobalt fused magnets (20 x 20 x 10 mm in size) placed bitemporally. Magnetic induction intensity was 100 mT on the surface of the head. Duration of magnetic field application was 15 min. An electrocardiogram was recorded from limb lead II, and both heart rate (average duration of cardiac cycles) and heart rhythmicity were analyzed before and after SMF application. SMF evoked changes in both heart rate and rhythm in 80% of the animals; the predominant effects were bradycardia and disappearance of respiratory sinus arrhythmia. However, the effectiveness of SMF in large measure depends on both functional peculiarities and functional activities of brain autonomic centers.     

Coat Polymorphism in Eurasian Lynx: Adaptation to Environment or Phylogeographic Legacy?

Journal of Mammalian Evolution - We studied the relationship between the variability and contemporary distribution of pelage phenotypes in one of most widely distributed felid species and an array...