Intercellular junctions in the uterine epithelium of Salamandra salamandra (L.) (Amphibia,Urodela)

Summary Intercellular junctions in the uterine epithelium of the ovoviviparous urodele Salamandra salamandra were studied in pregnant and non-pregnant females by freeze-fracture technique. Junctional complexes consist of zonulae occludentes (tight junctions) and numerous maculae adhaerentes (desmosomes); z. adhaerentes and nexuses (gap junctions) could not be identified. Tight junctions are of the flexible type exhibiting loosely interconnected fibrils. The fibrillary network appears stretched more often in pregnant females possibly due to the mechanical stress of pregnancy. The structure and occurrence of the junctions identified, especially that of the tight junctions, is discussed with regard to the functions of the uterus during pregnancy.Zusammenfassung Mit Hilfe der Gefrierbruchtechnik wurden im Uterus-epithel trächtiger und nichtträchtiger Feuersalamanderweibchen (Salamandra salamandra) Zonulae occludentes und Maculae adhaerentes, jedoch keine Z. adhaerentes sowie Nexus identifiziert. Die Z. occludentes sind flexibel. Ihr fibrilläres Netzwerk ist bei trächtigen Weibchen öfter gestreckt; das ist möglicherweise auf die stärkere Ausdehnung des Uterusgewebes während der Trächtigkeit zurückzuführen. Das Vorkommen der verschiedenen Kontakt-strukturen, namentlich das der Z. occludentes, wird im Hinblick auf die Funktionen des Uterus während der Trächtigkeit diskutiert.We are indebted to Mrs. K. Ott for excellent technical assistance and to Miss Dr. U. Beigel for linguistic help     

Innervation of the synovial membrane of the cats joint capsule

Summary Results of investigations on the occurrence of nerve fibres and endings in the synovial membrane of the knee and elbow joint in the cat are reported. The stratum synoviale contains only autonomic fibres, running in the adventitia of arteries.Free nerve endings are lacking in the stratum synoviale. Simple Pacinian corpuscles with an inner core are occasionally observed in the border zone between the stratum synoviale and fibrosum. The ultrastructure of these endorgans resembles that of Pacinian corpuscles in the hairless and hairy skin of the cat.     

Personalisierte Medizin – Vision oder Fiktion? Beispiel: Altersdiabetes

Typical civilization diseases, such as type II diabetes, are common, complex in the underlying pathogenic mechanisms, heterogenous in the phenotype and multifactorial due to a wide variety of possible combinations of disease susceptibility or protective genes in different relevant tissues and negative or positive environmental factors. This is in sharp contrast to classical inherited diseases, such as Chorea Huntington, which are often caused by complete loss‐ or gain‐of‐function mutations in a single gene. The causative polymorphisms of susceptibility genes, however, are characterized by relative subtle alterations in the function of the corresponding gene product, which per se do not support the pathogenesis, by high frequency, high expenditure for their identification and rather low predictive value. Consequently, the reliable and early diagnosis of civilization diseases depends on the individual determination of all (or as many as possible) polymorphisms of each susceptibility gene together with the corresponding gene products and the metabolites emerging thereof.     

Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study

Background

Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.

Methods and Findings

We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%–6%; p = 0.001) per 10 µg/dl increase in serum iron.

Conclusions

Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made. Please see later in the article for the Editors'' Summary     

Maßgeschneiderte Mikroorganismen

Tailor‐made microorganisms Microbial diversity provides unlimited resources for the development of novel industrial processes and products. Since the beginning of the 20th century microorganisms have been successfully applied for the large scale production of bio‐based products. In recent years, modern methods of strain development and Synthetic Biology have enabled biotech engineers to design even more sophisticated and tailor‐made microorganisms. These microbes serve industrial processes for the production of bulk chemicals, enzymes, polymers, biofuels as well as plant‐derived ingredients such as Artemisinin in an ecologically and economically sustainable and attractive fashion. In the future, production of advanced biofuels, microbial fuel cells, CO₂ as feedstock and microbial cellulose are research topics as well as challenges of global importance. Continuous efforts in microbiology and biotechnology research will be pivotal for white biotechnology to gain more momentum in transforming the chemical industry towards a knowledge based bio‐economy.     

Population genetic variation in gene expression is associated with phenotypic variation in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>

Background

The relationship between genetic variation in gene expression and phenotypic variation observable in nature is not well understood. Identifying how many phenotypes are associated with differences in gene expression and how many gene-expression differences are associated with a phenotype is important to understanding the molecular basis and evolution of complex traits.

Results

We compared levels of gene expression among nine natural isolates of Saccharomyces cerevisiae grown either in the presence or absence of copper sulfate. Of the nine strains, two show a reduced growth rate and two others are rust colored in the presence of copper sulfate. We identified 633 genes that show significant differences in expression among strains. Of these genes, 20 were correlated with resistance to copper sulfate and 24 were correlated with rust coloration. The function of these genes in combination with their expression pattern suggests the presence of both correlative and causative expression differences. But the majority of differentially expressed genes were not correlated with either phenotype and showed the same expression pattern both in the presence and absence of copper sulfate. To determine whether these expression differences may contribute to phenotypic variation under other environmental conditions, we examined one phenotype, freeze tolerance, predicted by the differential expression of the aquaporin gene AQY2. We found freeze tolerance is associated with the expression of AQY2.

Conclusions

Gene expression differences provide substantial insight into the molecular basis of naturally occurring traits and can be used to predict environment dependent phenotypic variation.

     

Evolution of competitive fitness in experimental populations of E. coli: What makes one genotype a better competitor than another?

An important problem in microbial ecology is to identify those phenotypic attributes that are responsible for competitive fitness in a particular environment. Thousands of papers have been published on the physiology, biochemistry, and molecular genetics of Escherichia coli and other bacterial models. Nonetheless, little is known about what makes one genotype a better competitor than another even in such well studied systems. Here, we review experiments to identify the phenotypic bases of improved competitive fitness in twelve E. coli populations that evolved for thousands of generations in a defined environment, in which glucose was the limiting substrate. After 10000 generations, the average fitness of the derived genotypes had increased by 50% relative to the ancestor, based on competition experiments using marked strains in the same environment. The growth kinetics of the ancestral and derived genotypes showed that the latter have a shorter lag phase upon transfer into fresh medium and a higher maximum growth rate. Competition experiments were also performed in environments where other substrates were substituted for glucose. The derived genotypes are generally more fit in competition for those substrates that use the same mechanism of transport as glucose, which suggests that enhanced transport was an important target of natural selection in the evolutionary environment. All of the derived genotypes produce much larger cells than does the ancestor, even when both types are forced to grow at the same rate. Some, but not all, of the derived genotypes also have greatly elevated mutation rates. Efforts are now underway to identify the genetic changes that underlie those phenotypic changes, especially substrate specificity and elevated mutation rate, for which there are good candidate loci. Identification and subsequent manipulation of these genes may provide new insights into the reproducibility of adaptive evolution, the importance of co-adapted gene complexes, and the extent to which distinct phenotypes (e.g., substrate specificity and cell size) are affected by the same mutations.     

Spontaneously arising mutL mutators in evolving Escherichia coli populations are the result of changes in repeat length

Over the course of thousands of generations of growth in a glucose-limited environment, 3 of 12 experimental populations of Escherichia coli spontaneously and independently evolved greatly increased mutation rates. In two of the populations, the mutations responsible for this increased mutation rate lie in the same region of the mismatch repair gene mutL. In this region, a 6-bp repeat is present in three copies in the gene of the wild-type ancestor of the experimental populations but is present in four copies in one of the experimental populations and two copies in the other. These in-frame mutations either add or delete the amino acid sequence LA in the MutL protein. We determined that the replacement of the wild-type sequence with either of these mutations was sufficient to increase the mutation rate of the wild-type strain to a level comparable to that of the mutator strains. Complementation of strains bearing the mutator mutations with wild-type copies of either mutL or the mismatch repair gene uvrD rescued the wild-type mutation rate. The position of the mutator mutations-in the region of MutL known as the ATP lid-suggests a possible deficiency in MutL's ATPase activity as the cause of the mutator phenotype. The similarity of the two mutator mutations (despite the independent evolutionary histories of the populations that gave rise to them) leads to a discussion of the potential adaptive role of DNA repeats.