«Smarter Medicine»: 5 Interventionen, die in der ambulanten allgemeinen inneren Medizin vermieden werden sollten

Seit 2012 befasst sich die Schweizerische Gesellschaft für Allgemeine Innere Medizin mit der Problematik der Überdiagnostik und Überversorgung in der Medizin. Nun hat sie beschlossen, eine Liste mit fünf Untersuchungen auf dem Gebiet der ambulanten allgemeinen inneren Medizin zusammenzustellen, die ohne oder mit nur geringem Nutzen bei zahlreichen Patienten durchgeführt werden, gleichzeitig jedoch unerwünschte Nebenwirkungen haben können und zum Anstieg der Gesundheitskosten beitragen

Untersuchungen zur Populationsgenetik der Minderempfindlichkeit des Apfelwicklers gegenüber Cydia pomonella Granulovirus (CpGV)

The Codling moth granulovirus (Cydia pomonella granulovirus, CpGV, Baculoviridae) is one of the most important bio control agents of the codling moth in apple production. Since 2003, codling moth populations have been observed in Germany and France, which show an up to thousand fold decreased susceptibility to CpGV. A spread of this phenomenon is a severe threat to the efficient control of the codling moth, particularly in organic farming. In order to prevent this development, investigations on the popula-tion genetics of codling moth populations in Germany were initiated to assess the baseline susceptibilities of selected populations. Furthermore, the genetic and biologi-cal background of resistance of the codling moth to CpGV are being elucidated by crossing susceptible and low susceptible codling moth populations. These investiga-tions will help to develop new control strategies or to restore high susceptibility to-wards CpGV. Mapping of traits involved in resistance will be performed. Involved loci will be identi-fied with the help of amplified fragment length polymorphism (AFLP). Loci coupled with susceptibility can help to elucidate resistance mechanisms. Analysis of comple-mentary DNA amplified fragment length polymorphism (cDNA-AFLP) will be per-formed to display differences in expression rate of particular genes. If there are differ-ences between sensitive and non-sensitive strains, the genes will be isolated and sequenced. Putative sequence homologies give the direction of the functional sense of the mentioned gene and further conclusion of the mechanisms of the susceptibility of CpGV

How did the toad get over the sea to Skye? Tracing the colonisation of Scottish inshore islands by common toads (Bufo bufo)

Processes of island colonisation have long been of interest to biologists. Colonisation events themselves are rarely observed, but the processes involved may be inferred using genetic approaches. We investigated possible means of island colonisation by common toads (Bufo bufo) in western Scotland (the Isle of Skye and five neighbouring small islands), using evidence derived from nuclear microsatellites and mitochondrial (mt) DNA. Levels of microsatellite allelic richness for populations on Skye were high and comparable to adjacent mainland populations, but lower for populations on small islands. Pairwise measures of genetic distances between populations and a clustering algorithm were both suggestive of frequent gene flow between Skye and the mainland. For small islands the levels of genetic differentiation were higher, implying stronger isolation and no evidence for inbreeding. The distribution of mtDNA haplotypes broadly mirrored the genetic structure revealed by microsatellites. Reconciled with existing palaeoclimatological evidence, since the last glaciation, our findings rule out the possibility that the B. bufo populations stem from glacial refugia, or that recent anthropogenic transfer of toads is responsible for their current distribution. The most parsimonious explanation of our data is that the studied inshore islands have been repeatedly colonised via rafting from the mainland or neighbouring islands. This may give us insights into the processes likely to take place when ice sheets retreat poleward as a result of climate change. It also has implications for the colonisation of both native and invasive non-native species, and hence the biosecurity of island refugia

Genetic and migratory evidence for sympatric spawning of tropical pacific eels from Vanuatu

The spawning areas of tropical anguillid eels in the South Pacific are poorly known, and more information about their life histories is needed to facilitate conservation. We genetically characterized 83 out of 84 eels caught on Gaua Island (Vanuatu) and tagged 8 eels with pop-up satellite transmitters. Based on morphological evidence, 32 eels were identified as Anguilla marmorata, 45 as A. megastoma and 7 as A. obscura. Thirteen of these eels possessed a mitochondrial DNA sequence (control region, 527 bp) or nuclear haplotype (GTH2b, 268 bp) conflicting with their species designation. These individuals also had multi-locus genotypes (6 microsatellite loci) intermediate between the species, and 9 of these eels further possessed heterozygote genotypes at species-diagnostic nuclear single nucleotide polymorphisms (SNPs). We classified these individuals as possibly admixed between A. marmorata and A. megastoma. One A. marmorata and one A. megastoma migrated 634 and 874 km, respectively, towards the border between the South Equatorial Current and the South Equatorial Counter Current. Both species descended from around 200 m depth at night to 750 m during the day. Lunar cycle affected the upper limit of migration depths of both species. The tags remained attached for 3 and 5 mo and surfaced <300 km from the pop-up location of a previously tagged A. marmorata. A salinity maximum at the pop-up locations corresponding to the upper nighttime eel migration depths may serve as a seamark of the spawning area. The similar pop-up locations of both species and the evidence for admixture suggest that these tropical eels share a sympatric spawning area

Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity

The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell-intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity

A toy model of the five-dimensional universe with the cosmological constant

A value of the cosmological constant in a toy model of the five-dimensional universe is calculated in such a manner that it remains in agreement with both astronomical observations and the quantum field theory concerning the zero-point fluctuations of the vacuum. The (negative) cosmological constant is equal to the inverse of the Planck length squared, which means that in the toy model the vanishing of the observed value of the cosmological constant is a consequence of the existence of an energy cutoff exactly at the level of the Planck scale. In turn, a model for both a virtual and a real particle-antiparticle pair is proposed which describes properly some energetic properties of both the vacuum fluctuations and created particles, as well as it allows one to calculate the discrete "bare" values of an elementary-particle mass, electric charge and intrinsic angular momentum (spin) at the energy cutoff. The relationships between the discussed model and some phenomena such as the Zitterbewegung and the Unruh-Davies effect are briefly analyzed, too. The proposed model also allows one to derive the Lorentz transformation and the Maxwell equations while considering the properties of the vacuum filled with the sea of virtual particles and their antiparticles. Finally, the existence of a finite value of the vacuum-energy density resulting from the toy model leads us to the formulation of dimensionless Einstein field equations which can be derived from the Lagrangian with a dimensionless (naively renormalized) coupling constant.Comment: 52 pages, 1 figure; a post-final, rewritten version with a number of new remarks and conclusion

A new role for FBP21 as regulator of Brr2 helicase activity

Splicing of eukaryotic pre-mRNA is carried out by the spliceosome, which assembles stepwise on each splicing substrate. This requires the concerted action of snRNPs and non-snRNP accessory proteins, the functions of which are often not well understood. Of special interest are B complex factors that enter the spliceosome prior to catalytic activation and may alter splicing kinetics and splice site selection. One of these proteins is FBP21, for which we identified several spliceosomal binding partners in a yeast-two-hybrid screen, among them the RNA helicase Brr2. Biochemical and biophysical analyses revealed that an intrinsically disordered region of FBP21 binds to an extended surface of the C-terminal Sec63 unit of Brr2. Additional contacts in the C-terminal helicase cassette are required for allosteric inhibition of Brr2 helicase activity. Furthermore, the direct interaction between FBP21 and the U4/U6 di-snRNA was found to reduce the pool of unwound U4/U6 di-snRNA. Our results suggest FBP21 as a novel key player in the regulation of Brr2