Variation in complement factor 3 is associated with risk of age-related macular degeneration

The association of variants in complement factors H and B with age-related macular degeneration has led to more intense genetic and functional analysis of the complement pathway. We identify a nonsynonymous coding change in complement factor 3 that is strongly associated with risk of age-related macular degeneration in a large case-control sample.     

The cold case: Are rhinoviruses perfectly adapted pathogens?

Rhinoviruses, which cause common cold, belong to the Picornaviridae family, small non-enveloped viruses (diameter 15-30 nm) containing a single-stranded RNA genome (about 7 kb). Over 100 different rhinoviral serotypes have been identified thus far, establishing rhinoviruses as the most diverse group of Picornaviridae. Based on receptor binding properties, rhinoviruses are divided into two classes: the major group binding to intracellular adhesion molecule-1 and the minor group binding to the very low density lipoprotein receptors. Interactions between virus and the receptor molecules cause a conformational change in the capsid, which is a prerequisite for viral uptake. Rhinoviruses trigger a chemokine response upon infection that may lead to exacerbation of the symptoms of common cold, i.e. asthma and inflammation. The following review aims to summarize the knowledge about rhinoviral infections and discusses therapeutical approaches against this almost perfectly adapted pathogen.     

Global Optimization in Any Minkowski Metric: A Permutation-Translation Simulated Annealing Algorithm for Multidimensional Scaling

It is well known that considering a non-Euclidean Minkowski metric in Multidimensional Scaling, either for the distance model or for the loss function, increases the computational problem of local minima considerably. In this paper, we propose an algorithm in which both the loss function and the composition rule can be considered in any Minkowski metric, using a multivariate randomly alternating Simulated Annealing procedure with permutation and translation phases. The algorithm has been implemented in Fortran and tested over classical and simulated data matrices with sizes up to 200 objects. A study has been carried out with some of the common loss functions to determine the most suitable values for the main parameters. The experimental results confirm the theoretical expectation that Simulated Annealing is a suitable strategy to deal by itself with the optimization problems in Multidimensional Scaling, in particular for City-Block, Euclidean and Infinity metrics.     

Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-L?ken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.     

Die bakteriostatische Wirkung von Chalkon,Flavanon, Flavon und Flavonol

Summary Chalcone, flavanone, flavone, and its derivatives had a certain bacteriostatic effect onSt. aureus. Flavonol has no activity and morin, a derivative of flavonol, showed only a weak inhibition of the bacterial growth.Cystein did not have any antagonistic effect.Extracts of drugs, which contain natural flavanones, flavones, isoflavones and flavonols, are more or less bacteriostatic.