Novel class of polytopic proteins with domains associated with putative protease activity

A significant proportion of early onset Alzheimer's disease (AD) is caused by mutations in human genes for amyloid precursor protein (APP), presenilins 1 and 2 (PSEN1,2). AD associated mutations in PSEN1,2 genes alter the -secretase cleavage activity of APP resulting in increased production of amyloidogenic A42. PSEN dependent intramembrane proteolysis was described as an important step required for cleavage of Notch receptors, Notch-dependent signal transduction, and processing of other proteins. It is still unclear whether presenilins are unusual intramembrane proteases or they are necessary cofactors of -secretase cleavage of APP and Notch. Identification of other proteins similar to presenilins may resolve this dilemma. We describe here the identification of novel families of genes encoding polytopic transmembrane proteins of Eukaryotes (IMPASes) and Arachaea (membrases). These proteins have a predicted structure similar to presenilins. The amino acid similarity is significant in domains carrying invariant amino acid residues, which are critical in specific presenilin-regulated endoproteolysis. Many members of the IMPAS family have protease associated domains (PA) typical of proteases. We identified and cloned five human IMPAS genes. Expression analysis of the hIMP1 gene (located on chromosome 20) was performed in human cell tissues and transfected cell cultures. The data demonstrate that a conservative class of putative protease-related polytopic proteins related to presenilins exists in multicellular eukaryotes and microorganisms.     

Phototherapie gegen Rückenschmerzen

Phototherapy Miniaturization of electronics, small enough to be integrated into textiles, offer new opportunities for medical technology and phototherapy. Measuring physiological body functions and the use of semiconductors like light emitting diodes (LEDs) actively influencing physiology are examples for these kinds of innovations.     

Genotype‐dependent consequences of traumatic stress in four inbred mouse strains

Post‐traumatic stress disorder (PTSD) is an anxiety disorder that develops in predisposed individuals following a terrifying event. Studies on isogenic animal populations might explain susceptibility to PTSD by revealing associations between the molecular and behavioural consequences of traumatic stress. Our study employed four inbred mouse strains to search for differences in post‐stress response to a 1.5‐mA electric foot shock. One day to 6 weeks after the foot shock anxiety, depression and addiction‐like phenotypes were assessed. In addition, expression levels of selected stress‐related genes were analysed in hippocampus and amygdala. C57BL/6J mice exhibited up‐regulation in the expression of Tsc22d3, Nfkbia, Plat and Crhr1 genes in both brain regions. These alterations were associated with an increase of sensitized fear and depressive‐like behaviour over time. Traumatic stress induced expression of Tsc22d3, Nfkbia, Plat and Fkbp5 genes and developed social withdrawal in DBA/2J mice. In 129P3/J strain, exposure to stress produced the up‐regulation of Tsc22d3 and Nfkbia genes and enhanced sensitivity to the rewarding properties of morphine. Whereas, SWR/J mice displayed increase only in Pdyn expression in the amygdala and had the lowest conditioned fear. Our results reveal a complex genetic background of phenotypic variation in response to stress and indicate the SWR/J strain as a valuable model of stress resistance. We found potential links between the alterations in expression of Tsc22d3, Nfkbia and Pdyn, and different aspects of susceptibility to stress.     

The complete sequence of the mitochondrial genome of the African Penguin (Spheniscus demersus)

The complete mitochondrial genome of the African Penguin (Spheniscus demersus) was sequenced. The molecule was sequenced via next generation sequencing and primer walking. The size of the genome is 17,346 bp in length. Comparison with the mitochondrial DNA of two other penguin genomes that have so far been reported was conducted namely; Little blue penguin (Eudyptula minor) and the Rockhopper penguin (Eudyptes chrysocome). This analysis made it possible to identify common penguin mitochondrial DNA characteristics. The S. demersus mtDNA genome is very similar, both in composition and length to both the E. chrysocome and E. minor genomes. The gene content of the African penguin mitochondrial genome is typical of vertebrates and all three penguin species have the standard gene order originally identified in the chicken. The control region for S. demersus is located between tRNA-Glu and tRNA-Phe and all three species of penguins contain two sets of similar repeats with varying copy numbers towards the 3′ end of the control region, accounting for the size variance. This is the first report of the complete nucleotide sequence for the mitochondrial genome of the African penguin, S. demersus. These results can be subsequently used to provide information for penguin phylogenetic studies and insights into the evolution of genomes.     

Archaeological records indicate a complex history of Pleistocene hunter-gatherer societies in Arabia

Paleolithic research on the Arabian Peninsula is still in its early stage. During the last decade, however, an increasing number of field projects were conducted and added significant data to the record. This development in addition to substantial paleoenvironmental research on Pleistocene climate and habitat changes creates a promising setting for research on human evolution in arid landscapes. Here I provide an overview of the main Paleolithic field projects conducted in Arabia and summarize their results.     

Crystal structure of D-erythronate-4-phosphate dehydrogenase complexed with NAD

Pyridoxal-5′-phosphate (the active form of vitamin B6) is an essential cofactor in many enzymatic reactions. While animals lack any of the pathways for de novo synthesis and salvage of vitamin B6, it is synthesized by two distinct biosynthetic routes in bacteria, fungi, parasites, and plants. One of them is the PdxA/PdxJ pathway found in the γ subdivision of proteobacteria. It depends on the pdxB gene, which encodes erythronate-4-phosphate dehydrogenase (PdxB), a member of the d-isomer specific 2-hydroxyacid dehydrogenase superfamily. Although three-dimensional structures of other functionally related dehydrogenases are available, no structure of PdxB has been reported. To provide the missing structural information and to gain insights into the catalytic mechanism, we have determined the first crystal structure of erythronate-4-phosphate dehydrogenase from Pseudomonas aeruginosa in the ligand-bound state. It is a homodimeric enzyme consisting of 380-residue subunits. Each subunit consists of three structural domains: the lid domain, the nucleotide-binding domain, and the C-terminal dimerization domain. The latter domain has a unique fold and is largely responsible for dimerization. Interestingly, two subunits of the dimeric enzyme are bound with different combinations of ligands in the crystal and they display significantly different conformations. Subunit A is bound with NAD and a phosphate ion, while subunit B, with a more open active site cleft, is bound with NAD and l(+)-tartrate. Our structural data allow a detailed understanding of cofactor and substrate recognition, thus providing substantial insights into PdxB catalysis.     

Photochemical study of a cyanobacterial chloride-ion pumping rhodopsin

Mastigocladopsis repens halorhodopsin (MrHR) is a Cl^?-pumping rhodopsin that belongs to a distinct cluster far from other Cl^? pumps. We investigated its pumping function by analyzing its photocycle and the effect of amino acid replacements. MrHR can bind I^? similar to Cl^? but cannot transport it. I^?-bound MrHR undergoes a photocycle but lacks the intermediates after L, suggesting that, in the Cl^?-pumping photocycle, Cl^? moves to the cytoplasmic (CP) channel during L decay. A photocycle similar to that of the I^?-bound form was also observed for a mutant of the Asp200 residue, which is superconserved and assumed to be deprotonated in most microbial rhodopsins. This residue is probably close to the Cl^?-binding site and the protonated Schiff base, in which a chromophore retinal binds to a specific Lys residue. However, the D200N mutation affected neither the Cl^?-binding affinity nor the absorption spectrum, but completely eliminated the Cl^?-pumping function. Thus, the Asp200 residue probably protonates in the dark state but deprotonates during the photocycle. Indeed, a H⁺ release was detected for photolyzed MrHR by using an indium?tin oxide electrode, which acts as a good time-resolved pH sensor. This H⁺ release disappeared in the I^?-bound form of the wild-type and Cl^?-bound form of the D200N mutant. Thus, Asp200 residue probably deprotonates during L decay and then drives the Cl^? movement to the CP channel.     

Serine recombinases as tools for genome engineering

The serine recombinases differ mechanistically from the tyrosine recombinases and include proteins such as ?C31 integrase which, unlike Cre and Flp, promote unidirectional reactions. The serine recombinase family is large and includes many other proteins besides ?C31 integrase with the potential to be widely used in genome engineering. Here we review the details of the mechanism of the reactions promoted by the serine recombinases and discuss how these not only limit the utility of this class of recombinase but also creates opportunities for the engineering of new enzymes. We discuss the unanswered questions posed by genome engineering experiments in a variety of systems in which the serine recombinases have been used and finally describe more recently discovered serine recombinases that have the potential to be used in genome engineering.