Hsp110 is a nucleotide-activated exchange factor for Hsp70

Hsp110 proteins constitute a subfamily of the Hsp70 chaperones and are potent nucleotide exchange factors (NEFs) for canonical Hsp70s of the eukaryotic cytosol. Here, we show that the NEF activity of the yeast Hsp110 homologue Sse1 itself is controlled by nucleotide. Nucleotide binding results in formation of a stabilized conformation of Sse1 that is required for association with the yeast Hsp70 Ssa1. The interaction triggers release of bound ADP from Ssa1, but nucleotide persists bound to Sse1 in the complex. Surprisingly, removal of this nucleotide does not affect the integrity of the complex. Instead, rebinding of ATP to the Hsp70 prompts the dissociation of the complex. Our data demonstrate that in contrast to previously characterized NEFs for Hsp70 chaperones, the NEF activity of Sse1 requires nucleotide binding and let us propose a new model for Hsp110 function.     

Acquisition of full-field strain distributions on ovine fracture callus cross-sections with electronic speckle pattern interferometry

This study evaluated the feasibility of assessing continuous strain distributions on fracture callus cross-sections with an electronic speckle pattern interferometry (ESPI) system. Mid-sagittal callus cross-sections were harvested from ovine tibiae. One low stiffness (LS) specimen and one high stiffness (HS) specimen were selected to evaluate the feasibility for strain acquisition over a range of callus properties. The HS specimen was 147 times stiffer in compression than the LS specimen. ESPI captured continuous strain distributions on both specimens. Peak strain was located adjacent to cortical boundaries in the osteotomy gap. In response to 5N compression, peak compressive strain of 5.8% in the LS specimen was over two orders of magnitude higher than peak compressive strain of 0.013% in the HS specimen. In conclusion, ESPI-based strain acquisition enables reproducible quantification of strain distributions on callus cross-sections. Such measurements may support validation of computational models and evaluation of experimental results in fracture healing research.     

Sophisticated selectionism as a general theory of knowledge

Human knowledge is a phenomenon whose roots extend from the cultural, through the neural and the biological and finally all the way down into the Precambrian “primordial soup.” The present paper reports an attempt at understanding this Greater System of Knowledge (GSK) as a hierarchical nested set of selection processes acting concurrently on several different scales of time and space. To this end, a general selection theory extending mainly from the work of Hull and Campbell is introduced. The perhaps most drastic change from previous similar theories is that replication is revealed as a composite function consisting of what is referred to as memory and synthesis. This move is argued to drastically improve the fit between theory and human-related knowledge systems. The introduced theory is then used to interpret the subsystems of the GSK and their interrelations. This is done to the end of demonstrating some of the new perspectives offered by this view.

A new UV-B absorbing mycosporine with photo protective activity from the lichenized ascomycete Collema cristatum.

A novel photo protective mycosporine was isolated from the lichenized ascomycete Collema cristatum. Biological activity was measured in terms of protection against UV-B induced membrane destruction and pyrimidine dimer formation in cultured human keratinocytes, and prevention of UV-B induced erythema. It was found that the pure isolated compound prevented UV-B induced cell destruction in a dose-dependent manner, that the compound partially prevented pyrimidine dimer formation and completely prevented UV-B induced erythema when applied to the skin prior to irradiation.     

Effects of Furfural on the Respiratory Metabolism of Saccharomyces cerevisiae in Glucose-Limited Chemostats

Effects of furfural on the aerobic metabolism of the yeast Saccharomyces cerevisiae were studied by performing chemostat experiments, and the kinetics of furfural conversion was analyzed by performing dynamic experiments. Furfural, an important inhibitor present in lignocellulosic hydrolysates, was shown to have an inhibitory effect on yeast cells growing respiratively which was much greater than the inhibitory effect previously observed for anaerobically growing yeast cells. The residual furfural concentration in the bioreactor was close to zero at all steady states obtained, and it was found that furfural was exclusively converted to furoic acid during respiratory growth. A metabolic flux analysis showed that furfural affected fluxes involved in energy metabolism. There was a 50% increase in the specific respiratory activity at the highest steady-state furfural conversion rate. Higher furfural conversion rates, obtained during pulse additions of furfural, resulted in respirofermentative metabolism, a decrease in the biomass yield, and formation of furfuryl alcohol in addition to furoic acid. Under anaerobic conditions, reduction of furfural partially replaced glycerol formation as a way to regenerate NAD⁺. At concentrations above the inlet concentration of furfural, which resulted in complete replacement of glycerol formation by furfuryl alcohol production, washout occurred. Similarly, when the maximum rate of oxidative conversion of furfural to furoic acid was exceeded aerobically, washout occurred. Thus, during both aerobic growth and anaerobic growth, the ability to tolerate furfural appears to be directly coupled to the ability to convert furfural to less inhibitory compounds.     

Similarities and differences between the responses induced in human phagocytes through activation of the medium chain fatty acid receptor GPR84 and the short chain fatty acid receptor FFA2R

GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively. Compared to our earlier characterization of the short chain fatty acid receptor FFA2R which is functionally expressed in neutrophils but not in monocytes, GPR84 is expressed in both cell types and in monocyte-derived macrophages. In neutrophils, the GPR84 agonist had an activation profile very similar to that of FFA2R. The GPR84-mediated superoxide release was low in naïve cells, but the response could be significantly primed by TNFα and by the actin cytoskeleton disrupting agent Latrunculin A. Similar to that of FFA2R, a desensitization mechanism bypassing the actin cytoskeleton was utilized by GPR84. All ZQ16-mediated cellular responses were sensitive to GLPG1205, confirming the GPR84-dependency. Finally, our data of in vivo transmigrated tissue neutrophils indicate that both GPR84 and FFA2R are involved in neutrophil recruitment processes in vivo.In summary, we show functional similarities but also some important differences between GPR84 and FFA2R in human phagocytes, thus providing some mechanistic insights into GPR84 regulation in blood neutrophils and cells recruited to an aseptic inflammatory site in vivo.     

A missense mutation in the FALDH gene identified in Sjögren-Larsson syndrome patients originating from the northern part of Sweden

Sjögren-Larsson syndrome (SLS) is an autosomal recessive disorder characterized by congenital ichthyosis, spastic di- or tetraplegia, and mental retardation. SLS has been reported to occur in many populations but the highest incidence is in the north of Sweden. The gene causing SLS encodes a fatty aldehyde dehydrogenase (FALDH). In the present study, a point mutation in exon 7 of the FALDH gene was found in SLS patients of northern Swedish origin. The mutation consists of a C-to-T exchange at nucleotide position 943 in the cDNA. As a consequence, a highly conserved proline is replaced by a serine. The mutation was found in 49 out of 58 affected chromosomes and could be the most widely spread SLS mutation in the world.     

Fine mapping of the gene for autosomal dominant juvenile-onset glaucoma with iridogoniodysgenesis in 6p25-tel

Glaucoma is a group of ocular disorders leading to reduced visual capabilities and sometimes blindness. The biochemical defect is unknown but it is shown that reduced drainage of the aqueous humour from the anterior chamber may lead to increased intraocular pressure and gradual atrophy of the optic neurons. Families with various forms of autosomal dominant (AD) glaucoma have been linked to 1q21-31, 2cen-q13, 4q25-27, and 13q14 and autosomal recessive congenital glaucoma have been localized to chromosome 1p36 and 2p21. Recently, a locus for AD iridogoniodysgenesis anomaly (IGDA) was mapped to chromosome 6p25. This study refines the localization of IGDA to an approximately 6–cM interval between D6S1600 and D6S1617/D6S1713 at 6p25-tel, based on recombinations in affected individuals with AD juvenile-onset glaucoma and concomitant iridogoniodysgenesis. Received: 5 May 1997 / Accepted: 15 June 1997