Algorithm of OMA for large-scale orthology inference

Background  

OMA is a project that aims to identify orthologs within publicly available, complete genomes. With 657 genomes analyzed to date, OMA is one of the largest projects of its kind.     

Effect of benzothiadiazole on the metabolome of Arabidopsis thaliana

Benzothiadiazole (BTH) is a functional analog of the plant endogenous hormone-like compound, salicylic acid (SA), which is required for the induction of plant defense genes leading to systemic acquired resistance (SAR). Previous molecular and genetic studies have suggested that BTH itself might potentiate SAR resulting in the induction of several pathogenesis-related (PR) genes. However, the changes in the metabolome, which occur as a result of BTH-treatment, remain unclear. In this study, metabolic alterations in BTH-treated Arabidopsis thaliana were investigated using nuclear magnetic resonance (NMR) spectroscopy followed by multivariate data analyses such as principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). Both PCA and PLS-DA show that increase of glucose, glutamine, inositol, malic acid, sucrose, and threonine as well as BTH and its degraded metabolites contribute to the clear discrimination of the metabolome of BTH-treated Arabidopsis from control plants. However, the levels of phenolic metabolites, which have generally been observed to be induced by other signaling molecules were significantly reduced in BTH-treated Arabidopsis. In addition to these changes due to BTH-treatment, it was also found that the EtOH used as a solvent in this treatment may per se act as an inducer of the accumulation of a flavonoid.     

Improved cholesterol phenotype analysis by a model relating lipoprotein life cycle processes to particle size

Increased plasma cholesterol is a known risk factor for cardiovascular disease. Lipoprotein particles transport both cholesterol and triglycerides through the blood. It is thought that the size distribution of these particles codetermines cardiovascular disease risk. New types of measurements can determine the concentration of many lipoprotein size-classes but exactly how each small class relates to disease risk is difficult to clear up. Because relating physiological process status to disease risk seems promising, we propose investigating how lipoprotein production, lipolysis, and uptake processes depend on particle size. To do this, we introduced a novel model framework (Particle Profiler) and evaluated its feasibility. The framework was tested using existing stable isotope flux data. The model framework implementation we present here reproduced the flux data and derived lipoprotein size pattern changes that corresponded to measured changes. It also sensitively indicated changes in lipoprotein metabolism between patient groups that are biologically plausible. Finally, the model was able to reproduce the cholesterol and triglyceride phenotype of known genetic diseases like familial hypercholesterolemia and familial hyperchylomicronemia. In the future, Particle Profiler can be applied for analyzing detailed lipoprotein size profile data and deriving rates of various lipolysis and uptake processes if an independent production estimate is given.     

Influence of Aggregation and Route of Injection on the Biodistribution of Mouse Serum Albumin

Protein aggregates are a major risk factor for immunogenicity. Until now most studies on aggregate-driven immunogenicity have focused on linking physicochemical features of the aggregates to the formation of anti-drug antibodies. Lacking is however, basic knowledge on the effect of aggregation on the biodistribution and clearance of therapeutic proteins in vivo. The aim of current study was to get insight into the effect of aggregation on biodistribution in mice using different routes of administration. Fluorescently labeled stressed and unstressed mouse serum albumin was injected via different routes in mice and detected via in vivo fluorescence imaging up to 48 hrs post-injection. We found that biodistribution of stressed MSA significantly differed from its unstressed counterpart. Subcutaneous and intramuscular administration resulted in accumulation of protein at the site of injection, from which clearance of stressed MSA was considerably slower than clearance of unstressed MSA. Upon intravenous and intraperitoneal injection of stressed MSA, fluorescent “hotspots” were observed in the spleens, livers and lungs. Further and more detailed examination of biodistribution after intraperitoneal injection showed higher fluorescence in most of tested organs suggesting more efficient diffusion and/or lymphatic uptake from peritoneum of unstressed MSA than the stressed formulation.     

The essential fatty acid status in phenylketonuria patients under treatment

Phenylketonuric patients are on a special diet that lacks certain essential fatty acids. This study evaluates the essential fatty acid status of a group of phenylketonuric patients in the Netherlands undergoing dietary treatment. To this end, the essential fatty acid status of nine phenylketonuria patients was studied. On the basis of age and gender, two control subjects were selected for each patient. The essential fatty acid composition of duplicate food portions and the essential fatty acid status of plasma and erythrocytes were analyzed. Phenylketonuria subjects had a different essential fatty acid profile from their peers, especially concerning the n-3 fatty acids. N-6 and n-3 fatty long-chain polyenes were hardly consumed by phenylketonuria subjects, in contrast to the control subjects. Linoleic acid, on the other hand, was consumed in significantly higher amounts by phenylketonuria subjects and made up about 40% of their daily fat consumption. The essential fatty acid consumption pattern of the phenylketonuria subjects is mirrored by the essential fatty acid concentrations in blood. The essential fatty acid status of the phenylketonuric diet should be improved in order to prevent deficiency in n-3 fatty acids.     

Myofascial force transmission between a single muscle head and adjacent tissues: length effects of head III of rat EDL.

Force transmission from muscle fibers via the connective tissue network (i.e., myofascial force transmission) is an important determinant of muscle function. This study investigates the role of myofascial pathways for force transmission from multitendoned extensor digitorum longus (EDL) muscle within an intact anterior crural compartment. Effects of length changes exclusively of head III of rat EDL muscle (EDL III) on myofascial force transmission were assessed. EDL III was lengthened at the distal tendon. For different lengths of EDL III, isometric forces were measured at the distal tendon of EDL III, as well as at the proximal tendon of whole EDL and at the distal tendons of tibialis anterior and extensor hallucis longus (TA+EHL) muscles. Lengthening of EDL III caused high changes in force exerted at the distal tendon of EDL III (from 0 to 1.03 +/- 0.07 N). In contrast, only minor changes were found in force exerted at the proximal EDL tendon (from 2.37 +/- 0.09 to 2.53 +/- 0.10 N). Increasing the length of EDL III decreased TA+EHL force significantly (by 7%, i.e., from 5.62 +/- 0.27 to 5.22 +/- 0.32 N). These results show that force is transmitted between EDL III and adjacent tissues via myofascial pathways. Optimal force exerted at the distal tendon of EDL III (1.03 +/- 0.07 N) was more than twice the force expected on the basis of the physiological cross-sectional area of EDL III muscle fibers (0.42 N). Therefore, a substantial fraction of this force must originate from sources other than EDL III. It is concluded that myofascial pathways play an important role in force transmission from multitendoned muscles.     

Molecular characterization of the brassinosteroid-deficient lkb mutant in pea

The brassinosteriod-deficient lkb mutant of garden pea (Pisum sativum L.) is characterized by an erectoides phenotype (reduced internode length, thickened stems, epinastic leaves), which is rescued by application of exogenous brassinolide. We show that the LKB gene is the Arabidopsis DIMINUTO/DWARF-1 (DIM/DWF1) homologue of pea. The DIM/DWF1 homologue from lkb plants contains a mutation that may result in reduced enzyme function, thus resulting in the previously shown accumulation of 24-methylenecholesterol and a deficiency of its hydrogenated product, campesterol. This ultimately leads to a deficiency of the biologically active brassionolide. The mutation in the lkb sequence cosegregates with the lkb phenotype. Northern analyis of the LKB gene revealed that the gene is ubiquitously expressed around the plant and that there is no evidence for negative feedback regulation of the gene.     

Photocontrol of anthocyanin biosynthesis in tomato

Juvenile anthocyanin biosynthesis has been studied in dark-grown seedlings of tomato (Lycopersicon esculentum Mill.) wild types (WTs) and photomorphogenic mutants. During a subsequent 24-hr period of monochromatic irradiation at different fluence rates of red light (R) the fluence-rate response relationships for induction of anthocyanin in all the WTs are similar, yet complex, showing a response at low fluence rates (LFRR) followed by a fluence rate-dependent high irradiance response (HIR). In the hypocotyl this response is restricted to the sub-epidermal layer of cells. The high-pigment-1 (hp-1) mutant exhibits a strong amplification of both response components. Theatroviolacea (atv) mutant shows strongest amplification of the HIR component. In contrast, a transgenic line overexpressing an oat phytochrome A gene (PHYA3 ⁺) shows a most dramatic amplification of the LFRR component. The far-red light (FR)-insensitive (fri) mutant, deficient in phytochrome A (phyA), lacks the LFRR component whilst retaining a normal HIR. The temporarily R-insensitive (tri) mutant, deficient in phytochrome B1 (phyB1) retains the LFRR, but lacks the HIR. Thehp-1,fri andhp-1,tri double mutant, exhibit amplified, yet qualitatively similar responses to the monogenicfri andtri mutants. Thefri,tri double mutant lacks both response components in R, but a residual response to blue light (B) remains. Similarly, theaurea (au) mutant deficient in phytochrome chromophore biosynthesis and presumably all phytochromes, lacks both response components in the R and FR regions of the spectrum. Experiments at other wavelengths demonstrate that while there is only a small response in the FR spectral region (729 nm) in tomato, there is an appreciable HIR response in the near FR at 704 nm, which is retained in thetri mutant. This suggests that the labile phyA pool participates in the HIR at this wavelength. The intense pigmentation (Ip) mutant appears to be specifically deficient in the B1 induced anthocyanin biosynthesis. Adult plants, grown under fluorescent light/dark cycles, show a reduction of anthocyanin content of young developing leaves upon application of supplemtary or end-of-day FR. The involvement of different phytochrome species in anthocyanin biosynthesis based on micro-injection studies into theau mutant and studies using type specific phytochrome mutants is discussed.