Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.     

Mutagenesis of hydroxylamine oxidoreductase in Nitrosomonas europaea by transformation and recombination.

Mutagenesis of Nitrosomonas europaea was achieved by electroporation and recombination. To demonstrate this, an aminoglycoside 3'-phosphotransferase (kan) gene was specifically inserted into each of the three gene copies of hao individually. Southern hybridizations and PCR analysis showed the incorporation of the kan gene at the chosen genetic loci. The isolation of mutant strains was achieved in 7 to 14 days when the strains were grown on solid medium. The induced mutations were stable even in the absence of kanamycin-selective pressure for periods of up to 45 days in culture. The mutant strains did not show an observable phenotype different from that of the wild type when grown under the same conditions.     

Comparative analysis of the cattle and human genomes: detection of ZOO-FISH and gene mapping-based chromosomal homologies

Comparative chromosome painting with individual human chromosome-specific libraries (CSLs) on cattle metaphase chromosomes delineated 46 homologous chromosomal segments between the two species. Continuous arrangement of these segments on individual cattle chromosomes demonstrates a nearly complete coverage of the bovine karyotype and shows physical boundaries of bovine chromosomal segments homologous to individual human chromosomes. Alignment of the available comparative gene mapping data with the homologous segments strongly supports the detected gross homologies between the karyotypes of the two species. In addition to cattle, four human CSLs were hybridized to sheep metaphase chromosomes also, to further verify the known karyotype homology within the Bovidae. Besides its application to karyotype evolution research, the comparative knowledge provides for rapid expansion of the much needed Type I locus-based bovine gene map. Received: 9 September 1995 / Accepted: 4 December 1995     

Current and emerging commercial optical biosensors.

The field of commercial optical biosensors is rapidly evolving, with new systems and detection methods being developed each year. This review outlines the currently available biosensor hardware and highlights unique features of each platform. Affinity-based biosensor technology, with its high sensitivity, wide versatility and high throughput, is playing a significant role in basic research, pharmaceutical development, and the food and environmental sciences. Likewise, the increasing popularity of biosensors is prompting manufacturers to develop new instrumentation for dedicated applications. We provide a preview of some of the emerging commercial systems that are dedicated to drug discovery, proteomics, clinical diagnostics and routine biomolecular interaction analysis.     

Photosynthetic pigment concentration, organization and interconversions in a pale green Syrian landrace of barley (Hordeum vulgare L., Tadmor) adapted to harsh climatic conditions

Tadmor is a Syrian barley landrace that has adapted to semi-arid environments. Its leaves are pale green because of a 30% decrease in the chlorophyll and the carotenoid content of the chloroplasts (leading to a 7·5% decrease in light absorption) compared with barley genotypes that are not adapted to harsh Mediterranean climatic conditions (e.g. Plaisant). This difference in pigment content was attenuated during growth of the plants in strong light, but was strongly amplified when strong light was combined with a high growth temperature. The low pigment content of Tadmor leaves was not associated with significant changes in the pigment distribution between the photosystems or between the reaction centres of the photosystems and their associated chlorophyll antennae. No significant difference in the photosynthetic activity (O₂ production per unit absorbed light) was observed between Tadmor and Plaisant. The conversion of violaxanthin to zeaxanthin in strong light and its reversal in darkness were much faster and operated at a higher capacity in Tadmor leaves compared with Plaisant leaves, resulting in an increased photostability of photosystem II in the former leaves. The accelerated xanthophylls interconversion in the Syrian landrace was associated with, and possibly related to, an increased fluidity of the thylakoid membranes. The lipid peroxide level was lower in Tadmor compared with Plaisant. In contrast, no difference was found in the non-photochemical quenching of chlorophyll fluorescence between the two barley genotypes. The data indicate that the pale green Syrian landrace is equipped to survive excessive irradiance through a passive reduction of the light absorptance of its leaves, which mitigates the heating effects of strong light, and through the active protection of its photochemical apparatus by a rapid xanthophyll cycling.     

Failure of testicular development associated with a rearrangement of 9p24.1 proximal to the SNF2 gene

In 46,XY individuals, testes are determined by the activity of the SRY gene (sex-determining region Y), located on the short arm of the Ychromosome. The other genetic components of the cascade that leads to testis formation are unknown and may be located on the Xchromosome or on the autosomes. Evidence for the existence of several loci associated with failure of male sexual development is indicated by reports of 46,XY gonadal dysgenesis associated with structural abnormalities of the Xchromosome or of autosomes (chromosomes9, 10, 11 and 17). In this report, we describe the investigation of a child presenting with multiple congenital abnormalities, mental retardation and partial testicular failure. The patient had a homogeneous de novo 46,XY,inv dup(9)(pter→p24.1::p21.1 →p23.3::p24.1→qter) chromosome complement. No deletion was found by either cytogenetic or molecular analysis. The SRY gene and DSS region showed no abnormalities. Southern blotting dosage analysis with 9p probes and fluorescent in situ hybridisation data indicated that the distal breakpoint of the duplicated fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest that a gene involved in normal testicular development and/or maintenance is present at this position on chromosome 9. Received: 20 January 1997 / Accepted: 5 November 1997     

Hormonal adaptation determines the increase in muscle mass and strength during low-intensity strength training without relaxation

The study was designed to test the hypothesis that, during strength training, a restricted blood supply to the working muscles stimulates the secretion of anabolic hormones and an increase in the muscle mass and strength can be achieved with significantly lower training loads. During eight weeks, three times a week, 18 young, physically active males trained their leg extensor muscles. Nine subjects (group I) worked at 80% of the maximal voluntary contraction (MVC), whereas the rest (group II) performed their exercise without relaxation and at a lower load (50% MVC). The total training load in group II was significantly lower than in group I (77 ± 5 vs. 157 ± 7 kJ, respectively). The eight-week training of both groups significantly increased the mean maximum strength (by 35 and 21% in groups I and II, respectively) and volume (by 17 and 9%, respectively) of the muscles trained (however, the differences between the groups with respect to these changes were nonsignificant). Group I displayed a higher increase in the blood level of creatine phosphokinase than group II, while group II showed a greater increase in the blood concentration of lactate. In contrast to group I, group II displayed a significant increase in the blood concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), and cortisol. Hence, the suggestion that the secretion of metabolic hormones is triggered by a metabolic, rather than mechanical, stimulus from working muscles seems plausible.     

Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents

We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote “healthy” chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects.