The ratio of serum 24,25-dihydroxyvitamin D(3) to 25-hydroxyvitamin D(3) is predictive of 25-hydroxyvitamin D(3) response to vitamin D(3) supplementation

24,25-Dihydroxyvitamin D (24,25VD) is a major catabolite of 25-hydroxyvitamin D (25VD) metabolism, and may be physiologically active. Our objectives were to: (1) characterize the response of serum 24,25VD(3) to vitamin D(3) (VD(3)) supplementation; (2) test the hypothesis that a higher 24,25VD(3) to 25VD(3) ratio (24,25:25VD(3)) predicts 25VD(3) response. Serum samples (n=160) from wk 2 and wk 6 of a placebo-controlled, randomized clinical trial of VD(3) (28,000IU/wk) were analyzed for serum 24,25VD(3) and 25VD(3) by mass spectrometry. Serum 24,25VD(3) was highly correlated with 25VD(3) in placebo- and VD(3)-treated subjects at each time point (p<0.0001). At wk 2, the 24,25:25VD(3) ratio was lower with VD(3) than with placebo (p=0.035). From wk 2 to wk 6, the 24,25:25VD(3) ratio increased with the VD(3) supplement (p<0.001) but not with placebo, such that at wk 6 this ratio did not significantly differ between groups. After correcting for potential confounders, we found that 24,25:25VD(3) at wk 2 was inversely correlated to the 25VD(3) increment by wk 6 in the supplemented group (r=-0.32, p=0.02) but not the controls. There is a strong correlation between 24,25VD(3) and 25VD(3) that is only modestly affected by VD(3) supplementation. This indicates that the catabolism of 25VD(3) to 24,25VD(3) rises with increasing 25VD(3). Furthermore, the initial ratio of serum 24,25VD(3) to 25VD(3) predicted the increase in 25VD(3). The 24,25:25VD(3) ratio may therefore have clinical utility as a marker for VD(3) catabolism and a predictor of serum 25VD(3) response to VD(3) supplementation.     

Longitudinal exchange: an alternative strategy towards quantification of dynamics parameters in ZZ exchange spectroscopy

Longitudinal exchange experiments facilitate the quantification of the rates of interconversion between the exchanging species, along with their longitudinal relaxation rates, by analyzing the time-dependence of direct correlation and exchange cross peaks. Here we present a simple and robust alternative to this strategy, which is based on the combination of two complementary experiments, one with and one without resolving exchange cross peaks. We show that by combining the two data sets systematic errors that are caused by differential line-broadening of the exchanging species are avoided and reliable quantification of kinetic and relaxation parameters in the presence of additional conformational exchange on the ms-μs time scale is possible. The strategy is applied to a bistable DNA oligomer that displays different line-broadening in the two exchanging species.     

The role of plastids in plant speciation

Understanding the molecular basis of how new species arise is a central question and prime challenge in evolutionary biology and includes understanding how genomes diversify. Eukaryotic cells possess an integrated compartmentalized genetic system of endosymbiotic ancestry. The cellular subgenomes in nucleus, mitochondria and plastids communicate in a complex way and co-evolve. The application of hybrid and cybrid technologies, most notably those involving interspecific exchanges of plastid and nuclear genomes, has uncovered a multitude of species-specific nucleo-organelle interactions. Such interactions can result in plastome-genome incompatibilities, which can phenotypically often be recognized as hybrid bleaching, hybrid variegation or disturbance of the sexual phase. The plastid genome, because of its relatively low number of genes, can serve as a valuable tool to investigate the origin of these incompatibilities. In this article, we review progress on understanding how plastome-genome co-evolution contributes to speciation. We genetically classify incompatible phenotypes into four categories. We also summarize genetic, physiological and environmental influence and other possible selection forces acting on plastid-nuclear co-evolution and compare taxa providing molecular access to the underlying loci. It appears that plastome-genome incompatibility can establish hybridization barriers, comparable to the Dobzhansky-Muller model of speciation processes. Evidence suggests that the plastid-mediated hybridization barriers associated with hybrid bleaching primarily arise through modification of components in regulatory networks, rather than of complex, multisubunit structures themselves that are frequent targets.     

Introgression potential between safflower (Carthamus tinctorius) and wild relatives of the genus Carthamus

Background  

Safflower, Carthamus tinctorius, is a thistle that is grown commercially for the production of oil and birdseed and recently, as a host for the production of transgenic pharmaceutical proteins. C. tinctorius can cross with a number of its wild relatives, creating the possibility of gene flow from safflower to weedy species. In this study we looked at the introgression potential between different members of the genus Carthamus, measured the fitness of the parents versus the F1 hybrids, followed the segregation of a specific transgene in the progeny and tried to identify traits important for adaptation to different environments.     

PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice

Cellular dipeptidyl peptidase IV (DP IV, CD26) and amino-peptidase N (APN, CD13) play regulatory roles in T cell activation and represent potential targets for treatment of inflammatory disorders. We have developed a novel therapeutic strategy, 'peptidase-targeted Immunoregulation' (PETIR?), which simultaneously targets both cellular DP IV and APN via selective binding sites different from the active sites with a single inhibitor. To prove the therapeutic concept of PETIR? in autoimmunity of the central nervous system (CNS), we evaluated the effect of a single substance, PETIR-001, in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. Administration of PETIR-001 significantly delayed and decreased clinical signs of active EAE, when given in a therapeutic manner intraperitoneally from day 15 to day 24 after induction of EAE. Both the acute phase and the first relapse of EAE were markedly inhibited. Importantly, a similar therapeutic benefit was obtained after oral administration of PETIR-001 from day 12 to day 21 after disease induction. Our results demonstrate that PETIR-001 exhibits a therapeutic effect on EAE in SJL/J mice. Thus, PETIR? represents a novel and efficient therapeutic approach for immunotherapy of CNS inflammation.     

Distribution and cellular localization of caldendrin immunoreactivity in adult human forebrain.

We investigated by immunohistochemistry (IHC) the distribution of caldendrin, the founding member of a novel family of neuronal calcium-binding proteins closely related to calmodulin, in human forebrain. Caldendrin immunoreactivity was unevenly distributed, with prominent staining in the paleo- and neocortex, hippocampus, and hypothalamus. With the exception of the hypothalamus, labeling was restricted to the somato-dendritic compartment of neurons. This distribution completely matches that reported in rat, indicating that the cellular function is most likely conserved among species. Therefore, one prerequisite for functional studies in rodent models aimed at elucidation of mechanisms with relevance for humans can be based on the present findings.     

Embryonic and larval development of jundiá (Rhamdia quelen, Quoy and Gaimard, 1824, Pisces, TeleosteI), a South American catfish.

The jundiá (Rhamdia quelen, Quoy and Gaimard) is an endemic South American fish species. Because this species supports cold winters and grows faster during warm months, it has begun to be viewed as an ideal species for fish production in southern South America. In the present study, jundiá oocytes used were obtained by extrusion from females after hormone injection. Soon after hydration, the eggs were transferred to 50 L conic glass incubators, with constant and controlled water influx. Samples of fertilized eggs were transferred to Petri dishes and, examined under a stereoscopic microscope, were spherical, demersal, and non-adhesive with defined perivitelline space and resistant chorion. Cleavage stages occurred during the first 3.5 h. After hatching, larvae were transferred to 200 L glass fiber incubators. First signs of embryo movement were observed 21 h after fertilization; larval eclosion occurred 30.5 h after fertilization. Present findings may provide a basis for studies aimed at determining the complete ontogeny of jundiá and may be useful in eco-toxicological studies.     

The apertospathulidae, a new family of haptorid ciliates (protozoa, ciliophora)

We studied the morphology of three rare haptorid ciliates, using live observation and silver impregnation: Apertospathula verruculifera n. sp., Longispatha elegans n. gen., n. sp., and Rhinothrix porculus (Penard, 1922) n. gen., n. comb. Simple ethanol fixation (50-70%, v/v) is recommended to reveal the ciliary pattern of "difficult" ciliates, such as R. porculus, by protargol impregnation. The three genera investigated have a distinct feature in common, viz., a lasso-shaped oral bulge and circumoral kinety, where the right half is slightly to distinctly longer than the left and the circumoral kinety is open ventrally. Thus, they are united in a new spathidiid family, the Apertospathulidae n. fam., which probably evolved from a Bryophyllum-like ancestor by partial reduction of the oral bulge and circumoral kinety. Apertospathula verruculifera has a wart-like process, the palpus dorsalis, at the anterior end of the dorsal brush. The right branch of the circumoral kinety is only slightly longer than the left one. Longispatha elegans has a straight oral bulge and circumoral kinety, the right branch of which extends to the posterior end of the body while the left branch ends in the anterior third of the body. Rhinothrix porculus, a curious ciliate with a snout-like dorsal elongation of the oral bulge, the palpus oralis, has a highly characteristic ciliary pattern: the oral pattern is as in Longispatha, but the bulge and circumoral kinety extend spirally to the posterior end of the body while the somatic kineties course meridionally. This is achieved by inserting some shortened kineties in the curves of the oral bulge.