Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome?

In Down syndrome there is a high incidence of overt or subclinical hypothyroidism as well as some immunological defects, early thymic involution associated to low serum zinc levels. Zinc supplementation to the diet has been reported to transiently improve thymic function; moreover thymic function has been shown to be in relation with the pituitary-thyroid axis. The aim of this study was to evaluate if, in Down patients, zinc therapy could improve also thyroid function, by determining serum levels of total and free thyroid hormones and basal TSH levels. In 52 patients studied, we found a high incidence of subclinical hypothyroidism (30%); in 17 patients treated with zinc sulphate we showed a reduction of FT3. More significantly, we detected 9 patients with low zinc levels in which zinc supplementation improved thyroid function, thus reducing the incidence of subclinical hypothyroidism.     

A population ‘consensus’, partial linkage map of Picea abies Karst. based on RAPD markers

 We built a “consensus” partial linkage map based on RAPD markers using 48 sibships of eight megagametophytes each from a natural population of Norway spruce. A RAPD linkage map for a single individual from the same population had previously been constructed. Using 30 random decamers that had yielded 83 RAPD markers in the single-tree map, eight megagametophytes for each of the 48 sibships were screened. The linkage relationship among markers was estimated considering each family of eight megagametophytes as a progeny of a phase-unknown backcross mating between a heterozygous mother and a fictitious ‘recessive’ father. Markers were assigned to windows using LOD=2.0 and θ=0.4 as thresholds, and ordered using a criterion of interval support ≥2.0. For eight “windows” of recombination selected on the single-tree map, we investigated the consistency of marker order in the two maps. We adopted restrictive criteria for rejecting co-linearity between the two locus orders. For each window we imposed the most likely locus order obtained from one data set to the other (and vice versa), obtaining two symmetrical log-likelihood differences. We considered the hypothesis of co-linearity rejected when both symmetrical differences were significant (ΔLOD>3.0). By bootstrapping a subset of markers for each window (highly informative, ‘framework’ loci chosen on the previous single-tree map using a matrix correlation method) the sampling variability of the single-tree and population maps was estimated. As expected the population map was affected by a larger variability than the single-tree map. Heterogeneity in pairwise recombination fractions among groups of sibship revealed a (possible) alternative genomic arrangement detected within a single recombination window. Received : 4 January 1997 / Accepted : 24 January 1997     

Dimensions in solution of pyridoxylated apohemoglobin

Human apohemoglobin was labeled at Val-beta 1 with pyridoxamine 5'-phosphate. Correlation times were evaluated from steady-state fluorescence anisotropy and lifetime measurements upon quenching with KI. Multiple correlation times were present in the system with a major component of 23.3 ns and a minor component of less than 0.1 ns. The initial depolarization produced by these fast motions occurred in a cone with a semiangle near 33 degrees. The sedimentation velocity and circular dichroism spectra of pyridoxal 5'-phosphate labeled apohemoglobin were very similar to those of unlabeled apohemoglobin. Addition of 8-anilino-1-naphthalenesulfonate did not modify these parameters. Energy transfer of fluorescence was measured between the label, pyridoxamine 5'-phosphate, positioned at Val-beta 1, as donor, and 8-anilino-1-naphthalenesulfonate, bound inside the heme pocket, as acceptor. A quantum yield of 0.21 was measured for labeled apohemoglobin with a standard of pyridoxamine 5'-phosphate. Quenching of the lifetime and of the emission of the donor in the presence of acceptor was measured at 390 nm upon excitation at 313 nm. From these parameters, and on assumption of a random orientation of the fluorophores, an average distance of about 25 A was estimated between the two probes. Numerical correction for 85% saturation of the donor with acceptor produced distances near 23 A for the quenching of emission intensity and near 19 A for the quenching of lifetimes. In the tridimensional model of deoxyhemoglobin, the distance between Val-beta 1 and the nearest iron is about 22 A. Transfer to acceptors positioned in the alpha subunits was negligible. Taking into account the dimensions of the probes, it appears that removal of heme and the consequent loss of helical structure of the system did not produce an expansion of the beta subunits.     

Perthamide C Inhibits eNOS and iNOS Expression and Has Immunomodulating Activity In Vivo

Here we have characterized perthamide C, a cyclopeptide from a Solomon Lithistid sponge Theonella swinhoei, which displays an anti-inflammatory/immunomodulatory activity. The study has been performed using the carragenan-induced mouse paw edema that displays an early (0–6 h) and a late phase (24–96 h). Perthamide C significantly inhibits neutrophils infiltration in tissue both in the early and late phases. This effect was coupled to a reduced expression of the endothelial nitric oxide synthase (eNOS) in the early phase while cyclooxygenase-1 and 2 (COX-1, COX-2), and inducible NOS (iNOS) expression were unaffected. In the late phase perthamide C reduced expression of both NOS isoforms without affecting COXs expression. This peculiar selectivity toward the two enzymes deputed to produce NO lead us to investigate on a possible action of perthamide C on lymphocytes infiltration and activation. We found that perthamide C inhibited the proliferation of peripheral lymphocytes, and that this effect was secondary to its metabolic activation in vivo. Indeed, in vitro perthamide C did not inhibit proliferation as opposite to its metabolite perthamide H.In conclusion, perthamide C selectively interferes with NO generation triggered by either eNOS or iNOS without affecting either COX-1 or COX-2. This in turn leads to modulation of the inflammatory response through a reduction of vascular permeability, neutrophil infiltration as well as lymphocyte proliferation.     

Smooth Pursuit Eye Movements in Children with Strabismus and in Children with Vergence Deficits

Purpose

The objective of our study was to examine horizontal smooth pursuit performance in strabismic children and in children with vergence deficits, and to compare these data with those recorded in a group of control age-matched children.

Methods

Binocular eye movements were recorded by video-oculography in ten strabismic children (mean age: 9.8±0.8) and seven children with vergence deficits (mean age: 10.8±0.6). Data were compared to that of age-matched control children (mean age: 9.8±0.8 years).

Results

Catch-up saccades amplitude in strabismic children and in children with vergence deficits were significantly higher than in control age-matched children. Moreover, in strabismic children the amplitude of catch-up saccades was significantly higher in rightward than in leftward direction. The number of catch-up saccades was also significantly higher in rightward than in leftward direction. The gain value of pursuits in rightward direction was significantly higher in the right eye than in the left one; for the right eye, the gain value was significantly higher in rightward than in leftward direction. Binocular coordination of pursuit was better in control age-matched children than in children with vergence deficits and than in strabismic children.

Conclusions

Binocular coordination of pursuit is abnormal in children with vergence deficits and worse in strabismic children. Binocular vision plays an important role in improving binocular coordination of pursuit.     

Ecological Modeling from Time-Series Inference: Insight into Dynamics and Stability of Intestinal Microbiota

The intestinal microbiota is a microbial ecosystem of crucial importance to human health. Understanding how the microbiota confers resistance against enteric pathogens and how antibiotics disrupt that resistance is key to the prevention and cure of intestinal infections. We present a novel method to infer microbial community ecology directly from time-resolved metagenomics. This method extends generalized Lotka–Volterra dynamics to account for external perturbations. Data from recent experiments on antibiotic-mediated Clostridium difficile infection is analyzed to quantify microbial interactions, commensal-pathogen interactions, and the effect of the antibiotic on the community. Stability analysis reveals that the microbiota is intrinsically stable, explaining how antibiotic perturbations and C. difficile inoculation can produce catastrophic shifts that persist even after removal of the perturbations. Importantly, the analysis suggests a subnetwork of bacterial groups implicated in protection against C. difficile. Due to its generality, our method can be applied to any high-resolution ecological time-series data to infer community structure and response to external stimuli.