Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome

<p>Abstract</p> <p>Background</p> <p>Recessive mutations of fibroblast growth factor 3 (FGF3) can cause LAMM syndrome (OMIM 610706), characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia.</p> <p>Methods</p> <p>We performed a prospective molecular genetic and clinical study of families segregating hearing loss linked to <it>FGF3 </it>mutations. Ten affected individuals from three large Pakistani families segregating <it>FGF3 </it>mutations were imaged with CT, MRI, or both to detect inner ear abnormalities. We also modeled the three dimensional structure of FGF3 to better understand the structural consequences of the three missense mutations.</p> <p>Results</p> <p>Two families segregated reported mutations (p.R104X and p.R95W) and one family segregated a novel mutation (p.R132GfsX26) of <it>FGF3</it>. All individuals homozygous for p.R104X or p.R132GfsX26 had fully penetrant features of LAMM syndrome. However, recessive p.R95W mutations were associated with nearly normal looking auricles and variable inner ear structural phenotypes, similar to that reported for a Somali family also segregating p.R95W. This suggests that the mild phenotype is not entirely due to genetic background. Molecular modeling result suggests a less drastic effect of p.R95W on FGF3 function compared with known missense mutations detected in fully penetrant LAMM syndrome. Since we detected significant intrafamilial variability of the inner ear structural phenotype in the family segregating p.R95W, we also sequenced <it>FGF10 </it>as a likely candidate for a modifier. However, we did not find any sequence variation, pointing out that a larger sample size will be needed to map and identify a modifier. We also observed a mild to moderate bilateral conductive hearing loss in three carriers of p.R95W, suggesting either a semi-dominant effect of this mutant allele of <it>FGF3</it>, otitis media, or a consequence of genetic background in these three family members.</p> <p>Conclusions</p> <p>We noted a less prominent dental and external ear phenotype in association with the homozygous p.R95W. Therefore, we conclude that the manifestations of recessive <it>FGF3 </it>mutations range from fully penetrant LAMM syndrome to deafness with residual inner ear structures and, by extension, with minimal syndromic features, an observation with implications for cochlear implantation candidacy.</p

Interactive effects of pesticide exposure and habitat structure on behavior and predation of a marine larval fish

Coastal development has generated multiple stressors in marine and estuarine ecosystems, including habitat degradation and pollutant exposure, but the effects of these stressors on the ecology of fishes remain poorly understood. We studied the separate and combined effects of an acute 4 h sublethal exposure of the pyrethroid pesticide esfenvalerate and structural habitat complexity on behavior and predation risk of larval topsmelt (Atherinops affinis). Larvae were exposed to four nominal esfenvalerate concentrations (control, 0.12, 0.59, 1.18 μg/L), before placement into 12 L mesocosms with a three-spine stickleback (Gasterosteus aculeatus) predator. Five treatments of artificial eelgrass included a (1) uniform and (2) patchy distribution of eelgrass at a low density (500 shoots per m(2)), a (3) uniform and (4) patchy distribution of eelgrass at a high density (1,000 shoots per m(2)), and (5) the absence of eelgrass. The capture success of predators and aggregative behavior of prey were observed in each mesocosm for 10 min of each trial, and mortality of prey was recorded after 60 min. Exposure to esfenvalerate increased the proportion of larvae with swimming abnormalities. Surprisingly, prey mortality did not increase linearly with pesticide exposure but increased with habitat structure (density of eelgrass), which may have been a consequence of compensating predator behavior. The degree of prey aggregation decreased with both habitat structure and pesticide exposure, suggesting that anti-predator behaviors by prey may have been hampered by the interactive effects of both of these factors

Influence of some activators of alcoholic fermentation on amino acids composition and fermentability of <em>Vitis vinifera</em> cv. Muscadelle musts from permanent grass covered plots

The duration of alcoholic fermentation was very different with the no-tillage trial must and the other grass-cover musts. The duration was found to be quite closely correlated to the content of nitrogen components in the must and more particularly to amino acids. Several supplementations were tested during the two experimental years. It should be noted that European legislation doesn’t allow the use of some of them. The durations of alcoholic fermentation of musts with these added activators were shortened. Again, fermentation duration was quite closely correlated to the content of nitrogen components in the must and more particularly to amino acids. It is noteworthy that numerous kinds of amino acids were present. Some of them were very important either by virtue of their nature or their concentration levels. A statistical analysis showed some composition similarities between some musts, but there were composition differences which would explain their fermentation kinetics

Relation between kinetic of alcoholic fermentation and must nitrogen content. Influence of nitrogen fertilization on <em>Vitis vinifera</em> cv Muscadelle with permanent grass cover. Nature and concentration levels of some amino acids of musts

An experiment concerning the introduction of nitrogen fertilization on permanent grass cover was undertaken in 1995. This was done in order to determine both the role and the influence of nitrogen on the fermentability of must. Located in the Sainte-Foy La Grande area, the plot studied has a deep silty soil. The cultivar Muscadelle was grafted on the 3309 C rootstock. Four tests with several N-fertilizations were compared : 1 (no-tillage and 0 kg N/ha/year), 2 (permanent grass cover without N-fertilization), 3 (permanent grass cover and 30 kg N/ha/year) and 4 (permanent grass cover and 60 kg N/ha/year). Nitrogen was added at springtime, on the total interrow area as weIl as on the narrow strip around the vines. The grass cover (with or without N-fertilization) had a great effect on yield : it decreased the latter by about 38 percent compared to the no-tillage trial. Moreover, the total acidity values were lower for the musts in trials 2,3 and 4 than in the control 1. Inversely, the initial sugar values were greater in the grass cover trials. The duration of alcoholic fermentation was very different with the no-tillage test and the others : 17 days were necessary for the first, and 42 to 50 for the other musts. This parameter was quite cIosely correlated to the content of nitrogen composites in the must and more particularly to amino acids. The global amino acid contents of must and wine were higher in test 1 than in the others. It is noteworthy that numerous kinds of amino acids were present but it seems likely that some of them were very important by virtue of their nature or their concentration levels. Among the principal amino acids, proline represented at least 20 percent of the global amino acids content for musts 2 and 4, and 14 to 19 percent for musts 3 and 1. Arginine was present only in the must of the grass-cover trials. Proline, arginine, alanine, asparagine/glutamine and aspartic acid represented about 50 to 60 percent of the global amino acids content of the musts. A statistical analysis of the four musts and wines showed a clear differentiation between the no-tillage trial (1) and the others. However, there seemed to be some composition similarities between musts 1 and 4, but the fermentation kinetic was different probably because of the lack of, or the lower concentration of, some of amino acids in case 4

Influence of nitrogen fertilization on <em>Vitis vinifera</em> cv. Merlot with permanent grass cover. (Nitrogen content, nature and concentration levels of some amino acids of musts and wines)

Since 1995, it has heen running an experiment on the introduction of nitrogen fertilization on permanent grass cover. This has been done in order to determine both the role and the influence of nitrogen on the fermentability of the must. Located south of Saint-Emilion, the plot area studied has a regular, sandy, clayey soil 60 centimeters deep. The cultivar Merlot is grafted on the Riparia Gloire from Montpellier rootstock. Five N- fertilizations were compared : T (0 kg N/ha/year), A (30 kg N/ha/year), 8 (60 kg N/ha/year), C ( 90 kg N/ha/year), and D (45 kg N/ha at springtime and 45 kg N/ha at flowering period). For the different N-fertilizations, the numher of clusters per vine was the same for the two experimental years. The mean cluster weight allowed for evaluating the nitrogen effect on the yield. Nitrogen fertilization on the permanent grass cover in the vineyard depends upon climatic conditions in the spring and, more specifically, upon the rainfall pattern. Varietal vigor can he increased or decreased with the level of nitrogen. However, in all cases studied, late contribution of nitrogen was found to he harmful. In fact, most nitrogen added at springtime was used by the grass cover and the competitiveness of the latter was increased. Only test « C » proved to be adequate to satisfy both vineyard and grass cover needs (this is shown in the study of the pruning wood weight variation compared to the standard « T»). The duration of alcoholic fermentation is quite closely correlated to the content of nitrogen composites in the must and more particularly in amino acids. The global amino acid contents of musts and wines were higher in 1996 than in 1995, but in this last case more numerous kinds of amino acids were present. However, for both years studied, proline represented at least 50 percent of the global amino acids content. A statistical analysis on the five N-fertilizations showed a clear differentiation between the two vintages studied ; that is to say, each vintage was identified by specific amino acid profiles. This « vintage » effect was proved by tasting results