A short in-frame deletion in NTRK1 tyrosine kinase domain caused by a novel splice site mutation in a patient with congenital insensitivity to pain with anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). -- Case Presentation: We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G > A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A > G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G > A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A > G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. --Conclusions: We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.

Measures of Plant Surface-areas for Eurasian Watermilfoil and Water Stargrass

Plant surface areas were measured from samples of two common submersed aquatics with widely diverging morphologies: Eurasian watermilfoil ( Myriophyllum spicatum L.) and water stargrass ( Heteranthera dubia (Jacq.) MacM.). Measures for the highly dissected leaves of Eurasian watermilfoil involved development of a regression equation relating leaf length to direct measures of a subsample of leaf parts. Measures for the simple leaves of the stargrass were sums of measured triangles. Stem surfaces for both species were calculated as measured cylinders. Though the means of the stem length and leaf length were larger for stargrass samples, their mean surface area was 95 cm 2 which was less than the 108 cm 2 recorded for Eurasian watermilfoil samples. Relating surface area to dry weight for the stargrass was straightforward, with 1 mg of dry weight yielding an average 0.678 cm 2 of surface area. Biomass measures for the water milfoil were confounded by the additional weight of epiphytic algae persisting on cleaned samples. The results suggest that a lesstime consuming method for surface area measures of plants with highly dissected leaves and a caveat for using biomass measures to estimate surface area in such plants.

[R_Enciso_Concepcion] Levantamiento topográfico de la ermita y el crucero de la Concepción (Enciso, La Rioja)

[ES] Este proyecto tiene una continuación en el siguiente registro:

Stock assessment of protogynous fish: evaluating measures of spawning biomass used to estimate biological reference points

In stock assessments, recruitment is typically modeled as a function of females only. For protogynous stocks, however, disproportionate fishing on males increases the possibility of reduced fertilization rates. To incorporate the importance of males in protogynous stocks, assessment models have been used to predict recruitment not just from female spawning biomass (Sf), but also from that of males (Sm) or both sexes (Sb). We conducted a simulation study to evaluate the ability of these three measures to estimate biological reference points used in fishery management. Of the three, Sf provides best estimates if the potential for decreased fertilization is weak, whereas Sm is best only if the potential is very strong. In general, Sb estimates the true reference points most closely, which indicates that if the potential for decreased fertilization is moderate or unknown, Sb should be used in assessments of protogynous stocks. Moreover, for a broad range of scenarios, relative errors from Sf and Sb occur in opposite directions, indicating that estimates from these measures could be used to bound uncertainty.

Computation of turbulence-generated noise by large-eddy simulation

The hybrid method of large eddy simulation (LES) and the Lighthill analogy is being developed to compute the sound radiated from turbulent flows. The results obtained from the hybrid method are often contaminated by the absence of small scales in LES, since the energy level of sound is much smaller than that of turbulent flows. Previous researches investigate the effects of subgrid sacle (SGS) eddies on the frequency spectra of sound radiated by isotropic turbulence and suggest a SGS noise model to represent the SGS contributions to the frequency spectra. Their investigations are conducted in physical space and are unavoidably influenced by boundary conditions. In this paper, we propose to perform such calculations in Fourier space so that the effects of boundary conditions can be correctly treated. Posteriori tests are carried out to investigate the SGS contribution to the sound. The results obtained recover the -7/2 law within certain wave-number ranges, but under-estimate the amplitudes of the frequency spectra. The reason for the underestimation is also discussed.