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.

A short survey of the environment at the dumping site for Santa Cruz Harbor dredging and A study of seaward dipping internal structures in marine ripple marks at Whaler's Cove, California. Annual report, Part 4, August 1972

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Short communication: Rapid separation of cis9, trans11- and trans7,cis9-18:2 (CLA) isomers from ruminant tissue using a 30 m SLB-IL111 ionic column

[EN]Rumenic acid (cis9,trans11-18:2) is the main natural isomer of conjugated linoleic acid (CLA). Rumenic acid has many purported health benefits, but effects of most other CLA isomers are unknown. Typically trans7,cis9-18:2 is the second most abundant CLA isomer, but it co-elutes with rumenic acid on conventional polar gas chromatography (GC) columns, requiring complimentary analysis with silver-ion high performance liquid chromatography (Ag(+)-HPLC). Herein we report a rapid method for analyzing rumenic acid and trans7,cis9-18:2 using a 30 m ionic-liquid GC column. Optimal resolution of the two CLA isomers was at 145 degrees C and analysis of backfat from barley-fed cattle compared well with GC/Ag(+)-HPLC (y =0.978x - 0.031, r =0.985, P <0.001).

O legislativo e política pública de enfrentamento do uso do crack

Analisa a política pública apresentada para combater, tratar e reinserir o dependente de drogas ilícitas, especificamente o usuário do crack (substância derivada da pasta da cocaína) no seio da sociedade

A Finite Element Analysis of a Crack Penetrating or Deflecting into an Interface in a Thin Laminate

The crack tip driving force of a crack growing from a pre-crack that is perpendicular to and terminating at an interface between two materials is investigated using a linear fracture mechanics theory. The analysis is performed both for a crack penetrating the interface, growing straight ahead, and for a crack deflecting into the interface. The results from finite element calculations are compared with asymptotic solutions for infinitesimally small crack extensions. The solution is found to be accurate even for fairly large amounts of crack growth. Further, by comparing the crack tip driving force of the deflected crack with that of the penetrating crack, it is shown how to control the path of the crack by choosing the adhesion of the interface relative to the material toughness.

Short-Term Nonlinear Response of Tension Leg Platform in Random Sea Waves

Most of the existing mathematical models for analyzing the dynamic response of TLP are based on explicit or implicit assumptions that motions (translations and rotations) are small magnitude. However, when TLP works in severe adverse conditions, the a priori assumption on small displacements may be inadequate. In such situation, the motions should be regarded as finite magnitude. This paper will study stochastic nonlinear dynamic responses of TLP with finite displacements in random waves. The nonlinearities considered are: large amplitude motions, coupling the six degrees-of-freedom, instantaneous position, instantaneous wet surface, free surface effects and viscous drag force. The nonlinear dynamic responses are calculated by using numerical integration procedure in the time domain. After the time histories of the dynamic responses are obtained, we carry out cycle counting of the stress histories of the tethers with rain-flow counting method to get the stress range distribution.

Two-phase Flow in Fuel Cells in Short-term Microgravity Condition

A visual observation of liquid-gas two-phase flow in anode channels of a direct methanol proton exchange membrane fuel cells in microgravity has been carried out in a drop tower. The anode flow bed consisted of 2 manifolds and 11 parallel straight channels. The length, width and depth of single channel with rectangular cross section was 48.0 mm, 2.5 mm and 2.0 mm, respectively. The experimental results indicated that the size of bubbles in microgravity condition is bigger than that in normal gravity. The longer the time, the bigger the bubbles. The velocity of bubbles rising is slower than that in normal gravity because buoyancy lift is very weak in microgravity. The flow pattern in anode channels could change from bubbly flow in normal gravity to slug flow in microgravity. The gas slugs blocked supply of reactants from channels to anode catalyst layer through gas diffusion layer. When the weakened mass transfer causes concentration polarization, the output performance of fuel cells declines.

Discontinuous growth mechanisms of mode II crack under high-speed impact conditions

A recoverable plate impact testing technology has been used for studying the growth mechanisms of mode II crack. The results show that interactions of microcracks ahead of a crack tip cause the crack growth unsteadily. Failure mode transitions of materials were observed. Based on the observations, a discontinuous crack growth model was established. Analysis shows that the shear crack grows unsteady as the growth speed is between the Rayleigh wave speed c(R) and the shear wave speed c(s); however, when the growth speed approaches root 2c(s), the crack grows steadily. The transient microcrack growth makes the main crack speed to jump from subsonic to intersonic and the steady growth of all the sub-cracks leads the main crack to grow stably at an intersonic speed.

Subsonic interface crack with crack face contact

A steady-state subsonic interface crack propagating between an elastic solid and a rigid substrate with crack face contact is studied. Two cases with respective to the contact length are considered, i.e., semi-infinite and finite crack face contact. Different from a stationary or an open subsonic interface crack, stress singularity at the crack tip in the present paper is found to be non-oscillatory. Furthermore, in the semi-infinite contact case, the singularity of the stress field near the crack tip is less than 1/2. In the finite contact case, no singularity exists near the crack tip, but less than 1/2 singularity does at the end of the contact zone. In both cases, the singularity depends on the linear contact coefficient and the crack speed. Asymptotic solutions near the crack tip are given and analyzed. In order to satisfy the contact conditions, reasonable region of the linear contact coefficient is found. In addition, the solution predicts a non-zero-energy dissipation rate due to crack face contact.

Study on fatigue crack nucleation of electrodeposited nanocrystalline nickel

The mechanism of fatigue crack nucleation for nanocrystalline (nc) nickel was experimentally investigated in this paper. The samples of electrodeposited ne nickel were loaded cyclically by using a three point bending instrument at first. Then, atomic force microscopy (AFM) was used to scanning the sample surface after fatigue testing. The results indicated that, after fatigue testing, there are vortex-like cells with an average size of 108nm appeared along the crack on nc nickel sample. And, the roughness of sample surface increased with the maximum stress at the surface.