Cloning of a cDNA for the Human Cell Adhesion Kinase β

Cell adhesion kinase beta (CAKbeta) is the second protein-tyrosine kinase (PTK) of the focal adhesion kinase (FAK) subfamily with large N- and C-domains in addition to the central kinase domain but without Src homology 2 and 3 (SH-2 and SH-3) domains. In this paper, cloning and sequencing of a cDNA encoding human CAKβ are described. A full-length clone (clone B) contained 4,157- base pairs of human CAKβ cDNA including 243-base pairs of the 5\u27-untranslated sequence and 881-base pairs of the 3\u27-untranslated sequence with a polyadenyla-tion signal (ATTAAA). The clone B of human CAKβ cDNA has an open read-ing frame encoding 1009 amino acid residues ; the human CAKβ has the same number of amino acid residues in the N-, C-, and kinase-domains as rat CAKβ . The amino acid sequence of human CAKβ is 95.4% identical with that of rat CAKβ . The species difference is most prominent in the C-domain. All three previously-recognized, subfamily-specific residues in the kinase domains of FAK and the rat CAKβ are also found in the human CAKβ . The residues V??? and A???, which have been considered to be characteristic to CAKβ , are found to be conserved also in the human CAK? . It has been postulated that CAKβ is important as a docking protein. The autophosphorylation site and also the ligand site to the SH-2 domains of the Src-family PTKs, Y???AEI, are found to be conserved in the human CAKβ . The ligand sequence for the Grb2 SH-2 domain, Y???HNV of the rat CAKβ , is found functionally conserved in the human CAKβ , Y???LNV. The third ligand sequence, E???PPPKPSR, participating in the binding to the SH-3 domains of pp130cas and Efs, is also found conserved in the human CAKβ . The extreme N- terminal 88 amino acid residues of the rat CAKβ were previously found entirely different from FAK and found unique to CAK? . Ninety four percent of those 88 residues in the human CAKβ are found identical with the rat CAKβ . This high sequence homology strongly suggeststhat this region is involved in the specific function of CAKβ different from FAK

Cutaneous symptoms such as acneform eruption and pigmentation are closely associated with blood levels of 2,3,4,7,8-penta-chlorodibenzofurans in Yusho patients, using data mining analysis

<p>Abstract</p> <p>Background</p> <p>Yusho an intoxication caused by oral dioxins and polychlorinated biphenyls occurred in 1968. Patients suffered from various systemic symptoms, including general fatigue, nausea, muscular and articular pain, acneform eruptions, black comedones, cutaneous and oral pigmentation, and increased eye discharge. The major causative factor was the contamination of rice oil with 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF). Recent technical advances have allowed us to measure blood levels of PeCDF. However, there is little information on which symptoms and laboratory data are directly associated with PeCDF levels.</p> <p>Methods</p> <p>Yusho patients underwent annual medical check-ups from 2001 to 2003. Blood PeCDF levels were correlated with the presence or absence of symptoms in medical, hematological, dermatological, dental and ophthalmological examinations. This study analyzed all combinations by using the association analysis. This is the most suitable method to evaluate all combinations of the data comprehensively. This method was used to determine the rate of patients with high PeCDF level in the population with each symptom, and to extract combinations of three symptoms which were strongly associated with high PeCDF level.</p> <p>Results and Conclusion</p> <p>The rate of the patients with high PeCDF level was high in populations with high uric acid, black comedones (face), second highest quartile of age, or high urea nitrogen. The combination of three symptoms associated with the highest rate of patients with high PeCDF level was "high uric acid, female sexuality, and history of acneform eruptions", followed by "history of Yusho in and after 1968, high cholesterol level, and subjective symptoms." This analysis newly suggested that PeCDF concentration may be associated with history of dermatological symptoms, high uric acid, and elevated erythrocyte sedimentation rate.</p

Relation between biomolecular dissociation and energy of secondary electrons generated in liquid water by fast heavy ions

In this work, we measured and simulated the dissociation of biomolecules in liquid water induced by secondary electrons ejected from water molecules during fast heavy-ion irradiation. We calculated the energy spectra of secondary electrons generated along carbon ion tracks in liquid water in the Bragg peak region. The calculation was done using the Particle and Heavy Ion Transport code System (PHITS) in carbon track structure mode. This mode enables simulation of inelastic collisions along a carbon ion track based on the cross sections considered in the Monte Carlo code KURBUC. To understand the biomolecular dissociation processes in our previous MeV-SIMS experiments with microdroplet targets of glycine solution, we calculated the collision spectra of secondary electrons produced near liquid surfaces using PHITS. Furthermore, we examined the relationship between the secondary electron energy and formation of positive and negative glycine fragments. The results showed that the formation of methylene amine cations is caused by secondary electrons with energies of 13–100 eV. The formation of glycine-related negative ions such as cyanide anion, formate anion, and deprotonated glycine was found to be caused by low-energy (less than 13 eV) secondary electrons. These ions are known products of dissociative electron attachment