DNA copy number gains in head and neck squamous cell carcinoma.

Gene amplification, a common mechanism for oncogene activation in cancer, has been used as a tag for the identification of novel oncogenes. DNA amplification is frequently observed in head and neck squamous cell carcinoma (HNSCC) and potential oncogenes have already been reported. We applied restriction landmark genome scanning (RLGS) to study gene amplifications and low-level copy number changes in HNSCC in order to locate previously uncharacterized regions with copy number gains in primary tumor samples. A total of 63 enhanced RLGS fragments, indicative of DNA copy number changes, including gains of single alleles, were scored. Enhanced sequences were identified from 33 different chromosomal regions including those previously reported (e.g. 3q26.3 and 11q13.3) as well as novel regions (e.g. 3q29, 8q13.1, 8q22.3, 9q32, 10q24.32, 14q32.32, 17q25.1 and 20q13.33). Furthermore, our data suggest that amplicons 11q13.3 and 3q26.3-q29 may be divided into possibly two and three independent amplicons, respectively, an observation supported by published microarray expression data.

The molecular mechanism of force generation in striated muscle.

An electrostatic mechanism for force generation in muscle is proposed which does not require bond formation between thick and thin filaments nor movement of the cross bridges. The myosin heads, which project from the thick filaments and touch the thin filaments, possess a high negative surface charge density. Owing to their large dielectric increment, the thin filaments are polarized by the electric field generated by the myosin heads. The polarized thin filaments tend to move toward the center of the sarcomere. Myosin ATPase activity is increased in the overlap region to maintain the negative surface potential. Thus, ATP hydrolysis provides the energy for shortening. Calculations give estimated tensions generated by this model that are comparable to those observed experimentally for vertebrate striated muscle.

Detection of jitter in intertarget spacing by the big brown bat Eptesicus fuscus.

We trained bats to detect intertarget jitter, i.e., relative motion between two virtual (electronically synthesized) targets. Both targets were themselves moving with respect to nearby objects (e.g., the microphone and speaker used to create the virtual targets) so that the only reliable cue available to the bats was variation in intertarget spacing. Given a target at 80 cm and another at 95, 110 or 125 cm, the threshold for intertarget jitter (ITJ) of the two bats tested was < 10 microseconds, corresponding to < 1.7 mm of range. When, for one bat, we increased the range instability of the targets by adding varying amounts of random range shift to the target complex (while preserving the correct intertarget spacing), ITJ threshold worsened. When we presented three targets, one of which was jittering, the bat's threshold improved to 0.9 microsecond (equivalent to 0.16 mm). If no second target was presented, i.e., if the task was to detect jitter added to a single moving target, then bats' jitter threshold was very high (> 200 microseconds). Eptesicus fuscus appears to be very good at detecting changes in intertarget spacing, which might prove valuable for detecting targets moving relative to the background or for constructing a spatial image of a complex environment.

Gene expression in papillary thyroid carcinoma reveals highly consistent profiles.

Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligo-based DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase-PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8/8 tumors for 24 genes and in 7/8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase-PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6/6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49/52 and 39/52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7/8 tumors for eight genes and decreased in 6/8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use.