Prestin, the fifth member of the anion transporter family SLC26, is the outer hair cell molecular motor thought to be responsible for active mechanical amplification in the mammalian cochlea. Active amplification is present in a variety of other auditory systems, yet the prevailing view is that prestin is a motor molecule unique to mammalian ears. Here we identify prestin-related SLC26 proteins that are expressed in the auditory organs of nonmammalian vertebrates and insects. Sequence comparisons revealed the presence of SLC26 proteins in fish (Danio, GenBank accession no. AY278118, and Anguilla, GenBank accession no. BAC16761), mosquitoes (Anopheles, GenBank accession nos. EAA07232 and EAA07052), and flies (Drosophila, GenBank accession no. AAF49285). The fly and zebrafish homologues were cloned and, by using in situ hybridization, shown to be expressed in the auditory organs. In mosquitoes, in turn, the expression of prestin homologues was demonstrated for the auditory organ by using highly specific riboprobes against rat prestin. We conclude that prestinrelated SLC26 proteins are widespread, possibly ancestral, constituents of auditory organs and are likely to serve salient roles in mammals and across taxa.T he mammalian cochlea achieves its sensitivity and frequency selectivity by a process of active mechanical amplification that is based on voltage-dependent contractions of outer hair cells (for reviews see refs. 1-5). A molecular motor driving this cellular electromotility has been identified recently to be prestin, a membrane-based molecule that seems to change its conformation in a voltage-dependent way (6-9).Apart from mammals, active mechanical amplification also improves hearing in other animals, i.e., lower tetrapods (for reviews see refs. 10 and 11) and insects (12, 13). In these animals, mechanical amplification is deemed to involve motor mechanisms other than prestin; proposed candidate motors include myosin-based adaptation motors and Ca 2ϩ -dependent reclosure motions of mechanotransduction channels in lower tetrapods (11), whereas microtubule-dependent, ciliary motors have been indicated to bring about active mechanical amplification in the auditory systems of insects (13). Hence, different taxa may have solved the need for sensitive hearing in analogous ways, with the prestin motor being an evolutionary innovation unique to the mammalian cochlea.Prestin, encoded by 18 exons, shows highest homology to other members of the newly discovered solute carrier (SLC) anion transport family SLC26 within the sulfate transport region between residue 98-135 (6). Amino acid sequence and genestructure analysis identified prestin to be the fifth member of this family (prestin, SLC26A5) (14). Apart from prestin, this family includes, among others, pendrin (PDS, SLC26A4) (15), downregulated in adenoma (DRA, SLC26A3) (16), diastrophic dysplasia sulfate transporter (DTDST, SLC26A2) (17), and SLC26A6 (18). Functionally, SLC26 proteins have been proposed to serve as chloride-iodide transporters, Cl Ϫ ͞HCO 3 Ϫ excha...

Five patients had persistent, pulling pain in the sternum, clavicles, and upper ribs that was exacerbated by cold and dampness. Clublike, symmetrical enlargement of the clavicles was seen and, in two patients, venous congestion of the upper half of the body. All patients had a constantly elevated erythrocyte sedimentation rate. Radiologically there was symmetrical hyperostosis of the sternal and middle portions of the clavicles, synostosis of the sternoclavicular joints, a widened and thickened sternum, and varying degrees of involvement of the upper ribs. X-ray findings did not change over several years. Phlebography showed bilateral subclavian vein occlusion in three patients and unilateral occlusion in one. Biopsies of the clavicles showed a characteristic hyperostotic sclerosis of the spongiosa. The cause of this sternocostoclavicular hyperostosis is unknown, but clinical, radiologic, and histologic findings indicate that it may represent a distinct, hitherto undescribed entity.

Persistent pulling pain in the sternum, clavicles and both first ribs, especially during cold and wet weather, necessitated medical investigations and treatment in 3 patients. Externally a cylindrical or spindle-shaped swelling of the clavicles was noticeable and two patients had signs of superior caval obstruction in addition. X-rays showed hyperostosis of the sternal and middle part of the clavicle, synostosis of the sternoclavicular joints with involvement of the two first ribs as well as a thickening and increase in breadth of the sternum. In one patient there were additional swellings of the first to fourth ribs bilaterally. During the period of observation there was no radiological progression of the bone disease. Apart from a consistently raised erythrocyte sedimentation rate blood chemistry was normal. The sterno-costo-clavicular hyperostosis led to bilateral occlusion of the subclavian veins with resulting upper venous congestion in two patients. Histology of the biopsy samples showed a characteristic hyperostotic spongiosclerosis in all three cases. The cause of this sterno-costo-clavicular hyperostosis is unknown. Clinical, radiological and histological findings indicate that it is a uniform disease which has not previously been described.

A case is described in which bilateral subclavian vein occlusion was caused by fusiform expansion of the clavicle with hyperostosis, ankylosis of the sterno-clavicular joint, widening and thickening of the sternum and ossification of the costal cartilage of the first ribs. Histologically this proved to be due to an hyperostotic spongiosclerosis.