Induction of chromosome abnormalities by reversal of colcemid inhibition in leucocyte cultures

Zusammenfassung Menschliche Leukozyten, die vorher 2 resp. 4 h der Wirkung von Colcemid ausgesetzt worden waren, ergaben in Zellkulturen 45 resp. über 50% Zellen mit 45 oder weniger Chromosomen im Vergleich zu 10% in Kontrollkulturen ohne Colcemid.

---

---

This work is supported financially by Schering Chemicals Ltd., Burgess Hill, Sussex. We would like to thank Dr.A. G. Pitchford for advice and MissE. Gristwood for technical assistance.     

Tritium analyses of groundwater from the Gort Lowland of Western Ireland

Zusammenfassung Grundwasserproben aus der Gort-Ebene (West-Irland) wurden auf Tritium-Gehalt analysiert und die Ergebnisse mit dem bereits bekannten Tritium-Einstrom dieser Gegend verglichen. Registrierungen des «World Precipitation Network» in Wien ergaben den Nachweis eines offenbar langsamen Durchflusses in das Grundwasser-Aquifer-System.

---

---

Acknowledgments. The authors are indebted to the Nuclear Physics Division, Atomic Energy Research Establishment, Harwell (England) for tritium analyses and to Mr.B. R. Payne, Section of Isotope Hydrology, IAEA, Wien (Austria) for providing unpublished tritium data from Valentia for the period 1966 to 1971.     

Cadherin 23 is a component of the tip link in hair-cell stereocilia

Mechanoelectrical transduction, the conversion of mechanical force into electrochemical signals, underlies a range of sensory phenomena, including touch, hearing and balance. Hair cells of the vertebrate inner ear are specialized mechanosensors that transduce mechanical forces arising from sound waves and head movement to provide our senses of hearing and balance; however, the mechanotransduction channel of hair cells and the molecules that regulate channel activity have remained elusive. One molecule that might participate in mechanoelectrical transduction is cadherin 23 (CDH23), as mutations in its gene cause deafness and age-related hearing loss. Furthermore, CDH23 is large enough to be the tip link, the extracellular filament proposed to gate the mechanotransduction channel. Here we show that antibodies against CDH23 label the tip link, and that CDH23 has biochemical properties similar to those of the tip link. Moreover, CDH23 forms a complex with myosin-1c, the only known component of the mechanotransduction apparatus, suggesting that CDH23 and myosin-1c cooperate to regulate the activity of mechanically gated ion channels in hair cells.     

Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors

Inherited defects of base excision repair have not been associated with any human genetic disorder, although mutations of the genes mutM and mutY, which function in Escherichia coli base excision repair, lead to increased transversions of G:C to T:A. We have studied family N, which is affected with multiple colorectal adenomas and carcinoma but lacks an inherited mutation of the adenomatous polyposis coli gene (APC) that is associated with familial adenomatous polyposis. Here we show that 11 tumors from 3 affected siblings contain 18 somatic inactivating mutations of APC and that 15 of these mutations are G:C-->A transversions--a significantly greater proportion than is found in sporadic tumors or in tumors associated with familial adenomatous polyposis. Analysis of the human homolog of mutY, MYH, showed that the siblings were compound heterozygotes for the nonconservative missense variants Tyr165Cys and Gly382Asp. These mutations affect residues that are conserved in mutY of E. coli (Tyr82 and Gly253). Tyrosine 82 is located in the pseudo-helix-hairpin-helix (HhH) motif and is predicted to function in mismatch specificity. Assays of adenine glycosylase activity of the Tyr82Cys and Gly253Asp mutant proteins with 8-oxoG:A and G:A substrates show that their activity is reduced significantly. Our findings link the inherited variants in MYH to the pattern of somatic APC mutation in family N and implicate defective base excision repair in predisposition to tumors in humans.     

SHRIMP dating of zircons from the Caledonian Xiongdian eclogite, western Dabie Mountains, China

This note reports the SHRIMP U-Pb data of zircons from the Caledonian Xiongdian eclogite, western Dabie Mountains. Zircons from the rock occur mainly in garnet and other metamorphic minerals with sharp boundaries and exhibit textures growing under metamorphic conditions. Analyses of 7 grains give ²⁰⁶Pb/²³⁸U ages ranging from 335 to 424 Ma, showing a certain degree of radiogenic lead loss. This suggests a minimum age of (424±5) Ma for the metamorphic zircons, as well as the high-pressure metamorphic event. The outer peripheral zone of a zircon gives ²⁰⁶Pb/²³⁸U age of about 300 Ma. Combined with Sm-Nd, ⁴⁰Ar-³⁹Ar, U-Pb and ²⁰⁷Pb/²⁰⁶Pb ages, the peak metamorphism of the Xiongdian eclogite is documented between 424—480 Ma.     

Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells

Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP(3) receptors had no effect. These data suggest that PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis.     

Three-dimensional structure of the ion-coupled transport protein NhaA

Ion-coupled membrane-transport proteins, or secondary transporters, comprise a diverse and abundant group of membrane proteins that are found in all organisms. These proteins facilitate solute accumulation and toxin removal against concentration gradients using energy supplied by ion gradients across membranes. NhaA is a Na+/H+ antiporter of relative molecular mass 42,000, which is found in the inner membrane of Escherichia coli, and which has been cloned and characterized. NhaA uses the H+ electrochemical gradient to expel Na+ from the cytoplasm, and functions primarily in the adaptation to high salinity at alkaline pH. Most secondary transporters, including NhaA, are predicted to have 12 transmembrane helices. Here we report the structure of NhaA, at 7 A resolution in the membrane plane and at 14 A vertical resolution, determined from two-dimensional crystals using electron cryo-microscopy. The three-dimensional map of NhaA reveals 12 tilted, bilayer-spanning helices. A roughly linear arrangement of six helices is adjacent to a compact bundle of six helices, with the density for one helix in the bundle not continuous through the membrane. The molecular organization of NhaA represents a new membrane-protein structural motif and offers the first insights into the architecture of an ion-coupled transport protein.