Germline mutations in RAD51D confer susceptibility to ovarian cancer

Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.01). The association found here was principally with ovarian cancer, with three mutations identified in the 59 pedigrees with three or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 × 10(-6)). By contrast, we estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). These data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers.     

Bidirectional motility of kinesin-5 motor proteins: structural determinants,cumulative functions and physiological roles

Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942–4954, 2011; Roostalu et al., Science 332:94–99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed. In addition, the essential intracellular functions of kinesin-5 motors in separating spindle poles during mitosis can only be accomplished by plus end-directed motility during antiparallel sliding of the spindle MTs. Thus, the mechanism and possible physiological role of the minus end-directed motility of kinesin-5 motors remain unclear. Experimental and theoretical studies from several laboratories in recent years have identified additional kinesin-5 motors that are bidirectional, revealed structural determinants that regulate directionality, examined the possible mechanisms involved and have proposed physiological roles for the minus end-directed motility of kinesin-5 motors. Here, we summarize our current understanding of the remarkable ability of certain kinesin-5 motors to switch directionality when moving along MTs.     

ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma

Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) = 1.45, P = 1.2 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 10(-6)). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.     

Electron diffraction of the metallic elements in the pineal organ of a freshwater fish,Mystus vittatus (Bloch.)

Summary By electron diffraction pattern the presence of metallic elements, particularly chromium-nickel, chromium phosphide, copper, aluminum-copper and zinc has been shown in the pineal organ of a freshwater teleost,M. vittatus. It is likely that their occurrence within the pineal is due to binding with the neurosecretory material fractions/ligands.The technical assistance of O.N. Srivastava and financial assistance of CSIR, India, are gratefully acknowledged.     

Sterilization of solanaceous hadda, Epilachna vigintioctopunctata F. by irradiating pupae using gamma radiation.

Sterility in males and females was observed in the resulting adults when 3--4-day-old pupae of solanaceous hadda, Epilachna vigintioctopunctata F. were exposed to gamma radiation doses of 2000 rad and 2500 rad. However, at 2500 rad longevity of treated insects was adversely affected.     

Rhythmicity of aminotransferase in the cockroach,Periplaneta americana

Summary Aspartate (AAT) and alanine aminotransferase (AIAT) activities in nervous system and coxal leg muscle of the cockroach showed circadian variations with maximal activity around midnight, alternating with minimal activity at 12.00 noon of the solar day. The enhanced activity levels of the enzymes observed during night dark hours may be related to higher energy requirements during increased locomotor activity of the animals.We thank Prof. K. S. Swami, for providing facilities. The financial help rendered by UGC and CSIR, in the form of Junior (to SV) and Senior (to TPK) Research Fellowships is acknowledged.     

Hepatic silver binding protein (Ag BP) from sparrow (Passer domesticus)

Summary A silver binding protein (Ag BP) has been identified in the liver ofsparrows administered a tracer dose of^110mAg. The protein as purified by gel-filtration shows a major absorption maximum at 260 nm and a minor one at 225 nm. It has a mol.wt of 9500 daltons and is stable when exposed to high temperature (64°C for 15 min) as well as to acidic pH (2.2).