Alopecia in a Viable Phospholipase C Delta 1 and Phospholipase C Delta 3 Double Mutant

BACKGROUND: Inositol 1,4,5trisphosphate (IP(3)) and diacylglycerol (DAG) are important intracellular signalling molecules in various tissues. They are generated by the phospholipase C family of enzymes, of which phospholipase C delta (PLCD) forms one class. Studies with functional inactivation of Plcd isozyme encoding genes in mice have revealed that loss of both Plcd1 and Plcd3 causes early embryonic death. Inactivation of Plcd1 alone causes loss of hair (alopecia), whereas inactivation of Plcd3 alone has no apparent phenotypic effect. To investigate a possible synergy of Plcd1 and Plcd3 in postnatal mice, novel mutations of these genes compatible with life after birth need to be found. METHODOLOGY/PRINCIPAL FINDINGS: We characterise a novel mouse mutant with a spontaneously arisen mutation in Plcd3 (Plcd3(mNab)) that resulted from the insertion of an intracisternal A particle (IAP) into intron 2 of the Plcd3 gene. This mutation leads to the predominant expression of a truncated PLCD3 protein lacking the N-terminal PH domain. C3H mice that carry one or two mutant Plcd3(mNab) alleles are phenotypically normal. However, the presence of one Plcd3(mNab) allele exacerbates the alopecia caused by the loss of functional Plcd1 in Del(9)olt1Pas mutant mice with respect to the number of hair follicles affected and the body region involved. Mice double homozygous for both the Del(9)olt1Pas and the Plcd3(mNab) mutations survive for several weeks and exhibit total alopecia associated with fragile hair shafts showing altered expression of some structural genes and shortened phases of proliferation in hair follicle matrix cells. CONCLUSIONS/SIGNIFICANCE: The Plcd3(mNab) mutation is a novel hypomorphic mutation of Plcd3. Our investigations suggest that Plcd1 and Plcd3 have synergistic effects on the murine hair follicle in specific regions of the body surface

Nanobuckling And X-Ray Photoelectron Spectra Of Carbyne-Rich Tetrahedral Carbon Films Deposited By Femtosecond Laser Ablation At Cryogenic Temperatures

The growth, surface morphology, and electronic binding states of diamondlike films deposited by femtosecond laser ablation on Si wafers at 77 K have been studied in order to elucidate the mechanical properties of this material. Nanoscale buckling has been observed and is found to have a morphology that exhibits a strong dependence on film thickness. Nanobuckling takes the form of quasiperiodic discrete pointlike excursions extending over widths of 50–100 nm. This morphology converts to a regular structure of grooves/ripples with a modulation period of 30–50 nm as the film thickness increases to 300–600 nm. We find that microhardness is not changed in regions where nanobuckling is present. Analysis of Raman and x-ray photoelectron spectra (XPS) demonstrate that nanobuckling can be attributed to the relaxation of internal stress and to the formation of strong C-Si covalent bonds at the C-Si interface. XPS spectra show that the C 1s peak is broadened compared to that found in spectra of films deposited using nanosecond laser ablation. This is found to be consistent with a composition that includes sp, sp2, and sp3-bonded carbon. The unique composition of these films suggests that these materials may find application in electromechanical devices