William W. Cole

Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome

Basement membrane (BM) morphogenesis is critical for normal kidney function. Heterotrimeric type IV collagen, composed of different combinations of six α-chains (1–6), is a major matrix component of all BMs (ref. 2). Unlike in other BMs, glomerular BM (GBM) contains primarily the α3(IV) and α4(IV) chains, together with the α5(IV) chain. A poorly understood, coordinated temporal and spatial switch in gene expression from ubiquitously expressed α1(IV) and α2(IV) collagen to the α3(IV), α4(IV) and α5(IV) chains occurs during normal embryogenesis of GBM (ref. 4). Structural abnormalities of type IV collagen have been associated with diverse biological processes including defects in molecular filtration in Alport syndrome, cell differentiation in hereditary leiomyomatosis, and autoimmunity in Goodpasture syndrome; however, the transcriptional and developmental regulation of type IV collagen expression is unknown. Nail patella syndrome (NPS) is caused by mutations in LMX1B, encoding a LIM homeodomain transcription factor. Some patients have nephrosis-associated renal disease characterized by typical ultrastructural abnormalities of GBM (refs. 8,9). In Lmx1b−/− mice, expression of both α(3)IV and α(4)IV collagen is strongly diminished in GBM, whereas that of α1, α2 and α5(IV) collagen is unchanged. Moreover, LMX1B binds specifically to a putative enhancer sequence in intron 1 of both mouse and human COL4A4 and upregulates reporter constructs containing this enhancer-like sequence. These data indicate that LMX1B directly regulates the coordinated expression of α3(IV) and α4(IV) collagen required for normal GBM morphogenesis and that its dysregulation in GBM contributes to the renal pathology and nephrosis in NPS.

Differential ovule development following self- and cross-pollination: the basis of self-sterility in Narcissus triandrus (Amaryllidaceae)

Self-pollination results in significantly lower seed set than cross-pollination in tristylous Narcissus triandrus. We investigated structural and functional aspects of pollen-pistil interactions and ovule-seed development following cross- and self-pollination to assess the timing and mechanism of self-sterility. Ovule development within an ovary was asynchronous at anthesis. There were no significant differences in pollen tube behavior following cross- vs. self-pollination during the first 6 d of growth, regardless of style morph type. Double fertilization was significantly higher following cross- vs. self-pollination. Aborted embryo development was not detected following either pollination type up to seed maturity. Prior to pollen tube entry, a significantly greater number of ovules ceased to develop following self- vs. cross-pollination. These results indicate that self-sterility in N. triandrus operates prezygotically but does not involve differential pollen tube growth typical of many self-incompatibility (SI) systems. Instead, low seed set following self-pollination is caused by a reduction in ovule availability resulting from embryo sac degeneration. We hypothesize that this is due to the absence of a required stimulus for normal ovule development. If this is correct, current concepts of SI may need to be broadened to include a wider range of pollen-pistil interactions.

The mating consequences of sexual segregation within inflorescences of flowering plants

Many co–sexual plants segregate female and male function among flowers on an inflorescence through dichogamy or the production of unisexual flowers. Sexual segregation may reduce self–pollination among flowers within inflorescences (geitonogamy), thereby increasing the pollen available for export to other plants. To assess these complementary roles we manipulated the simultaneously hermaphroditic (adichogamous) flowers of Eichhornia paniculata to produce ten–flowered inflorescences with either female above male flowers (female/male inflorescences) or male/female inflorescences, which competed for mating opportunities with five–flowered adichogamous inflorescences. Because of the upward movement of bumble–bees, selfing increased upward in adichogamous inflorescences (overall female selfing rate s ± s.e.=0.320±0.026). Female flowers of male/female inflorescences selfed less than flowers in corresponding positions in adichogamous inflorescences so s fell to 0.135±0.027. In contrast, all–female flowers of female/male inflorescences selfed similarly to upper flowers on adichogamous inflorescences, elevating s (0.437±0.043). During 1997, male/female inflorescences sired more outcrossed seeds than female/male or adichogamous inflorescences, whereas during 1994 flowers on male/female inflorescences received fewer visits than those of adichogamous inflorescences, reducing their outcross siring success. Hence, sexual segregation limits geitonogamy and enhances outcross siring success when it does not affect pollinator behaviour, illustrating the importance of both female and male function in inflorescence design.

Effects of flower number and position on self-fertilization in experimental populations of Eichhornia paniculata (Pontederiaceae)

We examined the effects of daily inflorescence size (three-, six-, nine- and 12-flowered) and the position of flowers within an inflorescence (bottom, middle and top) on the frequency of self-fertilization using genetic markers and experimental manipulation of garden populations of Eichhornia paniculata, a self-compatible bee-pollinated plant. Based on the observed tendency for bees to forage upwards on inflorescences and a model of the relation between pollen carry-over and the number of flowers visited per inflorescence, we predicted that the frequency of self-fertilization should increase from bottom to top flowers and with increasing inflorescence sizes. Electrophoretic analysis of open-pollinated progeny arrays supported both of these predictions

Imatinib mesylate: An attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans

To document the clinical activity of imatinib mesyalte in a child with a dermatofibrosarcoma protuberans (DFSP). An 18‐month‐old girl presented with a large extremity DFSP. As surgical resection would have caused unacceptable functional defects, imatinib mesylate was administered to induce tumor reduction and or stabilization. After 23 weeks of therapy, magnetic resonance imaging (MRI) of the tumor showed a reduction in the subcutaneous thickness in the transverse plane. The drug was tolerated well without any adverse reactions. Imatinib mesylate offers a non‐surgical alternative for the treatment of large DFSP in children.

Evolutionary maintenance of stigma-height dimorphism in Narcissus papyraceus (Amaryllidaceae)

Stigma-height dimorphism is a sexual polymorphism in which plant populations are composed of two floral morphs that differ significantly in style length but not anther position. The morphs exhibit approach and reverse herkogamy, floral designs that in most species typically occur as monomorphic conditions. We investigated the floral biology of stigma-height dimorphism in the Mediterranean geophyte Narcissus papyraceus (Amaryllidaceae) in an effort to understand the evolutionary forces maintaining stylar polymorphism. Our survey of 66 populations in Spain, Portugal, and Morocco indicated that 56% were dimorphic with the long-styled morph at an average frequency of 0.79. The remaining 44% of populations sampled were monomorphic for the long-styled morph. In dimorphic populations there was a significant positive relation between population size and the frequency of the short-styled morph. Controlled pollinations demonstrated that N. papyraceus is self-sterile with no significant differences in female fertility between intra- and intermorph crosses. Prior self-pollination reduced seed set in flowers that were subsequently cross-pollinated. Estimates of mating patterns using allozyme markers in eight populations indicated that N. papyraceus is largely outcrossing (mean t(m) = 0.81) with no significant differences between monomorphic and dimorphic populations or style morphs. Stigma-height dimorphism in N. papyraceus is maintained in populations by insect-mediated cross-pollination with biased morph ratios and stylar monomorphism likely resulting from the combined influence of the inheritance of the polymorphism, morph-specific differences in assortative mating and founder effects.

Sexual polymorphisms in Narcissus triandrus (Amaryllidaceae): is this species tristylous?

The sexual polymorphism tristyly is well documented in three flowering plant families (Lythraceae, Oxalidaceae and Pontederiaceae). Controversy has arisen as to whether the polymorphism exists in Narcissus triandrus L. of the Amaryllidaceae. Surveys of floral variation in 80 populations in Spain and Portugal were undertaken to determine the nature of sexual polymorphisms in the species. Most populations (85 per cent) contained three discrete floral morphs that differ from one another in the sequence in which the stigma and the two anther levels within a flower are presented. Hence, the species is genuinely tristylous. Floral morph frequencies deviated strongly from the isoplethic expectations (1:1:1) typical of tristylous species. Average frequencies for the morphs were L morph = 0.59, M morph = 0.19 and S morph = 0.22. In 15 per cent of the populations sampled, the mid-styled morph was absent. Controlled crosses indicated that individuals are moderately self-sterile but cross-compatible with other individuals, regardless of morph. Therefore, the species does not possess a conventional heteromorphic incompatibility system. Self-sterility operates in the ovary, and prior self-pollination of flowers renders ovules nonfunctional as judged by reduced seed-set in subsequent cross-pollinations. Multilocus outcrossing estimates in four tristylous populations averaged t = 0.77, range 0.68–0.87, with significant variation evident among morphs but not populations. All population estimates were less than 1, indicating significant amounts of selfing. Although N. triandrus is clearly tristylous, the expression of the polymorphism is unique among tristylous families.

Botany: Specialized bird perch aids cross-pollination

Birds may hover over or perch on flowers when feeding on nectar, and this assists cross-pollination if they then visit other plants. Here we investigate the curious sterile inflorescence axis of the South African Cape endemic ‘rats tail’ plant (Babiana ringens, Iridaceae), whose function — unlike in other bird-pollinated plants — is exclusively to provide a perch for foraging birds. We find that this structure promotes the plants mating success by causing the malachite sunbird (Nectarinia famosa), its main pollinator, to adopt a position ideal for the cross-pollination of its unusual ground-level flowers.

MR imaging of simple bone cysts in children: not so simple.

Objective. The unicameral bone cyst (UBC) is a common cystic bone lesion seen in children. We review and summarize its MR findings, focusing on their appearance following contrast enhancement, and correlating them to known histologic features of UBC. Subjects and methods. A retrospective review of 20 cases (13 boys, 7 girls; age range, 1–17 years; mean age, 8.9) diagnosed as UBC was conducted. Clinical histories, radiographic and MR features, follow-up data, and available pathologic findings were noted. Results. At initial presentation 18 (90 %) of the patients with UBC had a history of acute or remote pathologic fracture. Cysts with history of fracture displayed heterogeneous fluid signals on T1- (n = 9, 50 %), and T2-weighted (n = 15, 83 %) MR images. Gadolinium-enhanced images were obtained in 15 of the 18 UBC cases with history of previous fracture. All showed enhancement with focal, thick peripheral, heterogeneous, or subcortical patterns. Focal nodules of homogeneous enhancement (diameter > 1 cm) within the UBC (n = 5) correlated with areas of ground-glass opacification on plain film. Other interesting MR features were fluid-fluid levels (n = 11), “fallen-leaf” sign (n = 1), soft-tissue changes (n = 2), and detection of septations not seen on plain film (n = 2). Conclusion. UBCs frequently appear complicated on MR imaging, with heterogeneous fluid signals and regions of nodular and thick peripheral enhancement related to previous pathologic fracture and early healing.

Mating patterns and genetic diversity in the wild Daffodil Narcissus longispathus (Amaryllidaceae)

Despite the importance of Narcissus to ornamental horticulture, there have been no population genetic studies of wild species, many of which have narrow distributions. Here, we measure selfing rates and levels of genetic diversity at allozyme loci in six populations of Narcissus longispathus, a self-compatible daffodil endemic to a few mountain ranges in southeastern Spain. The populations were distributed among four distinct river valleys encompassing two main watersheds in the Sierra de Cazorla mountains. Selfing rates averaged 0.37 (range 0.23–0.46), resulting in significant inbreeding coefficients for the progeny (f=0.324). In contrast, estimates of inbreeding in parental genotypes were not significantly different from zero (f=0.001), indicating that few selfed offspring survive to maturity because of inbreeding depression. Species-wide estimates of genetic diversity for the six populations were Ps=0.38, Hes=0.119 and As=1.27 with significant genetic differentiation among populations θ=0.15. The observed patterns of genetic differentiation among populations are likely influenced by the mating system, and a combination of local topography, watershed affinities and gene flow.