Expression of a truncated Brca1 protein delays lactational mammary development in transgenic mice

To address the hypothesis that certain disease-associated mutants of the breast-ovarian cancer susceptibility gene BRCA1 have biological activity in vivo, we have expressed a truncated Brca1 protein (trBrca1) in cell-lines and in the mammary gland of transgenic mice. Immunofluorescent analysis of transfected cell-lines indicates that trBRCA1 is a stable protein and that it is localized in the cell cytoplasm. Functional analysis of these cell-lines indicates that expression of trBRCA1 confers an increased radiosensitivity phenotype on mammary epithelial cells, consistent with abrogation of the BRCA1 pathway. MMTV-trBrca1 transgenic mice from two independent lines displayed a delay in lactational mammary gland development, as demonstrated by altered histological profiles of lobuloalveolar structures. Cellular and molecular analyses indicate that this phenotype results from a defect in differentiation, rather than altered rates of proliferation or apoptosis. The results presented in this paper are consistent with trBrca1 possessing dominant-negative activity and playing an important role in regulating normal mammary development. They may also have implications for germline carriers of BRCA1 mutations.

Parasite distribution on client reef fish determines cleaner fish foraging patterns

Recent evidence suggests that cleaner fish Labroides dimidiatus effectively control parasite densities on client reef fish that actively visit them to have parasites and dead or infected tissue removed. These findings support the hypothesis that clients benefit from cleaning, However, they do not show how cleaners reduce the parasite load of their clients. Cleaners could selectively feed on parasites or parasite removal could be a side product of cleaners foraging indifferently on the client surface, resulting in the removal of healthy mucus and scales also. To investigate cleaner fish foraging behaviour, we infected individuals of the surgeon fish Ctenochaetus striatus, with parasitic monogeneans on one body side, while the other body side was parasite free. We then allowed these clients to interact with L, dimidiatus. We found that the duration of interactions depended on parasite load, and that cleaners spent both more time and took more bites per time unit on the infected than on the uninfected side, Our data thus support the idea that parasite abundance determines food patch quality for cleaners. The overall outcome of cleaning interactions is thus likely to benefit the clients.

Molecular rates parallel diversification contrasts between carnivorous plant sister lineages

In the carnivorous plant family Lentibulariaceae, the bladderwort lineage (Utricularia and Genlisea) is substantially more species-rich and morphologically divergent than its sister lineage, the butterworts (Pinguicula). Bladderworts have a relaxed body plan that has permitted the evolution of terrestrial, epiphytic, and aquatic forms that capture prey in intricately designed suction bladders or corkscrew-shaped lobster-pot traps. In contrast, the flypaper-trapping butterworts maintain vegetative structures typical of angiosperms. We found that bladderwort genomes evolve significantly faster across seven loci (the trnL intron, the second trnL exon, the trnL-F intergenic spacer, the rps16 intron, rbcL, coxI, and 5.8S rDNA) representing all three genomic compartments. Generation time differences did not show a significant association. We relate these findings to the contested speciation rate hypothesis, which postulates a relationship between increased nucleotide substitution and increased cladogenesis. (C) 2002 The Willi Hennig Society.

Transpecific microsatellites for hard pines M. Shepherd, M. Cross, T. Maguire, M. Dieters, C. Williams, R. Henry

Microsatellites are difficult to recover from large plant genomes so cross-specific utilisation is an important source of markers. Fifty micro satellites were tested for cross-specific amplification and polymorphism to two New World hard pine species, slash pine (Pinus elliottii var. elliottii) and Caribbean pine (R caribaea var. hondurensis). Twenty-nine (58%) markers amplified in both hard pine species, and 23 of these 29 were polymorphic. Soft pine (subgenus Strobus) microsatellite markers did amplify, but none were polymorphic. Pinus elliottii var. elliottii and R caribaea var. hondurensis showed mutational changes in the flanking regions and the repeat motif that were informative for Pinus spp. phylogenetic relationships. Most allele length variation could be attributed to variability in repeat unit number. There was no evidence for ascertainment bias.

Convergent maternal care strategies in ungulates and macropods

Mammals show extensive interspecific variation in the form of maternal care. Among ungulates, there is a dichotomy between species in which offspring follow the mother (following strategy) versus species in which offspring remain concealed (hiding strategy). Here we reveal that the same dichotomy exists among macropods (kangaroos, wallabies and allies). We test three traditional adaptive explanations and one new life history hypothesis. and find very similar patterns among both ungulates and macropods. The three traditional explanations that we tested were that a ''following'' strategy is associated with (1) open habitat, (2) large mothers, and (3) gregariousness. Our new life-history hypothesis is that a following strategy'' is associated with delayed weaning, and thus with the slow end of the slow-fast mammalian life-history continuum, because offspring devote resources to locomotion rather than rapid growth. Our comparative test strongly supports the habitat structure hypothesis and provides some support for this new delayed weaning hypothesis for both ungulates and macropods. We propose that sedentary young in closed habitats benefit energetically by having milk brought to them. In open habitats, predation pressure will select against hiding. Followers will suffer slower growth to independence. Taken together, therefore, our results provide the first quantitative evidence that macropods and ungulates are convergent with respect to interspecific variation in maternal care strategy. In both clades, differences between species in the form of parental care are due to a similar interaction between habitat, social behavior, and life history.

Interspecific variation in plumage colour among birds: species recognition or light environment?

The traditional explanation for interspecific plumage colour variation in birds is that colour differences between species are adaptations to minimize the risk of hybridization. Under this explanation, colour differences between closely related species of birds represent reproductive character displacement. An alternative explanation is that interspecific variation in plumage colour is an adaptive response to variation in light environments across habitats. Under this explanation, differences in colour between closely related species are a product of selection on signal efficiency. We use a comparative approach to examine these two hypotheses, testing the effects of sympatry and habitat use, respectively, on divergence in male plumage colour. Contrary to the prediction of the Species Isolation Hypothesis, we find no evidence that sympatric pairs of species are consistently more divergent in coloration than are allopatric pairs of species. However, in agreement with the Light Environment Hypothesis, we find significant associations between plumage coloration and habitat use. All of these results remain qualitatively unchanged irrespective of the statistical methodology used to compare reflectance spectra, the body regions used in the analyses, or the exclusion of areas of plumage not used in sexual displays. Our results suggest that, in general, interspecific variation in plumage colour among birds is more strongly influenced by the signalling environment than by the risk of hybridization.

Establishment of Nilaparvata Iugens Stl in rice crop nurseries: a possible source of outbreaks

We tested the hypothesis that early-planted seedbeds of rioe are mere heavily infested with brown planthopper (BPH) than later seedbeds, and that transplanted plants with lBPH are a source of subsequent population increase and possible outbreaks. The experiments were conducted at CARDI and Takeo province in wet season 2000 and early wet 2 season 200 I. BPH at O. 25. 50, 100, 200 1m were infested onto plants with low and high fertilizer treatments. Rice seeds of varieties moderately and highly susceptible to BPH were sown 3 weeks early, 2 weeks early, at the normal time, and later than normal (5 weeks) and treated with low and high fertilizer rates. At Takeo, the 3< weeks early seedbeds were infested by BPH migration, and both varieties with high fertilizer caught more immigrant insects and subsequently had damaging outbreaks of BPH in the third generation. At CARDl, no seedbeds were infested with immigrant BPH. Seedbeds in areas with continuous cropping of rice have a high risk of BPH attack, Seedlings infested with 200, 100, and 50 BPI[/m2 resulted in death of the plant. Plants with 100 and 200 BPH/m'! were kj[Jed sooner. With 25 BPIVm2 plants were not kllled, but subsequent population increase caused yi eld reduction. Yield loss was high ill higlh fertilizer treated plants. Key words , ,

Testing insect movement theory: empirical analysis of pest data routinely collected from agricultural crops

Observations of an insect's movement lead to theory on the insect's flight behaviour and the role of movement in the species' population dynamics. This theory leads to predictions of the way the population changes in time under different conditions. If a hypothesis on movement predicts a specific change in the population, then the hypothesis can be tested against observations of population change. Routine pest monitoring of agricultural crops provides a convenient source of data for studying movement into a region and among fields within a region. Examples of the use of statistical and computational methods for testing hypotheses with such data are presented. The types of questions that can be addressed with these methods and the limitations of pest monitoring data when used for this purpose are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.

Differential requirements for COPI coats in formation of replication complexes among three genera of Picornaviridae

Picornavirus RNA replication requires the formation of replication complexes (RCs). consisting of virus-induced vesicles associated with viral nonstructural proteins and RNA. Brefeldin A (BFA) has been shown to strongly inhibit RNA replication of poliovirus but not of encephalomyocarditis virus (EMCV). Here, we demonstrate that the replication of parechovirus 1 (ParV1) is partly resistant to BFA, whereas echovirus 11 (EV11) replication is strongly inhibited. Since BFA inhibits COPI-dependent steps in endoplasmic reticulum (ER)-Golgi transport, we tested a hypothesis that different picornaviruses may have differential requirements for COPI in the formation of their RCs. Using immunofluorescence and cryo-immunoelectron microscopy we examined the association of a COPI component, beta-COP, with the RCs of EMCV, ParV1, and EV11 EMCV RCs did not contain beta-COP. In contrast, beta-COP appeared to be specifically distributed to the RCs of EV11 In ParV1-infected cells beta-COP was largely dispersed throughout the cytoplasm, with some being present in the RCs. These results suggest that there are differences in the involvement of COPI in the formation of the RCs of various picornaviruses, corresponding to their differential sensitivity to BFA. EMCV RCs are likely to be formed immediately after vesicle budding from the ER, prior to COPI association with membranes. ParV1 RCs are formed from COPI-containing membranes but COPI is unlikely to be directly involved in their formation, whereas formation of EV11 RCs appears to be dependent on COPI association with membranes.

Corporate stadium sponsorships, signaling theory, agency conflicts, and shareholder wealth

Contrary to the plethora of critical articles recently appearing in both the popular and business press, this carefully controlled investigation of 49 stadium- and arena-naming-rights agreement announcements provides striking evidence that such sponsorships can significantly enhance the stock prices of sponsoring companies. Indeed, the results of the study show that the average stadium sponsor's stock prices increased by 1.65 percent at the time of announcement of the programs-a result considerably in excess of the returns associated with other major marketing programs such as the signing of Olympic sponsorships and celebrity endorsers. A multiple regression analysis employing firm-specific changes in stock prices as the dependent variable and quantifiable corporate and sponsorship-related attributes as independent variables is also presented. Variables positively and significantly correlated with perceived sponsorship success include team-winning percentages, contract length, and high technology and locally based companies. Overall, the findings of the study are consistent with the novel hypothesis that, for some firms, the real value-added of a stadium sponsorship may lie in its ability to serve as an effective or honest signal of managerial confidence in the future of the company.

Complex language functions and subcortical mechanisms: evidence from Huntington's disease and patients with non-thalamic subcortical lesions

The neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non-thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non-thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n=13) were compared with those of an age- and education-matched group of patients with chronic NTS lesions following stroke (n=13) and a non-neurologically impaired control group (n=13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive-linguistic battery employed selected subtests from The Test of Language Competence-Expanded, The Test of Word Knowledge and The Word Test-Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p<0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico-semantic tasks (e. g. the Boston Naming Test and providing definitions), on both single-word and sentence-level generative tasks (e. g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non-thalamic subcortex resulting from either focal neurological insult or a degenerative disease.

Germline BRCA1 promoter deletions in UK and Australian familial breast cancer patients: Identification of a novel deletion consistent with BRCA1 :psi VBRCA1 recombination

Inherited susceptibility to breast cancer results from germline mutations in one of a number of genes including BRCA1. A significant number of BRCA1-linked familial breast cancer patients, however, have no detectable BRCA1 mutation. This could be due in part to the inability of commonly used mutation-detection techniques to identify mutations outside the BRCA1 coding region. This paper addresses the hypothesis that non coding region mutations, specifically in the BRCA1 promoter, account for some of these cases. We describe a new and detailed restriction map of the 5' region of the BRCA1 gene including the nearby NBR2, psiBRCA1, and NBR1 genes and the isolation of a number of new informative hybridization probes suitable for Southern analysis. Using this information we screened DNA from lymphoblastoid cell-lines made from 114 UK familial breast cancer patients and detected one large deletion in the 5' region of BRCA1. We show that the breakpoints for this deletion are in BRCA1 intron 2 and between NBR2 and exon 2 of psiBRCA1, raising the possibility that this deletion arose via a novel mechanism involving BRCA1:psiBRCA1 recombination. We have also screened 60 familial breast cancer patients from the Australian population, using an amplification refractory mutation system (ARMS) technique described previously by our group, and found one patient with a genotype consistent with a BRCA1 promoter deletion. These findings indicate that germline BRCA1 promoter deletions are a rare and yet significant mutation event and that they could arise via a novel genetic mechanism. Hum Mutat 19:435-442, 2002. (C) 2002 Wiley-Liss, Inc.

The role of Doppler left ventricular filling indexes and Doppler tissue echocardiography in the assessment of cardiac involvement in hereditary hemochromatosis

Although cardiac dysfunction in hereditary hemochromatosis (HHC) can be evaluated by conventional echocardiography, findings are often not specific. To test the hypothesis that the assessment of (1) conventional Doppler left ventricular filling indexes and (2) intrinsic elastic properties of the myocardium by Doppler tissue echocardiography can both enhance the accuracy of echocardiographic diagnosis of cardiac involvement in HHC, a group of 18 patients with HHC (mean age 50+/-7 years) and 22 age-matched healthy subjects were studied. The following indexes were characteristic for HHC: (1) the duration of atrial reversal measured from pulmonary venous flow (ms) was longer(118+/-20 vs 90+/-16; P

Skeletal muscle mitochondrial ATP production rate and walking performance in peripheral arterial disease

This study tested the hypotheses that skeletal muscle mitochondrial ATP production rate (MAPR) is impaired in patients with peripheral arterial disease (PAD) and that it relates positively to their walking performances. Seven untrained patients, eight exercise-trained patients and 11 healthy controls completed a maximal walking test and had muscle sampled from the gastrocnemius medialis muscle. Muscle was analysed for its MAPR in the presence of pyruvate, palmitoyl-L-carnitine or both, as well as citrate synthase (CS) activity. MAPRs were not different between untrained PAD and controls. In contrast, MAPRs (pyruvate) were significantly higher in trained PAD vs. controls. MAPR (pyruvate combinations) was also significantly higher in trained than untrained PAD muscle. MAPR and CS activity were highly correlated with walking performance in patients, but not in controls. These data do not support the hypothesis that isolated mitochondria are functionally impaired in PAD and demonstrate that the muscle mitochondrial capacity to oxidize carbohydrate is positively related to walking performance in these patients.

Heterogeneous nuclear ribonucleoprotein A3, a novel RNA trafficking response element-binding protein

The cis-acting response element, A2RE, which is sufficient for cytoplasmic mRNA trafficking in oligodendrocytes, binds a small group of rat brain proteins. Predominant among these is heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a trans-acting factor for cytoplasmic trafficking of RNAs bearing A2RE-like sequences. We have now identified the other A2RE-binding proteins as hnRNP A1/A1(B), hnRNP B1, and four isoforms of hnRNP A3. The rat and human hnRNP A3 cDNAs have been sequenced, revealing the existence of alternatively spliced mRNAs. In Western blotting, 38-, 39-, 41 -, and 41.5-kDa components were all recognized by antibodies against a peptide in the glycine-rich region of hnRNP A3, but only the 41- and 41.5-kDa bands bound antibodies to a 15-residue N-terminal peptide encoded by an alternatively spliced part of exon 1. The identities of these four proteins were verified by Edman sequencing and mass spectral analysis of tryptic fragments generated from electrophoretically separated bands. Sequence-specific binding of bacterially expressed hnRNP A3 to A2RE has been demonstrated by biosensor and UV cross-linking electrophoretic mobility shift assays. Mutational analysis and confocal microscopy data support the hypothesis that the hnRNP A3 isoforms have a role in cytoplasmic trafficking of RNA.