The human eye malformation aniridia results from haploinsufficiency of PAX6, a paired box DNA-binding protein. To study this dosage effect, we characterized two PAX6 mutations in a family segregating aniridia and a milder syndrome consisting of congenital cataracts and late onset corneal dystrophy. The nonsense mutations, at codons 103 and 353, truncate PAX6 within the N-terminal paired and C-terminal PST domains, respectively. The wild-type PST domain activates transcription autonomously and the mutant form has partial activity. A compound heterozygote had severe craniofacial and central nervous system defects and no eyes. The pattern of malformations is similar to that in homozygous Sey mice and suggests a critical role for PAX6 in controlling the migration and differentiation of specific neuronal progenitor cells in the brain.

Dome growth at the Soufriere Hills volcano (1996 to 1998) was frequently accompanied by repetitive cycles of earthquakes, ground deformation, degassing, and explosive eruptions. The cycles reflected unsteady conduit flow of volatile-charged magma resulting from gas exsolution, rheological stiffening, and pressurization. The cycles, over hours to days, initiated when degassed stiff magma retarded flow in the upper conduit. Conduit pressure built with gas exsolution, causing shallow seismicity and edifice inflation. Magma and gas were then expelled and the edifice deflated. The repeat time-scale is controlled by magma ascent rates, degassing, and microlite crystallization kinetics. Cyclic behavior allows short-term forecasting of timing, and of eruption style related to explosivity potential.

BackgroundMolecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2). The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer.MethodsWe studied 54 women who were diagnosed with high-grade, triple-negative invasive breast cancer at or before age 40. These women were selected for study because they had little or no family history of breast or ovarian cancer and they did not qualify for genetic testing using conventional family history criteria. BRCA1 screening was performed using a combination of fluorescent multiplexed-PCR analysis, BRCA1 exon-13 6 kb duplication screening, the protein truncation test (PTT) and fluorescent multiplexed denaturing gradient gel electrophoresis (DGGE). All coding exons of BRCA1 were screened. The two large exons of BRCA2 were also screened using PTT. All mutations were confirmed with direct sequencing.ResultsFive deleterious BRCA1 mutations and one deleterious BRCA2 mutation were identified in the 54 patients with early-onset, triple-negative breast cancer (11%).ConclusionWomen with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer.

Abstract.The

Four mechanisms caused tephra fallout at Soufrière Hills Volcano, Montserrat, during the 1995-1999 period: explosive activity (mainly of Vulcanian type), dome collapses, ash-venting and phreatic explosions. The first two mechanisms contributed most of the tephra-fallout deposits (minimum total dense-rock equivalent volume of 23 x 106 m3), which vary from massive to layered and represent the amalgamation of the deposits from a large numbers of events. The volume of co-pyroclastic-flow fallout tephra is in the range 4-16° of the associated pyroclastic flow deposits. Dome-collapse fallout tephra is characterized by ash particles generated by fragmentation in the pyroclastic flows and by elutriation of fines. Vulcanian fallout tephra is coarser grained, as it is formed by magma fragmentation in the conduit and by elutriation from the fountain-collapse flows and initial surges. Vulcanian fallout tephra is typically polymodal, whereas dome-collapse fallout tephra is predominantly unimodal. Polymodality is attributed to: overlapping of fallout tephra of different types, premature fallout of fine particles, multiple tephra-fallout sources, and differences in density and grain-size distribution of different components. During both dome collapses and explosions, ash fell as aggregates of various sizes and types. Accretionary lapilli grain size is independent of their diameter and is characterized by multiple subpopulations with a main mode at 5ø. Satellite data indicate that very fine ash can stay in a volcanic cloud for several hours and show that exponential thinning rates observed in proximal areas cannot apply in distal areas.

Abstract.From

Fluorescence in situ hybridization (FISH) with single-color chromosome-specific probes was used to study the rates of disomy for chromosome 1, 16, X, and Y in sperm of fertile and infertile subjects. Diploidy rates were studied using a two-color cocktail of probes for chromosomes 17 and 18 in the same sperm samples. Two-color methodology was not available at the outset of the study. A total of 450,580 spermatozoa were studied from 21 subjects (9 fertile, 12 infertile). Significant differences were observed in the disomy rates between chromosomes with the highest frequency observed for chromosome 16 (0.17%) and the lowest for the Y chromosome (0.10%). No differences were observed between fertile and infertile subjects for either diploidy or disomy. Total disomy rates for chromosomes 1, 16, X and Y ranged from 0.34% to 0.84% among infertile subjects, and 0.32% to 0.61% among fertile subjects. Our data suggest that generalized aneuploidy in sperm is not a major contributor to unexplained infertility.

Abstract. The recent eruption of the Soufriere Hills Volcano in Montserrat (July, 1995, to present; September, 1997) has produced an andesitic dome (SiO 2 -59-61 wt.%). The eruption has been caused by invasion of mafic magma into a preexisting andesitic magma storage region (P -130 MPa' >5 km depth). The composition of the andesite has remained essentially constant throughout the eruption, but heating by the mafic magma increased the andesite temperature from <830øC to <880øC. Prior to being heated, the stable mineral assemblage in the andesite was plagioclase + amphibole + orthopyroxene + titanomagnetite + ilmenite + quartz. The rise in temperature from _<830øC to _<880øC (fo2 -1 log unit above NNO) has caused quartz to become unstable, and has also caused changes in silicate and Fe-Ti oxide mineral compositions. The andesitic magma is likely saturated with an H20-rich vapor phase in the upper part of the magma storage region. Melt H20 content is -4.7 wt.%.