Repeating deep earthquakes: evidence for fault reactivation at great depth.

We have identified three groups of deep earthquakes showing nearly identical waveforms in the Tonga slab. Relocation with a cross-correlation method shows that each cluster is composed of 10 to 30 earthquakes along a plane 10 to 30 kilometers in length. Some of the earthquakes are colocated, demonstrating repeated rupture of the same fault, and one pair of events shows identical rupture complexity, suggesting that the temporal and spatial rupture pattern was repeated. Recurrence intervals show an inverse time distribution, indicating a strong temporal control over fault reactivation. Runaway thermal shear instabilities may explain temporally clustered earthquakes with similar waveforms located along slip zones weakened by shear heating. Earthquake doublets that occur within a few hours are consistent with events recurring before the thermal energy of the initial rupture can diffuse away.

A complex pattern of mantle flow in the Lau backarc.

Shear-wave splitting analysis of local events recorded on land and on the ocean floor in the Tonga arc and Lau backarc indicate a complex pattern of azimuthal anisotropy that cannot be explained by mantle flow coupled to the downgoing plate. These observations suggest that the direction of mantle flow rotates from convergence-parallel in the Fiji plateau to north-south beneath the Lau basin and arc-parallel beneath the Tonga arc. These results correlate with helium isotopes that map mantle flow of the Samoan plume into the Lau basin through an opening tear in the Pacific plate.

Simulated microgravity and hypergravity attenuate heart tissue development in explant culture.

Exposure to altered gravity may disturb the cytoskeleton-cell surface-extracellular matrix (ECM) interface of embryonic cells. Development of organs such as the heart depends on dynamic interactions across cell surfaces. Fibronectin (FN), for example, a glycoprotein that links the ECM to the cytoskeleton through integrin surface receptors, is required for normal heart development. Thus, altered gravity may perturb organogenesis. We cultured precardiac explants from chick embryos in a rotating bioreactor vessel to simulate microgravity (microG), or in a tissue culture centrifuge, for 18 h during heart development. Bioreactor microG did not alter external morphology of explants, but did significantly reduce the proportion that developed contractions. Immunostaining for FN of explant sections showed that it also significantly reduced the linear extent of staining present in basement membrane regions. Analysis of ultrastructure revealed a significant reduction in the number of desmosomes per unit area and other differences. Hypergravity dramatically abolished development of contractions and altered morphogenesis. The results indicate a probable sensitivity of cardiomyogenic development involving FN to altered gravity.

Isotretinoin alters morphology, polarity, and motility of neural crest cells in culture.

Migrating neural crest cells (NCCs) contribute to a diverse array of vertebrate head and neck structures. Retinoids are proven human and animal teratogens. To elucidate isotretinoin's effects, cranial and trunk neural folds were microdissected from chick embryos and cultured. Image analysis and immunostaining were used to quantitate cell behavior. We found that a higher proportion of Stage 8, 9, and 10 treated NCCs were rounded and clustered. Medians and means for cell area, perimeter, and elongation index were lower for treated cells from Stage 9 and 10 embryos, but not from Stage 8. Cumulative medians and means for changes in area and perimeter, and cell migration were similarly lower. Thus interference with the transitory basal activity of the cytoskeleton that adjusts and determines cell-substratum adhesion, spreading, elongation, and migration may be the mechanism by which isotretinoin acts on NCCs in slightly older embryos.

Subjective work noise: a major risk factor in myocardial infarction.

The relationship between subjective work noise exposure and the risk of myocardial infarction (MI) was assessed in a population based case-control study. 395 MI patients (31-65 years) were compared to 2148 controls from a random population sample with the same agelsex distribution. The relative risk (RR) for MI-adjusted for control variables (smoking, age, social status, etc.)-was found to increase significantly and steadily with noise category. Subjective work noise exposure was the second greatest risk factor for MI after smoking. Possible bias due to overreporting of subjective noise exposure is discussed. Interdisciplinary studies on the relationship between cardiovascular diseases and work-related stressors including subjective and objective noise assessment are needed to quantify the risk of MI due to work noise.

Tomography of the Source Area of the 1995 Kobe Earthquake: Evidence for Fluids at the Hypocenter?

Seismic tomography revealed a low seismic velocity (-5%) and high Poisson's ratio (+6%) anomaly covering about 300 square kilometers at the hypocenter of the 17 January 1995, magnitude 7.2, Kobe earthquake in Japan. This anomaly may be due to an overpressurized, fluid-filled, fractured rock matrix that contributed to the initiation of the Kobe earthquake.

An alternative model for cell sheet migration on fibronectin during heart formation.

The emergence of animal form and function depends on cell migrations in the embryo. Some migrations are accomplished by cells individually, and the mechanism of movement is predictable by contemporary models of cell adhesion and cytoskeletal function. However, other migrations occur that involve layers or sheets of cells connected by junctions, and the mechanism of migration is obscure. An example is the precardiac mesoderm, an epithelium that migrates anteriorly and ventrally in the early amniote embryo to the position of heart formation. It moves upon and is influenced by the adjacent endoderm, which has produced an extracellular matrix. The matrix contains the cell adhesion and cytoskeleton-activating glycoprotein fibronectin. Some immunolocalization studies have reported that fibronectin is arrayed in an anterior-to-posterior gradient, and it has been suggested that directional migration results from a haptotactic response of each cell to the gradient, a model derived from and supported by experiments with individual cells in culture. However, we have produced evidence from immunostaining that suggests fibronectin is arrayed as a localized anterior patch rather than a gradient. We propose an alternative model for precardiac epithelial migration in which only the anterior cells attach effectively to fibronectin. Thus adhered, their cytoskeletal contractile activity generates force which propagates throughout the layer of connected cells, and efficiently pulls them in the proper direction, following the bending and extending movements of the foregut, notochord and other structures of the head. Theoretical implications of the two models are discussed.

Developmental expression of connexins in the chick embryo myocardium and other tissues.

BACKGROUND: Connexins are cell surface proteins that form specialized regions of cell-cell communication called gap junctions. These allow impulse conduction in in voluntary muscle tissue such as the heart, but also allow the formation of communities of like cells during development of organs. METHODS: We used an antipeptide antibody to connexin 43 in immunolocalization studies and an anti-peptide antibody to an external loop domain common to most connexins in Western blotting of total heart protein to measure the accumulation of connexins in the heart as it develops from 33 hours to 21 days (hatching), and in the adult. RESULTS: Immunolocalization revealed that connexin 43 is widely distributed in the earliest organ rudiments. It is especially prominent in the neural tube and its derivatives, in the lens and nasal placodes, in the foregut and its derivatives, in the somites, in the mesonephric tubules, and in the heart and major arteries. Heart tissue staining grew more intense with development through day 8. However, at day 11 and day 15, and in the adult, heart staining diminished. Endocardium and valve tissue did not stain. Western blotting of heart homogenates with the antibody directed against the external loop domain peptide showed 26, 32, 43, 45, and 56 kilodalton connexins, which changed in relative abundance, displaying unique patterns during development. CONCLUSIONS: Our results show patterns of connexin immunolocalization in early germ layers and organ rudiments that are similar to those known in the mouse, but with certain differences. Our results show a distinctive pattern of multiple connexin gene expression in the developing heart from days 2-21.

Early heart development in the chick embryo: effects of isotretinoin on cell proliferation, alpha-actin synthesis, and development of contractions.

Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. Though very effective, it is teratogenic if administered during pregnancy, and its teratogenic effect may be related to the normal activity of retinoids as signalling molecules in the embryo. Although its exact mechanism of action is unknown, it has been suggested that it causes its characteristic pattern of defects that includes heart defects, by inhibiting the migration of neural crest cells. However, other effects on cells are known. We studied early cardiac cell proliferation using incorporation of bromodeoxyuridine (BrdU) and detection with a monoclonal anti-BrdU. Proliferation in heart tissue of whole embryo cultures was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level in myocardium. We studied its effects in culture on precardiac explant development in the absence of the neural crests. Culture of precardiac mesodermal-endodermal explants revealed that development of heart vesicles from the mesoderm was little affected, but the development of heartbeat was inhibited depending on dose in the 10(-5) to 10(-7) M range. The effect on development of contractions was augmented in the presence of serum; it could be duplicated by all-trans-retinoic acid, and it was reversible. Synthesis of the alpha-actin isotype, analyzed by isoelectric focusing, was found to be inhibited or delayed. The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis.

Casein, actin, and tubulin expression during early involution in bovine and murine mammary tissue.

Hybridization methods and in vitro translation were used to examine the expression and functional condition of messenger RNA encoding caseins and cytoskeletal proteins in the mammary gland during early involution. In the mouse, steady state mRNA levels for alpha-, beta-, and gamma-caseins coordinately decreased to 20% of initial levels between 12 and 72 h after pup removal. In vitro translatability of mouse casein mRNA, as determined by immunoprecipitation, electrophoresis, and gel slice counting, revealed a pattern that closely paralleled mRNA expression. In contrast, bovine casein mRNA levels were only slightly reduced by 72 h postmilking, whereas in vitro translatability decreased by about one-half. Northern blot analysis of total mouse mammary RNA that were hybridized with probes to cytoskeletal proteins showed a gradual decrease of alpha-tubulin mRNA, but an increase in beta-actin mRNA during early involution. Two-dimensional gel analysis of in vitro translated products indicated a concordant increase in beta-gamma-actin. In the cow, beta-actin mRNA at 72 h of involution was equal to or greater than that during lactation. These results demonstrate the generally slower involution response in the cow and suggest that differing regulations are involved. Early events of cellular involution may be related to a reorganization of the cytoskeleton.

Computer applications for staff development and patient education.

The changing and evolving profession of nursing necessitates extensive staff development activities on the part of nursing management. This ongoing responsibility is essential to maintaining the currency and competence of practicing nurses and facilitating their professional growth. Simultaneously there are economic constraints coinciding with increased consumer demands for patient education. The purpose of this paper is to explore an innovative teaching method, the use of instructional computing for staff development and patient education programs. The theoretical frameworks for this instructional modality are identified and general advantages and disadvantages of instructional computing applications are described. Specific examples of programs from the literature are briefly discussed.

Milk protein expression and ductal morphogenesis in the mammary gland in vitro: hormone-dependent and -independent phases of adipocyte-mammary epithelial cell interaction.

Epithelial cell differentiation frequently occurs in situ in conjunction with supporting mesenchyme or connective tissue. In embryonic development the importance of the supporting mesenchyme for cytodifferentiation and morphogenesis has been demonstrated in several epithelial tissues, but the importance of epithelial-connective tissue interactions is less well studied in adult epithelial organs. We have investigated the interaction of adult mammary epithelial cells with adipocytes, which compose the normal supporting connective tissue in the mammary gland. Mammary epithelial cells from mice in various physiological states were cultured on cellular substrates of adipocytes formed from cells of the 3T3-L1 preadipocyte cell line. We found that there were two distinct phases to the interaction of epithelial cells with adipocytes. Cytodifferentiation of the epithelial cells and milk protein production were dependent on lactogenic hormones (insulin, hydrocortisone, and prolactin), whereas ductal morphogenesis was lactogenic hormone independent. When cultured on preadipocytes or adipocytes, mammary epithelial cells from never pregnant, pregnant, lactating, and involuting mice responded to lactogenic hormones rapidly by producing and secreting large amounts of alpha-, beta-, and gamma-casein and alpha-lactalbumin. This response was seen in individual as well as in clusters of epithelial cells, but was not seen if the same cells were cultured on tissue culture dishes without adipocytes, on fibroblasts (human newborn foreskin fibroblasts) or in the presence of adipocytes but in the absence of lactogenic hormones. Continued incubation of mammary epithelial cells on adipocytes in the presence or absence of lactogenic hormones resulted in the formation of a branching ductal system. Mammary epithelial cells in ducts that formed in the absence of lactogenic hormones produced no casein, but rapidly synthesized casein when subsequently exposed to these hormones. Ultrastructural studies revealed that the formation of a basement membrane occurs only in co-cultures of mammary epithelium with adipocytes or preadipocytes. Ultrastructural changes associated with secretion occurred only in the presence of lactogenic hormones. We propose that growth and formation of a ductal system in vitro can occur in the absence of lactogenic hormones, but that certain environment-associated events must occur if the epithelium is to become responsive to lactogenic hormones and undergo the cytodifferentiation associated with lactation.

Reproductive success, spontaneous embryo abortion, and genetic load in flowering plants.

Reproductive success is divided into two phases: preemergent (the number of viable seeds that enter the ambient environment) and postemergent (the percentage of progeny that survive to reproduce). We studied preemergent reproductive success (PERS) in flowering plants by measuring the fruit/flower (Fr/Fl) ratio and the seed/ovule (S/O) ratio in a number of species of outcrossing and inbreeding plants, where PERS=the product of (Fr/Fl) and (S/O). In order to determine the influence of the ambient environment (including resource availability) we studied pairs of outcrossing and inbreeding species occurring in the same habitat. Among outcrossing species PERS averaged about 22%, whereas in inbreeding species the average was approximately 90%. The progeny/zygote (P/Z) ratio was studied in hand-pollinated populations in Epilobium angustifolium (a strongly outcrossing species) from populations in Oregon and Utah, by direct observation of embryogenesis at twoday intervals throughout the course of seed development. The P/Z ratio in both populations averaged near 30%, and the developing embryos showed a surprising array of abnormalities that resulted in embryo death. During early development >95% of the ovules had normally developing globular embryos, but beginning with differentiation (cotyledon formation) about 70% of the original globular embryos aborted during the course of embryogenesis and seed development. The clustering of developmental lethals during peroids of major differentiation events parallels the animal model of development. We found little evidence that PERS was limited by the ambient environment (including resource availability), pollination, or factors associated with the inbreeding habit. Instead, PERS was found to be inextricably linked to outcrossing plants, whose breeding systems promote genetic variability. The high incidence of developmental lethals in E. angustifolium and the resulting low P/Z ratio (ca. 30%) is attributed to genetic load (any lethal mutation or allelic combination) possibly working in combination with developmental selection (interovarian competition among genetically diverse embryos). Examples of maternally controlled, fixed patterns of ovule abortion with respect to position or number are discussed. However, we found no need to employ "female choice" as a hypothesis to explain our results for the extensive, seemingly random patterns of embryo abortion in E. angustifolium and other outcrossing species. A more parsimonious, mechanistic explanation based on genetic load-developmental selection is sufficient to account for the differential survivorship of embryos. Likewise, the traditional concept of a positive growth regulator feedback system based on the number of surviving ovules in an ovary can account for subsequent fruit survivorship.

Impaired brain functions due to diazepam and meprobamate abuse in a 53-year-old-male.

The following case study demonstrates the important influence of diazepam and meprobamate on a patient's neuropsychological test performance. This article includes: a brief medical history and summary of previous physical examinations; brief description of the neuropsychological test battery; formulation of the original neuropsychological test findings; follow-up neuropsychological testing; and discussion. The profound interaction effect of these prescribed drugs revealed severe cognitive, memory, and motor function deficits in a 53-year-old male. These findings are in contrast to reports in the literature.

Precardiac mesoderm differentiation in vitro. Actin-isotype synthetic transitions, myofibrillogenesis, initiation of heartbeat, and the possible involvement of collagen.

The differentiation of precardiac mesoderm into beating heart tissue was examined during explant culture. Explanted tissue forms tubular heart-like vesicles and initiates rhythmic contractility within 18-24 h in vitro, a developmental time-course approximating that observed during in vivo development. Electron-microscopic observations reveal that beating heart cells are rich in cytoplasmic myofibrils in varying degrees of order, with some regions containing highly organized myofibrillar arrays. The analysis of actin-isotype biosynthesis, using metabolic labeling with [35S]-methionine and isoelectric-focusing resolution of the synthesized radioactive polypeptides, demonstrates that the initiation of cardiac alpha-actin synthesis and the pattern of transition in the synthesis of alpha-, beta-, and gamma-actin isotypes is equivalent to the initiation time and pattern observed in vivo. A possible collagen involvement in the differentiation process was investigated by assessing the effects of collagen-synthesis inhibitors on the development of the explant cultures. Two different agents, alpha, alpha'-dipyridyl and L-azetidine-2-carboxylic acid, exhibited a dose-dependent ability to inhibit the formation of beating heart tissue. When examined by electron microscopy, the nonbeating tissue exhibited a drastic depression of myofibrillogenesis, but otherwise appeared healthy. Further examination of the effect of L-azetidine-2-carboxylic acid demonstrated that the inhibition of myofibril formation and heartbeat was correlated with a 60% inhibition of native collagen synthesis; however, the time-course and pattern of actin-isotype biosynthesis was completely unaffected. The data suggest a possible involvement in heart differentiation that is necessary for either the synthesis of non-actin cardiac contractile proteins or the assembly of cardiac contractile proteins into myofibrils.

Permanent translocation heterozygosity and sex determination in East african mistletoes.

Viscum fischeri has 2n = 23 chromosomes in male plants. These fornm 7 bivalents and a translocation chain of 9 chromosomes during meiosis. Pollen with 11-and 12-chromosome genomes is thus produced. Female plants have 2n = 22 chromosomes and produce 11 bivalents during meiosis. Sex determination is technically a rare multiple X-multiple Y type, but more importantly it provides the mechanism whereby permanent translocation heterozygosity is maintained in the system. In a second species, Viscum engleri, male plants have 2n=28 chromosomes associating as 11 bivalents and a ring of 6 chomosomes at meiosis.