First PEX11ß patient extends spectrum of peroxisomal biogenesis disorder phenotypes.

Among the human PEX genes associated with peroxisome biogenesis disorders, only the PEX11 family genes had not previously been associated with human disease. A new study identifies the first patient with a mutation in PEX11ß. The patient presents with symptoms atypical for peroxisome biogenesis disorders. Peroxisomes in cells derived from this patient appear enlarged and undivided, complying with the role of PEX11 proteins in peroxisome proliferation and division. These new findings widen the spectrum of clinical and cellular phenotypes of diseases associated with defective peroxisome formation.

Electronic control of coherence in a two-dimensional array of photonic crystal surface emitting lasers.

We demonstrate a semiconductor PCSEL array that uniquely combines an in-plane waveguide structure with nano-scale patterned PCSEL elements. This novel geometry allows two-dimensional electronically controllable coherent coupling of remote vertically emitting lasers. Mutual coherence of the PCSEL elements is verified through the demonstration of a two-dimensional Young's Slits experiment. In addition to allowing the all-electronic control of the interference pattern, this type of device offers new routes to power and brightness scaling in semiconductor lasers, and opportunities for all-electronic beam steering.

Anterior segment metastases from an ovarian choriocarcinoma.

A 28-year old woman with ovarian choriocarcinoma developed a uveitis in her left eye. Subsequently, a mass was observed in the anterior segment of that eye together with a subconjunctival mass that appeared to extend from it. Biopsy of the subconjunctival nodule showed two different cell types consistent with the cytotrophoblastic and syncytiotrophoblastic elements typical and choriocarcinoma. No abnormalities of the posterior segment were found on careful examination. Treatment consisted of systemic chemotherapy with a variety of therapeutic agents, argon laser photocoagulation of tumor seedings in the anterior chamber angle, radiation to the eye, and finally, subconjunctival injections of methotrexate. The eye became blind and painful and was enucleated. Histopathologic examination revealed residual tumor cells in the anterior segment indicating treatment changes, but there were no abnormalities posteriorly. Choriocarcinoma metastatic to the eye has been reported infrequently, and this is the first case in which anterior segment metastases have been observed and the effects of treatment thoroughly documented.

Dynamical mechanism of antifreeze proteins to prevent ice growth.

The fascinating ability of algae, insects, and fishes to survive at temperatures below normal freezing is realized by antifreeze proteins (AFPs). These are surface-active molecules and interact with the diffusive water-ice interface thus preventing complete solidification. We propose a dynamical mechanism on how these proteins inhibit the freezing of water. We apply a Ginzburg-Landau-type approach to describe the phase separation in the two-component system (ice, AFP). The free-energy density involves two fields: one for the ice phase with a low AFP concentration and one for liquid water with a high AFP concentration. The time evolution of the ice reveals microstructures resulting from phase separation in the presence of AFPs. We observed a faster clustering of pre-ice structure connected to a locking of grain size by the action of AFP, which is an essentially dynamical process. The adsorption of additional water molecules is inhibited and the further growth of ice grains stopped. The interfacial energy between ice and water is lowered allowing the AFPs to form smaller critical ice nuclei. Similar to a hysteresis in magnetic materials we observe a thermodynamic hysteresis leading to a nonlinear density dependence of the freezing point depression in agreement with the experiments.

Application of discriminant analysis with clustered data to determine anthropogenic metals contamination.

Environmental site assessments involve, among other things, characterization of the nature and extent of contamination. In general, environmental assessors are interested in empirical methodologies that can be applied to a broad range of environmental media (e.g., soils, sediments, etc.) and situations. To date, no unified guidance has been adopted, and site investigations usually involve a tiered process with multiple analyses. We propose a multivariate analysis methodology utilizing discriminant analysis with clustered chemical concentrations as a novel application to environmental site assessments that determine, in relative order of magnitude, contaminated chemicals. Finite mixture models are presented as a means to assess latent chemical clusters with some basis in statistical inference. The methodology is illustrated with a typical localized data set containing total metal and metalloid (i.e., chemical) concentrations, extracted from bulk soil collected from reference and site-related locations, obtained from a former military installation in the southeast United States. The illustration is particularly applicable because site-related soils inherently possessed higher background chemical levels than reference soils, which biased conventional analyses. However, contrasting chemical compositions were inferred within site-related samples illustrating the versatility of the proposed methodology. Using these results along with known information regarding the history of contamination at the site, a qualitative and quantitative assessment of contaminated chemicals was made. Results are intended for illustration purposes only and are discussed within the context of environmental site assessment.

Retinoic acid-induced pattern duplication in regenerating urodele limbs.

The effects of varying doses of retinoic acid on forelimb regeneration in larval Ambystoma mexicanum amputated through the wrist joint and in adult Notophthalmus viridescens amputated through the basal carpals were compared. In both species, the major effect of retinoic acid was to cause the proximodistal duplication, in the regenerate, of stump segments proximal to the amputation plane. Transverse axial duplications (anteroposterior and dorsoventral) occurred in a smaller percentage of cases; these consisted of cartilage spurs in axolotls, and extra digits in newts. The frequency and magnitude of the proximodistal and (in the newt) transverse duplications were dose dependent, and the regenerating limbs were maximally sensitive to the retinoid during the period of dedifferentiation and accumulation of blastema cells. The effect of retinoic acid is exerted on cells local to the amputation surface, as shown by the fact that retinoic acid caused the proximodistal duplication of stump segments in regenerates derived from amputated distal lower arm segments grafted to the eyesocket .

Retinoic-acid-induced pattern completion in regenerating double anterior limbs of urodeles.

The effects of retinoic acid on the regeneration of double anterior lower arms in the adult newt, Notophthalmus viridescens, were investigated. Normally, double anterior lower arms regenerate a hypomorphic, symmetrical pattern of structures, which are distally complete; and double anterior upper arms regenerate a hypomorphic, symmetrical but distally incomplete pattern of structures. In limbs with a normal anteroposterior axis, the major effect of retinoic acid is to alter the proximodistal (PD) positional value of cells local at the amputation level to a much more proximal value, thereby creating duplications in the regenerate of structures proximal to the amputation plane (Thoms and Stocum, '84). Therefore, we predicted that double anterior lower arms treated with retinoic acid would regenerate like double anterior upper arms. However, in a substantial number of cases, each half of these double anterior lower arms regenerated a limb that was complete in the anteroposterior (AP) axis, with asymmetry corresponding to the half of origin. In addition, these regenerates were serially duplicated in the PD axis. These results indicate that retinoic acid can posteriorize the positional value of midline cells, leading to restoration of normal AP pattern, when the set of posterior-half positional values is removed from the cross section of the limb.

Caffeine blocks activation of cyclic AMP synthesis in Dictyostelium discoideum.

Cyclic AMP (cAMP) appears to play multiple roles in the development of the social ameba Dictyostelium discoideum, serving as the chemoattractant mediating aggregation, and perhaps also regulating gene transcription in both early and late stages of differentiation. Progress in understanding the mechanism of activation of the adenylate cyclase in D. discoideum has been frustrated by the inability to obtain its activation in vitro. Also, the lack of defined cAMP-defective mutants has prevented a causal relationship from being established between cAMP levels and gene expression. As an alternative approach to studying the role of cAMP in D. discoideum development, we have sought a compound which inhibits cAMP synthesis in a reasonably specific manner. Here we identify caffeine as a compound which rapidly and reversibly inhibits cAMP-dependent activation of the adenylate cyclase without affecting either cell viability or intracellular levels of ATP or GTP. Using this drug, we show that cAMP synthesis is not required for the cAMP-stimulated decrease in lightscattering, the increase in cyclic GMP synthesis, or for chemotaxis toward cAMP. Studies of the mechanism of action of caffeine show that the drug does not act by inhibiting a cAMP phosphodiesterase, by inhibiting binding of cAMP to its receptor, by itself binding to a physiological adenosine receptor, or by directly inhibiting the adenylate cyclase. Instead, caffeine blocks the cAMP-dependent activation of the adenylate cyclase. Since similar effects are obtained with the cation ionophore A23187, it is possible that caffeine exerts its effect by altering intracellular calcium distribution.

Pattern regulation and the origin of extra parts following axial misalignments in the urodele limb bud.

Pattern regulation following axial misalignments in the stage-38+to stage-40 urodele limb bud was studied on one newt and two salamander species. Grafts of the distal tip of the limb bud were made to the stump of a host limb bud from which a similar piece had been removed. The grafts were positioned with either their anteroposterior, dorsoventral, or both of these axes reversed with respect to the host axes. Mirror-imaged duplications, positioned posteriorly or both anteriorly and posteriorly, occurred nearly all (96%) of the time when the anteroposterior axis was reversed. Dorsoventral axial misalignment rarely promoted the generation of mirror-imaged duplication (8%) but did affect the organization along the anteroposterior axis by causing a serial repetition of either digit 2 or digit 3. Regulation, therefore, does not always occur along each axis independently of the others. Consistent with the data derived from reversing individual axes, most of the duplications which occurred when both axes were reversed were in the anteroposterior plane. Some were in the dorsoventral plane, and a few had intermediate positions. Of these duplications a few were neither right not left hands, rather they were of mixed handedness with a change in the dorsoventral polarity from the anterior border to the posterior border. Whether extra parts which result from axial misalignments arise from the graft, the host, or both the graft and the host was investigated using heteroplastic grafts and grafts exchanged between triploid and diploid axolotls. Duplications were found to have cellular contributions from both the graft and the host. In some cases on source would dominate but usually both made a substantial contribution. The diploid-triploid material suggests that a considerable mixing of host and graft cells may occur in duplications. Additionally, some digits of the graft sequence of digits can be derived from host tissue. The extra digit in those hands displaying a serial repetition was derived from host tissue in some cases and graft tissue in other cases.

The effects of two retinoids on limb regeneration in Pleurodeles waltl and Triturus vulgaris.

The effects of two vitamin A analogues, retinol palmitate and retinoic acid, on pattern formation during limb regeneration in larvae of two European newts, P. waltl and T. vulgaris are described. The response of the regenerating limb to retinoid treatment differed according to the larval stage of development for P. waltl. Young larval limbs, which were anterior limb buds at the time of amputation, duplicated transversely while limbs of older larvae duplicated proximodistally. Proximodistal duplications were usually limited to the production of supernumerary carpals or a second zeugopod. Complete limbs regenerating from a distal amputation plane were rarely seen. T. vulgaris larvae regenerated limbs with either one or the other type of duplication, but never both on the same limb, at all larval stages tested. When larval P. waltl were kept in normal laboratory light during the treatment with retinol palmitate suspended in the rearing water the percentage of limbs which duplicated was very small for young larvae and increased with the age of the larvae used. Keeping the animals in the dark during the treatment period greatly increased the percentage of duplicate limbs obtained on the young larvae but not on the older larvae. This result is discussed in terms of the photodegradation of the retinoid and the length of the sensitive period for the regenerating limb. A dose-response relationship between the dose of retinol palmitate and either the percentage of limbs duplicated or the degree of duplication was not found. Such a relationship, however, was observed when retinoic acid was injected intraperitoneally into stage-54+ P. waltl larvae. Additionally, this technique revealed a peak of sensitivity to retinoic acid on the 6th day after amputation. Limb regeneration in older larvae was temporarily blocked by retinoid treatment. The limbs showed little or no regression and began blastemal development shortly after the treatment ended. Limbs of young larvae, however, often regressed. Such regressions were followed by blastemal formation and middle- to late-bud blastemas were found at the end of 11 or 14 days treatments with retinol palmitate.

Model of the carbon concentrating mechanism in chloroplasts of eukaryotic algae.

A generic chloroplast-based model for the carbon concentrating mechanism (CCM) in eukaryotic algae is presented. The fine structure of chloroplasts is represented by separate compartments: marginal and bulk stroma, pyrenoid, girdle lamella, bulk thylakoids, and central lamella traversing the pyrenoid. The roles of the individual structural elements of the chloroplast with respect to the CCM and the effect of carbonic anhydrase activity in various compartments are analysed. Hypothetical HCO(-)(3)transport into the acidic thylakoid lumen is adjusted by imposing an optimization principle: a given [CO(2)] at the site of RuBisCO is achieved with minimum energy costs for the CCM. Our model is highly efficient in terms of saturation of RuBisCO carboxylase activity and the affinity of the chloroplast for CO(2), if either a girdle lamella or a pyrenoid is present. The highest efficiency is achieved with a pyrenoid. A eukaryotic CCM is not necessarily associated with accumulation of dissolved inorganic carbon (DIC) as in cyanobacteria. Chloroplasts are categorized into four types corresponding to morphological characteristics of all major algal classes with regard to the presence of pyrenoids, girdle lamellae, and the distribution of CA activity.

Fabrication of multipassband moiré resonators in fibers by the dual-phase-mask exposure method.

We report on the fabrication of in-fiber moiré filters by dual exposure of a nondedicated chirped phase mask. This simple technique produces broadband filters whose structure depends only on an intermediate stretch between two identical UV exposures. We demonstrate moiré filters with as many as four narrow passbands within a 2-nm stopband.