PAR Domains Research Articles

The Effectiveness of In-house Clear Aligners and Traditional Fixed Appliances in Achieving Good Occlusion in Complex Orthodontic Cases: A Randomized Control Clinical Trial.

Objective: To compare the effectiveness and efficiency of the in-house clear aligners with the traditional fixed appliances in treating premolar-extraction-based complex cases.Materials and methods: A single-centered, 2-arm parallel-group randomized controlled clinical trial was conducted on thirty-six (12 males, 24 females; mean age: 21.24 ± 2.33) patients with severe crowding who required orthodontic treatment with four first premolars extraction. The patients were equally and randomly divided into two groups: The in-house clear aligners (CA) group and the fixed appliances (FA) group. All the measurements were made on the pre-and post-treatment dental cast models. The effectiveness was evaluated using Little's irregularity index (LII) and the Peer Assessment Rating index (PAR). The efficiency was evaluated by studying the treatment duration. Two sample t-tests and chi-square tests were used to test for significant differences between the two groups. Bonferroni correction was applied, and the adjusted alpha level was set at 0.006. Results: Before treatment, there were no significant differences between the two groups regarding LII in the upper and lower jaws (p˃0.006). After treatment, the mean LII decreased in both groups, with no significant differences between the two studied groups (p˃0.006). There were no significant differences in all studied PAR domains between the two groups (p˃0.006). The mean score reduction in the CA group was 28.39 (±8.51) points, whereas it was 26.39 (±5.76) points in the FA group, with no significant differences between the two groups. All the patients in this study were improved. However, a great improvement was achieved in 88.9% of the patients in the CA group and 91.7% in the FA group, with no significant differences between them (p=0.674). The average treatment duration in the CA group was 23.27 (±5.28) months, whereas the average was 26.20 (±5.27) in the FA group, with no significant difference between the two groups.Conclusion: In-house clear aligners can be effective as fixed appliances in achieving good occlusion when treating complex orthodontic cases when suitable teeth movement protocol is used.

Midnight Sun to Polar Night: A Model of Seasonal Light in the Barents Sea

AbstractArctic marine ecosystems are strongly influenced by the extreme seasonality of light in the region. Accurate determination of light is essential for building a comprehensive understanding of the dynamics of animal and aquatic algae populations. Current approaches to underwater light field parameterisations rely upon shortwave radiation (300–3000 nm) estimates from satellites or surface radiometry measurements to populate full radiative transfer software. Due to the inaccessibility of many regions in the Arctic, measured data is not widely available. This study presents a model of spectrally resolved underwater light in ice‐free conditions in the Barents Sea. Given a location and time, the model accounts for downwelling spectral irradiance in the photosynthetically active radiation (PAR, 400–700 nm) range (ED PAR) at the ocean surface from solar, lunar, and galactic light sources, modulated by local cloud cover. We demonstrate the ability to extend over the full year into the period of Polar Night, validated in both broadband PAR and spectral domains. Using a bio‐optical model of diffuse attenuation developed for the Barents Sea, we show accurate calculations to depth for inhomogeneous water columns over a spatial‐temporal range, validated against time series irradiance data from the ArcLight observatory in Ny‐Ålesund, Svalbard and in‐situ irradiance sensors deployed in the Barents Sea. Finally, in comparison to state‐of‐the‐art radiative transfer models, averaged over the water column we demonstrate a typical mean absolute error of <1 μmol m−2 s−1 in ED PAR for overcast conditions (<6 μmol m−2 s−1 for clear‐sky) and reduced execution time of factor 20.

Tubulogenesis in a simple cell cord requires the formation of bi-apical cells through two discrete Par domains

Apico-basal polarization is a crucial step in the de novo formation of biological tubes. In Ciona notochord, tubulogenesis occurs in a single file of cells in the absence of cell proliferation. This configuration presents a unique challenge for the formation of a continuous lumen. Here, we show that this geometric configuration is associated with a novel polarization strategy: the generation of bipolar epithelial cells possessing two apical/luminal domains instead of one, as in the conventional epithelium. At the molecular level, cells establish two discrete Par3/Par6/aPKC patches, and form two sets of tight junctions, in opposite points of the cells. The key molecule controlling the formation of both domains is Par3. Changing the position of the cells within the organ fundamentally changes their polarity and the number of apical domains they develop. These results reveal a new mechanism for tubulogenesis from the simplest cell arrangement, which occurs in other developmental contexts, including vertebrate vascular anastomosis.

Principles of PAR polarity in Caenorhabditis elegans embryos

A hallmark of cell polarity in metazoans is the distribution of partitioning defective (PAR) proteins into two domains on the membrane. Domain boundaries are set by the collective integration of mechanical, biochemical and biophysical signals, and the resulting PAR domains define areas of cytosol specialization. However, the complexity of the signals acting on PAR proteins has been a barrier to uncovering the general principles of PAR polarity. We propose that physical studies, when combined with genetic data, provide new understanding of the mechanisms of polarity establishment in the Caenorhabditis elegans embryo and other organisms.

Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes

A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex1, 2. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance1, 2, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3/aPKC complex to leave the cortex. Our findings illustrate how microtubules, independent of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC.

PAR-3 Oligomerization May Provide an Actin-Independent Mechanism to Maintain Distinct Par Protein Domains in the Early Caenorhabditis elegans Embryo

Par proteins establish discrete intracellular spatial domains to polarize many different cell types. In the single-cell embryo of the nematode worm Caenorhabditis elegans, the segregation of Par proteins is crucial for proper division and cell fate specification. Actomyosin-based cortical flows drive the initial formation of anterior and posterior Par domains, but cortical actin is not required for the maintenance of these domains. Here we develop a model of interactions between the Par proteins that includes both mutual inhibition and PAR-3 oligomerization. We show that this model gives rise to a bistable switch mechanism, allowing the Par proteins to occupy distinct anterior and posterior domains seen in the early C. elegans embryo, independent of dynamics or asymmetries in the actin cortex. The model predicts a sharp loss of cortical Par protein asymmetries during gradual depletion of the Par protein PAR-6, and we confirm this prediction experimentally. Together, these results suggest both mutual inhibition and PAR-3 oligomerization are sufficient to maintain distinct Par protein domains in the early C. elegans embryo.

PAR proteins diffuse freely across the anterior–posterior boundary in polarized C. elegans embryos

Polarization of cells by PAR proteins requires the segregation of antagonistic sets of proteins into two mutually exclusive membrane-associated domains. Understanding how nanometer scale interactions between individual PAR proteins allow spatial organization across cellular length scales requires determining the kinetic properties of PAR proteins and how they are modified in space. We find that PAR-2 and PAR-6, which localize to opposing PAR domains, undergo exchange between well mixed cytoplasmic populations and laterally diffusing membrane-associated states. Domain maintenance does not involve diffusion barriers, lateral sorting, or active transport. Rather, both PAR proteins are free to diffuse between domains, giving rise to a continuous boundary flux because of lateral diffusion of molecules down the concentration gradients that exist across the embryo. Our results suggest that the equalizing effects of lateral diffusion are countered by actin-independent differences in the effective membrane affinities of PAR proteins between the two domains, which likely depend on the ability of each PAR species to locally modulate the membrane affinity of opposing PAR species within its domain. We propose that the stably polarized embryo reflects a dynamic steady state in which molecules undergo continuous diffusion between regions of net association and dissociation.

Long Astral Microtubules and RACK-1 Stabilize Polarity Domains during Maintenance Phase in Caenorhabditis elegans Embryos

Cell polarity is a very well conserved process important for cell differentiation, cell migration, and embryonic development. After the establishment of distinct cortical domains, polarity cues have to be stabilized and maintained within a fluid and dynamic membrane to achieve proper cell asymmetry. Microtubules have long been thought to deliver the signals required to polarize a cell. While previous studies suggest that microtubules play a key role in the establishment of polarity, the requirement of microtubules during maintenance phase remains unclear. In this study, we show that depletion of Caenorhabditis elegans RACK-1, which leads to short astral microtubules during prometaphase, specifically affects maintenance of cortical PAR domains and Dynamin localization. We then investigated the consequence of knocking down other factors that also abolish astral microtubule elongation during polarity maintenance phase. We found a correlation between short astral microtubules and the instability of PAR-6 and PAR-2 domains during maintenance phase. Our data support a necessary role for astral microtubules in the maintenance phase of cell polarity.

SPAT-1/Bora acts with Polo-like kinase 1 to regulate PAR polarity and cell cycle progression

During asymmetric cell division, cell polarity and cell cycle progression are tightly coordinated, yet mechanisms controlling both these events are poorly understood. Here we show that the Bora homologue SPAT-1 regulates both PAR polarity and cell cycle progression in C. elegans embryos. We find that, similarly to mammalian cells, SPAT-1 acts with PLK-1 and not with the mitotic kinase Aurora A (AIR-1), as shown in Drosophila. SPAT-1 binds to PLK-1, and depletion of SPAT-1 or PLK-1 leads to similar cell division defects in early embryos, which differ from the defects caused by depletion of AIR-1. Additionally, SPAT-1 and PLK-1 depletion causes impaired polarity with abnormal length of the anterior and posterior PAR domains, and partial plk-1(RNAi) or spat-1(RNAi), but not air-1(RNAi), can rescue the lethality of a par-2 mutant. SPAT-1 is enriched in posterior cells, and this enrichment depends on PAR polarity and PLK-1. Taken together, our data suggest a model in which SPAT-1 promotes the activity of PLK-1 to regulate both cell polarity and cell cycle timing during asymmetric cell division, providing a link between these two processes.

Cortical domain correction repositions the polarity boundary to match the cytokinesis furrow in C. elegans embryos

In asymmetrically dividing cells, a failure to coordinate cell polarity with the site of cell division can lead to cell fate transformations and tumorigenesis. Cell polarity in C. elegans embryos is defined by PAR proteins, which occupy reciprocal halves of the cell cortex. During asymmetric division, the boundary between the anterior and posterior PAR domains precisely matches the site of cell division, ensuring exclusive segregation of cell fate. The PAR domains determine the site of cell division by positioning the mitotic spindle, suggesting one means by which cell polarity and cell division might be coordinated. Here, we report that cell polarity and cell division are coordinated through an additional mechanism: the site of cell division repositions the PAR-2 boundary. Galpha-mediated microtubule-cortex interactions appear to direct cortical flows of PAR-2 and myosin toward the site of cell division, which acts as a PAR-2 and myosin sink. Embryos with defects in PAR-2 boundary correction undergo mis-segregation of cortical polarity and cytoplasmic determinants, suggesting that PAR domain correction might help prevent cell fate transformation.

The Rho GTPase-activating proteins RGA-3 and RGA-4 are required to set the initial size of PAR domains in Caenorhabditis elegans one-cell embryos

Caenorhabditis elegans embryos establish cortical domains of PAR proteins of reproducible size before asymmetric cell division. The ways in which the size of these domains is set remain unknown. Here we identify the GTPase-activating proteins (GAPs) RGA-3 and RGA-4, which regulate the activity of the small GTPase RHO-1. rga-3/4(RNAi) embryos have a hypercontractile cortex, and the initial relative size of their anterior and posterior PAR domains is altered. Thus, RHO-1 activity appears to control the level of cortical contractility and concomitantly the size of cortical domains. These data support the idea that in C. elegans embryos the initial size of the PAR domains is set by regulating the contractile activity of the acto-myosin cytoskeleton through the activity of RHO-1. RGA-3/4 have functions different from CYK-4, the other known GAP required for the first cell division, showing that different GAPs cooperate to control the activity of the acto-myosin cytoskeleton in the first cell division of C. elegans embryos.

An Essential Function of the C. elegans Ortholog of TPX2 Is to Localize Activated Aurora A Kinase to Mitotic Spindles

In vertebrates, the microtubule binding protein TPX2 is required for meiotic and mitotic spindle assembly. TPX2 is also known to bind to and activate Aurora A kinase and target it to the spindle. However, the relationship between the TPX2-Aurora A interaction and the role of TPX2 in spindle assembly is unclear. Here, we identify TPXL-1, a C. elegans protein that is the first characterized invertebrate ortholog of TPX2. We demonstrate that an essential role of TPXL-1 during mitosis is to activate and target Aurora A to microtubules. Our data suggest that this targeting stabilizes microtubules connecting kinetochores to the spindle poles. Thus, activation and targeting of Aurora A appears to be an ancient and conserved function of TPX2 that plays a central role in mitotic spindle assembly.

Bio-optical properties of the northern Red Sea and the Gulf of Eilat (Aqaba) during winter 1999

Underwater light field, chlorophyll-a concentration , phytoplankton absorption spectra, chlorophyll-a specific absorption coefficients, and phytoplankton diversity in the Gulf of Eilat (Aqaba) and northern Red Sea, were studied during a cruise on the RV ‘Meteor’ in winter - early spring, February–March 1999. The mean euphotic depth of the entire area was 86 ± 8 m. The vertical attenuation coefficient, K d (PAR), averaged from the surface down to 100 m depth, was only 0.054 ± 0.006 m − 1, as might be expected from the low chlorophyll-a concentrations (< 0.4 μg l − 1). The spectral attenuation coefficients were similar in the entire area. The contribution of yellow substances to attenuation was negligible. Chlorophyll-a specific absorption coefficients for both the UV and PAR domains in the entire study area were representative of the dominant picophytoplankton. When mixing depth reached 600 m, on average each alga was exposed to 3% of surface light. Phytoplankton populations, as quantified by flow cytometry, were typical of oligotrophic oceans. In the Red Sea, the deep chlorophyll maximum developed at about 50–60 m, ∼ 1 × 10 8 cells l − 1, dominated by high concentrations of Prochlorococcus (∼ 75%) , whereas in the Gulf of Eilat (Aqaba), ∼ 4 × 10 7 cells l − 1, eukaryotic algae (∼ 20%), cyanobacteria ( Synechococcus) (∼ 50%), and Prochlorococcus (∼ 25%), were distributed throughout the water column. The cell size and pigment concentrations did not depend on depth distribution or geographic location. The northern Red Sea is permanently stratified, while at that time of year, the Gulf waters were deeply mixed. The results illustrate the common features of these two domains, while underscoring their differences. Even though they share the typical phytoplankton attributes of oligotrophic ocean provinces, mixing regimes still set them apart.

The Drosophila PAR Domain Protein 1 (Pdp1) Gene Encodes Multiple Differentially Expressed mRNAs and Proteins through the Use of Multiple Enhancers and Promoters

Transcription factors are often expressed at several times and in multiple tissues during development and regulate diverse sets of downstream target genes by varying their combinatorial interactions with other transcription factors. The Drosophila Tropomyosin I (TmI) gene is regulated by a complex of proteins within the enhancer that synergistically interacts with MEF2 to activate TmI transcription as muscle cells fuse and differentiate. One of the components of this complex is PDP1 (PAR domain protein 1), a basic leucine zipper transcription factor that is highly homologous to three vertebrate genes that are members of the PAR domain subfamily. We have isolated and describe here the structure of the Pdp1 gene. The Pdp1 gene is complex, containing at least four transcriptional start sites and producing at least six different mRNAs and PDP1 isoforms. Five of the PDP1 isoforms differ by the substitution or insertion of amino acids at or near the N-terminal of the protein. At least three of these alternately spliced transcripts are differentially expressed in different tissues of the developing embryo in which PDP1 expression is correlated with the differentiation of different cell types. A sixth isoform is produced by splicing out part of the PAR and basic DNA binding domains, and DNA binding and transient transfection experiments suggest that it functions as a dominant negative inhibitor of transcription. Furthermore, two enhancers have been identified within the gene that express in the somatic mesodermal precursors to body wall muscles and fat body and together direct expression in other tissues that closely mimics that of the endogenous gene. These results show that Pdp1 is widely expressed, including in muscle, fat, and gut precursors, and is likely involved in the transcriptional control of different developmental pathways through the use of differentially expressed PDP1 isoforms. Furthermore, the similarities between Pdp1 and the other PAR domain genes suggest that Pdp1 is the homologue of the vertebrate genes.

Optical properties of polystyrene and polyarylate block copolymer and their control by morphology generation

Relationship between phase morphology and optical properties of polystyrene and polyarylate (PS-PAr) block copolymers synthesized from telechelic polystyrene has been investigated. In the PS-PAr block copolymers, the PAr domains with higher melt viscosity were dispersed in the PS phase matrix with lower melt viscosity over the wide range of their composition from PS/PAr = 25/75 to 75/25 (wt ratio). The PAr domain size was dependent on the reactive ratio of PAr determined analogously by the mole fraction of the fed telechelic polystyrene. By controlling the mole fraction of the telechelic polystyrene more than 0.016 in synthesizing the PS-PAr block copolymer, the size of PAr domains could be reduced to the microscopic scale (smaller than 100 nm). Then, the PS-PAr block copolymers exhibited almost the same transparency as PAr in spite of the large difference in the refractive index between the PS and the PAr phase. Birefringence free condition for the PS-PAr block copolymers was determined by not only the PS/PAr composition but also the balance in the degree of molecular orientation of these chains. The latter factor suggests that PS and PAr chains undergo inhomogeneous stress and relaxation history during the injection process. By controlling Mn (number average molecular weight) and weight fraction of the fed OH-PS-OH around 20 000 and 55 wt %, respectively, in the synthesis of the PS-PAr block copolymer, the PS-PAr block copolymer exhibited almost zero birefringence without any sacrifice of transparency. Because in the PS-PAr block copolymer low birefringence and high transparency can coexist by controlling the adequate feeding condition in the synthesis process, the PS-PAr block copolymer would be a promising material for optical applications, such as a substrate of optical disks or optical lenses. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 953–961, 2000