Aurora A triggers Lgl cortical release during symmetric division to control planar spindle orientation

Mitotic spindle orientation is essential to control cell-fate specification and epithelial architecture. The tumor suppressor Lgl localizes to the basolateral cortex of epithelial cells, where it acts together with Dlg and Scrib to organize apicobasal polarity. Dlg and Scrib also control planar spindle orientation, but how the organization of polarity complexes is adjusted to control symmetric division is largely unknown. Here, we show that the Dlg complex is remodeled during Drosophila follicular epithelium cell division, when Lgl is released to the cytoplasm. Lgl redistribution during epithelial mitosis is reminiscent of asymmetric cell division, where it is proposed that Aurora A promotes aPKC activation to control the localization of Lgl and cell-fate determinants. We show that Aurora A controls Lgl localization directly, triggering its cortical release at early prophase in both epithelial and S2 cells. This relies on double phosphorylation within the putative aPKC phosphorylation site, which is required and sufficient for Lgl cortical release during mitosis and can be achieved by a combination of aPKC and Aurora A activities. Cortical retention of Lgl disrupts planar spindle orientation, but only when Lgl mutants that can bind Dlg are expressed. Hence, our work reveals that Lgl mitotic cortical release is not specifically linked to the asymmetric segregation of fate determinants, and we propose that Aurora A activation breaks the Dlg/Lgl interaction to allow planar spindle orientation during symmetric division via the Pins (LGN)/Dlg pathway.We thank J. Knoblich, D. St Johnston, D. Bilder, D. Glover, S. Brogna, R. Martinho, H. Maiato, D. Bergstralh, and the Bloomington Stock Center for fly stocks and reagents. This work was funded by FEDER funds through the Operational Competitiveness Programme COMPETE and by National Funds through FCT (Fundação para a Ciência e a Tecnologia) under the project FCOMP-01-0124-FEDER-019738 (PTDC/BIA-BCM/120132/2010), which also supported fellowships to C.C. and S.M. E.M. was funded by a Marie Curie-IEF and currently holds a FCT Investigator position

Optical Coherence Tomography Features of Active and Inactive Retinal Neovascularization in Proliferative Diabetic Retinopathy

PURPOSE: To describe spectral domain-optical coherence tomography features of retinal neovascularization in proliferative diabetic retinopathy and thus to identify novel signs of new vessel activity. METHODS: Retrospective, cross-sectional study. Data were collected over a 9-month period. Spectral domain optical coherence tomography scans were performed over areas of new vessel complexes (NVC) in both the disk and elsewhere, and were qualitatively graded by two masked observers. New vessel complexes activity was determined using clinical and angiographic criteria and correlated with spectral domain optical coherence tomography features. RESULTS: Forty-three eyes of 30 patients with proliferative diabetic retinopathy were included. Sixty-one NVC lesions (neovascularization of the disk—37.7%, neovascularization elsewhere—62.3%) were captured by spectral domain-optical coherence tomography and analyzed. Among them, 63.9% were classified as active and 36.1% as quiescent. Five distinctive features were identified as significantly different between active and quiescent NVC: the presence of vitreous hyperreflective dots in active NVC (P = 0.002) and the presence of epiretinal membrane (P = 0.04), inner retinal tissue contracture (P = 0.03), vitreous invasion (P = 0.02), and protrusion towards vitreous (P = 0.002) in quiescent NVC. CONCLUSION: In this exploratory study, the presence of vitreous hyperreflective dots, epiretinal membrane, inner retinal tissue contracture, vitreous invasion, and vitreous protrusion were identified as distinct signs of disease activity. Such parameters may be useful as a noninvasive imaging modality in eyes undergoing treatment for proliferative diabetic retinopathy

Memoria sobre el estado de la Biblioteca Provincial y Universitaria de Sevilla en el año de 1862 : lectores que han concurrido, obras que mas se han solicitado y reformas que la experiencia acredita como convenientes : escrita con arreglo a la base 29ª del Real Decreto de 8 de mayo de 1859

Anteport

Integration of aqueous (micellar) two-phase systems on the proteins separation

A two-step approach combining an aqueous two-phase system (ATPS) and an aqueous micellar two-phase system (AMTPS), both based on the thermo-responsive copolymer Pluronic L-35, is here proposed for the purification of proteins and tested on the sequential separation of three model proteins, cytochrome c, ovalbumin and azocasein. Phase diagrams were established for the ATPS, as well as co-existence curves for the AMTPS. Then, by scanning and choosing the most promising systems, the separation of the three model proteins was performed. The aqueous systems based on Pluronic L-35 and potassium phosphate buffer (pH = 6.6) proved to be the most selective platform to separate the proteins (SAzo/Cyt = 1667; SOva/Cyt = 5.33 e SAzo/Ova = 1676). The consecutive fractionation of these proteins as well as their isolation from the aqueous phases was proposed, envisaging the industrial application of this downstream strategy. The environmental impact of this downstream process was studied, considering the carbon footprint as the final output. The main contribution to the total carbon footprint comes from the ultrafiltration (~ 49%) and the acid precipitation (~ 33%) due to the energy consumption in the centrifugation. The ATPS step contributes to ~ 17% while the AMTPS only accounts for 0.30% of the total carbon footprint.publishe

A High Diffusive Model for Nanomaterials

Considerable attention is today devoted to the engineering of films widely used in photocatalytic, solar energy converters, photochemical and photoelectrochemical cells, dye-sensitized solar cells (DSSCs), to optimize electronic time response following photogeneration. However, the precise nature of transport processes in these systems has remained unresolved. To investigate such aspects of carrier dynamics, we have suggested a model for the calculation of correlation functions, expressed as the Fourier transform of the frequency-dependent complex conductivity σ(ω). Results are presented for the velocity correlation functions, the mean square deviation of position and the diffusion coefficient in systems, like TiO2 and doped Si, of large interest in present devices. Fast diffusion occurs in short time intervals of the order of few collision times. Consequences for efficiency of this fast response are discussed in relation to nanostructured devices

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

Sharing Detailed Research Data Is Associated with Increased Citation Rate

BACKGROUND: Sharing research data provides benefit to the general scientific community, but the benefit is less obvious for the investigator who makes his or her data available. PRINCIPAL FINDINGS: We examined the citation history of 85 cancer microarray clinical trial publications with respect to the availability of their data. The 48% of trials with publicly available microarray data received 85% of the aggregate citations. Publicly available data was significantly (p = 0.006) associated with a 69% increase in citations, independently of journal impact factor, date of publication, and author country of origin using linear regression. SIGNIFICANCE: This correlation between publicly available data and increased literature impact may further motivate investigators to share their detailed research data

Pax6 Expression Is Sufficient to Induce a Neurogenic Fate in Glial Progenitors of the Neonatal Subventricular Zone

The forebrain subventricular zone (SVZ) of neonatal mammals contains a large, heterogeneous population of migratory and proliferating precursors of interneurons and glia. These cell types are produced in large numbers in the immediate postnatal period, the glioblasts populating the hemispheres with astrocytes and oligodendrocytes, the neuroblasts migrating to the olfactory bulb to become interneurons. How cell fate decisions are determined or stabilized in this mixed population is not clear, although previous studies indicate the importance of two transcription factors, Pax6 in neurons and Olig2 in glia, and suggest there may be reciprocal repression between these genes.In examining the SVZ of neonatal mouse and rat brain, we find that the very large majority of SVZ cells express either Pax6 or Olig2, but few express both. We have used in vivo retro- and lenti-virus injections into the neonatal SVZ and in vitro gene transfer to demonstrate that pax6 over-expression is sufficient to down-regulate olig2 and to promote a neuronal lineage development and migration pattern in olig2-expressing cells. Furthermore, we provide evidence that Pax6 binds to the olig2 promoter and that an HEB sequence in the promoter is required for the Pax6 repression of olig2 transcription. Lastly, we constructed a lentivirus to target olig2-expressing cells in the SVZ to trace their fates, and found that the very large majority developed into glia.We provide evidence for a direct repression of olig2 by Pax6. Since SVZ cells can display developmental plasticity in vitro, the cross-repression promotes a stabilization of cell fates. This repression may be critical in a germinal zone in which immature cells are highly migratory and are not organized into an epithelium

UK Neovascular Age-Related Macular Degeneration Database. Report 6: time to retreatment after a pause in therapy. Outcomes from 92 976 intravitreal ranibizumab injections.

BACKGROUND/AIMS: To study the time to retreatment in eyes with neovascular age-related macular degeneration (nAMD) that had been treatment-free for intervals of 3 months, 6 months, 9 months and 12 months during the maintenance phase of ranibizumab therapy within the UK National Health Service. METHODS: In this multicentre national nAMD database study, structured data were collected from 14 centres (involving 12 951 eyes receiving 92 976 ranibizumab injections). Patients were treated with three fixed, monthly injections in a loading phase of treatment, followed by a pro re nata retreatment regimen in a maintenance phase. Eyes with a treatment-free interval (TFI) of 3 months, 6 months, 9 months or 12 months in the maintenance phase were identified and the time to retreatment after these TFIs was determined. RESULTS: The time to retreatment for the 20th and 50th centiles was 0.58/2.54 months after a 3-month TFI, 2.07/9.62 months after a 6-month TFI, 3.69/15.84 months after a 9-month TFI and 5.90/22.49 months after a 12-month TFI. Following a TFI of 3 months, 6 months, 9 months and 12 months, 68%, 44%, 31% and 21% of eyes required retreatments after an additional 6 months of follow-up, respectively. Similarly, after 12 months of follow-up, 77%, 56%, 43% and 34% of these eyes required retreatment. CONCLUSIONS: This study provides times to retreatment in eyes with nAMD that have been treatment-free for intervals of 3-12 months and demonstrates the likelihood of repeat therapy within the next year, even after a TFI of 12 months. These outcomes can help plan appropriate follow-up intervals for patients who have been treatment-free for intervals of up to 12 months