Arl13b belongs to the ADP-ribosylation factor family within the Ras superfamily of regulatory GTPases. Mutations in Arl13b cause Joubert syndrome, which is characterized by congenital cerebellar ataxia, hypotonia, oculomotor apraxia, and mental retardation. Arl13b is highly enriched in cilia and is required for ciliogenesis in multiple organs. Nevertheless, the precise role of Arl13b remains elusive. Here we report that the exocyst subunits Sec8, Exo70, and Sec5 bind preferentially to the GTP-bound form of Arl13b, consistent with the exocyst being an effector of Arl13b. Moreover, we show that Arl13b binds directly to Sec8 and Sec5. In zebrafish, depletion of arl13b or the exocyst subunit sec10 causes phenotypes characteristic of defective cilia, such as curly tail up, edema, and abnormal pronephric kidney development. We explored this further and found a synergistic genetic interaction between arl13b and sec10 morphants in cilia-dependent phenotypes. Through conditional deletion of Arl13b or Sec10 in mice, we found kidney cysts and decreased ciliogenesis in cells surrounding the cysts. Moreover, we observed a decrease in Arl13b expression in the kidneys from Sec10 conditional knockout mice. Taken together, our results indicate that Arl13b and the exocyst function together in the same pathway leading to functional cilia.

The mechanisms by which the pigment melanin is transferred from melanocytes and processed within keratinocytes to achieve skin pigmentation remain ill-characterized. Nevertheless, several models have emerged in the past decades to explain the transfer process. Here, we review the proposed models for melanin transfer in the skin epidermis, the available evidence supporting each one, and the recent observations in favor of the exo/phagocytosis and shed vesicles models. In order to reconcile the transfer models, we propose that different mechanisms could co-exist to sustain skin pigmentation under different conditions. We also discuss the limited knowledge about melanin processing within keratinocytes. Finally, we pinpoint new questions that ought to be addressed to solve the long-lasting quest for the understanding of how basal skin pigmentation is controlled. This knowledge will allow the emergence of new strategies to treat pigmentary disorders that cause a significant socio-economic burden to patients and healthcare systems worldwide and could also have relevant cosmetic applications.

Melanin transfer from melanocytes to keratinocytes and subsequent accumulation in the supranuclear region is a critical process in skin pigmentation and protection against UVR. We have previously proposed that the main mode of transfer between melanocytes and keratinocytes is through exo/endocytosis of the melanosome core, termed melanocore. In this study, we developed an in vitro uptake assay using melanocores secreted by melanocytes. We show that the uptake of melanocores, but not melanosomes, by keratinocytes is protease-activated receptor-2-dependent. Furthermore, we found that the silencing of the early endocytic regulator Rab5b, but not the late endocytic regulators Rab7a or Rab9a, significantly impairs melanocore uptake by keratinocytes. After uptake, we observed that melanin accumulates in compartments that are positive for both early and late endocytic markers. We found that melanin does not localize to either highly degradative or acidic organelles, as assessed by LysoTracker and DQ-BSA staining, despite the abundance of these types of organelles within keratinocytes. Therefore, we propose that melanocore uptake leads to storage of melanin within keratinocytes in hybrid endocytic compartments that are not highly acidic or degradative. By avoiding lysosomal degradation, these specialized endosomes may allow melanin to persist within keratinocytes for long periods.

Skin pigmentation involves the production of the pigment melanin by melanocytes, in melanosomes and subsequent transfer to keratinocytes. Within keratinocytes, melanin polarizes to the apical perinuclear region to form a protective cap, shielding the DNA from ultraviolet radiation‐induced damage. Previously, we found evidence to support the exocytosis by melanocytes of the melanin core, termed melanocore, followed by endo/phagocytosis by keratinocytes as a main form of transfer, with Rab11b playing a key role in the process. Here, we report the requirement for the exocyst tethering complex in melanocore exocytosis and transfer to keratinocytes. We observed that the silencing of the exocyst subunits Sec8 or Exo70 impairs melanocore exocytosis from melanocytes, without affecting melanin synthesis. Moreover, we confirmed by immunoprecipitation that Rab11b interacts with Sec8 in melanocytes. Furthermore, we found that the silencing of Sec8 or Exo70 in melanocytes impairs melanin transfer to keratinocytes. These results support our model as melanocore exocytosis from melanocytes is essential for melanin transfer to keratinocytes and skin pigmentation and suggest that the role of Rab11b in melanocore exocytosis is mediated by the exocyst.

Teotónio of Braganza (1530Braganza ( -1602 was the fifth son of Duke Jaime I of Braganza and his second wife, Joana de Mendonza. The Braganza's were the most important of the Portuguese noble families, which became the 4 th and last dynasty of the kingdom. Teotónio rose to archiepiscopal rank in 1544 and became the 4 th Archbishop of Évora from 1578 until his death. He also held other several ecclesiastical positions, namely Bishop of Fez and royal adviser of King Philip II. D. Teotónio met and kept up correspondence with people as Teresa de Ávila and Bartolomeu dos Mártires and he had in his service artists like the painter Duarte Frisão and the goldsmith João Duarte. He founded in his archdiocese several monasteries, convents and hospitals, including the Monastery of the Carthusian of Scala Coeli (1587) that received his library, consisting of rare printed and manuscript books. Under his governance, the archbishop's palace and the cathedral suffered renovation and restoration works to where he ordered a new set of ecclesiastical vestments and liturgical objects. The liturgical cope (ME 172/1) under study ( Fig. 1), together with a dalmatic, belong nowadays to the Évora Museum and make part of one of those set of ecclesiastical vests. From the same set, a chasuble, with the court of arm of D. Teotónio, is in the Sacred Art Museum and the altar frontal is in Saint Vincent church, belonging to the Town Hall. In order to clarify if these four objects belong to the same set, their material study is a fundamental issue. Thirty eight samples, between 3 and 5 mm from different points representing the different metal thread typologies and coloured silk yarns were collected for the material studies. Optical observation of sampled metal threads and silk yarns was carried out in a Leica M205C microscope. A Hitachi S-3700N variable pressure scanning electron microscope coupled with a Brüker energy dispersive X-ray spectrometer were used for surface and cross-section morphological characterisation and chemical analysis of the metal threads. Acceleration voltages of 5.0 kV (for the fibres) and 15.0 kV (for the metal threads) were used for SEM imaging and 20.0 kV was used for EDS analyses. An LCQ Advantage ThermoFinnigan mass spectrometer equipped with an ESI source, using an ion trap mass analyser and a PDA detector was coupled to an HPLC system and was used for dyed fibres analysis. The Liturgical Cope was made of a variety of materials that included two different typologies of metal threads, dyed silk yarns and vegetable yarns used in the warp/weft. It is in good conservation status, although some damaged areas were found either due to mechanical action or microbiological attack. The two main types of metal threads recorded were silver drawn wire and silver strips or gilded silver strips wound around a yellow silk core. Gilding is more extensive on the external side of the threads. The Ag-based alloy wire composition is ca. 97% silver, 1.5% gold and 1.5% copper (%wt). For the strips, there is no difference in composition be...