Genome-Wide Analysis Reveals a Major Role in Cell Fate Maintenance and an Unexpected Role in Endoreduplication for the Drosophila FoxA Gene Fork Head

Transcription factors drive organogenesis, from the initiation of cell fate decisions to the maintenance and implementation of these decisions. The Drosophila embryonic salivary gland provides an excellent platform for unraveling the underlying transcriptional networks of organ development because Drosophila is relatively unencumbered by significant genetic redundancy. The highly conserved FoxA family transcription factors are essential for various aspects of organogenesis in all animals that have been studied. Here, we explore the role of the single Drosophila FoxA protein Fork head (Fkh) in salivary gland organogenesis using two genome-wide strategies. A large-scale in situ hybridization analysis reveals a major role for Fkh in maintaining the salivary gland fate decision and controlling salivary gland physiological activity, in addition to its previously known roles in morphogenesis and survival. The majority of salivary gland genes (59%) are affected by fkh loss, mainly at later stages of salivary gland development. We show that global expression of Fkh cannot drive ectopic salivary gland formation. Thus, unlike the worm FoxA protein PHA-4, Fkh does not function to specify cell fate. In addition, Fkh only indirectly regulates many salivary gland genes, which is also distinct from the role of PHA-4 in organogenesis. Our microarray analyses reveal unexpected roles for Fkh in blocking terminal differentiation and in endoreduplication in the salivary gland and in other Fkh-expressing embryonic tissues. Overall, this study demonstrates an important role for Fkh in determining how an organ preserves its identity throughout development and provides an alternative paradigm for how FoxA proteins function in organogenesis

Biology of human hair: Know your hair to control it

Hair can be engineered at different levels—its structure and surface—through modification of its constituent molecules, in particular proteins, but also the hair follicle (HF) can be genetically altered, in particular with the advent of siRNA-based applications. General aspects of hair biology are reviewed, as well as the most recent contributions to understanding hair pigmentation and the regulation of hair development. Focus will also be placed on the techniques developed specifically for delivering compounds of varying chemical nature to the HF, indicating methods for genetic/biochemical modulation of HF components for the treatment of hair diseases. Finally, hair fiber structure and chemical characteristics will be discussed as targets for keratin surface functionalization

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The use of the LittlEARS Auditory Questionnaire in assessing children before and after cochlear implantation

Abstract Background The age of cochlear implant (CI) is a crucial factor that affects auditory skills and speech outcome in children after CI. Speech and auditory skills outcome using the Arabic form of the LittlEARS Auditory Questionnaire (LEAQ) on Arabic-speaking cochlear-implanted children is not sufficiently studied. Objective The aim of the present study was to assess. the use of the Arabic form of the LEAQ to determine the effect of age of CI on the outcome of auditory skills in children with CIs, to enhance better intervention protocols for children in need of CI and to achieve the best communicative skills for those children. Patients and Methods A total of 45 children with CI were classified into three groups according to their ages, and they were assessed using the Arabic version of LEAQ preoperatively as well as 6 and 18 months after mapping. Results Significant improvement in auditory skills and speech was reported in the three groups. The improvement was highly significant in the youngest group in comparison with the other two groups 6 and 18 months after mapping. In addition, speech and auditory skills were highly significant in each group after CI. Conclusion The age of the child at which CI is placed is a crucial factor in speech and auditory skills development. The earlier the age of CI, the better the result

Dermal papilla cells and melanocytes response to physiological oxygen levels depends on their interactions

Background: Human dermal papilla (DP) cells and melanocytes (hMel) are central players in hair growth and pigmentation, respectively. In hair follicles (HFs), oxygen (O2) levels average 5%, being coupled with the production of reactive oxygen species (ROS), necessary to promote hair growth.Materials and Methods: DP cell and hMel proliferation and phenotype were stud-ied under physiological (5%O2, physoxia) or atmospheric (21%O2, normoxia) oxygen levels. hMel-DP cells interactions were studied in indirect co-culture or by directly co-culturing hMel with DP spheroids, to test whether their interaction affected the response to physoxia.Results: Physoxia decreased DP cell senescence and improved their secretome and phenotype, as well as hMel proliferation, migration, and tyrosinase activity. In indi-rect co- cultures, physoxia affected DP cellsâ alkaline phosphatase (ALP) activity but their signalling did not influence hMel proliferation or tyrosinase activity. Additionally, ROS production was higher than in monocultures but a direct correlation between ROS generation and ALP activity in DP cells was not observed. In the 3D aggregates, where hMel are organized around the DP, both hMel tyrosinase and DP cells ALP ac-tivities, their main functional indicators, plus ROS production were higher in physoxia than normoxia.Conclusions: Overall, we showed that the response to physoxia differs according to hMel-DP cells interactions and that the microenvironment recreated when in direct contact favours their functions, which can be relevant for hair regeneration purposes.We thank Dr Luca Gasperini for his technical assistance in the image analysis using the CellProfiler™ software. The authors also thank the financial support given by the European Research Council through the consolidator grant “ECM_INK” (ERC-2016-COG-726061) and by FCT/MCTES (Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia, e Ensino Superior) through the PD/59/2013, PD/BD/113800/2015 (C. Abreu) and IF/00945/2014 (A. P. Marques) grants