The role of Eya1 and Eya2 in the taste system of mice from embryonic stage to adulthood

Members of the Eya family, which are a class of transcription factors with phosphatase activity, are widely expressed in cranial sensory organs during development. However, it is unclear whether these genes are expressed in the taste system during development and whether they play any role in specifying taste cell fate. In this study, we report that Eya1 is not expressed during embryonic tongue development but that Eya1-expressing progenitors in somites or pharyngeal endoderm give rise to tongue musculature or taste organs, respectively. In the Eya1-deficient tongues, these progenitors do not proliferate properly, resulting in a smaller tongue at birth, impaired growth of taste papillae, and disrupted expression of Six1 in the papillary epithelium. On the other hand, Eya2 is specifically expressed in endoderm-derived circumvallate and foliate papillae located on the posterior tongue during development. In adult tongues, Eya1 is predominantly expressed in IP3R3-positive taste cells in the taste buds of the circumvallate and foliate papillae, while Eya2 is persistently expressed in these papillae at higher levels in some epithelial progenitors and at lower levels in some taste cells. We found that conditional knockout of Eya1 in the third week or Eya2 knockout reduced Pou2f3+, Six1+ and IP3R3+ taste cells. Our data define for the first time the expression patterns of Eya1 and Eya2 during the development and maintenance of the mouse taste system and suggest that Eya1 and Eya2 may act together to promote lineage commitment of taste cell subtypes

Smarca4 deficiency induces Pttg1 oncogene upregulation and hyperproliferation of tubular and interstitial cells during kidney development

Kidney formation and nephrogenesis are controlled by precise spatiotemporal gene expression programs, which are coordinately regulated by cell-cycle, cell type-specific transcription factors and epigenetic/chromatin regulators. However, the roles of epigenetic/chromatin regulators in kidney development and disease remain poorly understood. In this study, we investigated the impact of deleting the chromatin remodeling factor Smarca4 (Brg1), a human Wilms tumor-associated gene, in Wnt4-expressing cells. Smarca4 deficiency led to severe tubular defects and a shortened medulla. Through unbiased single-cell RNA sequencing analyses, we identified multiple types of Wnt4Cre-labeled interstitial cells, along with nephron-related cells. Smarca4 deficiency increased interstitial cells but markedly reduced tubular cells, resulting in cells with mixed identity and elevated expression of cell-cycle regulators and genes associated with extracellular matrix and epithelial-to-mesenchymal transition/fibrosis. We found that Smarca4 loss induced a significant upregulation of the oncogene Pttg1 and hyperproliferation of Wnt4Cre-labeled cells. These changes in the cellular state could hinder the cellular transition into characteristic tubular structures, eventually leading to fibrosis. In conclusion, our findings shed light on novel cell types and genes associated with Wnt4Cre-labeled cells and highlight the critical role of Smarca4 in regulating tubular cell differentiation and the expression of the cancer-causing gene Pttg1 in the kidney. These findings may provide valuable insights into potential therapeutic strategies for renal cell carcinoma resulting from SMARCA4 deficiency

Descope of the ALIA mission

The present work reports on a feasibility study commissioned by the Chinese Academy of Sciences of China to explore various possible mission options to detect gravitational waves in space alternative to that of the eLISA/LISA mission concept. Based on the relative merits assigned to science and technological viability, a few representative mission options descoped from the ALIA mission are considered. A semi-analytic Monte Carlo simulation is carried out to understand the cosmic black hole merger histories starting from intermediate mass black holes at high redshift as well as the possible scientific merits of the mission options considered in probing the light seed black holes and their coevolution with galaxies in early Universe. The study indicates that, by choosing the armlength of the interferometer to be three million kilometers and shifting the sensitivity floor to around one-hundredth Hz, together with a very moderate improvement on the position noise budget, there are certain mission options capable of exploring light seed, intermediate mass black hole binaries at high redshift that are not readily accessible to eLISA/LISA, and yet the technological requirements seem to within reach in the next few decades for China

Case-control study of diarrheal disease etiology in individuals over 5 years in southwest China

Acute diarrhea is one of the major public health problems worldwide. Most of studies on acute diarrhea have been made on infants aged below 5 years and few efforts have been made to identify the etiological agents of acute diarrhea in people over five, especially in China. 271 diarrhea cases and 149 healthy controls over 5 years were recruited from four participating hospitals between June 2014 and July 2015. Each stool specimen was collected to detect a series of enteric pathogens, involving five viruses (Rotavirus group A, RVA; Norovirus, NoV; Sapovirus, SaV; Astrovirus, As; and Adenovirus, Ad), seven bacteria (diarrheagenic Escherichia coli, DEC; non-typhoidal Salmonella, NTS; Shigella spp.; Vibrio cholera; Vibrio parahaemolyticus ; Aeromonas spp.; and Plesiomonas spp.) and three protozoa (Cryptosporidium spp., Giardia lamblia, G. lamblia, and Blastocystis hominis, B. hominis). Standard microbiological and molecular methods were applied to detect these pathogens. Data was analyzed using Chi square, Fisher-exact tests and logistic regressions. The prevalence of at least one enteric pathogen was detected in 29.2% (79/271) acute diarrhea cases and in 12.1% (18/149) in healthy controls (p < 0.0001). Enteric viral infections (14.4%) were the most common in patients suffering from acute diarrhea, followed by bacteria (13.7%) and intestinal protozoa (4.8%). DEC (12.5%) was the most common causative agent in diarrhea cases, followed by NoV GII (10.0%), RVA (7.4%) and B. hominis (4.8%). The prevalence of co-infection was statistically higher (p = 0.0059) in the case group (7.7%) than in the healthy control (1.3%). RVA-NoV GII (3.0%) was the most common co-infection in symptomatic cases. DEC was the most predominant pathogen in diarrhea cases, but it was largely overlooked because the lack of laboratory capacities. Because of the high prevalence of co-infections, it is recommended the urgent development of alternative laboratory methods to assess polymicrobial infections. Such methodological improvements will result in a better prevention and treatment strategies to control diarrhea illness in China. The online version of this article (doi:10.1186/s13099-016-0141-1) contains supplementary material, which is available to authorized users

EYA1 and SIX1 drive the neuronal developmental program in cooperation with the SWI/SNF chromatin-remodeling complex and SOX2 in the mammalian inner ear

Inner ear neurogenesis depends upon the function of the proneural basic helix-loop-helix (bHLH) transcription factors NEUROG1 and NEUROD1. However, the transcriptional regulation of these factors is unknown. Here, using loss- and gain-of-function models, we show that EYA1 and SIX1 are crucial otic neuronal determination factors upstream of NEUROG1 and NEUROD1. Overexpression of both Eya1 and Six1 is sufficient to convert non-neuronal epithelial cells within the otocyst and cochlea as well as the 3T3 fibroblast cells into neurons. Strikingly, all the ectopic neurons express not only Neurog1 and Neurod1 but also mature neuronal markers such as neurofilament, indicating that Eya1 and Six1 function upstream of, and in the same pathway as, Neurog1 and Neurod1 to not only induce neuronal fate but also regulate their differentiation. We demonstrate that EYA1 and SIX1 interact directly with the SWI/SNF chromatin-remodeling subunits BRG1 and BAF170 to drive neurogenesis cooperatively in 3T3 cells and cochlear nonsensory epithelial cells, and that SOX2 cooperates with these factors to mediate neuronal differentiation. Importantly, we show that the ATPase BRG1 activity is required for not only EYA1- and SIX1-induced ectopic neurogenesis but also normal neurogenesis in the otocyst. These findings indicate that EYA1 and SIX1 are key transcription factors in initiating the neuronal developmental program, probably by recruiting and interacting with the SWI/SNF chromatin-remodeling complex to specifically mediate Neurog1 and Neurod1 transcription

Six1 is essential for differentiation and patterning of the mammalian auditory sensory epithelium

International audienceThe organ of Corti in the cochlea is a two-cell layered epithelium: one cell layer of mechanosensory hair cells that align into one row of inner and three rows of outer hair cells interdigitated with one cell layer of underlying supporting cells along the entire length of the cochlear spiral. These two types of epithelial cells are derived from common precursors in the four- to five-cell layered primordium and acquire functionally important shapes during terminal differentiation through the thinning process and convergent extension. Here, we have examined the role of Six1 in the establishment of the auditory sensory epithelium. Our data show that prior to terminal differentiation of the precursor cells, deletion of Six1 leads to formation of only a few hair cells and defective patterning of the sensory epithelium. Previous studies have suggested that downregulation of Sox2 expression in differentiating hair cells must occur after Atoh1 mRNA activation in order to allow Atoh1 protein accumulation due to antagonistic effects between Atoh1 and Sox2. Our analysis indicates that downregulation of Sox2 in the differentiating hair cells depends on Six1 activity. Furthermore, we found that Six1 is required for the maintenance of Fgf8 expression and dynamic distribution of N-cadherin and E-cadherin in the organ of Corti during differentiation. Together, our analyses uncover essential roles of Six1 in hair cell differentiation and formation of the organ of Corti in the mammalian cochlea

Version management for business process schema evolution

The current business environment changes rapidly, dictated by user requirements and market opportunities. Organisations are therefore driven to continuously adapt their business processes to new conditions. Thus, management of business process schema evolution, particularly process version control, is in great demand to capture the dynamics of business process schema changes. This paper aims to facilitate version control for business process schema evolution, with an emphasis on version compatibility, co-existence of multiple versions and dynamic version shifts. A multi-level versioning approach is established to specify dependency between business process schema evolutions, and a novel version preserving graph model is proposed to record business process schema evolutions. A set of business process schema updating operations is devised to support the entire set of process change patterns. By maintaining sufficient and necessary schema and version information, our approach provides comprehensive support for navigating process instance executions of different and changing versions, and deriving the process schema of a certain version. A prototype is also implemented for the proof-of-concept purpose