Tissue and molecular heterogeneities are present in the developing secondary palate along the anteroposterior (AP) axis in mice. Here, we show that Wnt5a and its receptor Ror2 are expressed in a graded manner along the AP axis of the palate. Wnt5a deficiency leads to a complete cleft of the secondary palate, which exhibits distinct phenotypic alterations at histological, cellular and molecular levels in the anterior and posterior regions of the palate. We demonstrate that there is directional cell migration within the developing palate. In the absence of Wnt5a, this directional cell migration does not occur. Genetic studies and in vitro organ culture assays further demonstrate a role for Ror2 in mediating Wnt5a signaling in the regulation of cell proliferation and migration during palate development. Our results reveal distinct regulatory roles for Wnt5a in gene expression and cell proliferation along the AP axis of the developing palate, and an essential role for Wnt5a in the regulation of directional cell migration.

Cleft palate is a congenital disorder arising from a failure in the multistep process of palate development. In its mildest form the cleft affects only the posterior soft palate. In more severe cases the cleft includes the soft (

The short stature homeobox gene SHOX is associated with idiopathic short stature in humans, as seen in Turner syndrome and Leri-Weill dyschondrosteosis, while little is known about its close relative SHOX2. We report the restricted expression of Shox2 in the anterior domain of the secondary palate in mice and humans. Shox2-/- mice develop an incomplete cleft that is confined to the anterior region of the palate, an extremely rare type of clefting in humans. The Shox2-/- palatal shelves initiate, grow and elevate normally, but the anterior region fails to contact and fuse at the midline, owing to altered cell proliferation and apoptosis, leading to incomplete clefting within the presumptive hard palate. Accompanied with these cellular alterations is an ectopic expression of Fgf10 and Fgfr2c in the anterior palatal mesenchyme of the mutants. Tissue recombination and bead implantation experiments revealed that signals from the anterior palatal epithelium are responsible for the restricted mesenchymal Shox2 expression. BMP activity is necessary but not sufficient for the induction of palatal Shox2 expression. Our results demonstrate an intrinsic requirement for Shox2 in palatogenesis, and support the idea that palatogenesis is differentially regulated along the anteroposterior axis. Furthermore, our results demonstrate that fusion of the posterior palate can occur independently of fusion in the anterior palate.

Plant pathogenic bacteria cause high crop and economic losses to human societies [1][2][3] . Infections by such pathogens are challenging to control as they often arise through complex interactions between plants, pathogens and the plant microbiome 4,5 . This natural ecosystem is rarely studied experimentally at the microbiome-wide scale, and consequently we poorly understand how taxonomic and functional microbiome composition and the resulting ecological interactions affect pathogen growth and disease outbreak. Here we combine DNA-based soil microbiome analysis with in vitro and in planta bioassays to show that competition for iron via secreted siderophore molecules is a good predictor of microbe-pathogen interactions and plant protection. We examined the ability of 2150 individual bacterial members of 80 rhizosphere microbiomes, covering all major phylogenetic lineages, to suppress the bacterium Ralstonia solanacearum, a global phytopathogen capable of infecting various crops 6,7 . We found that secreted siderophores altered microbiome-pathogen interactions from complete pathogen suppression to strong facilitation. Rhizosphere microbiome members with growth-inhibitory siderophores could often suppress the pathogen in vitro, in natural and greenhouse soils, and protect tomato plants from infection.Conversely, rhizosphere microbiome members with growth-promotive siderophores were often inferior in competition and facilitated plant infection by the pathogen. Because siderophores are a #

In the past few decades, several devastating heat wave events have significantly challenged public health. As these events are projected to increase in both severity and frequency in the future, it is important to assess the relationship between heat waves and the health indicators that can be used in the early warning systems to guide the public health response. Yet there is a knowledge gap in the impact of heat waves on morbidity. In this study, a comprehensive review was conducted to assess the relationship between heat waves and different morbidity indicators, and to identify the vulnerable populations. The PubMed and ScienceDirect database were used to retrieve published literature in English from 1985 to 2014 on the relationship between heat waves and morbidity, and the following MeSH terms and keywords were used: heat wave, heat wave, morbidity, hospital admission, hospitalization, emergency call, emergency medical services, and outpatient visit. Thirty-three studies were included in the final analysis. Most studies found a short-term negative health impact of heat waves on morbidity. The elderly, children, and males were more vulnerable during heat waves, and the medical care demand increased for those with existing chronic diseases. Some social factors, such as lower socioeconomic status, can contribute to heat-susceptibility. In terms of study methods and heat wave definitions, there remain inconsistencies and uncertainties. Relevant policies and guidelines need to be developed to protect vulnerable populations. Morbidity indicators should be adopted in heat wave early warning systems in order to guide the effective implementation of public health actions.

IntroductionDengue is endemic in more than 100 countries, mainly in tropical and subtropical regions, and the incidence has increased 30-fold in the past 50 years. The situation of dengue in China has become more and more severe, with an unprecedented dengue outbreak hitting south China in 2014. Building a dengue early warning system is therefore urgent and necessary for timely and effective response.Methodology and Principal FindingsIn the study we developed a time series Poisson multivariate regression model using imported dengue cases, local minimum temperature and accumulative precipitation to predict the dengue occurrence in four districts of Guangzhou, China. The time series data were decomposed into seasonal, trend and remainder components using a seasonal-trend decomposition procedure based on loess (STL). The time lag of climatic factors included in the model was chosen based on Spearman correlation analysis. Autocorrelation, seasonality and long-term trend were controlled in the model. A best model was selected and validated using Generalized Cross Validation (GCV) score and residual test. The data from March 2006 to December 2012 were used to develop the model while the data from January 2013 to September 2014 were employed to validate the model. Time series Poisson model showed that imported cases in the previous month, minimum temperature in the previous month and accumulative precipitation with three month lags could project the dengue outbreaks occurred in 2013 and 2014 after controlling the autocorrelation, seasonality and long-term trend.ConclusionsTogether with the sole transmission vector Aedes albopictus, imported cases, monthly minimum temperature and monthly accumulative precipitation may be used to develop a low-cost effective early warning system.

This study emphasises how cold weather is responsible for most part of the temperature-related CVD death burden. Our results may have important implications for the development of policies to reduce CVD mortality from extreme temperatures.

The temporomandibular joint (TMJ) is a unique synovial joint whose development differs from the formation of other synovial joints. Mutations have been associated with the developmental defects of the TMJ only in a few genes. In this study, we report the expression of the homeobox gene Shox2 in the cranial neural crest derived mesenchymal cells of the maxilla-mandibular junction and later in the progenitor cells and undifferentiated chondrocytes of the condyle as well as the glenoid fossa of the developing TMJ. A conditional inactivation of Shox2 in the cranial neural crest-derived cells causes developmental abnormalities in the TMJ, including dysplasia of the condyle and glenoid fossa. The articulating disc forms but fuses with the fibrous layers of the condyle and glenoid fossa, clinically known as TMJ ankylosis. Histological examination indicates a delay in development in the mutant TMJ, accompanied by a significantly reduced rate of cell proliferation. In situ hybridization further demonstrates an altered expression of several key osteogenic genes and a delayed expression of the osteogenic differentiation markers. Shox2 appears to regulate the expression of osteogenic genes and is essential for the development and function of the TMJ. The Shox2 conditional mutant thus provides a unique animal model of TMJ ankylosis.