Background: Fig pollinating wasps form obligate symbioses with their fig hosts. This mutualism arose approximately 75 million years ago. Unlike many other intimate symbioses, which involve vertical transmission of symbionts to host offspring, female fig wasps fly great distances to transfer horizontally between hosts. In contrast, male wasps are wingless and cannot disperse. Symbionts that keep intimate contact with their hosts often show genome reduction, but it is not clear if the wide dispersal of female fig wasps will counteract this general tendency. We sequenced the genome of the fig wasp Ceratosolen solmsi to address this question. Results: The genome size of the fig wasp C. solmsi is typical of insects, but has undergone dramatic reductions of gene families involved in environmental sensing and detoxification. The streamlined chemosensory ability reflects the overwhelming importance of females finding trees of their only host species, Ficus hispida, during their fleeting adult lives. Despite long-distance dispersal, little need exists for detoxification or environmental protection because fig wasps spend nearly all of their lives inside a largely benign host. Analyses of transcriptomes in females and males at four key life stages reveal that the extreme anatomical sexual dimorphism of fig wasps may result from a strong bias in sex-differential gene expression. Conclusions: Our comparison of the C. solmsi genome with other insects provides new insights into the evolution of obligate mutualism. The draft genome of the fig wasp, and transcriptomic comparisons between both sexes at four different life stages, provide insights into the molecular basis for the extreme anatomical sexual dimorphism of this species.

Chromosome 4q deletion is one of the most frequently detected genomic imbalance events in congenital heart disease (CHD) patients. However, a portion of CHD-associated 4q deletions without known CHD genes suggests unknown CHD genes within these intervals. Here, we have shown that knockdown of SORBS2, a 4q interval gene, disrupted sarcomeric integrity of cardiomyocytes and caused reduced cardiomyocyte number in human embryonic stem cell differentiation model. Molecular analyses revealed decreased expression of second heart field (SHF) marker genes and impaired NOTCH and SHH signaling in SORBS2-knockdown cells. Exogenous SHH rescued SORBS2 knockdown-induced cardiomyocyte differentiation defects. Sorbs2^-/- mouse mutants had atrial septal hypoplasia/aplasia or double atrial septum (DAS) derived from impaired posterior SHF with a similar expression alteration. Rare SORBS2 variants were significantly enriched in a cohort of 300 CHD patients. Our findings indicate that SORBS2 is a regulator of SHF development and its variants contribute to CHD pathogenesis. The presence of DAS in Sorbs2^-/- hearts reveals the first molecular etiology of this rare anomaly linked to paradoxical thromboembolism.

County-based spatial distribution characteristics and the related geological factors for iodine in drinking-water were studied in Shandong Province (China). Spatial autocorrelation analysis and spatial scan statistic were applied to analyze the spatial characteristics. Generalized linear models (GLMs) and geographically weighted regression (GWR) studies were conducted to explore the relationship between water iodine level and its related geological factors. The spatial distribution of iodine in drinking-water was significantly heterogeneous in Shandong Province (Moran’s I = 0.52, Z = 7.4, p < 0.001). Two clusters for high iodine in drinking-water were identified in the south-western and north-western parts of Shandong Province by the purely spatial scan statistic approach. Both GLMs and GWR indicated a significantly global association between iodine in drinking-water and geological factors. Furthermore, GWR showed obviously spatial variability across the study region. Soil type and distance to Yellow River were statistically significant at most areas of Shandong Province, confirming the hypothesis that the Yellow River causes iodine deposits in Shandong Province. Our results suggested that the more effective regional monitoring plan and water improvement strategies should be strengthened targeting at the cluster areas based on the characteristics of geological factors and the spatial variability of local relationships between iodine in drinking-water and geological factors.

Congenital heart defects (CHDs) are the most common birth defects worldwide. 22q11.2 deletion syndrome is the most common microdeletion disorder that has been frequently associated with conotruncal malformations. By now, the dosage-sensitive gene TBX1 has been adopted as the major pathogenic gene responsible for 22q11.2 deletion, which is regulated by canonical Wnt/β-catenin signaling pathway in heart outflow tract development. Here, we report the long noncoding RNA (lncRNA) lnc-TSSK2-8, which is encompassed in the 22q11.2 region, that can activate canonical Wnt/β-catenin signaling by protecting β-catenin from degradation, which could result from decreased ubiquitination. Such effects were mediated by two short heat shock proteins HSPA6 and α-β-crystallin (CRYAB), whose expression was regulated by lnc-TSSK2-8 through a competing endogenous RNA (ceRNA) mechanism. In clinical practice, the pathogenesis of copy number variation (CNV) was always attributed to haploinsufficiency of protein-coding genes. Here, we report that the 22q11.2 lncRNA lnc-TSSK2-8 significantly activated canonical Wnt/β-catenin signaling, which has major roles in cardiac outflow tract development and should act upstream of TBX1. Our results suggested that lncRNAs should contribute to the etiology of CNV-related CHD.

Copy number variations (CNVs) have long been recognized as pathogenic factors for congenital heart disease (CHD). Few CHD associated CNVs could be interpreted as dosage effect due to disruption of coding sequences. Emerging evidences have highlighted the regulatory roles of long noncoding RNAs (lncRNAs) in cardiac development. Whereas it remains unexplored whether lncRNAs within CNVs (CNV-lncRNAs) could contribute to the etiology of CHD associated CNVs. Here we constructed coexpression networks involving CNV-lncRNAs within CHD associated CNVs and protein coding genes using the human organ developmental transcriptomic data, and showed that CNV-lncRNAs within 10 of the non-syndromic CHD associated CNVs clustered in the most significant heart correlated module, and had highly correlated coexpression with multiple key CHD genes. HSALNG0104472 within 15q11.2 region was identified as a hub CNV-lncRNA with heart-biased expression and validated experimentally. Our results indicated that HSALNG0104472 should be a main effector responsible for cardiac defects of 15q11.2 deletion through regulating cardiomyocytes differentiation. Our findings suggested that CNV-lncRNAs could potentially contribute to the pathologies of a maximum proportion of 68.4% (13/19) of non-syndromic CHD associated CNVs. These results indicated that explaining the pathogenesis of CHD associated CNVs should take account of the noncoding regions.

The emergence and spread of highly pathogenic avian influenza (HPAI) A virus subtype H5N1 in Asia, Europe and Africa has had an enormously socioeconomic impact and presents an important threat to human health because of its efficient animal-to-human transmission. Many factors contribute to the occurrence and transmission of HPAI H5N1 virus, but the role of environmental temperature remains poorly understood. Based on an approach of integrating a Bayesian Cox proportional hazards model and a Besag-York-Mollié (BYM) model, we examined the specific impact of environmental temperature on HPAI H5N1 outbreaks in domestic poultry around the globe during the period from 1 December 2003 to 31 December 2009. The results showed that higher environmental temperature was a significant risk factor for earlier occurrence of HPAI H5N1 outbreaks in domestic poultry, especially for a temperature of 25 °C. Its impact varied with epidemic waves (EWs), and the magnitude of the impact tended to increase over EWs.