Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting in X-linked agammaglobulinemia (XLA).

The gene responsible for X-linked agammaglobulinemia (XLA) has been recently identified to code for a cytoplasmic tyrosine kinase (Bruton's agammaglobulinemia tyrosine kinase, BTK), required for normal B cell development. BTK, like many other cytoplasmic tyrosine kinases, contains Src homology domains (SH2 and SH3), and catalytic kinase domain. SH3 domains are important for the targeting of signaling molecules to specific subcellular locations. We have identified a family with XLA whose affected members have a point mutation (g-->a) at the 5' splice site of intron 8, resulting in the skipping of coding exon 8 and loss of 21 amino acids forming the COOH-terminal portion of the BTK SH3 domain. The study of three generations within this kinship, using restriction fragment length polymorphism and DNA analysis, allowed identification of the mutant X chromosome responsible for XLA and the carrier status in this family. BTK mRNA was present in normal amounts in Epstein-Barr virus-induced B lymphoblastoid cell lines established from affected family members. Although the SH3 deletion did not alter BTK protein stability and kinase activity of the truncated BTK protein was normal, the affected patients nevertheless have a severe B cell defect characteristic for XLA. The mutant protein was modeled using the normal BTK SH3 domain. The deletion results in loss of two COOH-terminal beta strands containing several residues critical for the formation of the putative SH3 ligand-binding pocket. We predict that, as a result, one or more crucial SH3 binding proteins fail to interact with BTK, interrupting the cytoplasmic signal transduction process required for B cell differentiation

Soil phosphorus heterogeneity promotes tree species diversity and phylogenetic clustering in a tropical seasonal rainforest

The niche theory predicts that environmental heterogeneity and species diversity are positively correlated in tropical forests, whereas the neutral theory suggests that stochastic processes are more important in determining species diversity. This study sought to investigate the effects of soil nutrient (nitrogen and phosphorus) heterogeneity on tree species diversity in the Xishuangbanna tropical seasonal rainforest in southwestern China. Thirty-nine plots of 400 m2 (20 × 20 m) were randomly located in the Xishuangbanna tropical seasonal rainforest. Within each plot, soil nutrient (nitrogen and phosphorus) availability and heterogeneity, tree species diversity, and community phylogenetic structure were measured. Soil phosphorus heterogeneity and tree species diversity in each plot were positively correlated, while phosphorus availability and tree species diversity were not. The trees in plots with low soil phosphorus heterogeneity were phylogenetically overdispersed, while the phylogenetic structure of trees within the plots became clustered as heterogeneity increased. Neither nitrogen availability nor its heterogeneity was correlated to tree species diversity or the phylogenetic structure of trees within the plots. The interspecific competition in the forest plots with low soil phosphorus heterogeneity could lead to an overdispersed community. However, as heterogeneity increase, more closely related species may be able to coexist together and lead to a clustered community. Our results indicate that soil phosphorus heterogeneity significantly affects tree diversity in the Xishuangbanna tropical seasonal rainforest, suggesting that deterministic processes are dominant in this tropical forest assembly

Multi-Modal Spectral Image Super-Resolution

Recent advances have shown the great power of deep convolutional neural networks (CNN) to learn the relationship between low and high-resolution image patches. However, these methods only take a single-scale image as input and require large amount of data to train without the risk of overfitting. In this paper, we tackle the problem of multi-modal spectral image super-resolution while constraining our-selves to a small dataset. We propose the use of different modalities to improve the performance of neural networks on the spectral super-resolution problem. First, we use multiple downscaled versions of the same image to infer a better high-resolution image for training, we refer to these inputs as a multi-scale modality. Furthermore, color images are usually taken at a higher resolution than spectral images, so we make use of color images as another modality to improve the super-resolution network. By combining both modalities, we build a pipeline that learns to super-resolve using multi-scale spectral inputs guided by a color image. Finally, we validate our method and show that it is economic in terms of parameters and computation time, while still producing state-of-the-art results

Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Xu, X., Li, G., Li, C., Zhang, J., Wang, Q., Simmons, D. K., Chen, X., Wijesena, N., Zhu, W., Wang, Z., Wang, Z., Ju, B., Ci, W., Lu, X., Yu, D., Wang, Q., Aluru, N., Oliveri, P., Zhang, Y. E., Martindale, M. Q., & Liu, J. Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis. National Science Review, 6(5), (2019):993-1003, doi:10.1093/nsr/nwz064.Major evolutionary transitions are enigmas, and the most notable enigma is between invertebrates and vertebrates, with numerous spectacular innovations. To search for the molecular connections involved, we asked whether global epigenetic changes may offer a clue by surveying the inheritance and reprogramming of parental DNA methylation across metazoans. We focused on gametes and early embryos, where the methylomes are known to evolve divergently between fish and mammals. Here, we find that methylome reprogramming during embryogenesis occurs neither in pre-bilaterians such as cnidarians nor in protostomes such as insects, but clearly presents in deuterostomes such as echinoderms and invertebrate chordates, and then becomes more evident in vertebrates. Functional association analysis suggests that DNA methylation reprogramming is associated with development, reproduction and adaptive immunity for vertebrates, but not for invertebrates. Interestingly, the single HOX cluster of invertebrates maintains unmethylated status in all stages examined. In contrast, the multiple HOX clusters show dramatic dynamics of DNA methylation during vertebrate embryogenesis. Notably, the methylation dynamics of HOX clusters are associated with their spatiotemporal expression in mammals. Our study reveals that DNA methylation reprogramming has evolved dramatically during animal evolution, especially after the evolutionary transitions from invertebrates to vertebrates, and then to mammals.This work was supported by the National Key Research and Development Program of China (2018YFC1003303), the Strategic Priority Research Program of the CAS (XDB13040200), the National Natural Science Foundation of China (91519306, 31425015), the Youth Innovation Promotion Association of the CAS and the Key Research Program of Frontier Sciences, CAS (QYZDY-SSW-SMC016)

Quantification of Cell Signaling Networks Using Kinase Activity Chemosensors

The ability to directly determine endogenous kinase activity in tissue homogenates provides valuable insights into signaling aberrations that underlie disease phenotypes. When activity data is collected across a panel of kinases, a unique “signaling fingerprint” is generated that allows for discrimination between diseased and normal tissue. Here we describe the use of peptide-based kinase activity sensors to fingerprint the signaling changes associated with disease states. This approach leverages the phosphorylation-sensitive sulfonamido-oxine (Sox) fluorophore to provide a direct readout of kinase enzymatic activity in unfractionated tissue homogenates from animal models or clinical samples. To demonstrate the application of this technology, we focus on a rat model of nonalcoholic fatty liver disease (NAFLD). Sox-based activity probes allow for the rapid and straightforward analysis of changes in kinase enzymatic activity associated with disease states, providing leads for further investigation using traditional biochemical approaches

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

In silico and in vitro analysis of lncRNA XIST reveals a panel of possible lung cancer regulators and a five-gene diagnostic signature

© 2020 by the authors. Long non-coding RNAs (lncRNAs) perform a wide functional repertoire of roles in cell biology, ranging from RNA editing to gene regulation, as well as tumour genesis and tumour progression. The lncRNA X-inactive specific transcript (XIST) is involved in the aetiopathogenesis of non-small cell lung cancer (NSCLC). However, its role at the molecular level is not fully elucidated. The expression of XIST and co-regulated genes TSIX, hnRNPu, Bcl-2, and BRCA1 analyses in lung cancer (LC) and controls were performed in silico. Differentially expressed genes (DEGs) were determined using RNA-seq in H1975 and A549 NSCLC cell lines following siRNA for XIST. XIST exhibited sexual dimorphism, being up-regulated in females compared to males in both control and LC patient cohorts. RNA-seq revealed 944 and 751 DEGs for A549 and H1975 cell lines, respectively. These DEGs are involved in signal transduction, cell communication, energy pathways, and nucleic acid metabolism. XIST expression associated with TSIX, hnRNPu, Bcl-2, and BRCA1 provided a strong collective feature to discriminate between controls and LC, implying a diagnostic potential. There is a much more complex role for XIST in lung cancer. Further studies should concentrate on sex-specific changes and investigate the signalling pathways of the DEGs following silencing of this lncRNA

Arsenic distribution and speciation in the fronds of the hyperaccumulator Pteris vittata

Pteris vittata is the first plant reported to be a hyperaccumulator of arsenic (As), and little is known about the mechanisms of As hyperaccumulation in this plant. Arsenic distribution at the whole plant (fronds) and cellular level was investigated using chemical analyses and energy dispersive X-ray microanalyses (EDXA). Speciation of As in the fronds was determined using X-ray absorption near edge spectroscopy (XANES) analyses. The majority of As was found in the pinnae (96% of total As). The concentration of As in pinnae decreased from the base to the apex of the fronds. Arsenic concentrations in spores and midribs were much lower than in the pinnae. EDXA analyses revealed that As was compartmentalized mainly in the upper and lower epidermal cells, probably in the vacuoles. The distribution pattern of potassium was similar to As, whereas other elements (Ca, Cl, K, Mg, P and S) were distributed differently. XANES analyses showed that approximately 75% of the As in fronds was present in the As(III) oxidation state and the remaining as As(V)

Promoting influenza prevention for elderly people in Hong Kong using health action process approach: Study protocol

Background: People 65 years or older are at greater risk of serious complications from the seasonal influenza compared with young. To promote elderly people's behavioral compliance toward influenza prevention, the aim of the current project is to develop, implement, and evaluate a theory-based low-administration-cost intervention building on a leading psychological theory, the Health Action Process Approach (HAPA). Methods: The target group is Hong Kong Chinese elderly people aged 65 or older who rarely or never adopt any preventive actions. This project will be conducted in three phases over 24 months. In phase 1, intervention program will be developed building on the HAPA theoretical framework which comprises both the initiation and maintenance of influenza prevention behaviors. In phase 2, intervention will be implemented and evaluated using a randomized controlled trial, including: (a) behavior initiation only, (b) behavior initiation + behavior maintenance, and (c) control group. Both the initiation and maintenance components will comprise weekly-delivered telephone-based individual intervention sessions in 3 months. In phase 3, outcome evaluation of behavioral and psychological variables and process evaluation will be conducted. The effectiveness of the intervention will be analyzed using a series of linear mixed models on each behavioral and psychological outcome variable. Structural equation modelling will be used to test the hypothesized theoretical sequence in the HAPA model. Discussion: The proposed project is expected to design theory-based intervention materials to promote the influenza prevention behaviors in Hong Kong elderly people and provide information on its effectiveness and the potential changing mechanism of behavior initiation and maintenance. Trial registration: This randomized controlled trial was funded by the Health and Medical Research Fund (HMRF), Food and Health Bureau of the Government of the Hong Kong Special Administrative Region (Ref: 16151222) and was registered on 13/10/2017 at CCRB Clinical Trials Registry of the Chinese University of Hong Kong, a Partner Registry of a WHO Primary Registry (Ref: CUHK-CCRB00567)