WW Domain-Containing Proteins YAP and TAZ in the Hippo Pathway as Key Regulators in Stemness Maintenance, Tissue Homeostasis, and Tumorigenesis

The Hippo pathway is a conserved signaling pathway originally defined in Drosophila melanogaster two decades ago. Deregulation of the Hippo pathway leads to significant overgrowth in phenotypes and ultimately initiation of tumorigenesis in various tissues. The major WW domain proteins in the Hippo pathway are YAP and TAZ, which regulate embryonic development, organ growth, tissue regeneration, stem cell pluripotency, and tumorigenesis. Recent reports reveal the novel roles of YAP/TAZ in establishing the precise balance of stem cell niches, promoting the production of induced pluripotent stem cells (iPSCs), and provoking signals for regeneration and cancer initiation. Activation of YAP/TAZ, for example, results in the expansion of progenitor cells, which promotes regeneration after tissue damage. YAP is highly expressed in self-renewing pluripotent stem cells. Overexpression of YAP halts stem cell differentiation and yet maintains the inherent stem cell properties. A success in reprograming iPSCs by the transfection of cells with Oct3/4, Sox2, and Yap expression constructs has recently been shown. In this review, we update the current knowledge and the latest progress in the WW domain proteins of the Hippo pathway in relevance to stem cell biology, and provide a thorough understanding in the tissue homeostasis and identification of potential targets to block tumor development. We also provide the regulatory role of tumor suppressor WWOX in the upstream of TGF-β, Hyal-2, and Wnt signaling that cross talks with the Hippo pathway

Zfra affects TNF-mediated cell death by interacting with death domain protein TRADD and negatively regulates the activation of NF-κB, JNK1, p53 and WOX1 during stress response

<p>Abstract</p> <p>Background</p> <p>Zfra is a 31-amino-acid zinc finger-like protein, which is known to regulate cell death by tumor necrosis factor (TNF) and overexpressed TNF receptor- or Fas-associated death domain proteins (TRADD and FADD). In addition, Zfra undergoes self-association and interacts with c-Jun <it>N</it>-terminal kinase 1 (JNK1) in response to stress stimuli. To further delineate the functional properties of Zfra, here we investigated Zfra regulation of the activation of p53, WOX1 (WWOX or FOR), NF-κB, and JNK1 under apoptotic stress.</p> <p>Results</p> <p>Transiently overexpressed Zfra caused growth suppression and apoptotic death of many but not all types of cells. Zfra either enhanced or blocked cell death caused by TRADD, FADD, or receptor-interacting protein (RIP) in a dose-related manner. This modulation is related with Zfra binding with TRADD, NF-κB, JNK1 and WOX1, as determined by GST pull-down analysis, co-immunoprecipitation, and mapping by yeast two-hybrid analysis. Functionally, transiently overexpressed Zfra sequestered NF-κB (p65), WOX1, p53 and phospho-ERK (extracellular signal-activated kinase) in the cytoplasm, and TNF or UV light could not effectively induce nuclear translocation of these proteins. Zfra counteracted the apoptotic functions of Tyr33-phosphorylated WOX1 and Ser46-phosphorylated p53. Alteration of Ser8 to Gly abolished the apoptotic function of Zfra and its regulation of WOX1 and p53.</p> <p>Conclusion</p> <p>In response to TNF, Zfra is upregulated and modulates TNF-mediated cell death via interacting with TRADD, FADD and RIP (death-inducing signaling complex) at the receptor level, and downstream effectors NF-κB, p53, WOX1, and JNK1.</p

Identification of MicroRNAs in Two Species of Tomato, \u3ci\u3eSolanum lycopersicum\u3c/i\u3e and \u3ci\u3eSolanum habrochaites\u3c/i\u3e, by Deep Sequencing

MicroRNAs (miRNAs) are ~21 nucleotide (nt), endogenous RNAs that regulate gene expression in plants. Increasing evidence suggests that miRNAs play an important role in species-specific development in plants. However, the detailed miRNA profile divergence has not been performed among tomato species. In this study, the small RNA (sRNA) profiles of Solanum lycopersicum cultivar 9706 and Solanum habrochaites species PI 134417 were obtained by deep sequencing. Sixty-three known miRNA families were identified from these two species, of which 39 were common. Further miRNA profile comparison showed that 24 known non-conserved miRNA families were species-specific between these two tomato species. In addition, six conserved miRNA families displayed an apparent divergent expression pattern between the two tomato species. Our results suggested that species-specific, non-conserved miRNAs and divergent expression of conserved miRNAs might contribute to developmental changes and phenotypic variation between the two tomato species. Twenty new miRNAs were also identified in S. lycopersicum. This research significantly increases the number of known miRNA families in tomato and provides the first set of small RNAs in S. habrochaites. It also suggests that miRNAs have an important role in species-specific plant developmental regulation

Antarctic sea ice change based on a new sea ice dataset from 1992 to 2008

The sea ice concentration dataset (covering the period 1992-2008) used in this study is a new dataset based on the Sea Ice Climate Change Initiative (SICCI) algorithm. We investigate whether the SICCI dataset is on a par with other datasets for studying sea ice cover changes in the Southern Ocean. We then examine spatiotemporal variations in sea ice derived from the SICCI dataset over the Southern Ocean, and analyse relationships of sea ice with sea surface temperature (SST). The results indicate that there is no significant difference between the SICCI dataset and the NASA Team dataset, and therefore the former can also be used for studying sea ice changes. Both sea ice extent (SIE) and sea ice area (SIA) derived from the SICCI dataset over the Southern Ocean increased slightly from 1992 to 2008, at rates of (17.75 ± 11.50) × 10^3 and (17.37 ± 9.51) × 10^3 km^2 yr^(–1), respectively. Antarctic sea ice has significant seasonal variations; all seasonally averaged SIE and SIA show an increase, with spring showing the largest positive changing rate. The Weddell Sea, Ross Sea, and Indian Ocean have positive yearly changing rates in SIE and SIA, while the Bellingshausen/Amundsen seas and western Pacific Ocean have negative yearly changing rates. However, overall sea ice over the Southern Ocean has a slight positive trend, which is the same as the sea ice change pattern derived from the NASA Team dataset. This indicates that the contributions to the change in sea ice over the whole Southern Ocean due to the Weddell Sea, Ross Sea, and Indian Ocean dominate over those by the Bellingshausen/Amundsen seas and western Pacific Ocean. Further analysis shows that both SIE and SIA are negatively correlated with SST in the Southern Ocean or each of the 5 longitudinal sectors, and sea ice is more sensitive to SST in spring and autumn

Anti-Hepatitis B Virus X Protein in Sera Is One of the Markers of Development of Liver Cirrhosis and Liver Cancer Mediated by HBV

Hepatitis B virus X protein (HBx) plays a crucial role in the development of hepatocellular carcinoma (HCC). However, the significance of circulating antibody to hepatitis B virus X antigen (anti-HBx) in sera remains unclear. In the present study, we examined the titers of anti-HBx (IgG) in the sera from 173 patients with chronic hepatitis B (CHB), 106 liver cirrhosis (LC), and 61 HCC by enzyme-linked immunosorbent assay (ELISA), respectively. Our data showed that the positive rates of anti-HBx were higher in sera of LC (40.6%) and HCC (34.4%) than those of CHB (10.4%), P < .05. In all 40 patients with anti-HBx+ out of 340 patients, 39 (97.5%) were HBsAg/HBeAg/anti-HBc+ and 1 (2.5%) was anti-HBs+ (P < .01), suggesting that anti-HBx in sera is a marker of HBV replication rather than a protective antibody. Thus, our findings reveal that circulating anti-HBx in sera is one of the markers of development of LC and HCC mediated by HBV

UMARS: Un-MAppable Reads Solution

[[abstract]]Background: Un-MAppable Reads Solution (UMARS) is a user-friendly web service focusing on retrieving valuable information from sequence reads that cannot be mapped back to reference genomes. Recently, next-generation sequencing (NGS) technology has emerged as a powerful tool for generating high-throughput sequencing data and has been applied to many kinds of biological research. In a typical analysis, adaptor-trimmed NGS reads were first mapped back to reference sequences, including genomes or transcripts. However, a fraction of NGS reads failed to be mapped back to the reference sequences. Such un-mappable reads are usually imputed to sequencing errors and discarded without further consideration.Methods: We are investigating possible biological relevance and possible sources of un-mappable reads. Therefore, we developed UMARS to scan for virus genomic fragments or exon-exon junctions of novel alternative splicing isoforms from un-mappable reads. For mapping un-mappable reads, we first collected viral genomes and sequences of exon-exon junctions. Then, we constructed UMARS pipeline as an automatic alignment interface.Results: By demonstrating the results of two UMARS alignment cases, we show the applicability of UMARS. We first showed that the expected EBV genomic fragments can be detected by UMARS. Second, we also detected exon-exon junctions from un-mappable reads. Further experimental validation also ensured the authenticity of the UMARS pipeline. The UMARS service is freely available to the academic community and can be accessed via http://musk.ibms.sinica.edu.tw/UMARS/.Conclusions: In this study, we have shown that some un-mappable reads are not caused by sequencing errors. They can originate from viral infection or transcript splicing. Our UMARS pipeline provides another way to examine and recycle the un-mappable reads that are commonly discarded as garbage