Genome-wide identification and expression profiling analysis of brassinolide signal transduction genes regulating apple tree architecture

Brassinolide (BR) is crucial for regulating plant architecture. Apple dwarfing rootstocks are used to control apple tree size. However, information regarding the effects of BR on apple trees is limited. In addition, the molecular mechanism underlying the dwarfing of apple rootstocks is poorly understood. To elucidate the role of BR signal transduction genes in controlling apple tree architecture, five BR receptor kinase 1 (BRI1), nine BR-signaling kinase 1 (BSK1), two BRI1 KINASE INHIBITOR 1 (BKI1), and seven BR-insensitive 2 (BIN2) genes were analyzed. Bioinformatic analyses revealed that gene duplication events likely contributed to the expansion and evolution of the identified genes. Nine homologs between apple and Arabidopsis thaliana were also identified, and their expression patterns in different tissues were characterized. Exogenous BR treatments increased the primary shoot length and altered the expression of BR signal transduction genes (MdBRI1-5, MdBSK3-8, MdBKI1–2, MdBIN1–4, and MdBIN6/7). The scion of Fuji/Malling 9 (M.9) trees exhibited inhibited growth compared with that of Fuji/Fuji trees. The Fuji/M.9 trees had lower levels of the positive regulators of BR signaling (MdBRI1-5,MdBSK1, MdBSK4/7, and MdBSK6) and higher levels of the negative regulators (MdBIN5-7) compared with the Fuji/Fuji trees. Thus, the above-mentioned genes may help to regulate apple tree size in response to BR. In addition, MdBRI1–5, MdBSK1, MdBSK4/7, MdBSK6, and MdBIN5–7 have important roles in different grafting combinations. Our results may provide the basis for future analyses of BR signal transduction genes regarding their potential involvement in the regulation of plant architecture.     

Association of a novel point mutation in MSH2 gene with familial multiple primary cancers

Background

Multiple primary cancers (MPC) have been identified as two or more cancers without any subordinate relationship that occur either simultaneously or metachronously in the same or different organs of an individual. Lynch syndrome is an autosomal dominant genetic disorder that increases the risk of many types of cancers. Lynch syndrome patients who suffer more than two cancers can also be considered as MPC; patients of this kind provide unique resources to learn how genetic mutation causes MPC in different tissues.

Methods

We performed a whole genome sequencing on blood cells and two tumor samples of a Lynch syndrome patient who was diagnosed with five primary cancers. The mutational landscape of the tumors, including somatic point mutations and copy number alternations, was characterized. We also compared Lynch syndrome with sporadic cancers and proposed a model to illustrate the mutational process by which Lynch syndrome progresses to MPC.

Results

We revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent. Integrative analysis showed that truncating mutations of DNA mismatch repair (MMR) genes were significantly enriched in the patient. A mutation progress model that included germline mutations of MMR genes, double hits of MMR system, mutations in tissue-specific driver genes, and rapid accumulation of additional passenger mutations was proposed to illustrate how MPC occurs in Lynch syndrome patients.

Conclusion

Our findings demonstrate that both germline and somatic alterations are driving forces of carcinogenesis, which may resolve the carcinogenic theory of Lynch syndrome.

     

Phytochemical Investigation and Cytotoxic Evaluation of the Components of the Medicinal Plant Ligularia atroviolacea

A phytochemical investigation of the roots of Ligularia atroviolacea resulted in the isolation of 24 compounds including seven new eremophilanoids named eremophila‐3,7(11),8‐triene‐12,8;14,6α‐diolide ( 1 ), 3β‐(angeloyloxy)eremophil‐7(11)‐en‐12,8β‐olid‐14‐oic acid ( 2 ), 1α‐chloro‐10β‐hydroxy‐6β‐(2‐methylpropanoyloxy)‐9‐oxo‐7,8‐furoeremophilane ( 3 ), (10βH)‐8‐oxoeremophila‐3(4),6(7)‐diene‐12,14‐dioic acid ( 4 ), (10αH)‐8‐oxoeremophila‐3(4),6(7)‐diene‐12,14‐dioic acid ( 5 ), 8β‐[eremophila‐3′,7′(11′)‐diene‐12′,8′α;14′,6′α‐diolide]eremophila‐3,7(11)‐diene‐12,8α;14,6α‐diolide ( 6 ), and ligulatrovine A ( 7 ), eleven known eremophilanoids, 8 – 18 , four steroids, one glucose derivative, and one fatty acid. The structures of these compounds were elucidated by spectroscopic methods including 2D‐NMR experiments. The structure of 3 was also established by an X‐ray diffraction study. The in vitro cytotoxicity evaluation of selected compounds was performed on seven cultured tumor cell lines, i.e., KB, BEL‐7404, A549, HL‐60, HeLa, CNE, and P‐388D1. The preliminary taxonomy of this species was also discussed, and the possible biogenesis of a dimer possessing a new noreremophilanoid type skeleton, 7 , is presented in a preliminary form.     

Increased expression of mGITRL on D2SC/1 cells by particulate β-glucan impairs the suppressive effect of CD4+CD25+ regulatory T cells and enhances the effector T cell proliferation

β-Glucans have been shown to enhance immune responses for centuries, which contributes to their anti-tumor property. However, their mechanisms of action are still elusive. Dectin-1, the C-type lectin receptor for β-glucan, is expressed abundantly on dendritic cells (DCs). Activation of DCs via Dectin-1 can lead to the maturation of DC, inducing both innate and adaptive immune responses against tumor development and microbial infection. In this study, we found that particulate yeast-derived β-glucans could induce the maturation of murine dendritic cell line D2SC/1 cells and increase the expression of mGITRL on D2SC/1 cells via Dectin-1/Syk pathway in a dose dependent manner. Furthermore, we demonstrated that the increased mGITRL on D2SC/1 cells could impair the suppressive activity of CD4⁺CD25⁺ regulatory T cells (Tregs) and enhance the proliferation of CD4⁺CD25⁻ effector T cells (Teffs). These findings suggest that particulate β-glucan can be used as immunomodulator to stimulate potent T cell-mediated adaptive immunity while down-regulate immune suppressive activity, leading to a more efficient defense mechanism against tumor development or infectious diseases.     

Biodegradation of Benazolin-Ethyl by Strain Methyloversatilis sp. cd-1 Isolated from Activated Sludge

Benazolin-ethyl has been used on a wide range of weeds present in various crops since 1964. Because benazolin-ethyl is a potential hazard to the environment and human health, it is important to remove this herbicide from the environment. However, to the best of our knowledge, no report is available in the literature regarding the microbial degradation of benazolin-ethyl by bacteria. In this study, one strain named cd-1, which is capable of degrading benazolin-ethyl, was isolated from benazolin-ethyl wastewater treatment pool. The isolate was identified as Methyloversatilis sp. according to its morphological, physiological, biochemical properties, and 16S rRNA gene sequences analysis. This strain utilizes benazolin-ethyl as the sole carbon source. and degrades 100?mg?l^?1 benazolin-ethyl to non-detectable level within 48?h. Three metabolites were identified as benazolin, 7-chloro-3-methylbenzo[d]thiazol-2(3H)-one, and 2-chloro-6-(methyleneamino)benzenethiol based on the MS/MS and GC/MS analyses. The first step involved in the degradation of benazolin-ethyl was the cleavage of the ester bond to form benazolin. Benazolin was subsequently subjected to demethylation for decomposition into 7-chloro-3-methylbenzo[d]thiazol-2(3H)-one and methanol. The last step was to form 2-chloro-6-(methyleneamino)benzenethiol.     

The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor contains an immunoreceptor tyrosine-based inhibitory motif that activates Shp2

The Kaposi's sarcoma-associated herpesvirus (KSHV) G protein-coupled receptor (vGPCR) is a constitutively active, highly angiogenic homologue of the interleukin-8 (IL-8) receptors that signals in part via the cytoplasmic protein tyrosine phosphatase Shp2. We show that vGPCR contains a bona fide immunoreceptor tyrosine-based inhibitory motif (ITIM) that binds and constitutively activates Shp2.     

Plasmonic Semiconductor Nanocrystals as Chemical Sensors: Pb2+ Quantitation via Aggregation-Induced Plasmon Resonance Shift

Plasmonics - We demonstrate, for the first time, the use of plasmonic semiconductor nanocrystals for the analysis of heavy metal ions in water. This highly sensitive localized surface plasmon...     

Infiltration of Alternatively Activated Macrophages in Cancer Tissue Is Associated with MDSC and Th2 Polarization in Patients with Esophageal Cancer

Myeloid derived suppressor cells (MDSCs) expand in cancer bearing hosts and contribute to tumor immune evasion. M2 macrophages constitute a major cellular component of cancer-related inflammation. However, the correlation between circulating MDSCs and infiltrating M2 macrophages in tumor tissues from patients with esophageal cancer (ECA), and its potential relationship with the polarization of Th2 cells remain unclear. In the present study, we showed the level of MDSCs in PBMC and Arg1 in plasma were significantly elevated in ECA patients, and the increased ratio of MDSC in PBMC was closely related to the expression of CD163 in cancer tissues. In addition, the ECA patients exhibited remarkable increases in the mRNA levels of IL-4 and GATA3, as well as the protein levels of IL-13 and IL-6, but IFN-γ and IL-12 in peripheral blood were decreased. Our data indicate that the increased Th2 cytokines are associated with MDSCs and M2 macrophages polarization, and foster the infiltration of CD163⁺M2 macrophages in cancer tissues, which promote the formation of immunosuppressive microenvironment in ECA patients.     

Blocking autophagy enhances the apoptosis effect of bufalin on human hepatocellular carcinoma cells through endoplasmic reticulum stress and JNK activation

Bufalin extracts are a part of traditional Chinese medicine, Chansu. In the current study, we investigated the effect of bufalin on the proliferation of the human hepatocellular carcinoma (HCC) cell lines, Huh-7 and HepG-2, and explored the therapeutic potential of the drug. Our results demonstrated that bufalin markedly inhibited cell proliferation and promoted apoptosis in the Huh-7 and HepG-2 cells in vitro. The underlying mechanism of the bufalin-induced apoptosis was the induction of endoplasmic reticulum (ER) stress via the IRE1–JNK pathway. In addition, during the ER stress response, the autophagy pathway, characterized by the conversion of LC3-I to LC3-II, was activated, resulting in increased Beclin-1 protein levels, decreased p62 expression and stimulation of autophagic flux. Our data supported the pro-survival role of bufalin-induced autophagy when the autophagy pathway was blocked with specific chemical inhibitors; the involvement of the IRE1 pathway in the ER stress-induced autophagy was also demonstrated when the expression of IRE1 and CHOP was silenced using siRNA. These data indicate that combining bufalin with a specific autophagy inhibitor could be a promising therapeutic approach for the treatment of HCC.