Summary Phytases are a group of enzymes capable of releasing phosphates from phytates, one of the major forms of phosphorus (P) in animal feeds of plant origin. These enzymes have been widely used in animal feed to improve phosphorus nutrition and to reduce phosphorus pollution in animal waste. This review covers the basic nomenclature and crystal structures of phytases and emphasizes both the protein engineering strategies used for the development of new, effective phytases with improved properties and the potential biotechnological applications of phytases.

b-catenin is a multifunctional protein identified to be pivotal in embryonic patterning, organogenesis and adult homeostasis. It plays a critical structural role in mediating cadherin junctions and is also an essential transcriptional co-activator in the canonical Wnt pathway. Evidence has been documented that both the canonical Wnt pathway and cadherin junctions are deregulated or impaired in a plethora of human malignancies. In the light of this, there has been a recent surge in elucidating the mechanisms underlying the etiology of cancer development from the perspective of b-catenin. Here, we focus on the emerging roles of b-catenin in the process of tumorigenesis by discussing novel functions of old players and new proteins, mechanisms identified to mediate or interact with b-catenin and the most recently unraveled clinical implications of b-catenin regulatory pathways toward tumor suppression.Since its identification as an essential and central component in the Wnt signaling cascade, and the subsequent finding of its pivotal role in cadherin-based cell-cell adhesion, b-catenin has been critically studied to elucidate the coordination of these two pathways. The significance of this coordination is substantiated in a plethora of metabolic processes, such as axis and mesoderm formation, stem cell differentiation and carcinogenesis. 1,2 Generally, the Wnt pathway is divided into four branches, namely the canonical Wnt/b-catenin pathway, and the noncanonical (or heretical) Wnt/Ca 2þ and planar cell polarity pathways. Amongst them, the canonical Wnt pathway is the best studied and is reported to be highly conserved through evolution but is frequently altered in many human malignancies such as colorectal cancers, hepatocellular carcinomas and gastric cancers. 3-6 Ca 2þ -dependent cellcell adhesion in the cadherin family of proteins is typified by an extracellular segment that consists of five distinct Ca 2þ -binding domains and a conserved cytoplasmic domain, which interacts with b-catenin and p120 catenin (herein p120); b-catenin then provides a binding site for a-catenin. Cadherin junctions, among other cell-cell adhesion complexes, are essential for cellular processes such as cell polarity and migration. 7,8 Since an indispensible morphological hallmark of malignant tumors is reduced cell-cell adhesiveness, it is predicted that the components of cadherin junctions in many human malignancies, such as breast cancer, colorectal cancer and prostate cancer, are genetically altered. 9-11 Besides cellcell adhesion, cadherin junctions function as a potent competitor of free cytosolic b-catenin. This is supported by studies of the co-crystal structures of b-catenin/cadherin and b-catenin/TCF revealing that the two b-catenin ligands shared overlapping binding regions along b-catenin. 12 The role of the cadherin junction in the subcellular distribution of b-catenin has recently been further extended as discussed below.In this review, a myriad of recently emerged mechanisms governing the signaling and adhesive activity of ...

Aristolochic acids (AAs) are a group of toxins commonly present in the plants of genus Aristolochia and Asarum , which are spread all over the world. Since the 1990s, AA-induced nephropathy (AAN) and upper tract urothelial carcinoma (UTUC) have been reported in many countries. The underlying mechanisms of AAN and AA-induced UTUC have been extensively investigated. AA-derived DNA adducts are recognized as specific biomarkers of AA exposure, and a mutational signature predominantly characterized by A→T transversions has been detected in AA-induced UTUC tumor tissues. In addition, various enzymes and organic anion transporters are involved in AA-induced adverse reactions. The progressive lesions and mutational events initiated by AAs are irreversible, and no effective therapeutic regimen for AAN and AA-induced UTUC has been established until now. Because of several warnings on the toxic effects of AAs by the US Food and Drug Administration and the regulatory authorities of some other countries, the sale and use of AA-containing products have been banned or restricted in most countries. However, AA-related adverse events still occur, especially in the Asian and Balkan regions. Therefore, the use of AA-containing herbal remedies and the consumption of food contaminated by AAs still carry high risk. More strict precautions should be taken to protect the public from AA exposure.

Programmed −1 ribosomal frameshifting (−1 PRF) has been identified as a mechanism to regulate the expression of many viral genes and some cellular genes. The slippery site of −1 PRF has been well characterized, whereas the +1 PRF signal and the mechanism involved in +1 PRF remain poorly understood. Previous study confirmed that +1 PRF is required for the synthesis of protein products in several genes of ciliates from the genus Euplotes. To accurately assess the frequency of genes requiring frameshift in Euplotes, the macronuclear genome and transcriptome of Euplotes octocarinatus were analyzed in this study. A total of 3,700 +1 PRF candidate genes were identified from 32,353 transcripts, and the gene products of these putative +1 PRFs were mainly identified as protein kinases. Furthermore, we reported a putative suppressor tRNA of UAA which may provide new insights into the mechanism of +1 PRF in euplotids. For the first time, our transcriptome-wide survey of +1 PRF in E. octocarinatus provided a dataset which serves as a valuable resource for the future understanding of the mechanism underlying +1 PRF.

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MicroRNAs (miRNAs/miRs) are non-coding RNAs that post-transcriptionally control target genes, and are involved in tumorigenesis, apoptosis, proliferation, invasion, metastasis and chemoresistance. However, data concerning miRNAs in ovarian cancer remain incomplete. The present study aimed to identify miRNAs that affected the malignant phenotype of ovarian cancer, and to analyze their potential mechanisms. The data demonstrated that miR-205 promoted cell proliferation and invasion of ovarian cancer cells via suppressing Phosphatase and tensin homolog (PTEN)/mothers against decapentaplegic homolog 4 (SMAD4) expression. Based on the Cancer Genome Atlas database analysis results, it was identified that miR-205 was significantly upregulated in ovarian cancer tissues and markedly correlated with poor prognosis in patients with ovarian cancer; its abnormal expression was also confirmed in tissues from patients with ovarian cancer by reverse transcription quantitative polymerase chain reaction. Additional Gene Ontology analysis revealed that the target genes of miR-205 were associated with cell proliferation and invasion. Consistent with the database analysis, miR-205 overexpression significantly promoted ovarian cancer cell proliferation and invasion in vitro. To additionally explore the mechanism by which miR-205 was associated with proliferation and invasion of ovarian cancer cells, a protein-protein interaction network was constructed based on miR-205 target genes associated with proliferation and invasion, and it was revealed that PTEN and SMAD4 were key target genes of miR-205. In ovarian cancer tissues, the expression levels of PTEN and SMAD4 were significantly downregulated, suggesting that miR-205 may suppress the expression of PTEN and SMAD4 in vivo. In vitro, miR-205 overexpression markedly suppressed the expression of SMAD4 and PTEN, additionally verifying that PTEN and SMAD4 were the target genes of miR-205 in ovarian cancer cells. These results elucidated the tumor-promoting role of miR-205 and established miR-205 as a potential treatment target for ovarian cancer.

The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.

Transgenic plants with introduced pest-resistant gene offer an efficient alternative insect control. The novel insect-resistant gene combination, chitinase(chi) and BmkIT(Bmk), containing an insect-specific chitinase gene and a scorpion insect toxin gene was introduced into Brassica napus cultivar via Agrobacterium-mediated transformation. Fifty-seven regenerated plantlets with kanamycin-resistance were obtained. Transgenic plants were verified by Southern blot analysis. Enzyme-linked immunosorbent assay (ELISA) and bioassay of artificial inoculation with diamondback moth (Plutella maculipenis) (DBM) larvae indicated that some of the transgenic plants were high-level expression for both chitinase and scorpion toxin proteins and performed high resistance against the tested pest infestation. The genetic analysis of T(1) progeny confirmed that the inheritance of introduced genes followed the Mendelian rules.