Preventive treatment for diseases: A practice model. a challenge for hospital management in the field of integrative medicine

The concept of preventive treatment for diseases in the Chinese context originated in an ancient Chinese medical text called The Yellow Emperor's Inner Canon or The Inner Canon of Huangdi. This concept is that of taking treatment measures in order to prevent recurrence of diseases and consequent deterioration in health and well-being. There are three aspects of preventive treatment: 1) preventive measures before the onset of the illness; 2) measures taken against deterioration during the illness; and 3) measures taken against relapse after recovery.1 The authors introduced a Tradtional Chinese Medicine (TCM) model of preventive treatment for diseases into the clinical health care practice at Guangdong Women's and Children's Hospital (GDWCH). TCM principles and methodologies were applied along with modern medical practices of diagnosis and treatment. The study found that the new model of integrative medicine applied at GDWCH presented a wide range of possibilities for both social benefits and good medical prognosis

Cyanobacterial bloom mitigation using proteins with high isoelectric point and chitosan-modified soil

A new environmental friendly method was developed for cyanobacterial blooms mitigation using local lake shore soil modified by protein with high isoelectric point (pI) and chitosan jointly. Results suggested that 5 mg/L lysozyme (pI ≈ 11) and 100 mg/L bromelain (pI ≈ 9.5) modified 10 mg/L soil can both reduce the surface charge of microcystis aeruginosa, the dominant species forming cyanobacterial blooms, from -26 mv to -10 mv and remove 73% and 60% of algal cells in 30 min, respectively. The limited improvement of removal efficiency was due to the small flocs (< 60 μm) formed by charge neutralization, which need more than 90 min to settle in static condition. However, when the small flocs were linked and bridged by the other modifier, chitosan with long polymer chain, large flocs of about 800 μm and 300 μm were fomed and more than 80% of algal cells were removed in 5 min and 30 min by lysozyme-chitosan modified soil and bromelain-chitosan modified soil, respectively. The lower removal ability of bromelain-modified soil was due to the lower charge density leading to less powerful in destabilization of algal cells. Depending on the bi-component modification mechanism including charge neutralization of proteins with high pI and netting and bridging function of chitosan with long polymer chain, it is possible to flocculate cyanobacterial blooms in natural waters effectively using locally available materials

Measuring Dissociation Rate Constants of Protein Complexes through Subunit Exchange: Experimental Design and Theoretical Modeling

Protein complexes are dynamic macromolecules that constantly dissociate into, and simultaneously are assembled from, free subunits. Dissociation rate constants, koff, provide structural and functional information on protein complexes. However, because all existing methods for measuring koff require high-quality purification and specific modifications of protein complexes, dissociation kinetics has only been studied for a small set of model complexes. Here, we propose a new method, called Metabolically-labeled Affinity-tagged Subunit Exchange (MASE), to measure koff using metabolic stable isotope labeling, affinity purification and mass spectrometry. MASE is based on a subunit exchange process between an unlabeled affinity-tagged variant and a metabolically-labeled untagged variant of a complex. The subunit exchange process was modeled theoretically for a heterodimeric complex. The results showed that koff determines, and hence can be estimated from, the observed rate of subunit exchange. This study provided the theoretical foundation for future experiments that can validate and apply the MASE method

Liquid-gas phase transition in nuclear multifragmentation

The equation of state of nuclear matter suggests that at suitable beam energies the disassembling hot system formed in heavy ion collisions will pass through a liquid-gas coexistence region. Searching for the signatures of the phase transition has been a very important focal point of experimental endeavours in heavy ion collisions, in the last fifteen years. Simultaneously theoretical models have been developed to provide information about the equation of state and reaction mechanisms consistent with the experimental observables. This article is a review of this endeavour.Comment: 63 pages, 27 figures, submitted to Adv. Nucl. Phys. Some typos corrected, minor text change

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Autopiquer - a robust and reliable peak detection algorithm for mass spectrometry

We present a simple algorithm for robust and unsupervised peak detection by determining a noise threshold in isotopically resolved mass spectrometry data. Solving this problem will greatly reduce the subjective and time consuming manual picking of mass spectral peaks and so will prove beneficial in many research applications. The Autopiquer approach uses autocorrelation to test for the presence of (isotopic) structure in overlapping windows across the spectrum. Within each window, a noise threshold is optimized to remove the most unstructured data whilst keeping as much of the (isotopic) structure as possible. This algorithm has been successfully demonstrated for both peak detection and spectral compression on data from many different classes of mass spectrometer and for different sample types and this approach should also be extendible to other types of data that contain regularly spaced discrete peaks

An Atlas of the Speed of Copy Number Changes in Animal Gene Families and Its Implications

The notion that gene duplications generating new genes and functions is commonly accepted in evolutionary biology. However, this assumption is more speculative from theory rather than well proven in genome-wide studies. Here, we generated an atlas of the rate of copy number changes (CNCs) in all the gene families of ten animal genomes. We grouped the gene families with similar CNC dynamics into rate pattern groups (RPGs) and annotated their function using a novel bottom-up approach. By comparing CNC rate patterns, we showed that most of the species-specific CNC rates groups are formed by gene duplication rather than gene loss, and most of the changes in rates of CNCs may be the result of adaptive evolution. We also found that the functions of many RPGs match their biological significance well. Our work confirmed the role of gene duplication in generating novel phenotypes, and the results can serve as a guide for researchers to connect the phenotypic features to certain gene duplications

The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases

Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Assis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Gomes Araújo, Flávio M.. Fundación Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. Fundación Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Oliveira, Guilherme. Instituto Tecnológico Vale; Brasil. Fundación Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Complete Chloroplast Genome Sequence of an Orchid Model Plant Candidate: Erycina pusilla Apply in Tropical Oncidium Breeding

Oncidium is an important ornamental plant but the study of its functional genomics is difficult. Erycina pusilla is a fast-growing Oncidiinae species. Several characteristics including low chromosome number, small genome size, short growth period, and its ability to complete its life cycle in vitro make E. pusilla a good model candidate and parent for hybridization for orchids. Although genetic information remains limited, systematic molecular analysis of its chloroplast genome might provide useful genetic information. By combining bacterial artificial chromosome (BAC) clones and next-generation sequencing (NGS), the chloroplast (cp) genome of E. pusilla was sequenced accurately, efficiently and economically. The cp genome of E. pusilla shares 89 and 84% similarity with Oncidium Gower Ramsey and Phalanopsis aphrodite, respectively. Comparing these 3 cp genomes, 5 regions have been identified as showing diversity. Using PCR analysis of 19 species belonging to the Epidendroideae subfamily, a conserved deletion was found in the rps15-trnN region of the Cymbidieae tribe. Because commercial Oncidium varieties in Taiwan are limited, identification of potential parents using molecular breeding method has become very important. To demonstrate the relationship between taxonomic position and hybrid compatibility of E. pusilla, 4 DNA regions of 36 tropically adapted Oncidiinae varieties have been analyzed. The results indicated that trnF-ndhJ and trnH-psbA were suitable for phylogenetic analysis. E. pusilla proved to be phylogenetically closer to Rodriguezia and Tolumnia than Oncidium, despite its similar floral appearance to Oncidium. These results indicate the hybrid compatibility of E. pusilla, its cp genome providing important information for Oncidium breeding

cDNA sequencing improves the detection of P53 missense mutations in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Recently published data showed discrepancies beteween <it>P53 </it>cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers.</p> <p>Methods</p> <p>To this end, we analyzed 23 colorectal cancers for <it>P53 </it>mutations and gene expression using both DNA and cDNA sequencing, real-time PCR and immunohistochemistry.</p> <p>Results</p> <p>We found <it>P53 </it>gene mutations in 16 cases (15 missense and 1 nonsense). Two of the 15 cases with missense mutations showed alterations based only on cDNA, and not DNA sequencing. Moreover, in 6 of the 15 cases with a cDNA mutation those mutations were difficult to detect in the DNA sequencing, so the results of DNA analysis alone could be misinterpreted if the cDNA sequencing results had not also been available. In all those 15 cases, we observed a higher ratio of the mutated to the wild type template by cDNA analysis, but not by the DNA analysis. Interestingly, a similar overexpression of <it>P53 </it>mRNA was present in samples with and without <it>P53 </it>mutations.</p> <p>Conclusion</p> <p>In terms of colorectal cancer, those discrepancies might be explained under three conditions: 1, overexpression of mutated <it>P53 </it>mRNA in cancer cells as compared with normal cells; 2, a higher content of cells without <it>P53 </it>mutation (normal cells and cells showing <it>K-RAS </it>and/or <it>APC </it>but not <it>P53 </it>mutation) in samples presenting <it>P53 </it>mutation; 3, heterozygous or hemizygous mutations of <it>P53 </it>gene. Additionally, for heterozygous mutations unknown mechanism(s) causing selective overproduction of mutated allele should also be considered. Our data offer new clues for studying discrepancy in <it>P53 </it>cDNA and DNA sequencing analysis.</p