Does loss of heterozygosity in critical genome regions predict a local relapse in patients after laryngectomy?

BACKGROUND: Patients, who had an upper aerodigestive tract malignancy, have a high incidence of succeeding tumor development. This has been attributed to the role of "field cancerization" in carcinogenesis. The aim of this study was analysis of loss of heterozygosity (LOH) in the regions frequently lost during the course of head and neck squamous cell carcinomas (HNSCC), especially at early stages, which could answer the clinicians' question, if LOH analysis has any "predictive" value in relation to tumor occurrence. MATERIAL AND METHODS: Sixty-five larynx cancer patients were examined for loss of heterozygosity on 3p, 7q, 8p, 9p and 18q chromosomal arms with the use of 12 microsatellite markers. The material from a single patient consisted of blood, tumor, safe margin and one or two clinically unchanged mucosal samples. During follow up, the material from brush specimens (14 patients) as well as laryngeal swabs (4 patients) was also examined. RESULTS: The highest frequency of LOH was detected for marker D3S1234 in tumor tissues (29%). Analysis of margin samples (b) revealed low LOH frequencies (2-5%) and complete retention of heterozygosity for markers: D3S1234, D7S486, D8S261, D8S264, D9S171 and D18S46. Similarly, for normal appearing mucosa from upper part of larynx (c) frequencies of LOH were low (2-6%), with the complete retention of heterozygosity for markers: D3S1284, D3S1304, D3S1234, D8S264 and D9S1870. We did not detect any LOH in the material of normal appearing mucosa from tracheostoma region (d). During follow up, LOH was detected for eight markers, with the highest incidence for markers D18S46 (six cases), D7S486 (four cases) and D3S1300 (three cases). CONCLUSIONS: The data, obtained during this investigation, did not reveal the predictive value of LOH with respect to local relapse occurrence in laryngeal cancer patients. However, time of follow up did not reach 5 years, so that further clinical monitoring should be conducted.     

Bis-class: a new classification tool of methylation status using bayes classifier and local methylation information

Background

Whole genome sequencing of bisulfite converted DNA (‘methylC-seq’) method provides comprehensive information of DNA methylation. An important application of these whole genome methylation maps is classifying each position as a methylated versus non-methylated nucleotide. A widely used current method for this purpose, the so-called binomial method, is intuitive and straightforward, but lacks power when the sequence coverage and the genome-wide methylation level are low. These problems present a particular challenge when analyzing sparsely methylated genomes, such as those of many invertebrates and plants.

Results

We demonstrate that the number of sequence reads per position from methylC-seq data displays a large variance and can be modeled as a shifted negative binomial distribution. We also show that DNA methylation levels of adjacent CpG sites are correlated, and this similarity in local DNA methylation levels extends several kilobases. Taking these observations into account, we propose a new method based on Bayesian classification to infer DNA methylation status while considering the neighborhood DNA methylation levels of a specific site. We show that our approach has higher sensitivity and better classification performance than the binomial method via multiple analyses, including computational simulations, Area Under Curve (AUC) analyses, and improved consistencies across biological replicates. This method is especially advantageous in the analyses of sparsely methylated genomes with low coverage.

Conclusions

Our method improves the existing binomial method for binary methylation calls by utilizing a posterior odds framework and incorporating local methylation information. This method should be widely applicable to the analyses of methylC-seq data from diverse sparsely methylated genomes. Bis-Class and example data are provided at a dedicated website (http://bibs.snu.ac.kr/software/Bisclass).

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-608) contains supplementary material, which is available to authorized users.     

Measure dynamics on a one-dimensional continuous trait space: theoretical foundations for adaptive dynamics

The measure dynamics approach to modelling single-species coevolution with a one-dimensional trait space is developed and compared to more traditional methods of adaptive dynamics and the Maximum Principle. It is assumed that individual fitness results from pairwise interactions together with a background fitness that depends only on total population size. When fitness functions are quadratic in the real variables parameterizing the one-dimensional traits of interacting individuals, the following results are derived. It is shown that among monomorphisms (i.e. measures supported on a single trait value), the continuously stable strategy (CSS) characterize those that are Lyapunov stable and attract all initial measures supported in an interval containing this trait value. In the cases where adaptive dynamics predicts evolutionary branching, convergence to a dimorphism is established. Extensions of these results to general fitness functions and/or multi-dimensional trait space are discussed.     

Searching for a successful HDL-based treatment strategy

Despite strong evidence that HDL-cholesterol levels predict atherosclerotic events in a population, attempts at using an HDL-based treatment strategy have not yet been successful. Most of the efforts to date have focused on raising plasma HDL-cholesterol levels. This brief review focuses on a different strategy, which is based on the use of 18-amino acid apoA-I mimetic peptides. The story of these peptides spans decades and illustrates the remarkable complexity of HDL-based treatment strategies, but suggests that such a strategy may still be successful.     

Modeling the potential suitable habitat of Impatiens hainanensis,a limestone-endemic plant北大核心CSCD

Aims Modelling potential distribution ranges of threatened species is of great significance for their conservation. In this paper, the distribution of potential suitable habitat of Impatiens hainanensis, a limestone-endemic and endangered plant in Hainan Island, was studied to provide scientific basis for their effective in situ conservation and re-introduction of I. hainanensis. Methods Based on eight occurrence sites and 12 environmental variables, the Maximum Entropy (MaxEnt) algorithm and GIS technology were used to create a model linking the distribution ranges of I. hainanensis with environments. With data on five actual distribution sites and five non-occurrence sites, four model evaluation metrics (area under the receiver operating characteristic curve (AUC), kappa coefficient, true skill statistic (TSS), overall accuracy) were used to evaluate the predictive performance and accuracy of this model. Important findings The results indicated that the indicative value of all four evaluation metrics were above 0.9, indicating that the MaxEnt model can effectively predict the potential suitable habitats of I. hainanensis. Slope, precipitation of the driest quarter and coefficients of precipitation variation were the three main environmental factors influencing the distribution of I. hainanensis. At present, the most suitable habitat includes western and southern parts of Baisha County, the central and southern parts of Changjiang County, the eastern part of the Dongfang City and northeastern Ledong County, accounting for 1.8% of land area on Hainan Island. Since the potential suitable habitat of I. hainanensis is rare and severely fragmented, the protection of this species is urgent. We suggest to collect the seeds of various geographic populations of I. hainanensis to establish a germplasm resource bank. The most suitable habitat of the species, including Tian’an Village and Jiangbian Village in Dongfang City, northeast of Ledong County (Jiaxi Reserve), should be selected as the priority places for future extensive field surveys and re-introduction. © Chinese Journal of Plant Ecology.     

Circadian Phase-Dependent Protein and Tissular Binding of Three Local Anesthetics (Bupivacaine,Etidocaine, and Mepivacaine) in Mice: A Possible Mechanismof Their Chronotoxicokinetics?

The aim of this study was to investigate the possible influence of the time of administration on bupivacaine (B), etidocaine (E), and mepivacaine (M) protein and tissue (brain and heart) binding. For each anesthetic agent, a single dose of B (20 mg/kg), E (40 mg/kg), or M (60 mg/kg) was administered intraperito-neally at 10:00,16:00,22:00, and 04:00 h. Blood and tissue samples were collected 15 min after drug administration. This study documents significant circadian variations in protein and tissue binding of the three local anesthetic agents. We did not demonstrate a temporal relationship between the respective free and tissue levels. Thus, the temporal variations of free plasma, brain, and heart levels do not seem to be involved in the temporal changes of induced mortality.     

Local Environmental Knowledge,Talk, and Skepticism: Using ‘LES’ to Distinguish ‘LEK’ from ‘LET’ in Newfoundland

The actual evidence observed in studies of LEK (local environmental knowledge) is nearly always talk about the environment, or what we refer to as LET (local environmental talk), with the claim of studying LEK usually being built upon the implicit assumption that talk about the environment is the expression of knowledge about the environment. We suggest that it is critically important for researchers to question this assumption, especially when the distinction between LET and LEK is also emphasized by local people themselves. In the case we present here, residents of small fishing villages on the Northern Peninsula of Newfoundland are routinely skeptical about what other local residents say about the environment; that is, they engage in LES (local environmental skepticism). We suggest that paying explicit attention to LES can help distinguish LEK from LET.