Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

BACKGROUND: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. RESULTS: We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.

Ultrasound-guided fine-needle aspiration of thyroid nodules: assessment of the ideal number of punctures

OBJECTIVE: To determine the number of punctures in fine-needle aspiration biopsies required for a safe cytological analysis of thyroid nodules. MATERIALS AND METHODS: Cross-sectional study with focus on diagnosis. The study population included 94 patients. RESULTS: The mean age of the patients participating in the study was 52 years (standard-deviation = 13.7) and 90.4% of them were women. Considering each puncture as an independent event, the first puncture has showed conclusive results in 78.7% of cases, the second, in 81.6%, and the third, in 71.8% of cases. With a view to the increasing chance of a conclusive diagnosis at each new puncture, two punctures have showed conclusive results in 89.5% of cases, and three punctures, in 90.6% of cases with at least one conclusive result. CONCLUSION: Two punctures in fine-needle aspiration biopsies of thyroid nodules have lead to diagnosis in 89.5% of cases in the study sample, suggesting that there is no need for multiple punctures to safely obtain the diagnosis of thyroid nodules.

DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR.

Copy number variations of colorectal cancer by whole exome sequencing data

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death worldwide. About 85% of the cases of CRC are known to have chromosomal instability, an allelic imbalance at several chromosomal loci, and chromosome amplification and translocation. The aim of this study is to determine the recurrent copy number variant (CNV) regions present in stage II of CRC through whole exome sequencing, a rapidly developing targeted next-generation sequencing (NGS) technology that provides an accurate alternative approach for accessing genomic variations. 42 normal-tumor paired samples were sequenced by Illumina Genome Analyzer. Data was analyzed with Varscan2 and segmentation was performed with R package R-GADA. Summary of the segments across all samples was performed and the result was overlapped with DEG data of the same samples from a previous study in the group1. Major and more recurrent segments of CNV were: gain of chromosome 7pq(13%), 13q(31%) and 20q(75%) and loss of 8p(25%), 17p(23%), and 18pq(27%). This results are coincident with the known literature of CNV in CRC or other cancers, but our methodology should be validated by array comparative genomic hybridisation (aCGH) profiling, which is currently the gold standard for genetic diagnosis of CNV.

A Case-based reasoning approach to validate grammatical gender and number agreement in Spanish language

Across Latin America 420 indigenous languages are spoken. Spanish is considered a second language in indigenous communities and is progressively introduced in education. However, most of the tools to support teaching processes of a second language have been developed for the most common languages such as English, French, German, Italian, etc. As a result, only a small amount of learning objects and authoring tools have been developed for indigenous people considering the specific needs of their population. This paper introduces Multilingual–Tiny as a web authoring tool to support the virtual experience of indigenous students and teachers when they are creating learning objects in indigenous languages or in Spanish language, in particular, when they have to deal with the grammatical structures of Spanish. Multilingual–Tiny has a module based on the Case-based Reasoning technique to provide recommendations in real time when teachers and students write texts in Spanish. An experiment was performed in order to compare some local similarity functions to retrieve cases from the case library taking into account the grammatical structures. As a result we found the similarity function with the best performance

Isolation of compounds attractive to the leaf-cutting ant Atta sexdens rubropilosa forel (hymenoptera: Formicidae) from Mabea fistulifera elaiosome

Mabea fistulifera (Euphorbiaceae)is a pioneer plant species with seeds dispersed by the ant Atta sexdens rubropilosa. Since the ants are attracted to the seeds to use its elaiosome as a source of energy, we investigated its composition. The elaiosomes from 13,000 seeds were extracted with a methanol:chloroform mixture (2:1 v/v) and yielded 22% of a residue. This residue was fractionated by column chromatography and its composition determined by infrared spectroscopy and chromatography/mass spectrometry (GC-MS). The elaiosome lipids are constituted mainly by free fatty acids, triacylglycerols and minor quantities of monoacylglycerols or diacylglycerols.

Optimization of the carrot leaf dehydration aiming at the preservation of omega-3 fatty acids

The carrot leaf dehydration conditions in air circulation oven were optimized through response surface methodology (RSM) for minimizing the degradation of polyunsaturated fatty acids, particularly alpha-linolenic (LNA, 18:3n-3). The optimized leaf drying time and temperature were 43 h and 70 ºC, respectively. The fatty acids (FA) were investigated using gas chromatography equipped with a flame ionization detector and fused silica capillary column; FA were identified with standards and based on equivalent-chain-length. LNA and other FA were quantified against C21:0 internal standard. After dehydration, the amount of LNA, quantified in mg/100 g dry matter of dehydrated carrot leaves, were 984 mg.

Leaf and root volatiles produced by tissue cultures of Alpinia zerumbet (pers.) Burtt & Smith under the influence of different plant growth regulators

Volatiles produced by plantlets of Alpinia zerumbet were obtained by means of simultaneous distillation-extraction (SDE). The effects of indole-3-acetic acid, kinetin, thidiazuron and 6-benzylaminopurine on leaf and root volatile composition obtained by tissue cultures were investigated. A higher content of b-pinene and a lower content of sabinene were observed in leaf volatile of plantlets cultured in control, IAA and IAA+ TDZ media, as compared with those of donor plants. In vitro conditions were favorable to increase caryophyllene content. Volatile compounds from the root were characterized mainly by camphene, fenchyl-acetate and bornyl acetate; which constitute about 60% of total volatile.

Epidemiology of apple leaf spot

Apple leaf spot (ALS) caused by Colletotrichum spp. is a major disease of apple (Malus domestica) in Southern Brazil. The epidemiology of this disease was studied in experiments carried out in the counties of Passo Fundo and Vacaria, State of Rio Grande do Sul, from February 1998 to October 2000. The disease was found in all the six apple orchards sampled in the growing seasons of 1997/98 and 1998/99. The fungus isolates associated with ALS fit the characteristics of C. gloeosporioides (75%), C. acutatum (8%), and Colletotrichum sp. (17%). The pathogen overwintered in dormant buds and twigs but not in dropped leaves or fruit mummies. Two sprays of copper oxychloride (at 0.3%) reduced the fungus initial inoculum by 65-84.6% in buds and 85.6-93.7% in twigs, but had no effect on the early season progress of the disease. Disease severity increased proportionally to elevation of temperature from 14 to 26-28 °C. At 34 °C, however, infection was completely inhibited. The duration of leaf wetness required for infection ranged from two hours at 30 °C to 32 h at 16 °C. The relationship of temperature (T) and leaf wetness (W) to disease severity (Y) was represented by the model equation Y = 0.00145[((T-13)1.78)((34.01-T )1.09)] * 25/[1+14 exp(-0.137W)], R² = 0.73 and P < 0.0001. Currently, this information is being used to manage the disease and to validate a forecast system for ALS.

Expression of resistance in rice hybrids to Pyricularia grisea

Thirty-nine rice (Oryza sativa) hybrids and their restorers were assessed for vertical resistance to Pyricularia grisea in the rice blast nursery, and in artificial inoculation tests with two pathotypes, under controlled greenhouse conditions. The hybrids were developed from cytoplasmic genetic male sterile lines 046I and IR 58025A, derived from WA cytoplasm. In the rice blast nursery all hybrids showed susceptible reaction varying from 5 to 9. Compatible and incompatible leaf blast reactions of hybrids to two pathotypes, IC-1 and IB-45, were observed in inoculation tests. A majority of the hybrids were resistant when the restorer was resistant. However, seven of the 25 F1 hybrids exhibited susceptible reactions even when one of the parents was resistant to a pathotype. The partial resistance of 11 hybrids and their parents that showed compatible reactions to two pathotypes was analyzed. Differential interaction between isolates and genotypes was observed for partial resistance in relation to both disease severity and lesion number indicating the specific nature of partial resistance.

Natural colonization of leaves of 'Pêra' sweet orange and related varieties by Guignardia citricarpa

The purpose of this research was to evaluate the differences in the colonization and production of structures in the leaves of 'Pêra' sweet orange (Citrus sinensis) clones and related varieties by Guignardia citricarpa. The natural colonization and the production of reproductive structures in the leaves and in vitro of ten 'Pêra' sweet orange was quantified in the following clones: Bianchi, Dibbern C.V., EEL, IAC 2000, Olímpia 15161, Premunizada 1212, Premunizada 1743/82, R. Gullo 1569/244, R. Gullo 1570/246 and Vimusa; and in five related varieties: Redonda C.N, Ovale 968, Ovale San Lio 969, Lamb Summer and Corsa Tardia. The quantification of the colonization density of G. citricarpa in the leaves was obtained through isolation. Incidence and colonization density (cm²) were calculated for each clone. The production of reproductive structures was accomplished through the moistening and drying process of the leaves. The incidence (percentage of affected leaves) and the leaf surface percentage occupied by the reproductive fungus structures were quantified. The in vitro production of reproductive structures was accomplished in water-agar medium. The number of immature and total reproductive fungus structures (cm²), and the percentage of picnidia with liberation of spores were quantified. Significant differences were not observed among clones related to the colonization of the leaves. But there were differences in the induction experiments, i.e., in the leaf surface percentage occupied by the reproductive fungus structures and the in vitro production of reprodutive fungus structures.