Extensive genomic characterization of a set of near-isogenic lines for heterotic QTL in maize (Zea mays L.)

Background Despite the crucial role that heterosis has played in crop improvement, its genetic and molecular bases are still elusive. Several types of structured populations were used to discover the genetic architecture underlying complex phenotypes, and several QTL related to heterosis were detected. However, such analyses generally lacked the statistical power required for the detailed characterization of individual QTL. Currently, QTL introgression into near-isogenic materials is considered the most effective strategy to this end, despite such materials inevitably contain a variable, unknown and undesired proportion of non-isogenic genome. An introgression program based on residual heterozygous lines allowed us to develop five pairs of maize (Zea mays L.) near-isogenic lines (NILs) suitable for the fine characterization of three major heterotic QTL previously detected. Here we describe the results of the detailed genomic characterization of these NILs that we undertook to establish their genotypic structure, to verify the presence of the expected genotypes within target QTL regions, and to determine the extent and location of residual non-isogenic genomic regions. Results The SNP genotyping approach allowed us to determine the parent-of-origin allele for 14,937 polymorphic SNPs and to describe in detail the genotypic structure of all NILs. The correct introgression was confirmed for all target QTL in the respective NIL and several nonisogenic regions were detected genome-wide. Possible linkage drag effects associated to the specific introgressed regions were observed. The extent and position of other non-isogenic regions varied among NIL pairs, probably deriving from random segregating sections still present at the separation of lineages within pairs. Conclusions The results of this work strongly suggest that the actual isogenicity and the genotypic architecture of near-isogenic materials should be monitored both during the introgression procedure and on the final materials as a paramount requisite for a successful mendelization of target QTL. The information here gathered on the genotypic structure of NILs will be integrated in future experimental programs aimed at the fine mapping and isolation of major heterotic QTL, a crucial step towards the understanding of the molecular bases of heterosis in maize

Crocin from Crocus sativus possesses significant antiproliferation effects on human colorectal cancer cells

Aim: To investigate the anti-proliferative effects of Crocus sativus extract and its major constituent, crocin, on three colorectal cancer cell lines (HCT-116, SW-480, and HT-29). The cell growth inhibition effect was compared to that of non-small cell lung cancer (NSCLC) cells. In addition, Crocus sativus’ effect on non-cancer cells was evaluated. Methods: Using high performance liquid chromatography (HPLC), the purity of crocin and the content of crocin extract were determined. Anti-proliferative effects of Crocus sativus extract and crocin on test cells was evaluated by MTS assay. Results: The purity of crocin was found to be 95.9% and the content of crocin in the extract was 22.9%. Significant concentration-related inhibition effects of the extract on all three colorectal cancer cell lines were observed (P < 0.01). The proliferation was reduced most significantly in HCT-116 cells, to 45.5% at 1.0 mg/ml and to 6.8 % at 3.0 mg/ml. Crocin at 1.0 mM, significantly reduced HCT-116, SW-480, and HT-29 cell proliferation to 2.8%, 52%, and 16.8%, respectively (P < 0.01). Since 3.0 mg/ml Crocus sativus extract contained approximately 0.6 mM crocin, the observed effects suggest that crocin is a major responsible constituent in the extract. Significant anti-proliferative effects were also observed in non-small cell lung cancer cells. However, Crocus sativus extract did not significantly affect the growth of non-cancer young adult mouse colon cells. Conclusion: Data from this study demonstrated that Crocus sativus extract and its major constituent, crocin, significantly inhibited the growth of colorectal cancer cells while not affecting normal cells. Crocus sativus extract should be investigated further as a viable option in the treatment of colorectal cancer.Цель: исследовать антипролиферативный эффект экстракта Crocus sativus и его главного действующего вещества, кроцина, на три клеточные линии колоректального рака человека (HCT-116, SW-480 и HT-29). Эффект ингибирования роста клеток оценивали по отношению к таковому для клеток немелкоклеточного рака легкого (НМРЛ) и немалигнизированных клеток. Методы: для очистки кроцина и составляющих экстракта C. sativus применяли высокоэффективную жидкостную хроматографию (ВЭЖХ). Антипролиферативный эффект экстракта и кроцина по отношению к клеткам оценивали при помощи MTS-теста. Результаты: степень очистки кроцина составляла 95,9%, а содержание кроцина в экстракте –22,9%. Отмечали существенное дозозависимое угнетение пролиферации клеток трех линий экстрактом C. sativus (P < 0.01). Наиболее выраженное снижение пролиферативной активности оотмечали для клеток HCT-116 (дo 45,5 % при 1,0 мг/мл и до 6,8 % при 3,0 мг/мл). Кроцин в концентрации 1,0 мM, значительно ингибирует пролиферацию клеток HCT-116, SW-480 и HT-29 (до 2,8, 52 и 16,8% соответственно, P < 0,01). Поскольку 3,0 мг/мл экстракта C. sativus содержат приблизительно 0,6 мM кроцина, отмеченное действие первого подтверждает тот факт, что кроцин — главное действующее начало экстракта. Также показано существенное антипролиферативное действие по отношению к клеткам НМРЛ. Однако C. sativus не оказывал выраженного действия на рост немалигнизированных клеток толстого кишечника молодых мышей. Выводы: данные представленного исследования показывают, что экстракт Crocus sativus и его главный действующий компонент кроцин значительно ингибируют рост клеточных линий колоректального рака и в то же время не влияют на рост нормальных клеток. В дальнейшем следует изучить возможность применения Crocus sativus для лечения больных колоректальным раком

Evaluating the reliability of non-specialist observers in the behavioural assessment of semi-captive Asian elephant welfare

Recognising stress is an important component in maintaining the welfare of captive animal populations, and behavioural observation provides a rapid and non-invasive method to do this. Despite substantial testing in zoo elephants, there has been relatively little interest in the application of behavioural assessments to the much larger working populations of Asian elephants across Southeast Asia, which are managed by workers possessing a broad range of behavioural knowledge. Here, we developed a new ethogram of potential stress- and work-related behaviour for a semi-captive population of Asian elephants. We then used this to collect observations from video footage of over 100 elephants and evaluated the reliability of behavioural welfare assessments carried out by non-specialist observers. From observations carried out by different raters with no prior experience of elephant research or management, we tested the reliability of observations between-observers, to assess the general inter-observer agreement, and within-observers, to assess the consistency in behaviour identification. The majority of ethogram behaviours were highly reliable both between- and within-observers, suggesting that overall, behaviour was highly objective and could represent easily recognisable markers for behavioural assessments. Finally, we analysed the repeatability of individual elephant behaviour across behavioural contexts, demonstrating the importance of incorporating a personality element in welfare assessments. Our findings highlight the potential of non-expert observers to contribute to the reliable monitoring of Asian elephant welfare across large captive working populations, which may help to both improve elephant wellbeing and safeguard human workers

Demographic and reproductive associations with nematode infection in a long-lived mammal

Infection by macroparasites, such as nematodes, varies within vertebrate host systems; elevated infection is commonly observed in juveniles and males, and, for females, with different reproductive states. However, while such patterns are widely recognized in short-lived model systems, how they apply to long-lived hosts is comparatively understudied. Here, we investigated how infection varies with host age, sex, and female reproduction in a semi-captive population of individually marked Asian elephants Elephas maximus. We carried out 1,977 faecal egg counts (FECs) across five years to estimate nematode loads for 324 hosts. Infection patterns followed an established age-infection curve, whereby calves (5 years) exhibited the highest FECs and adults (45 years) the lowest. However, males and females had similar FECs across their long lifespan, despite distinct differences in life-history strategy and clear sexual dimorphism. Additionally, although mothers invest two years in pregnancy and a further three to five years into lactation, nematode load did not vary with four different measures of female reproduction. Our results provide a much-needed insight into the host-parasite dynamics of a long-lived host; determining host-specific associations with infection in such systems is important for broadening our knowledge of parasite ecology and provides practical applications for wildlife medicine and management.</p

Is bigger better? The relationship between size and reproduction in female Asian elephants

The limited availability of resources is predicted to impose trade-offs between growth, reproduction and self-maintenance in animals. However, although some studies have shown that early reproduction suppresses growth, reproduction positively correlates with size in others. We use detailed records from a large population of semi-captive elephants in Myanmar to assess the relationships between size (height and weight), reproduction and survival in female Asian elephants, a species characterized by slow, costly life history. Although female height gain during the growth period overlapped little with reproductive onset in the population, there was large variation in age at first reproduction and only 81% of final weight had been reached by peak age of reproduction at the population level (19 years). Those females beginning reproduction early tended to be taller and lighter later in life, although these trends were not significant. We found that taller females were more likely to have reproduced by a given age, but such effects diminished with age, suggesting there may be a size threshold to reproduction which is especially important in young females. Because size was not linked with female survival during reproductive ages, the diminishing effect of height on reproduction with age is unlikely to be due to biased survival of larger females. We conclude that although reproduction may not always impose significant costs on growth, height may be a limiting factor to reproduction in young female Asian elephants, which could have important implications considering their birth rates are low and peak reproduction is young – 19 years in this population. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology</p

Asian elephant calf physiology and mahout perspectives during taming in Myanmar

A quarter of Asian elephants are captive, with greater than 90% of these tamed and cared for by handlers (mahouts) in Asia. Although taming is a much-discussed welfare issue, no studies to our knowledge have empirically assessed its impact on calves, and dialogue surrounding taming often lacks perspectives of those involved. Here, we interviewed mahouts involved in taming and monitored five physiological measures (faecal glucocorticoid metabolites (FGMs), serum cortisol, glucose, creatine kinase (CK) and heterophil:lymphocyte (H:L)) over the first 10 days of taming and following six months in 41 calves undergoing taming and 16 control individuals. These measures assess the duration and intensity of stress during taming. Interviews suggested mahouts had major concerns for their safety when discussing changing taming practices, an important consideration for future management. Calf physiological measures were elevated by 50–70% (FGMs/cortisol/glucose), 135% (H:L) and greater than 500% (CK) over the first few days of taming, indicative of elevated stress, not seen to the same extent in control adults. Some measures stabilized sooner (glucose/cortisol/CK/FGM: 7–10 days) than others (H:L: one–two months), indicating mostly acute stress. Our findings inform the welfare of approximately 15 000 captive elephants around the world. Future studies should compare taming in different populations and consider calf and mahout welfare

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Discovery of evolving convoys

10.1007/978-3-642-13818-8_16Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)6187 LNCS196-21

Towards Ad-hoc circles in Social Networking Sites

10.1145/2304536.2304540Proceedings of the 2nd ACM SIGMOD Workshop on Databases and Social Networks, DBSocial 201219-2

Production of a multiparental RIL population for high-resolution mapping in maize

The development of advanced cross designs that might boost the power of detection of the genetic bases of complex traits remain a crucial goal of modern plant genetics. Here we describe the program currently ongoing for the development of an innovative advanced Recombinant Inbred Lines population, aimed at the genetic and molecular dissection of complex traits in maize. Eight maize inbred lines were selected to include a wide genetic variability for the expression of complex phenotypes and crossed according to a half-diallel design. This genetic material was used as the starting point for producing an extended (>2000) maize 8-ways RIL (8W-RIL) to be used for highresolution QTL mapping. According to what estimated by The Complex Trait Consortium, which first proposed this model for mouse, such a material should allow mapping QTL with effect size >5% of the total variance to an interval of 0.5 cM using fewer than 1000 lines. Twenty-eight F1 hybrids from the 8x8 half-diallel were crossed so that only crosses between entries with no parents in common (e.g. cross AB x CD) were allowed (but not AB x AD or AB x BF, etc.). Such obtained 4-ways hybrids (210) were bulked in 70 pools, each composed by all the three 4-ways hybrids bearing the same alleles in all possible parent-of-origin cis combinations (e.g. \u201cABCD\u201d pool included ABxCD, ACxBD and ADxBC 4-ways hybrids). 8-ways hybrids were then produced by crossing complementary 4-ways hybrids pools (e.g. ABCD x EFGH, CDFG x ABEH, etc.). The production of 8W-RIL by single-seed descent is currently at the third selfing generation (8W-RIL F3). Performing two generations of selfing per year, we expect to obtain a 8W-RI F6 mapping population by the end of 2010, whereas the molecular characterization of parental lines is scheduled to start in the fall of 2009. All 2-ways hybrids, 4-ways hybrids and 8-ways highlyrecombinant hybrids plus the parental inbreds will also be available for phenotypic evaluation of complex traits, including heterotic traits