Ultrastructure of cilia and flagella - back to the future!

Eukaryotic cilia and flagella perform motility and sensory functions which are essential for cell survival in protozoans, and to organism development and homoeostasis in metazoans. Their ultrastructure has been studied from the early beginnings of electron microscopy, and these studies continue to contribute to much of our understanding about ciliary biology. In the light of the progress made in the visualization of cellular structures over the last decade, we revisit the ultrastructure of cilia and flagella. We briefly describe the typical features of a 9+2 axoneme before focusing extensively on the transition zone, the ciliary necklace, the singlet zone, the ciliary cap and the ciliary crown. We discuss how the singlet zone is linked to sensory and/or motile function, the contribution of the ciliary crown to ovocyte and mucosal propulsion, and the relationship between the ciliary cap and microtubule growth and shortening, and its relation to ciliary beat. We further examine the involvement of the transition zone/the ciliary necklace in axonemal stabilization, autotomy and as a diffusion barrier.     

Heterocyclic aminopyrrolidine derivatives as melatoninergic agents

A series of chiral heterocyclic aminopyrrolidine derivatives was synthesized as novel melatoninergic ligands. Binding affinity assays were performed on cloned human MT₁ and MT₂ receptors, stably expressed in NIH3T3 cells. Compound 16 was identified as an orally bioavailable agonist at MT₁ and MT₂ melatonin receptors with low vasoconstrictive activity.     

Genome-wide association mapping of quantitative resistance to sudden death syndrome in soybean

Background

Sudden death syndrome (SDS) is a serious threat to soybean production that can be managed with host plant resistance. To dissect the genetic architecture of quantitative resistance to the disease in soybean, two independent association panels of elite soybean cultivars, consisting of 392 and 300 unique accessions, respectively, were evaluated for SDS resistance in multiple environments and years. The two association panels were genotyped with 52,041 and 5,361 single nucleotide polymorphisms (SNPs), respectively. Genome-wide association mapping was carried out using a mixed linear model that accounted for population structure and cryptic relatedness.

Result

A total of 20 loci underlying SDS resistance were identified in the two independent studies, including 7 loci localized in previously mapped QTL intervals and 13 novel loci. One strong peak of association on chromosome 18, associated with all disease assessment criteria across the two panels, spanned a physical region of 1.2 Mb around a previously cloned SDS resistance gene (GmRLK18-1) in locus Rfs2. An additional variant independently associated with SDS resistance was also found in this genomic region. Other peaks were within, or close to, sequences annotated as homologous to genes previously shown to be involved in plant disease resistance. The identified loci explained an average of 54.5% of the phenotypic variance measured by different disease assessment criteria.

Conclusions

This study identified multiple novel loci and refined the map locations of known loci related to SDS resistance. These insights into the genetic basis of SDS resistance can now be used to further enhance durable resistance to SDS in soybean. Additionally, the associations identified here provide a basis for further efforts to pinpoint causal variants and to clarify how the implicated genes affect SDS resistance in soybean.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-809) contains supplementary material, which is available to authorized users.     

A generalizable NLP framework for fast development of pattern-based biomedical relation extraction systems

Background

Text mining is increasingly used in the biomedical domain because of its ability to automatically gather information from large amount of scientific articles. One important task in biomedical text mining is relation extraction, which aims to identify designated relations among biological entities reported in literature. A relation extraction system achieving high performance is expensive to develop because of the substantial time and effort required for its design and implementation. Here, we report a novel framework to facilitate the development of a pattern-based biomedical relation extraction system. It has several unique design features: (1) leveraging syntactic variations possible in a language and automatically generating extraction patterns in a systematic manner, (2) applying sentence simplification to improve the coverage of extraction patterns, and (3) identifying referential relations between a syntactic argument of a predicate and the actual target expected in the relation extraction task.

Results

A relation extraction system derived using the proposed framework achieved overall F-scores of 72.66% for the Simple events and 55.57% for the Binding events on the BioNLP-ST 2011 GE test set, comparing favorably with the top performing systems that participated in the BioNLP-ST 2011 GE task. We obtained similar results on the BioNLP-ST 2013 GE test set (80.07% and 60.58%, respectively). We conducted additional experiments on the training and development sets to provide a more detailed analysis of the system and its individual modules. This analysis indicates that without increasing the number of patterns, simplification and referential relation linking play a key role in the effective extraction of biomedical relations.

Conclusions

In this paper, we present a novel framework for fast development of relation extraction systems. The framework requires only a list of triggers as input, and does not need information from an annotated corpus. Thus, we reduce the involvement of domain experts, who would otherwise have to provide manual annotations and help with the design of hand crafted patterns. We demonstrate how our framework is used to develop a system which achieves state-of-the-art performance on a public benchmark corpus.     

Sugar Sweetened Beverages and Weight Gain over 4 Years in a Thai National Cohort – A Prospective Analysis

Introduction

Sugar sweetened beverages (SSBs) are implicated in the rising prevalence of obesity and diet-related chronic diseases worldwide. However, little is known about their contribution to weight gain in Asian populations. This study aimed to investigate weight change associated with SSB consumption between 2005 and 2009 in a large national cohort of Thai university students.

Methods

Questionnaire data were collected from a large Thai cohort (the Thai Health-Risk Transition: a National Cohort Study). The analysis was based on responses from 59 283 of the 60 569 (98%) cohort members who had valid SSB consumption and weight variables in 2005 and 2009. The relationship between SSB consumption in 2005 and self-reported weight change was analysed using multiple linear regression models controlled for socio-demographic, activity and (non-validated) dietary factors shown to influence weight.

Results

Higher frequency of SSB consumption in 2005 was significantly associated with greater weight gain between 2005 and 2009 in all age groups and in both sexes (p<0.0001); persons who consumed SSBs at least once a day in 2005 gained 0.5 kg more than those who consumed SSBs less than once a month. The estimated weight gain for the average person in the sample was 1.9 kg (95% C I 1.95–1.96). The difference in weight gain between those who increased their consumption frequency (<once a month to > once per day) between 2005 and 2009 compared to those who maintained it was 0.3 kgs, while persons who reduced their consumption frequency (once a day to > once a month) gained 0.2 kgs less than those whose consumption remained unchanged.

Conclusion

SSB consumption is independently associated with weight gain in the Thai population. Research and health promotion in Thailand and other economically transitioning countries should focus on reducing their contribution to population weight gain and to diet-related chronic diseases.     

Use of Third Line Antiretroviral Therapy in Latin America

Background

Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known.

Methods

Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART.

Results

Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001).

Conclusions

Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.     

Effects of Age,Adipose Percent,and Reproduction on PCB Concentrations and Profiles in an Extreme Fasting North Pacific Marine Mammal

Persistent organic pollutants, including polychlorinated biphenyls (PCBs), are widely distributed and detectable far from anthropogenic sources. Northern elephant seals (Mirounga angustirostris) biannually travel thousands of kilometers to forage in coastal and open-ocean regions of the northeast Pacific Ocean and then return to land where they fast while breeding and molting. Our study examined potential effects of age, adipose percent, and the difference between the breeding and molting fasts on PCB concentrations and congener profiles in blubber and serum of northern elephant seal females. Between 2005 and 2007, we sampled blubber and blood from 58 seals before and after a foraging trip, which were then analyzed for PCBs. Age did not significantly affect total PCB concentrations; however, the proportion of PCB congeners with different numbers of chlorine atoms was significantly affected by age, especially in the outer blubber. Younger adult females had a significantly greater proportion of low-chlorinated PCBs (tri-, tetra-, and penta-CBs) than older females, with the opposite trend observed for hepta-CBs, indicating that an age-associated process such as parity (birth) may significantly affect congener profiles. The percent of adipose tissue had a significant relationship with inner blubber PCB concentrations, with the highest mean concentrations observed at the end of the molting fast. These results highlight the importance of sampling across the entire blubber layer when assessing contaminant levels in phocid seals and taking into account the adipose stores and reproductive status of an animal when conducting contaminant research.