A marker-assisted backcross approach for developing submergence-tolerant rice cultivars

Submergence stress regularly affects 15 million hectares or more of rainfed lowland rice areas in South and Southeast Asia. A major QTL on chromosome 9, Sub1, has provided the opportunity to apply marker assisted backcrossing (MAB) to develop submergence tolerant versions of rice cultivars that are widely grown in the region. In the present study, molecular markers that were tightly linked with Sub1, flanking Sub1, and unlinked to Sub1 were used to apply foreground, recombinant, and background selection, respectively, in backcrosses between a submergence-tolerant donor and the widely grown recurrent parent Swarna. By the BC₂F₂ generation a submergence tolerant plant was identified that possessed Swarna type simple sequence repeat (SSR) alleles on all fragments analyzed except the tip segment of rice chromosome 9 that possessed the Sub1 locus. A BC₃F₂ double recombinant plant was identified that was homozygous for all Swarna type alleles except for an approximately 2.3–3.4 Mb region surrounding the Sub1 locus. The results showed that the mega variety Swarna could be efficiently converted to a submergence tolerant variety in three backcross generations, involving a time of two to three years. Polymorphic markers for foreground and recombinant selection were identified for four other mega varieties to develop a wider range of submergence tolerant varieties to meet the needs of farmers in the flood-prone regions. This approach demonstrates the effective use of marker assisted selection for a major QTL in a molecular breeding program. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Hominin homoiology: an assessment of the impact of phenotypic plasticity on phylogenetic analyses of humans and their fossil relatives

Homoiologies are phylogenetically misleading morphological similarities that are due to nongenetic factors. It has been claimed that homoiologies are common in the hominin skull, especially in regions affected by masticatory strain, and that their prevalence is one reason why reconstructing hominin phylogenetic relationships is difficult. To evaluate this "homoiology hypothesis," we performed analyses on a group of extant primates for which a robust molecular phylogeny is available--the hominoids. We compiled a data set from measurements that developmental considerations and experimental evidence suggest differ in their likelihood of exhibiting masticatory-strain-induced phenotypic plasticity. We then used the coefficient of variation and t-tests to evaluate the phenotypic plasticity of the measurements. We predicted that, if the hypothesis is correct, the measurements of skeletal features that do not remodel and therefore are unaffected by phenotypic plasticity should be less variable than the measurements of skeletal features that remodel and are subject to low-to-moderate strains, and that the latter should be less variable than the measurements of skeletal features that remodel and are subject to moderate-to-high strains. Subsequently, we performed phylogenetic analyses on character state data derived from the measurements and compared the resulting phylogenetic hypotheses to the consensus molecular phylogeny for the hominoids. We predicted that, if the hypothesis is correct, agreement between the phylogenies should be best for the non-phenotypically-plastic characters, intermediate for the low-to-moderate-strain characters, and worst for the moderate-to-high-strain characters. The results of the coefficient of variation/t-test analyses were consistent with the predictions of the hypothesis to the extent that the moderate-to-high-strain measurements exhibited significantly more variability than the non-phenotypically-plastic and low-to-moderate-strain measurements. In contrast, the results of the phylogenetic analyses were not those predicted. The phylogeny derived from the moderate-to-high-strain characters matched the molecular phylogeny better than those obtained using the non-phenotypically-plastic and low-to-moderate-strain characters. Thus, our study supports the suggestion that mechanical loading results in phenotypic plasticity in the hominin skull, but it does not support the notion that homoiologies have a significant negative impact on hominin phylogenetics.     

T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?

Introduction

A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6⁺ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.

Methods

In total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN⁺) (n = 16) and negative (IFN^-) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4⁺CD45RO⁺CCR6⁺ T cells (CCR6⁺ cells) was measured with flow cytometry and compared between IFN⁺, IFN^- patients and HCs.

Results

Increased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ cells were observed in IFN⁺ patients compared with IFN^- patients and HCs. IL-17A and IL-17F expression within CCR6⁺ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)–a factor strongly correlating with IFN type I - and IL-21 producing CCR6⁺ cells.

Conclusions

We show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6⁺ memory T-helper cells in IFN⁺ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis.     

Analysing spatio-temporal clustering of meningococcal meningitis outbreaks in Niger reveals opportunities for improved disease control

Background

Meningococcal meningitis is a major health problem in the “African Meningitis Belt” where recurrent epidemics occur during the hot, dry season. In Niger, a central country belonging to the Meningitis Belt, reported meningitis cases varied between 1,000 and 13,000 from 2003 to 2009, with a case-fatality rate of 5–15%.

Methodology/Principal Findings

In order to gain insight in the epidemiology of meningococcal meningitis in Niger and to improve control strategies, the emergence of the epidemics and their diffusion patterns at a fine spatial scale have been investigated. A statistical analysis of the spatio-temporal distribution of confirmed meningococcal meningitis cases was performed between 2002 and 2009, based on health centre catchment areas (HCCAs) as spatial units. Anselin''s local Moran''s I test for spatial autocorrelation and Kulldorff''s spatial scan statistic were used to identify spatial and spatio-temporal clusters of cases. Spatial clusters were detected every year and most frequently occurred within nine southern districts. Clusters most often encompassed few HCCAs within a district, without expanding to the entire district. Besides, strong intra-district heterogeneity and inter-annual variability in the spatio-temporal epidemic patterns were observed. To further investigate the benefit of using a finer spatial scale for surveillance and disease control, we compared timeliness of epidemic detection at the HCCA level versus district level and showed that a decision based on threshold estimated at the HCCA level may lead to earlier detection of outbreaks.

Conclusions/Significance

Our findings provide an evidence-based approach to improve control of meningitis in sub-Saharan Africa. First, they can assist public health authorities in Niger to better adjust allocation of resources (antibiotics, rapid diagnostic tests and medical staff). Then, this spatio-temporal analysis showed that surveillance at a finer spatial scale (HCCA) would be more efficient for public health response: outbreaks would be detected earlier and reactive vaccination would be better targeted.     

Risk of resource failure and toolkit variation in small-scale farmers and herders

Recent work suggests that global variation in toolkit structure among hunter-gatherers is driven by risk of resource failure such that as risk of resource failure increases, toolkits become more diverse and complex. Here we report a study in which we investigated whether the toolkits of small-scale farmers and herders are influenced by risk of resource failure in the same way. In the study, we applied simple linear and multiple regression analysis to data from 45 small-scale food-producing groups to test the risk hypothesis. Our results were not consistent with the hypothesis; none of the risk variables we examined had a significant impact on toolkit diversity or on toolkit complexity. It appears, therefore, that the drivers of toolkit structure differ between hunter-gatherers and small-scale food-producers.     

An assessment of the impact of hafting on Paleoindian point variability

It has long been argued that the form of North American Paleoindian points was affected by hafting. According to this hypothesis, hafting constrained point bases such that they are less variable than point blades. The results of several studies have been claimed to be consistent with this hypothesis. However, there are reasons to be skeptical of these results. None of the studies employed statistical tests, and all of them focused on points recovered from kill and camp sites, which makes it difficult to be certain that the differences in variability are the result of hafting rather than a consequence of resharpening. Here, we report a study in which we tested the predictions of the hafting hypothesis by statistically comparing the variability of different parts of Clovis points. We controlled for the potentially confounding effects of resharpening by analyzing largely unused points from caches as well as points from kill and camp sites. The results of our analyses were not consistent with the predictions of the hypothesis. We found that several blade characters and point thickness were no more variable than the base characters. Our results indicate that the hafting hypothesis does not hold for Clovis points and indicate that there is a need to test its applicability in relation to post-Clovis Paleoindian points.     

Does phenotypic plasticity confound attempts to identify hominin fossil species? An assessment using extant Old World monkey craniodental data

It has been hypothesised recently that masticatory strain-induced phenotypic plasticity complicates efforts to delineate species in the hominin fossil record. Here, we report a study that evaluated this hypothesis by subjecting craniodental data from 8 Old World monkey species to ANOVA and discriminant analysis. The study does not support the hypothesis. Characters associated with high masticatory strains were found to exhibit significantly higher levels of variability than low-to-moderately strained characters and dental characters, but the three sets of characters did not differ markedly in taxonomic utility. Moreover, the best discrimination was achieved when all variables were employed. These results suggest that phenotypic plasticity likely plays only a minor confounding role in hominin taxonomy, and that, rather than attempting to exclude phenotypically plastic characters, researchers should simply maximise the number of characters examined.     

Effects of modifications of the linker in a series of phenylpropanoic acid derivatives: Synthesis, evaluation as PPARalpha/gamma dual agonists, and X-ray crystallographic studies

A new series of α-aryl or α-heteroarylphenyl propanoic acid derivatives was synthesized that incorporate acetylene-, ethylene-, propyl-, or nitrogen-derived linkers as a replacement of the commonly used ether moiety that joins the central phenyl ring with the lipophilic tail. The effect of these modifications in the binding and activation of PPARα and PPARγ was first evaluated in vitro. Compounds possessing suitable profiles were then evaluated in the ob/ob mouse model of type 2 diabetes. The propylene derivative 40 and the propyl derivative 53 demonstrated robust plasma glucose lowering activity in this model. Compound 53 was also evaluated in male Zucker diabetic fatty rats and was found to achieve normalization of glucose, triglycerides, and insulin levels. An X-ray crystal structure of the complex of 53 with the PPARγ-ligand-binding domain was obtained and discussed in this report.