Expression Analysis of the Theileria parva Subtelomere-Encoded Variable Secreted Protein Gene Family

Background The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs) form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm. Methodology/Principal Findings We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals. Conclusions Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic proteins.

Relaxation of species-specific neighborhood effects in Bornean rain forest under climatic perturbation

Evidence of negative conspecific density dependence (NDD) operating on seedling survival and sapling recruitment has accumulated recently. In contrast, evidence of NDD operating on growth of trees has been circumstantial at best. Whether or not local NDD at the level of individual trees leads to NDD at the level of the community is still an open question. Moreover, whether and how perturbations interfere with these processes have rarely been investigated. We applied neighborhood models to permanent plot data from a Bornean dipterocarp forest censused over two 10-11 year periods. Although the first period was only lightly perturbed, a moderately strong El Nino event causing severe drought occurred in the first half of the second period. Such events are an important component of the environmental stochasticity affecting the region. We show that local NDD on growth of small-to-medium-sized trees may indeed translate to NDD at the level of the community. This interpretation is based on increasingly negative effects of bigger conspecific neighbors on absolute growth rates of individual trees with increasing basal area across the 18 most abundant overstory species in the first period. However, this relationship was much weaker in the second period. We interpreted this relaxation of local and community-level NDD as a consequence of increased light levels at the forest floor due to temporary leaf and twig loss of large trees in response to the drought event. Mitigation of NDD under climatic perturbation acts to decrease species richness, especially in forest overstory and therefore has an important role in determining species relative abundances at the site.

Splitting of a prevalent Mycobacterium bovis spoligotype by variable-number tandem-repeat typing reveals high heterogeneity in an evolving clonal group

Mycobacterium bovis populations in countries with persistent bovine tuberculosis usually show a prevalent spoligotype with a wide geographical distribution. This study applied mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing to a random panel of 115 M. bovis isolates that are representative of the most frequent spoligotype in the Iberian Peninsula, SB0121. VNTR typing targeted nine loci: ETR-A (alias VNTR2165), ETR-B (VNTR2461), ETR-D (MIRU4, VNTR580), ETR-E (MIRU31, VNTR3192), MIRU26 (VNTR2996), QUB11a (VNTR2163a), QUB11b (VNTR2163b), QUB26 (VNTR4052), and QUB3232 (VNTR3232). We found a high degree of diversity among the studied isolates (discriminatory index [D] = 0.9856), which were split into 65 different MIRU-VNTR types. An alternative short-format MIRU-VNTR typing targeting only the four loci with the highest variability values was found to offer an equivalent discriminatory index. Minimum spanning trees using the MIRU-VNTR data showed the hypothetical evolution of an apparent clonal group. MIRU-VNTR analysis was also applied to the isolates of 176 animals from 15 farms infected by M. bovis SB0121; in 10 farms, the analysis revealed the coexistence of two to five different MIRU types differing in one to six loci, which highlights the frequency of undetected heterogeneity.

Crystal chemistry and hydrogen bonding of rustumite Ca10(Si2O7)2(SiO4)(OH)2Cl2 with variable OH, Cl, F

Three samples of the skarn mineral rustumite Ca10(Si2O7)2(SiO4)(OH)2Cl2, space group C2/c, a ≈7.6, b ≈ 18.5, c ≈ 15.5 Å, β ≈ 104°, with variable OH, Cl, F content were investigated by electron microprobe, single-crystal X-ray structure refinements, and Raman spectroscopy. “Rust1LCl” is a low chlorine rustumite Ca10(Si2O7)2(SiO4)(OH1.88F0.12)(Cl1.28,OH0.72) from skarns associated with the Rize batholith near Ikizedere, Turkey. “Rust2F” is a F-bearing rustumite Ca10(Si2O7)2(SiO4)(OH1.13F0.87) (Cl1 96OH0.04) from xenoliths in ignimbrites of the Upper Chegem Caldera, Northern Caucasus, Russia. “Rust3LClF” represents a low-Cl, F-bearing rustumite Ca10(Si2O7)2(SiO4)0.87(H4O4)0.13(OH1.01F0.99) (Cl1.00 OH1.00) from altered merwinite skarns of the Birkhin massif, Baikal Lake area, Eastern Siberia, Russia. Rustumite from Birkhin massif is characterized by a significant hydrogarnet-like or fluorine substitution at the apices of the orthosilicate group, leading to specific atomic displacements. The crystal structures including hydrogen positions have been refined from single-crystal X-ray data to R1 = 0.0205 (Rust1_LCl), R1 = 0.0295 (Rust2_F), and R1 = 0.0243 (Rust3_LCl_F), respectively. Depletion in Cl and replacement by OH is associated with smaller unit-cell dimensions. The substitution of OH by F leads to shorter hydrogen bonds O-H⋯F instead of O-H⋯OH. Raman spectra for all samples have been measured and confirm slight strengthening of the hydrogen bonds with uptake of F.This study discusses the complex crystal chemistry of the skarn mineral rustumite and may provide a wider understanding of the chemical reactions related to contact metamorphism of limestones.

Time-variable gravity signal in Greenland revealed by high-low satellite-to-satellite tracking

[1] In the event of a termination of the Gravity Recovery and Climate Experiment (GRACE) mission before the launch of GRACE Follow-On (due for launch in 2017), high-low satellite-to-satellite tracking (hl-SST) will be the only dedicated observing system with global coverage available to measure the time-variable gravity field (TVG) on a monthly or even shorter time scale. Until recently, hl-SST TVG observations were of poor quality and hardly improved the performance of Satellite Laser Ranging observations. To date, they have been of only very limited usefulness to geophysical or environmental investigations. In this paper, we apply a thorough reprocessing strategy and a dedicated Kalman filter to Challenging Minisatellite Payload (CHAMP) data to demonstrate that it is possible to derive the very long-wavelength TVG features down to spatial scales of approximately 2000 km at the annual frequency and for multi-year trends. The results are validated against GRACE data and surface height changes from long-term GPS ground stations in Greenland. We find that the quality of the CHAMP solutions is sufficient to derive long-term trends and annual amplitudes of mass change over Greenland. We conclude that hl-SST is a viable source of information for TVG and can serve to some extent to bridge a possible gap between the end-of-life of GRACE and the availability of GRACE Follow-On.

Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

The Quiet Eye and motor performance – Introducing fixation duration as an independent variable

Evidence suggests a strong relation between superior motor performance and the duration of the last fixation before movement initiation (called Quiet Eye, QE). Although this phenomenon proves to be quite robust, to date, only little is known about its functional role. Therefore, in two experiments, a novel paradigm is introduced, testing the QE as independent variable by experimentally manipulating the duration of the last fixation in a throwing task. In addition, this paradigm allowed for the manipulation of the predictability of the target position. Results of the first study revealed an increase in throwing accuracy as function of experimentally prolonged QE durations. Thus, the assumption that the QE does not surface as a mere by-product of superior performance could be confirmed. In the second study, this dependency was found only under high task-demand conditions in which the target position was not predictable. This finding confirms the hypothesis that it is the optimization of information processing which serves as the crucial mechanisms behind QE effects.

Plasticity to wind is modular and genetically variable in Arabidopsis thaliana

Thigmomorphogenesis, the characteristic phenotypic changes by which plants react to mechanical stress, is a widespread and probably adaptive type of phenotypic plasticity. However, little is known about its genetic basis and population variation. Here, we examine genetic variation for thigmomorphogenesis within and among natural populations of the model system Arabidopsis thaliana. Offspring from 17 field-collected European populations was subjected to three levels of mechanical stress exerted by wind. Overall, plants were remarkably tolerant to mechanical stress. Even high wind speed did not significantly alter the correlation structure among phenotypic traits. However, wind significantly affected plant growth and phenology, and there was genetic variation for some aspects of plasticity to wind among A. thaliana populations. Our most interesting finding was that phenotypic traits were organized into three distinct and to a large degree statistically independent covariance modules associated with plant size, phenology, and growth form, respectively. These phenotypic modules differed in their responsiveness to wind, in the degree of genetic variability for plasticity, and in the extent to which plasticity affected fitness. It is likely, therefore, that thigmomorphogenesis in this species evolves quasi-independently in different phenotypic modules.

Evidence of species-specific neighborhood effects in the dipterocarpaceae of a Bornean rain forest

Although accumulating evidence indicates that local intraspecific density-dependent effects are not as rare in species-rich communities as previously suspected, there are still very few detailed and systematic neighborhood analyses of species-rich communities. Here, we provide such an analysis with the overall goal of quantifying the relative importance of inter- and intraspecific interaction strength in a primary, lowland dipterocarp forest located at Danum, Sabah, Malaysia. Using data on 10 abundant overstory dipterocarp species from two 4-ha permanent plots, we evaluated the effects of neighbors on the absolute growth rate of focal trees (from 1986 to 1996) over increasing neighborhood radii (from 1 to 20 m) with multiple regressions. Only trees 10 cm to < 100 cm girth at breast height in 1986 were considered as focal trees. Among neighborhood models with one neighbor term, models including only conspecific larger trees performed best in five out of 10 species. Negative effects of conspecific larger neighbors were most apparent in large overstory species such as those of the genus Shorea. However, neighborhood models with separate terms and radii for heterospecific and conspecific neighbors accounted for more variability in absolute growth rates than did neighborhood models with one neighbor term. The conspecific term was significant for nine out of 10 species. Moreover, in five out of 10 species, trees without conspecific neighbors had significantly higher absolute growth rates than trees with conspecific neighbors. Averaged over the 10 species, trees without conspecific neighbors grew 32.4 cm(2) in basal area from 1986 to 1996, whereas trees with conspecific neighbors only grew 14.7 cm(2) in basal area, although there was no difference in initial basal area between trees in the two groups. Averaged across the six species of the genus Shorea, negative effects of conspecific larger trees were significantly stronger than for heterospecific larger neighbors. Thus, high local densities within neighborhoods of 20 m may lead to strong intraspecific negative and, hence, density-dependent, effects even in species rich communities with low overall densities at larger spatial scales. We conjecture that the strength of conspecific effects may be correlated with the degree of host specificity of ectomycorrhizae.

The relation between cognitive and motor performance and their relevance for children’s transition to school: A latent variable approach

Both theoretically and empirically there is a continuous interest in understanding the specific relation between cognitive and motor development in childhood. In the present longitudinal study including three measurement points, this relation was targeted. At the beginning of the study, the participating children were 5-6-year-olds. By assessing participants' fine motor skills, their executive functioning, and their non-verbal intelligence, their cross-sectional and cross-lagged interrelations were examined. Additionally, performance in these three areas was used to predict early school achievement (in terms of mathematics, reading, and spelling) at the end of participants' first grade. Correlational analyses and structural equation modeling revealed that fine motor skills, non-verbal intelligence and executive functioning were significantly interrelated. Both fine motor skills and intelligence had significant links to later school achievement. However, when executive functioning was additionally included into the prediction of early academic achievement, fine motor skills and non-verbal intelligence were no longer significantly associated with later school performance suggesting that executive functioning plays an important role for the motor-cognitive performance link.

Relations among fluid intelligence, sensory discrimination and working memory in middle to late childhood – A latent variable approach

Two factors that have been suggested as key in explaining individual differences in fluid intelligence are working memory and sensory discrimination ability. A latent variable approach was used to explore the relative contributions of these two variables to individual differences in fluid intelligence in middle to late childhood. A sample of 263 children aged 7–12 years was examined. Correlational analyses showed that general discrimination ability (GDA)and working memory (WM) were related to each other and to fluid intelligence. Structural equation modeling showed that within both younger and older age groups and the sample as a whole, the relation between GDA and fluid intelligence could be accounted for by WM. While WM was able to predict variance in fluid intelligence above and beyond GDA, GDA was not able to explain significant amounts of variance in fluid intelligence, either in the whole sample or within the younger or older age group. We concluded that compared to GDA, WM should be considered the better predictor of individual differences in fluid intelligence in childhood. WM and fluid intelligence, while not being separable in middle childhood, develop at different rates, becoming more separable with age.

Relationship between the objectively-assessed neighborhood area and activity behavior in Swiss youth

Background Neighborhood attributes are modifiable determinants of physical activity (PA) and sedentary behavior (SB). We tested whether the objectively-assessed built and social environment was associated with PA and SB in Swiss youth and whether sex, age and the socioeconomic position (Swiss-SEP) modified such associations. Methods We combined data of 1742 youth (ages 4 to 17) from seven studies conducted within Switzerland between 2005–2010. All youth provided accelerometer data and a home address, which was linked to objective environmental data and the Swiss-SEP-index. Associations between neighborhood attributes and PA were analyzed by multivariable multilevel regression analyses. Results The extent of green areas and building density was positively associated with PA in the total sample (p < 0.05). Factors representing centrally located areas, and more schoolchildren living nearby tended to increase PA in secondary schoolchildren, boys and those from lower-ranked socioeconomic areas. In primary schoolchildren, the extent of green areas was positively associated with PA (p = 0.05). Associations between neighborhood attributes and PA were more pronounced in youth from low socioeconomic areas. Conclusions The results indicate that some associations between neighborhood attributes and PA differ by age, sex and socioeconomic area. This should be taken into account when planning interventions to increase childhood PA.