Conformational Dynamics and Antigenicity in the Disordered Malaria Antigen Merozoite Surface Protein 2

Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonetheless, little is known about the implications of protein disorder for the development of an effective antibody response. We have therefore undertaken a detailed analysis of the conformational dynamics of the two allelic forms of MSP2 (3D7 and FC27) using NMR spectroscopy. Chemical shifts and NMR relaxation data indicate that conformational and dynamic properties of the N- and C-terminal conserved regions in the two forms of MSP2 are essentially identical, but significant variation exists between and within the central variable regions. We observe a strong relationship between the conformational dynamics and the antigenicity of MSP2, as assessed with antisera to recombinant MSP2. Regions of increased conformational order in MSP2, including those in the conserved regions, are more strongly antigenic, while the most flexible regions are minimally antigenic. This suggests that modifications that increase conformational order may offer a means to tune the antigenicity of MSP2 and other disordered antigens, with implications for vaccine design.     

Analysis of the Role of Interleukin 6 Receptor Haplotypes in the Regulation of Circulating Levels of Inflammatory Biomarkers and Risk of Coronary Heart Disease

Variants at the interleukin 6 receptor (IL6R) gene regulate inflammation and are associated with risk of coronary heart disease (CHD). The aim of the present study was to investigate the effects of IL6R haplotypes on circulating levels of inflammatory biomarkers and risk of CHD. We performed a discovery analysis in SHEEP, a myocardial infarction (MI) case control study (n = 2,774) and replicated our results in two large, independent European populations, PROCARDIS, a CHD case control study (n = 7,998), and IMPROVE (n = 3,711) a prospective cardiovascular cohort study. Two major haplotype blocks (rs12083537A/G and rs4075015A/T—block 1; and rs8192282G/A, rs4553185T/C, rs8192284A/C, rs4240872T/C and rs7514452T/C—block 2) were identified in the IL6R gene. IL6R haplotype associations with C-reactive protein (CRP), fibrinogen, IL6, soluble IL6R (sIL6R), IL6, IL8 and TNF-α in SHEEP, CRP and fibrinogen in PROCARDIS and CRP in IMPROVE as well as association with risk of MI and CHD, were analyzed by THESIAS. Haplotypes in block 1 were associated neither with circulating inflammatory biomarkers nor with the MI/CHD risk. Haplotypes in block 2 were associated with circulating levels of CRP, in all three study populations, with fibrinogen in SHEEP and PROCARDIS, with IL8 and sIL6Rin SHEEP and with a modest, non significant, increase (7%) in MI/CHD risk in the three populations studied. Our results indicate that IL6R haplotypes regulate the circulating levels of inflammatory biomarkers. Lack of association with the risk of CHD may be explained by the combined effect of SNPs with opposite effect on the CHD risk, the sample size as well as by structural changes affecting sIL6R stability in the circulation.     

Idealized Computational Models for Auditory Receptive Fields

We present a theory by which idealized models of auditory receptive fields can be derived in a principled axiomatic manner, from a set of structural properties to (i) enable invariance of receptive field responses under natural sound transformations and (ii) ensure internal consistency between spectro-temporal receptive fields at different temporal and spectral scales. For defining a time-frequency transformation of a purely temporal sound signal, it is shown that the framework allows for a new way of deriving the Gabor and Gammatone filters as well as a novel family of generalized Gammatone filters, with additional degrees of freedom to obtain different trade-offs between the spectral selectivity and the temporal delay of time-causal temporal window functions. When applied to the definition of a second-layer of receptive fields from a spectrogram, it is shown that the framework leads to two canonical families of spectro-temporal receptive fields, in terms of spectro-temporal derivatives of either spectro-temporal Gaussian kernels for non-causal time or a cascade of time-causal first-order integrators over the temporal domain and a Gaussian filter over the logspectral domain. For each filter family, the spectro-temporal receptive fields can be either separable over the time-frequency domain or be adapted to local glissando transformations that represent variations in logarithmic frequencies over time. Within each domain of either non-causal or time-causal time, these receptive field families are derived by uniqueness from the assumptions. It is demonstrated how the presented framework allows for computation of basic auditory features for audio processing and that it leads to predictions about auditory receptive fields with good qualitative similarity to biological receptive fields measured in the inferior colliculus (ICC) and primary auditory cortex (A1) of mammals.     

Female Gender Is a Social Determinant of Diabetes in the Caribbean: A Systematic Review and Meta-Analysis

BackgroundDiabetes (DM) is estimated to affect 10–15% of the adult population in the Caribbean. Preventive efforts require population wide measures to address its social determinants. We undertook a systematic review to determine current knowledge about the social distribution of diabetes, its risk factors and major complications in the Caribbean. This paper describes our findings on the distribution by gender.MethodsWe searched Medline, Embase and five databases through the Virtual Health Library, for Caribbean studies published between 2007 and 2013 that described the distribution by gender for: known risk factors for Type 2 DM, prevalence of DM, and DM control or complications. PRISMA guidance on reporting systematic reviews on health equity was followed. Only quantitative studies (n>50) were included; each was assessed for risk of bias. Meta-analyses were performed, where appropriate, on studies with a low or medium risk of bias, using random effects models.ResultsWe found 50 articles from 27 studies, yielding 118 relationships between gender and the outcomes. Women were more likely to have DM, obesity, be less physically active but less likely to smoke. In meta-analyses of good quality population-based studies odds ratios for women vs. men for DM, obesity and smoking were: 1.65 (95% CI 1.43, 1.91), 3.10 (2.43, 3.94), and 0.24 (0.17, 0.34). Three studies found men more likely to have better glycaemic control but only one achieved statistical significance.

Conclusion and Implications

Female gender is a determinant of DM prevalence in the Caribbean. In the vast majority of world regions women are at a similar or lower risk of type 2 diabetes than men, even when obesity is higher in women. Caribbean female excess of diabetes may be due to a much greater excess of risk factors in women, especially obesity. These findings have major implications for preventive policies and research.     

Molecular Characterization of Melanoma Cases in Denmark Suspected of Genetic Predisposition

Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.     

Anatomy,relationships and distribution of Taiwanassiminea affinis (Böttger) (Caenogastropoda: Assimineidae), with a reassessment of Cyclotropis Tapparone-Canefri

Assiminea affinis (Mousson ms) Böttger, 1887 Böttger, O. (1887) Aufzählung der zur Gattung Assiminea Fleming gehörigen Arten. Jahrbücher der Deutschen Malakozoologischen Gesellschaft 14, 147–234, pl. 6. [Google Scholar](=A. queenslandica [Pilsbry ms] Thiele, 1927 Thiele, J. (1927) Über die Schneckenfamilie Assimineidae. Zoologische Jahrbücher, Abteilung für Systematik, Ökologie und Geographie der Tiere 53, 114–146, pl. 1. [Google Scholar]), a previously unrecognised Australian assimineid species, is described anatomically and allocated to the genus Taiwanassiminea Kuroda and Habe, 1950 Kuroda, T. & Habe, T. (1950) Nomenclatural notes. Illustrated Catalogue of Japanese Shells 1, 16. [Google Scholar], first described from Taiwan. This is the first record of the genus from Australia. Taiwanassiminea affinis is found in slightly brackish waters in the upper tidal reaches of the larger rivers from northern Queensland to the Shoalhaven River in the southern half of New South Wales. The terrestrial Cyclotropis Tapparone-Canefri, 1883, which has somewhat similar shell and radular characters, is redefined and several species (Assiminea bedaliensis Rensch, 1934; Paludinella javana Thiele, 1927 Thiele, J. (1927) Über die Schneckenfamilie Assimineidae. Zoologische Jahrbücher, Abteilung für Systematik, Ökologie und Geographie der Tiere 53, 114–146, pl. 1. [Google Scholar]; Assiminea lentula, A. riparia and A. sororcula, all Benthem Jutting, 1963 Benthem Jutting, W.S.S. van. (1963) Non-marine Mollusca of west New Guinea Part 1, Mollusca from fresh and brackish waters. Nova Guinea, Zoology 20, 409–521. [Google Scholar]) previously included in Cyclotropis are transferred to Taiwanassiminea.     

Climate change‐induced vegetation change as a driver of increased subarctic biogenic volatile organic compound emissions

Emissions of biogenic volatile organic compounds (BVOCs) have been earlier shown to be highly temperature sensitive in subarctic ecosystems. As these ecosystems experience rapidly advancing pronounced climate warming, we aimed to investigate how warming affects the BVOC emissions in the long term (up to 13 treatment years). We also aimed to assess whether the increased litterfall resulting from the vegetation changes in the warming subarctic would affect the emissions. The study was conducted in a field experiment with factorial open‐top chamber warming and annual litter addition treatments on subarctic heath in Abisko, northern Sweden. After 11 and 13 treatment years, BVOCs were sampled from plant communities in the experimental plots using a push–pull enclosure technique and collection into adsorbent cartridges during the growing season and analyzed with gas chromatography–mass spectrometry. Plant species coverage in the plots was analyzed by the point intercept method. Warming by 2 °C caused a 2‐fold increase in monoterpene and 5‐fold increase in sesquiterpene emissions, averaged over all measurements. When the momentary effect of temperature was diminished by standardization of emissions to a fixed temperature, warming still had a significant effect suggesting that emissions were also indirectly increased. This indirect increase appeared to result from increased plant coverage and changes in vegetation composition. The litter addition treatment also caused significant increases in the emission rates of some BVOC groups, especially when combined with warming. The combined treatment had both the largest vegetation changes and the highest BVOC emissions. The increased emissions under litter addition were probably a result of a changed vegetation composition due to alleviated nutrient limitation and stimulated microbial production of BVOCs. We suggest that the changes in the subarctic vegetation composition induced by climate warming will be the major factor indirectly affecting the BVOC emission potentials and composition.     

Long‐term change in a behavioural trait: truncated spawning distribution and demography in Northeast Arctic cod

Harvesting may be a potent driver of demographic change and contemporary evolution, which both may have great impacts on animal populations. Research has focused on changes in phenotypic traits that are easily quantifiable and for which time series exist, such as size, age, sex, or gonad size, whereas potential changes in behavioural traits have been under‐studied. Here, we analyse potential drivers of long‐term changes in a behavioural trait for the Northeast Arctic stock of Atlantic cod Gadus morhua, namely choice of spawning location. For 104 years (1866–1969), commercial catches were recorded annually and reported by county along the Norwegian coast. During this time period, spawning ground distribution has fluctuated with a trend towards more northerly spawning. Spawning location is analysed against a suite of explanatory factors including climate, fishing pressure, density dependence, and demography. We find that demography (age or age at maturation) had the highest explanatory power for variation in spawning location, while climate had a limited effect below statistical significance. As to potential mechanisms, some effects of climate may act through demography, and explanatory variables for demography may also have absorbed direct evolutionary change in migration distance for which proxies were unavailable. Despite these caveats, we argue that fishing mortality, either through demographic or evolutionary change, has served as an effective driver for changing spawning locations in cod, and that additional explanatory factors related to climate add no significant information.     

Using basic plant traits to predict ungulate seed dispersal potential

Habitat fragmentation contributes to the decline of plant species by decreasing gene flow among populations. Restoring connectivity among habitat patches is therefore a major issue for plant conservation. However, deciding where to focus restoration efforts requires identifying suitable dispersers for each target plant species. We collected data from the literature on wild and domesticated ungulates, known to be effective seed dispersers, and on the plants they dispersed in Europe via epi‐ and/or endozoochory. We performed a systematic literature review to identify plant and animal traits relevant for seed dispersal. We first modeled the relationships between epi‐ or endozoochory and a priori selected plant traits (diaspore releasing height, length, shape and morphology, and habitat openness). The differences we underlined between the two dispersal mechanisms justified splitting our analyses accordingly. Then, for each dispersal mechanism, we asked whether basic plant traits could be used to predict specific traits of ungulates as endozoochorous or epizoochorous seed dispersers. We modeled the relationships between a priori selected ungulate traits for epizoochory (habitat openness, shoulder height, hair curliness, and hair length) and for endozoochory (habitat openness, body mass, feeding type and digestive system) and plant traits. Plant habitat openness and diaspore morphology were the predictors that most often explained differences among ungulates for epizoochory, whereas plant habitat openness and diaspore releasing height most often explained differences for endozoochory. Our trait‐based predictive models can help improve our ability to propose more precise management decisions for the conservation of plant populations worldwide by taking into account ungulate dispersers.