Adaptation Aftereffects in Vocal Emotion Perception Elicited by Expressive Faces and Voices

The perception of emotions is often suggested to be multimodal in nature, and bimodal as compared to unimodal (auditory or visual) presentation of emotional stimuli can lead to superior emotion recognition. In previous studies, contrastive aftereffects in emotion perception caused by perceptual adaptation have been shown for faces and for auditory affective vocalization, when adaptors were of the same modality. By contrast, crossmodal aftereffects in the perception of emotional vocalizations have not been demonstrated yet. In three experiments we investigated the influence of emotional voice as well as dynamic facial video adaptors on the perception of emotion-ambiguous voices morphed on an angry-to-happy continuum. Contrastive aftereffects were found for unimodal (voice) adaptation conditions, in that test voices were perceived as happier after adaptation to angry voices, and vice versa. Bimodal (voice + dynamic face) adaptors tended to elicit larger contrastive aftereffects. Importantly, crossmodal (dynamic face) adaptors also elicited substantial aftereffects in male, but not in female participants. Our results (1) support the idea of contrastive processing of emotions (2), show for the first time crossmodal adaptation effects under certain conditions, consistent with the idea that emotion processing is multimodal in nature, and (3) suggest gender differences in the sensory integration of facial and vocal emotional stimuli.     

Climate change impacts on biodiversity in Switzerland: A review

A noticeable increase in mean temperature has already been observed in Switzerland and summer temperatures up to 4.8 K warmer are expected by 2090. This article reviews the observed impacts of climate change on biodiversity and considers some perspectives for the future at the national level.The following impacts are already evident for all considered taxonomic groups: elevation shifts of distribution towards mountain summits, spread of thermophilous species, colonisation by new species from warmer areas and phenological shifts. Additionally, in the driest areas, increasing droughts are affecting tree survival and fish species are suffering from warm temperatures in lowland regions. These observations are coherent with model projections, and future changes will probably follow the current trends.These changes will likely cause extinctions for alpine species (competition, loss of habitat) and lowland species (temperature or drought stress). In the very urbanised Swiss landscape, the high fragmentation of the natural ecosystems will hinder the dispersal of many species towards mountains. Moreover, disruptions in species interactions caused by individual migration rates or phenological shifts are likely to have consequences for biodiversity. Conversely, the inertia of the ecosystems (species longevity, restricted dispersal) and the local persistence of populations will probably result in lower extinction rates than expected with some models, at least in 21st century. It is thus very difficult to estimate the impact of climate change in terms of species extinctions. A greater recognition by society of the intrinsic value of biodiversity and of its importance for our existence will be essential to put in place effective mitigation measures and to safeguard a maximum number of native species.     

Malaria Burden and Artemisinin Resistance in the Mobile and Migrant Population on the Thai–Myanmar Border, 1999–2011: An Observational Study

Background

The Shoklo Malaria Research Unit has been working on the Thai–Myanmar border for 25 y providing early diagnosis and treatment (EDT) of malaria. Transmission of Plasmodium falciparum has declined, but resistance to artesunate has emerged. We expanded malaria activities through EDT and evaluated the impact over a 12-y period.

Methods and Findings

Between 1 October 1999 and 30 September 2011, the Shoklo Malaria Research Unit increased the number of cross-border (Myanmar side) health facilities from two to 11 and recorded the number of malaria consultations. Changes in malaria incidence were estimated from a cohort of pregnant women, and prevalence from cross-sectional surveys. In vivo and in vitro antimalarial drug efficacy were monitored. Over this period, the number of malaria cases detected increased initially, but then declined rapidly. In children under 5 y, the percentage of consultations due to malaria declined from 78% (95% CI 76–80) (1,048/1,344 consultations) to 7% (95% CI 6.2–7.1) (767/11,542 consultations), p<0.001. The ratio of P. falciparum/P. vivax declined from 1.4 (95% CI 1.3–1.4) to 0.7 (95% CI 0.7–0.8). The case fatality rate was low (39/75,126; 0.05% [95% CI 0.04–0.07]). The incidence of malaria declined from 1.1 to 0.1 episodes per pregnant women-year. The cumulative proportion of P. falciparum decreased significantly from 24.3% (95% CI 21.0–28.0) (143/588 pregnant women) to 3.4% (95% CI 2.8–4.3) (76/2,207 pregnant women), p<0.001. The in vivo efficacy of mefloquine-artesunate declined steadily, with a sharp drop in 2011 (day-42 PCR-adjusted cure rate 42% [95% CI 20–62]). The proportion of patients still slide positive for malaria at day 3 rose from 0% in 2000 to reach 28% (95% CI 13–45) (8/29 patients) in 2011.

Conclusions

Despite the emergence of resistance to artesunate in P. falciparum, the strategy of EDT with artemisinin-based combination treatments has been associated with a reduction in malaria in the migrant population living on the Thai–Myanmar border. Although limited by its observational nature, this study provides useful data on malaria burden in a strategically crucial geographical area. Alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please see later in the article for the Editors'' Summary     

Matefin/SUN-1 Phosphorylation Is Part of a Surveillance Mechanism to Coordinate Chromosome Synapsis and Recombination with Meiotic Progression and Chromosome Movement

Faithful chromosome segregation during meiosis I depends on the establishment of a crossover between homologous chromosomes. This requires induction of DNA double-strand breaks (DSBs), alignment of homologs, homolog association by synapsis, and repair of DSBs via homologous recombination. The success of these events requires coordination between chromosomal events and meiotic progression. The conserved SUN/KASH nuclear envelope bridge establishes transient linkages between chromosome ends and cytoskeletal forces during meiosis. In Caenorhabditis elegans, this bridge is essential for bringing homologs together and preventing nonhomologous synapsis. Chromosome movement takes place during synapsis and recombination. Concomitant with the onset of chromosome movement, SUN-1 clusters at chromosome ends associated with the nuclear envelope, and it is phosphorylated in a chk-2- and plk-2-dependent manner. Identification of all SUN-1 phosphomodifications at its nuclear N terminus allowed us to address their role in prophase I. Failures in recombination and synapsis led to persistent phosphorylations, which are required to elicit a delay in progression. Unfinished meiotic tasks elicited sustained recruitment of PLK-2 to chromosome ends in a SUN-1 phosphorylation–dependent manner that is required for continued chromosome movement and characteristic of a zygotene arrest. Furthermore, SUN-1 phosphorylation supported efficient synapsis. We propose that signals emanating from a failure to successfully finish meiotic tasks are integrated at the nuclear periphery to regulate chromosome end–led movement and meiotic progression. The single unsynapsed X chromosome in male meiosis is precluded from inducing a progression delay, and we found it was devoid of a population of phosphorylated SUN-1. This suggests that SUN-1 phosphorylation is critical to delaying meiosis in response to perturbed synapsis. SUN-1 may be an integral part of a checkpoint system to monitor establishment of the obligate crossover, inducible only in leptotene/zygotene. Unrepaired DSBs and unsynapsed chromosomes maintain this checkpoint, but a crossover intermediate is necessary to shut it down.     

MMP-9 and CXCL8/IL-8 Are Potential Therapeutic Targets in Epidermolysis Bullosa Simplex

Epidermolysis bullosa refers to a group of genodermatoses that affects the integrity of epithelial layers, phenotypically resulting in severe skin blistering. Dowling-Meara, the major subtype of epidermolysis bullosa simplex, is inherited in an autosomal dominant manner and can be caused by mutations in either the keratin-5 (K5) or the keratin-14 (K14) gene. Currently, no therapeutic approach is known, and the main objective of this study was to identify novel therapeutic targets. We used microarray analysis, semi-quantitative real-time PCR, western blot and ELISA to identify differentially regulated genes in two K14 mutant cell lines carrying the mutations K14 R125P and K14 R125H, respectively. We found kallikrein-related peptidases and matrix metalloproteinases to be upregulated. We also found elevated expression of chemokines, and we observed deregulation of the Cdc42 pathway as well as aberrant expression of cytokeratins and junction proteins. We further demonstrated, that expression of these genes is dependent on interleukin-1 β signaling. To evaluate these data in vivo we analysed the blister fluids of epidermolysis bullosa simplex patients vs. healthy controls and identified matrix metalloproteinase-9 and the chemokine CXCL8/IL-8 as potential therapeutic targets.     

Honokiol: A non-adipogenic PPARγ agonist from nature

Background

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators.

Methods

We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists.

Results

The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain.

Conclusion

We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo.

General significance

This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine.     

CD8+ T-cell priming and boosting: more antigen-presenting DC, or more antigen per DC?

RNA transfection is a standard method to load dendritic cells (DC) with antigen for therapeutic cancer vaccination. While electroporation yields high transfection efficiency and satisfying expression levels, lipofection results in only few cells expressing high amounts of antigen. We compared antigen loading of human monocyte-derived DC by MelanA RNA electroporation and lipofection. No differences in phenotype or migrational capacity were detected, but lipofected DC induced stronger cytokine secretion by antigen-specific T cells and were superior in priming and boosting of MelanA-specific CD8⁺ T cells. Interestingly, T cells stimulated with the differently transfected DC did not differ in their functional avidity. To determine whether the amount of antigen per cell is indeed responsible for the superiority of the lipofected DC, we increased the amount of MelanA RNA fivefold and mixed those DC with mock-electroporated ones to mimic the antigen distribution of lipofected cells. This significantly improved the stimulatory capacity, indicating that indeed the amount of antigen per cell seems to be the responsible feature for the observed superiority of lipofected DCs. These data suggest that a few DC that express high amounts of antigen are more immunogenic than many DC expressing lower amounts, although this needs to be tested in a two-armed immunogenicity trial.     

Shifts in Antarctic megabenthic structure after ice-shelf disintegration in the Larsen area east of the Antarctic Peninsula

The aim of this study was to contribute to a general understanding of the response of the Antarctic macrobenthos to environmental variability and climate-induced changes. The change in population size of selected macrobenthic organisms was investigated in the Larsen A area east of the Antarctic Peninsula in 2007 and 2011 using ROV-based imaging methods. The results were complemented by data from the Larsen B collected in 2007 to allow a conceptual reconstruction of the environment-driven changes before the period of investigation. Both Larsen areas are characterised by ice-shelf disintegration in 1995 and 2002, respectively, as well as high inter-annual variability in sea-ice cover and oceanographic conditions. In 2007 one ascidian species, Molgula pedunculata, was abundant north and south of the stripe of remaining ice shelf between Larsen A and B. Population densities decreased drastically in the Larsen A between 2007 and 2011, coincident with the decrease in Corella eumyota, another ascidian. Among the ophiuroids, the population of deposit feeders increased, while suspension feeders halved their abundance. Current measurements indicated a northward flow between the Larsen B and Larsen A, suggesting that a major physical forcing on benthic population development comes from the South. The results demonstrate that Antarctic macrobenthic populations can exhibit dramatic population dynamics. Analyses of sea-ice dynamics, salinity, temperature and surprisingly ice-shelf disintegration history, however, did not provide any clear evidence for environmental drivers underlying the apparent changes.