Increased overlap between the brain areas involved in self-other distinction in schizophrenia

Self-awareness impairments are frequently mentioned as being responsible for the positive symptoms of schizophrenia spectrum disorders. However, the neural correlates of self-other distinction in this pathology are still poorly understood. In the present study, we developed an fMRI procedure in order to examine self-other distinction during speech exchange situations. Fifteen subjects with schizophrenia were compared to 15 matched controls. The results revealed an increased overlap between the self and non-self cortical maps in schizophrenia, in the medial frontal and medial parietal cortices, as well as in the right middle temporal cortex and the right inferior parietal lobule. Moreover, these neural structures showed less BOLD amplitude differences between the self and non-self conditions in the patients. These activation patterns were judged to be independent of mirror-like properties, familiarity or body-ownership processing. Significantly, the increase in the right IPL signal was found to correlate positively with the severity of first-rank symptoms, and thus could be considered a "state-marker" of schizophrenia, whereas temporal and medial parieto-frontal differences appear to be "trait-markers" of the disease. Such an increased overlap between self and non-self cortical maps might be considered a neuro-physiological signature of the well established self-awareness impairment in people suffering from schizophrenia.     

A novel strategy for the comprehensive analysis of the biomolecular composition of isolated plasma membranes

We manufactured a novel type of lipid‐coated superparamagnetic nanoparticles that allow for a rapid isolation of plasma membranes (PMs), enabling high‐resolution proteomic, glycomic and lipidomic analyses of the cell surface. We used this technology to characterize the effects of presenilin knockout on the PM composition of mouse embryonic fibroblasts. We found that many proteins are selectively downregulated at the cell surface of presenilin knockout cells concomitant with lowered surface levels of cholesterol and certain sphingomyelin species, indicating defects in specific endosomal transport routes to and/or from the cell surface. Snapshots of N‐glycoproteomics and cell surface glycan profiling further underscored the power and versatility of this novel methodology. Since PM proteins provide many pathologically relevant biomarkers representing two‐thirds of the currently used drug targets, this novel technology has great potential for biomedical and pharmaceutical applications.     

Hydrothermally generated aromatic compounds are consumed by bacteria colonizing in Atlantis II Deep of the Red Sea

Hydrothermal ecosystems have a wide distribution on Earth and many can be found in the basin of the Red Sea. Production of aromatic compounds occurs in a temperature window of ∼60–150 °C by utilizing organic debris. In the past 50 years, the temperature of the Atlantis II Deep brine pool in the Red Sea has increased from 56 to 68 °C, whereas the temperature at the nearby Discovery Deep brine pool has remained relatively stable at about 44 °C. In this report, we confirmed the presence of aromatic compounds in the Atlantis II brine pool as expected. The presence of the aromatic compounds might have disturbed the microbes in the Atlantis II. To show shifted microbial communities and their metabolisms, we sequenced the metagenomes of the microbes from both brine pools. Classification based on metareads and the 16S rRNA gene sequences from clones showed a strong divergence of dominant bacterial species between the pools. Bacteria capable of aromatic degradation were present in the Atlantis II brine pool. A comparison of the metabolic pathways showed that several aromatic degradation pathways were significantly enriched in the Atlantis II brine pool, suggesting the presence of aromatic compounds. Pathways utilizing metabolites derived from aromatic degradation were also significantly affected. In the Discovery brine pool, the most abundant genes from the microbes were related to sugar metabolism pathways and DNA synthesis and repair, suggesting a different strategy for the utilization of carbon and energy sources between the Discovery brine pool and the Atlantis II brine pool.     

Panton-Valentine leukocidin does play a role in the early stage of Staphylococcus aureus skin infections: a rabbit model

Despite epidemiological data linking necrotizing skin infections with the production of Panton-Valentine leukocidin (PVL), the contribution of this toxin to the virulence of S. aureus has been highly discussed as a result of inconclusive results of in vivo studies. However, the majority of these results originate from experiments using mice, an animal species which neutrophils--the major target cells for PVL--are highly insensitive to the action of this leukocidin. In contrast, the rabbit neutrophils have been shown to be as sensitive to PVL action as human cells, making the rabbit a better experimental animal to explore the PVL role. In this study we examined whether PVL contributes to S. aureus pathogenicity by means of a rabbit skin infection model. The rabbits were injected intradermally with 10(8) cfu of either a PVL positive community-associated methicillin-resistant S. aureus isolate, its isogenic PVL knockout or a PVL complemented knockout strain, and the development of skin lesions was observed. While all strains induced skin infection, the wild type strain produced larger lesions and a higher degree of skin necrosis compared to the PVL knockout strain in the first week after the infection. The PVL expression in the rabbits was indirectly confirmed by a raise in the serum titer of anti-LukS-PV antibodies observed only in the rabbits infected with PVL positive strains. These results indicate that the rabbit model is more suitable for studying the role of PVL in staphylococcal diseases than other animal models. Further, they support the epidemiological link between PVL producing S. aureus strains and necrotizing skin infections.     

Lipid nanocapsules loaded with rhenium-188 reduce tumor progression in a rat hepatocellular carcinoma model

Background

Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC¹⁸⁸Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC¹⁸⁸Re-SSS in a chemically induced hepatocellular carcinoma rat model.

Methodology/Principal Findings

Animals were treated with an injection of LNC¹⁸⁸Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and ¹⁸⁸Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC¹⁸⁸Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC¹⁸⁸Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process.

Conclusions/Significance

Overall, these results demonstrate that internal radiation with LNC¹⁸⁸Re-SSS is a promising new strategy for hepatocellular carcinoma treatment.     

Phenology drives mutualistic network structure and diversity

Several network properties have been identified as determinants of the stability and complexity of mutualistic networks. However, it is unclear which mechanisms give rise to these network properties. Phenology seems important, because it shapes the topology of mutualistic networks, but its effects on the dynamics of mutualistic networks have scarcely been studied. Here, we study these effects with a general dynamical model of mutualistic and competitive interactions where the interaction strength depends on the temporal overlap between species resulting from their phenologies. We find a negative complexity-stability relationship, where phenologies maximising mutualistic interactions and minimising intraguild competitive interactions generate speciose, nested and poorly connected networks with moderate asymmetry and low resilience. Moreover, lengthening the season increases diversity and resilience. This highlights the fragility of real mutualistic communities with short seasons (e.g. Arctic environments) to drastic environmental changes.     

Activity-dependent subcellular cotrafficking of the small GTPase Rem2 and Ca2+/CaM-dependent protein kinase IIα

Background

Rem2 is a small monomeric GTP-binding protein of the RGK family, whose known functions are modulation of calcium channel currents and alterations of cytoskeletal architecture. Rem2 is the only RGK protein found predominantly in the brain, where it has been linked to synaptic development. We wished to determine the effect of neuronal activity on the subcellular distribution of Rem2 and its interacting partners.

Results

We show that Rem2 undergoes activity-and N-Methyl-D-Aspartate Receptor (NMDAR)-dependent translocation in rat hippocampal neurons. This redistribution of Rem2, from a diffuse pattern to one that is highly punctate, is dependent on Ca²⁺ influx, on binding to calmodulin (CaM), and also involves an auto-inhibitory domain within the Rem2 distal C-terminus region. We found that Rem2 can bind to Ca²⁺/CaM-dependent protein kinase IIα (CaMKII) a in Ca²⁺/CaM-dependent manner. Furthermore, our data reveal a spatial and temporal correlation between NMDAR-dependent clustering of Rem2 and CaMKII in neurons, indicating co-assembly and co-trafficking in neurons. Finally, we show that inhibiting CaMKII aggregation in neurons and HEK cells reduces Rem2 clustering, and that Rem2 affects the baseline distribution of CaMKII in HEK cells.

Conclusions

Our data suggest a novel function for Rem2 in co-trafficking with CaMKII, and thus potentially expose a role in neuronal plasticity.     

Diversity-dependence brings molecular phylogenies closer to agreement with the fossil record

The branching times of molecular phylogenies allow us to infer speciation and extinction dynamics even when fossils are absent. Troublingly, phylogenetic approaches usually return estimates of zero extinction, conflicting with fossil evidence. Phylogenies and fossils do agree, however, that there are often limits to diversity. Here, we present a general approach to evaluate the likelihood of a phylogeny under a model that accommodates diversity-dependence and extinction. We find, by likelihood maximization, that extinction is estimated most precisely if the rate of increase in the number of lineages in the phylogeny saturates towards the present or first decreases and then increases. We demonstrate the utility and limits of our approach by applying it to the phylogenies for two cases where a fossil record exists (Cetacea and Cenozoic macroperforate planktonic foraminifera) and to three radiations lacking fossil evidence (Dendroica, Plethodon and Heliconius). We propose that the diversity-dependence model with extinction be used as the standard model for macro-evolutionary dynamics because of its biological realism and flexibility.     

Differences in HIV natural history among African and non-African seroconverters in Europe and seroconverters in sub-Saharan Africa

Introduction

It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations.

Methods

We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA.

Results

Of 1,959 (913 non-Africans, 302 Europeans - African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15–29 year old woman was 607 (588–627) (non-African European), 469 (442–497) (European - African origin) and 570 (551–589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228–289), 155 (110–200), and 199 (174–224) cells/µL (p<0.01).

Discussion

Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations.