Distinct Modulation of Event-Related Potentials during Motor Preparation in Patients with Motor Conversion Disorder

Objective

Conversion paresis patients and healthy people feigning weakness both exhibit weak voluntary movement without detectable neuropathology. Uniquely, conversion patients lack a sense of conscious awareness of the origin of their impairment. We investigated whether conversion paresis patients show distinct electroencephalographic (EEG) markers associated with their unconscious movement deficits.

Methods

Six unilateral upper limb conversion paresis patients, 12 feigning participants asked to mimic weakness and 12 control participants performed a precued reaction time task, requiring movements of either hand, depending on precue information. Performance measures (force, reaction and movement time), and event-related EEG potentials (ERP) were compared, between groups and across hands or hemisphere, using linear mixed models.

Results

Feigners generated the same inter-hand difference in reaction and movement time as expressed by patients, even though no specific targets were set nor feedback given on these measures. We found novel ERP signatures specific to patients. When the symptomatic hand was precued, the P3 ERP component accompanying the precue was dramatically larger in patients than in feigning participants. Additionally, in patients the earlier N1 ERP component was diminished when the precue signalled either the symptomatic or asymptomatic hand.

Conclusions

These results are consistent with previous suggestions that lack of awareness of the origin of their symptoms in conversion disorder patients may result from suppression of brain activity normally related to self-agency. In patients the diminished N1 to all precues is consistent with a generalised reduction in cognitive processing of movement-related precues. The P3 enhancement in patients is unlikely to simply reflect changes required for generation of impaired movements, because it was not seen in feigners showing the same behavioural deficits. Rather, this P3 enhancement in patients may represent a neural biomarker of unconscious processes, including additional emotional loading, related to active suppression of brain circuits involved in the attribution of self-agency.     

TLR3- and MyD88-Dependent Signaling Differentially Influences the Development of West Nile Virus-Specific B Cell Responses in Mice following Immunization with RepliVAX WN,a Single-Cycle Flavivirus Vaccine Candidate

Recognition of conserved pathogen-associated molecular patterns (PAMPs) by host pattern recognition receptors (PRRs) results in the activation of innate signaling pathways that drive the innate immune response and ultimately shape the adaptive immune response. RepliVAX WN, a single-cycle flavivirus (SCFV) vaccine candidate derived from West Nile virus (WNV), is intrinsically adjuvanted with multiple PAMPs and induces a vigorous anti-WNV humoral response. However, the innate mechanisms that link pattern recognition and development of vigorous antigen-specific B cell responses are not completely understood. Moreover, the roles of individual PRR signaling pathways in shaping the B cell response to this live attenuated SCFV vaccine have not been established. We examined and compared the role of TLR3- and MyD88-dependent signaling in the development of anti-WNV-specific antibody-secreting cell responses and memory B cell responses induced by RepliVAX WN. We found that MyD88 deficiency significantly diminished B cell responses by impairing B cell activation, development of germinal centers (GC), and the generation of long-lived plasma cells (LLPCs) and memory B cells (MBCs). In contrast, TLR3 deficiency had more effect on maintenance of GCs and development of LLPCs, whereas differentiation of MBCs was unaffected. Our data suggest that both TLR3- and MyD88-dependent signaling are involved in the intrinsic adjuvanting of RepliVAX WN and differentially contribute to the development of vigorous WNV-specific antibody and B cell memory responses following immunization with this novel SCFV vaccine.     

On the materials of mats: thinking through design in a Melanesian society

This article examines the selective use of plant materials in design in Melanesia. It explores – through an analysis of pandanus leaf mats in New Ireland, Papua New Guinea – how makers select fibres on the basis of their capacity to express social relations to varying temporalities before their natural decay. J.J. Gibson's theory of affordance and Donald Norman's concept of mapping are critically applied for this purpose. This approach emphasizes how social and temporal relations are condensed into objects, and refocuses anthropological attention towards materials and their affordances in the production of material culture.     

Influence of cell surface characteristics on adhesion of <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> to the biomaterial hydroxylapatite

The influence of the physicochemical properties of biomaterials on microbial cell adhesion is well known, with the extent of adhesion depending on hydrophobicity, surface charge, specific functional groups and acid–base properties. Regarding yeasts, the effect of cell surfaces is often overlooked, despite the fact that generalisations may not be made between closely related strains. The current investigation compared adhesion of three industrially relevant strains of Saccharomyces cerevisiae (M-type, NCYC 1681 and ALY, strains used in production of Scotch whisky, ale and lager, respectively) to the biomaterial hydroxylapatite (HAP). Adhesion of the whisky yeast was greatest, followed by the ale strain, while adhesion of the lager strain was approximately 10-times less. According to microbial adhesion to solvents (MATS) analysis, the ale strain was hydrophobic while the whisky and lager strains were moderately hydrophilic. This contrasted with analyses of water contact angles where all strains were characterised as hydrophilic. All yeast strains were electron donating, with low electron accepting potential, as indicated by both surface energy and MATS analysis. Overall, there was a linear correlation between adhesion to HAP and the overall surface free energy of the yeasts. This is the first time that the relationship between yeast cell surface energy and adherence to a biomaterial has been described.     

Growth and reproductive costs of larval defence in the aposematic lepidopteran Pieris brassicae

1.?Utilization of plant secondary compounds for antipredator defence is common in immature herbivorous insects. Such defences may incur a cost to the animal, either in terms of survival, growth rate or in the reproductive success. 2.?A common defence in lepidopterans is the regurgitation of semi-digested material containing the defensive compounds of the food plant, a defence which has led to gut specialization in this order. Regurgitation is often swift in response to cuticular stimulation and deters predators from consuming or parasitizing the larva. The loss of food and other gut material seems likely to impact on fitness, but evidence is lacking. 3.?Here, we raised larvae of the common crop pest Pieris brassicae on commercial cabbage leaves, simulated predator attacks throughout the larval period, and measured life-history responses. 4.?We found that the probability of survival to pupation decreased with increasing frequency of attacks, but this was because of regurgitation rather than the stimulation itself. There was a growth cost to the defence such that the more regurgitant that individuals produced over the growth period, the smaller they were at pupation. 5.?The number of mature eggs in adult females was positively related to pupal mass, but this relationship was only found when individuals were not subjected to a high frequency of predator simulation. This suggests that there might be cryptic fitness costs to common defensive responses that are paid despite apparent growth rate being maintained. 6.?Our results demonstrate a clear life-history cost of an antipredator defence in a model pest species and show that under certain conditions, such as high predation threat, the expected relationship between female body size and potential fecundity can be disrupted.     

Is Acanthamoeba pathogenicity associated with intracellular bacteria?

In addition to the possible role of Acanthamoeba as an evolutionary precursor of pathogenicity in microbial pathogens, it has been suggested that intracellular bacteria or other microbial endosymbionts may also enhance the pathogenicity of Acanthamoeba. Using transmission electron microscopy, polymerase chain reaction and simple culturing, our findings did not reveal any apparent evidence of microbial presence intracellularly of a recently recovered clinical isolate of Acanthamoeba. Based on these findings, it is tempting to speculate that the virulence of Acanthamoeba may not be attributed to the pathogenicity of the endosymbiont alone.     

Heteromultimerization of cannabinoid CB(1) receptor and orexin OX(1) receptor generates a unique complex in which both protomers are regulated by orexin A

Agonist-induced internalization was observed for both inducible and constitutively expressed forms of the cannabinoid CB(1) receptor. These were also internalized by the peptide orexin A, which has no direct affinity for the cannabinoid CB(1) receptor, but only when the orexin OX(1) receptor was co-expressed along with the cannabinoid CB(1) receptor. This effect of orexin A was concentration-dependent and blocked by OX(1) receptor antagonists. Moreover, the ability of orexin A to internalize the CB(1) receptor was also blocked by CB(1) receptor antagonists. Remarkably, orexin A was substantially more potent in producing internalization of the CB(1) receptor than in causing internalization of the bulk OX(1) receptor population, and this was true in cells in which the CB(1) receptor was maintained at a constant level, whereas levels of OX(1) could be varied and vice versa. Both co-immunoprecipitation and cell surface, homogenous time-resolved fluorescence resonance energy transfer based on covalent labeling of N-terminal "SNAP" and "CLIP" tags present in the extracellular N-terminal domain of the receptors confirmed the capacity of these two receptors to heteromultimerize. These studies confirm the capacity of the CB(1) and OX(1) receptors to interact directly and demonstrate that this complex has unique regulatory characteristics. The higher potency of the agonist orexin A to regulate the CB(1)-OX(1) heteromer compared with the OX(1)-OX(1) homomer present in the same cells and the effects of CB(1) receptor antagonists on the function of orexin A suggest an interplay between these two systems that may modulate appetite, feeding, and wakefulness.     

Raising the bar for systematic conservation planning

Systematic conservation planning (SCP) represents a significant step toward cost-effective, transparent allocation of resources for biodiversity conservation. However, research demonstrates important consequences of uncertainties in SCP and of basing methods on simplified circumstances involving few real-world complexities. Current research often relies on single case studies with unknown forms and amounts of uncertainty as well as low statistical power for generalizing results. Consequently, conservation managers have little evidence for the true performance of conservation planning methods in their own complex, uncertain applications. To build effective and reliable methods in SCP, there is a need for more challenging and integrated testing of their robustness to uncertainty and complexity, and much greater emphasis on generalization to real-world situations.