Echovirus 1 infection depends on biogenesis of novel multivesicular bodies

Non-enveloped picornavirus echovirus 1 (EV1) clusters its receptor α2β1 integrin and causes their internalization and accumulation in α2β1 integrin enriched multivesicular bodies (α2-MVBs). Our results here show that these α2-MVBs are distinct from acidic late endosomes/lysosomes by several criteria: (i) live intra-endosomal pH measurements show that α2-MVBs are not acidic, (ii) they are not positive for the late endosomal marker LBPA or Dil-LDL internalized to lysosomes, and (iii) simultaneous stimulation of epidermal growth factor receptor (EGFR) and α2β1 integrin clustering leads to their accumulation in separate endosomes. EGFR showed downregulation between 15 min and 2 h, whereas accumulation of α2β1 integrin/EV1 led to an increase of integrin fluorescence in cytoplasmic vesicles further suggesting that EV1 pathway is separate from the lysosomal downregulation pathway. In addition, the results demonstrate the involvement of ESCRTs in the biogenesis of α2-MVBs. Overexpression of dominant-negative form of VPS4 inhibited biogenesis of α2-MVBs and efficiently prevented EV1 infection. Furthermore, α2-MVBs were positive for some members of ESCRTs such as Hrs, VPS37A and VPS24 and the siRNA treatment of TSG101, VPS37A and VPS24 inhibited EV1 infection. Our results show that the non-enveloped EV1 depends on biogenesis of novel multivesicular structures for successful infection.     

Modeling Signal Transduction Leading to Synaptic Plasticity: Evaluation and Comparison of Five Models

An essential phenomenon of the functional brain is synaptic plasticity which is associated with changes in the strength of synapses between neurons. These changes are affected by both extracellular and intracellular mechanisms. For example, intracellular phosphorylation-dephosphorylation cycles have been shown to possess a special role in synaptic plasticity. We, here, provide the first computational comparison of models for synaptic plasticity by evaluating five models describing postsynaptic signal transduction networks. Our simulation results show that some of the models change their behavior completely due to varying total concentrations of protein kinase and phosphatase. Furthermore, the responses of the models vary when models are compared to each other. Based on our study, we conclude that there is a need for a general setup to objectively compare the models and an urgent demand for the minimum criteria that a computational model for synaptic plasticity needs to meet.     

Temporal associations between daytime physical activity and sleep in children

Objectives

We examined temporal associations between objectively-measured physical activity (PA) during the day and in the evening, and sleep quantity and quality.

Study Design

PA and sleep were measured by actigraphs for an average of one week in an epidemiological cohort study of 275 eight-year-old children.

Results

For each one standard deviation (SD) unit of increased PA during the day, sleep duration was decreased by 0.30, sleep efficiency by 0.16, and sleep fragmentation increased by 0.08 SD units that night. For each one SD unit increase in sleep duration and efficiency the preceding night, PA the following day decreased by 0.09 and 0.16 SD units, respectively. When we contrasted days with a high amount of moderate to vigorous activity during the day or in the evening to days with a more sedentary profile, the results were essentially similar. However, moderate to vigorous PA in the evening shortened sleep latency.

Conclusions

The relationship between a higher level of PA and poorer sleep is bidirectional. These within-person findings challenge epidemiological findings showing that more active people report better sleep. Since only a few studies using objective measurements of both PA and sleep have been conducted in children, further studies are needed to confirm/refute these results.     

Thioredoxin Is Involved in Endothelial Cell Extracellular Transglutaminase 2 Activation Mediated by Celiac Disease Patient IgA

Purpose

To investigate the role of thioredoxin (TRX), a novel regulator of extracellular transglutaminase 2 (TG2), in celiac patients IgA (CD IgA) mediated TG2 enzymatic activation.

Methods

TG2 enzymatic activity was evaluated in endothelial cells (HUVECs) under different experimental conditions by ELISA and Western blotting. Extracellular TG2 expression was studied by ELISA and immunofluorescence. TRX was analysed by Western blotting and ELISA. Serum immunoglobulins class A from healthy subjects (H IgA) were used as controls. Extracellular TG2 enzymatic activity was inhibited by R281. PX12, a TRX inhibitor, was also employed in the present study.

Results

We have found that in HUVECs CD IgA is able to induce the activation of extracellular TG2 in a dose-dependent manner. Particularly, we noted that the extracellular modulation of TG2 activity mediated by CD IgA occurred only under reducing conditions, also needed to maintain antibody binding. Furthermore, CD IgA-treated HUVECs were characterized by a slightly augmented TG2 surface expression which was independent from extracellular TG2 activation. We also observed that HUVECs cultured in the presence of CD IgA evinced decreased TRX surface expression, coupled with increased secretion of the protein into the culture medium. Intriguingly, inhibition of TRX after CD IgA treatment was able to overcome most of the CD IgA-mediated effects including the TG2 extracellular transamidase activity.

Conclusions

Altogether our findings suggest that in endothelial cells CD IgA mediate the constitutive activation of extracellular TG2 by a mechanism involving the redox sensor protein TRX.     

Does personality in small rodents vary depending on population density?

Personality means an individual's unique way of behaving and reacting to the environment. It is a stable and heritable trait, which is expressed consistently in different situations. The aim of our study was to develop novel tests to depict the personality structure of the bank vole Myodes glareolus, and to determine if the phase of the population cycle, i.e. population density, affects personality. We focused on some central aspects of bank vole behaviour: mobility, risk taking, exploratory behaviour, dominance, and aggressive behaviour towards pups. These behaviours were chosen because they directly affect bank vole survival or fitness or are classified as important factors of personality in other species. In total, 192 males from different populations went through four behavioural tests, in which 20 variables were measured. The tests were repeated after 3 weeks, which verified that all traits were stable, i.e. repeatable between trials. Three personality compounds emerged, named extroversion, novelty seeking and infanticide. Extroversion included dominance and mobility, while novelty seeking consisted of risk taking and exploration. Infanticide encompassed all indices measuring harmful behaviour towards pups. Mobility and dominance were connected, possibly because both seem to depend on condition. Time spent in captivity increased extroversion, which may be explained by good food, stable conditions and acclimation to strong social cues. Novelty seeking was connected to repeatability which could mean that novelty avoiding individuals adjust their behaviour to match new environments. Population density affected the infanticide trait but not novelty seeking or extroversion.     

Erratum to: Gene expression profiling in the submandibular gland,stomach, and duodenum of CAVI-deficient mice

Transgenic Research -     

Interactions between two closely related phytal harpacticoid copepods, asymmetric positive and negative effects

Competition for food is generally thought to exert a strong evolutionary pressure, driving trophic niche separation, either by specialization and/or by widening the choice of potential food resources. Harpacticoid copepods are common inhabitants of phytal assemblages, where several closely related species of the so-called phytal dwelling families often co-occur. However, direct competition among phytal harpacticoids has been thought to be unlikely, due to the abundant and continuously available food supplies. We conducted a series of field and laboratory studies to assess the role of competition in the abundance distribution of two closely related harpacticoid species, Mesochra rapiens and M. aestuari. We found that the abundance of both species co-varied on several seaweed species in the northern Baltic Sea, during a 3-month period. Stable isotope ratios in the green alga Cladophora glomerata field samples indicated different resource utilization of the two species, both in fresh and deteriorated C. glomerata, and in drifting algae. We tested in the laboratory if resource utilization was different between the species in sympatry and allopatry. We used enriched stable carbon isotope ratios (¹³C/¹²C) of the diatom Phaeodactylum tricornutum to trace the uptake in both species. Results from these experiments showed a much higher assimilation by M. aestuari in sympatry with M. rapiens, while the latter species showed a higher assimilation in allopatry. Our results show that while there is no apparent competition for resources between these two species in the field, there seems to be an asymmetric reaction when in sympatry and provided one single resource in the laboratory. We suggest that M. rapiens may facilitate assimilation by M. aestuari and discuss the mechanisms by which this may take place.     

Glyphosate translocation from plants to soil – does this constitute a significant proportion of residues in soil?

Thallium is an extremely toxic metal which, due to its similarities to K, is readily taken up by plants grown in Tl-contaminated soils. Thallium is also a precious metal nearly as economically valuable as gold. Thallium is efficiently hyperaccumulated in Iberis intermedia as aqueous Tl(I) with highest concentrations within the vascular network of leaves. In this study we examine the utility of synchrotron X-ray differential absorption-edge computed microtomography (CMT) in determining the distribution and compartmentalization of thallium (Tl) in Iberis intermedia. We found Tl to be distributed in solution throughout the vascular system of I. intermedia. Current laboratory experiments are examining the characteristics and potential recovery of Tl by I. intermedia with the objectives to remediate its toxic risks and to facilitate its reclamation for reuse. However, the recovery and reuse of Tl from I. intermedia by way of phytomining requires knowledge on the speciation, distribution and compartmentalization of thallium. CMT shows great promise for application in a wide variety of metal-related structural issues due to its high 3D resolution and being a non-destructive analysis tool. Electronic Supplementary Material Supplementary material is available in the online version of this article at and is accessible for authorized users. An erratum to this article can be found at