A Model of Postural Control in Quiet Standing: Robust Compensation of Delay-Induced Instability Using Intermittent Activation of Feedback Control

The main purpose of this study is to compare two different feedback controllers for the stabilization of quiet standing in humans, taking into account that the intrinsic ankle stiffness is insufficient and that there is a large delay inducing instability in the feedback loop: 1) a standard linear, continuous-time PD controller and 2) an intermittent PD controller characterized by a switching function defined in the phase plane, with or without a dead zone around the nominal equilibrium state. The stability analysis of the first controller is carried out by using the standard tools of linear control systems, whereas the analysis of the intermittent controllers is based on the use of Poincaré maps defined in the phase plane. When the PD-control is off, the dynamics of the system is characterized by a saddle-like equilibrium, with a stable and an unstable manifold. The switching function of the intermittent controller is implemented in such a way that PD-control is ‘off’ when the state vector is near the stable manifold of the saddle and is ‘on’ otherwise. A theoretical analysis and a related simulation study show that the intermittent control model is much more robust than the standard model because the size of the region in the parameter space of the feedback control gains (P vs. D) that characterizes stable behavior is much larger in the latter case than in the former one. Moreover, the intermittent controller can use feedback parameters that are much smaller than the standard model. Typical sway patterns generated by the intermittent controller are the result of an alternation between slow motion along the stable manifold of the saddle, when the PD-control is off, and spiral motion away from the upright equilibrium determined by the activation of the PD-control with low feedback gains. Remarkably, overall dynamic stability can be achieved by combining in a smart way two unstable regimes: a saddle and an unstable spiral. The intermittent controller exploits the stabilizing effect of one part of the saddle, letting the system evolve by alone when it slides on or near the stable manifold; when the state vector enters the strongly unstable part of the saddle it switches on a mild feedback which is not supposed to impose a strict stable regime but rather to mitigate the impending fall. The presence of a dead zone in the intermittent controller does not alter the stability properties but improves the similarity with biological sway patterns. The two types of controllers are also compared in the frequency domain by considering the power spectral density (PSD) of the sway sequences generated by the models with additive noise. Different from the standard continuous model, whose PSD function is similar to an over-damped second order system without a resonance, the intermittent control model is capable to exhibit the two power law scaling regimes that are typical of physiological sway movements in humans.     

Probing the conformation of the resting state of a bacterial multidrug ABC transporter,BmrA, by a site‐directed spin labeling approach

Previously published 3‐D structures of a prototypic ATP‐binding cassette (ABC) transporter, MsbA, have been recently corrected revealing large rigid‐body motions possibly linked to its catalytic cycle. Here, a closely related multidrug bacterial ABC transporter, BmrA, was studied using site‐directed spin labeling by focusing on a region connecting the transmembrane domain and the nucleotide‐binding domain (NBD). Electron paramagnetic resonance (EPR) spectra of single spin‐labeled cysteine mutants suggests that, in the resting state, this sub‐domain essentially adopts a partially extended conformation, which is consistent with the crystal structures of MsbA and Sav1866. Interestingly, one of the single point mutants (Q333C) yielded an immobilized EPR spectrum that could arise from a direct interaction with a vicinal tyrosine residue. Inspection of different BmrA models pointed to Y408, within the NBD, as the putative interacting partner, and its mutation to a Phe residue indeed dramatically modified the EPR spectra of the spin labeled Q333C. Moreover, unlike the Y408F mutation, the Y408A mutation abolished both ATPase activity and drug transport of BmrA, suggesting that a nonpolar bulky residue is required at this position. The spatial proximity of Q333 and Y408 was also confirmed by formation of a disulfide bond when both Q333 and T407 (or S409) were replaced jointly by a cysteine residue. Overall, these results indicate that the two regions surrounding Q333 and Y408 are close together in the 3‐D structure of BmrA and that residues within these two sub‐domains are essential for proper functioning of this transporter.     

Investigation on the occurrence of Echinococcus multilocularis in Central Italy

Background  

Feed contaminated with Salmonella spp. constitutes a risk of Salmonella infections in animals, and subsequently in the consumers of animal products. Salmonella are occasionally isolated from the feed factory environment and some clones of Salmonella persist in the factory environment for several years. One hypothesis is that biofilm formation facilitates persistence by protecting bacteria against environmental stress, e.g. disinfection. The aim of this study was to investigate the biofilm forming potential of Salmonella strains from feed- and fishmeal factories. The study included 111 Salmonella strains isolated from Norwegian feed and fish meal factories in the period 1991–2006 of serovar Agona, serovar Montevideo, serovar Senftenberg and serovar Typhimurium.     

Effects of Host Interspecific Interaction in the <Emphasis Type="Italic">Maculinea</Emphasis>–<Emphasis Type="Italic">Myrmica</Emphasis> Parasite–Host System

A model of interspecific host competition in a system with one parasite (butterfly—Maculinea) and multiple potential hosts (ants—Myrmica) is presented. Results indicate that host interspecific competition increases the occurrence of multiple host behaviour in Maculinea natural populations but decreases the ability of the parasite populations to adapt to the most abundant host species. These qualitative predictions were compared with data on host specificity, with good agreement. Analysis of the data also indicates that Maculinea teleius and Maculinea arion respond differently to changes in relative host abundances. Maculinea teleius shows a larger fraction of sites where it displays multiple host behaviour and a larger fraction of sites where the niches of the hosts overlap. In some instances, Maculinea teleius is adapted to Myrmica hosts that are present in lower frequencies. Maculinea arion is locally more host-specific and occurs at sites where host interspecific competition is unlikely and is more frequently adapted to the most abundant host species.     

Sur l'ultrastructure des ≪corps de call et d'exner≫ dans l'ovaire du lapin

Résumé On a effectué une étude ultrastructurale sur les corps de Call et d'Exner. Ceux-ci se montrent constitués, sous leur aspect le plus typique, par une couronne de cellules de la granulosa disposées autour d'une cavité pleine d'un liquide semblable au liquor folliculi .Les cellules, de forme irrégulière, accolées dans leur partie proche du corps et écartées dans celle éloignée, déterminent des fentes dans lesquelles s'insinuent des groupes d'autres cellules voisines; la membrane cytoplasmique, parfois présente sous forme de microvilloités, parfois incisée, montre de fréquentes interruptions; le cytoplasme riche en ribosomes libres et adhérant aux parois du réticule endoplasmique (ergastoplasme), possède en outre un appareil de Golgi modérément développé et de nombreuses mitochondries; le noyau, très volumineux, présente à l'intérieur un nucléole grossièrement réticulé.Le corps de Call et d'Exner proprement dit est, au contraire, constitué par une cavité unitaire d'aspect à peu près sphérique d'environ 15–30 de diamètre, pleine d'un liquide dont les caractéristiques sont comparables à celles du liquor folliculi; dans cette cavité on voit un fin réseau à mailles irrégulières, tandis que sa surface montre une mince zone de condensation.L'aspect ultrastructural des cellules disposées autour des corps de Call et d'Exner est caractérisé par des cellules en élaboration, ce qui laisse penser qu'une partie de cette élaboration peut être versée à l'intérieur du corps, en contribuant ainsi à l'augmentation de son volume.En ce qui concerne, enfin, le réticule que l'on voit à l'intérieur du corps il est vraisemblable qu'il soit du à des phénomènes de condensation et consécutif à un état physicochimique particulier du liquide endocavitaire.

---

Summary The so-called Call-Exner bodies have been found to be formed, in their most typical shape, by a ring of granulosa cells enclosing a cavity filled with a fluid comparable to the liquor folliculi. The cells, irregular in shape, lying side by side in their portions closer to the body and far apart in their distal portions leave open spaces which are occupied by prolongations of adjacent cells. The cytoplasmic membrane, sometimes forming mierovilli, sometimes incisions, presents a discontinuous aspect; the cytoplasm is very rich in ribosomes which can be free or sticking to the walls of the endoplasmic reticulum (ergastoplasm). It has a fairly developed Golgi's apparatus and numerous mitochondria, sometimes open. The very voluminous nucleus shows internally a roughly reticulated nucleolus.The Call-Exner body, on the other hand, is a unitary cavity approximately spherical in shape, having about a 15–30 micron diameter filled with a fluid characteristically similar to the liquor folliculi, which shows internally a fine reticulation of irregular meshwork, while a thin condensation zone can bee seen peripherically.The ultrastructural aspect of the cells radiating from the Call-Exner bodies is typical of cells in formation. Therefore we cannot exclude the possibility that a portion of the substances elaborated by the cells may be thrown into the center of the body, thus contributing to its increase in volume. The mesh-like structure visible inside the body may be due to condensation phenomena following a particular physico-chemichal change in the endocavitary luid.

     

Recruitment of OCRL and Inpp5B to phagosomes by Rab5 and APPL1 depletes phosphoinositides and attenuates Akt signaling

Sealing of phagosomes is accompanied by the disappearance of phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P(2)) from their cytoplasmic leaflet. Elimination of PtdIns(4,5)P(2), which is required for actin remodeling during phagosome formation, has been attributed to hydrolysis by phospholipase C and phosphorylation by phosphatidylinositol 3-kinase. We found that two inositol 5-phosphatases, OCRL and Inpp5B, become associated with nascent phagosomes. Both phosphatases, which are Rab5 effectors, associate with the adaptor protein APPL1, which is recruited to the phagosomes by active Rab5. Knockdown of APPL1 or inhibition of Rab5 impairs association of OCRL and Inpp5B with phagosomes and prolongs the presence of PtdIns(4,5)P(2) and actin on their membranes. Even though APPL1 can serve as an anchor for Akt, its depletion accentuated the activation of the kinase, likely by increasing the amount of PtdIns(4,5)P(2) available to generate phosphatidylinositol (3,4,5)-trisphosphate. Thus, inositol 5-phosphatases are important contributors to the phosphoinositide remodeling and signaling that are pivotal for phagocytosis.     

Characterization of a glial cell line persistently infected with borna disease virus (BDV): influence of neurotrophic factors on BDV protein and RNA expression.

Borna disease virus (BDV) infects cells of the nervous system in a wide range of species. Previous work suggests that there are differences in BDV replication in neuronal cells and glial cells. Many neurons are lysed by the immunopathologic response to BDV; lysis of dentate gyrus neurons in the absence of encephalitis is seen in rats inoculated with BDV as neonates. In contrast, persistently BDV-infected astrocytes increase over the course of BDV infection. Therefore, we compared BDV replication in neuronal (SK-N-SH and SK-N-SHEP) and astrocytic (C6) cell lines. While SK-N-SH cells produced more infectious virions per cell, the C6 cells contained more BDV proteins and RNA. BDV sequences in the supernatants of both cell types were identified, despite low titers of infectious virus, suggesting the release of incomplete virions into the medium. C6 cells secreted a factor or factors into the medium that enhanced the production of BDV proteins and RNA in other cell lines. In addition, nerve growth factor treatment produced the same enhancement. Thus, BDV replication in certain neural cells in vitro may be linked to the production of cell-specific factors which affect viral replication.     

Parasites in the neighbourhood: Interactions of the mistletoe Phoradendron affine (Viscaceae) with its dispersers and hosts in urban areas of Brazil

Mistletoes constitute an important food resource for animals in many ecosystems. However, these plants are considered pests in urban areas because of deleterious effects they have on the host trees. Studies in urban areas were mostly focused on listing host species or procedures to control the “pest”. In this sense, broader studies including several aspects of mistletoes ecology in urban ecosystems are still missing. We studied the interaction of the mistletoe, Phoradendron affine, with its dispersers and hosts in two urban sites in Uberlândia, Brazil. Phoradendron affine fruits were consumed almost exclusively by Euphonia chlorotica, which was crucial for seed germination. Parasitism was recorded in five hosts, two native (Handroanthus chrysotrichus and Tabebuia roseoalba) and three exotic species (Spathodea campanulata, Ligustrum lucidum and Melia azedarach). Mistletoes were found parasitizing larger host trees, a trend commonly reported for mistletoe-host interaction. Mistletoe seed germination was not affected by the trees species, whether host or non-host, but the radicle of germinated seeds could not penetrate the bark and seedlings invariably died in non-host species. We found a high prevalence of parasitism in our study, in comparison to what previous studies reported for natural areas. The spatial distribution of the hosts and high light incidence on isolated host trees may lead to this high prevalence in urban areas. Rather than eradicated, mistletoes in urban areas should be ecologically managed and their importance for bird species conservation must be considered. More studies to determine which bird species are favoured by mistletoe presence in urban areas will be essential for this purpose.     

Integrating dynamic environmental predictors and species occurrences: Toward true dynamic species distribution models

While biological distributions are not static and change/evolve through space and time, nonstationarity of climatic and land‐use conditions is frequently neglected in species distribution models. Even recent techniques accounting for spatiotemporal variation of species occurrence basically consider the environmental predictors as static; specifically, in most studies using species distribution models, predictor values are averaged over a 50‐ or 30‐year time period. This could lead to a strong bias due to monthly/annual variation between the climatic conditions in which species' locations were recorded and those used to develop species distribution models or even a complete mismatch if locations have been recorded more recently. Moreover, the impact of land‐use change has only recently begun to be fully explored in species distribution models, but again without considering year‐specific values. Excluding dynamic climate and land‐use predictors could provide misleading estimation of species distribution. In recent years, however, open‐access spatially explicit databases that provide high‐resolution monthly and annual variation in climate (for the period 1901–2016) and land‐use (for the period 1992–2015) conditions at a global scale have become available. Combining species locations collected in a given month of a given year with the relative climatic and land‐use predictors derived from these datasets would thus lead to the development of true dynamic species distribution models (D‐SDMs), improving predictive accuracy and avoiding mismatch between species locations and predictor variables. Thus, we strongly encourage modelers to develop D‐SDMs using month‐ and year‐specific climatic data as well as year‐specific land‐use data that match the period in which species data were collected.