Patterns of monosynaptic input to the giant interneurons 1–3 in the cereal system of the adult cockroach

1. The cerci of the cockroach Periplaneta americana bear filiform hair mechanoreceptors that are arranged in segmentally repeated rows and longitudinal columns. The monosynaptic connections between receptors of the same column or row and the 3 largest giant interneurons (GIs) were compared using the oil-gap single fibre technique.
2. For many columns, the synaptic efficacy of the afferents decreased gradually from the base to the tip of the cercus, but columns with an inverted gradient or without any gradient were also observed. On the ipsilateral side (relative to the GI axon), the inverted gradients were exclusively found for columns with short proximal hairs. For one column (d) and GI3, the ipsilateral and contralateral gradients were opposite.
3. Monosynaptic EPSPs evoked by stimulating different receptors of the same segment (segment 3) were of very different amplitudes, which partially account for the directional sensitivity of the GIs. Differences in the location, shape and size of the afferent terminals were not sufficient to explain these differences in connection strength.
4. No correlation was found between the size of the EPSPs produced by a sensory neuron and the length of its associated hair.

     

The Use of Actimetry to Assess Changes to the Rest–Activity Cycle

The endogenous circadian oscillator (the body clock) is slow to adjust to altered rest–activity patterns. As a result, several negative consequences arise during night work and after time‐zone transitions. The process of adjustment can be assessed by measurements of the sleep electroencephalogram (EEG), core temperature or melatonin secretion, for example, but these techniques are very difficult to apply in field studies, and make very great demands upon both experimenters and subjects. We have sought to establish if the activity record, measured conveniently and unobtrusively by a monitor attached to the wrist, can be treated in ways that enable estimates to be made of the disruption caused by changes to the rest–activity cycle, and the process of adjustment to them. In Part A, we describe the calculation and assessment of a series of “activity indices” that measure the overall activity pattern, activity when out of bed or in bed, or the activity in the hours adjacent to going to bed or getting up. The value of the indices was assessed by measuring changes to them in subjects undergoing night work or undergoing time‐zone transitions. In both cases, there is a large body of literature describing the changes that would be expected. First, night workers (working 2 to 4 successive night shifts) were investigated during rest days and night shifts. The indices indicated that night work was associated with lower activity when the subjects were out of bed and higher activity when in bed. Some indices also measured when subjects took an afternoon nap before starting a series of night shifts and gave information about the process of adjustment to night work and recovery from it. Second, in studies from travelers crossing six or more time zones to the east or west, the indices indicated that there were changes to the rest–activity cycle immediately after the flights, both in its overall profile and when activity of the subjects in bed or out of bed was considered, and that adjustment took place on subsequent days. By focusing on those indices describing the activity records during the last hour in bed (LHIB) and the first hour out of bed (FHOB), some evidence was found for incomplete adjustment of the body clock, and for differences between westward and eastward flights. In Part B, the battery of indices are applied to the activity records of long‐haul pilots, whose activity patterns showed a mixture of effects due to night work and time‐zone transitions. Actimetry was performed during the flights themselves and during the layover days (which were either rest or work days). The indices indicated that all pilots had disrupted rest–activity cycles caused by night flights, and that there were added problems for those who had also undergone time‐zone transitions. Rest days were valuable for normalizing the activity profile. For those pilots who flew to the west, adjustment was by delay, though not all aspects of the rest–activity cycle adjusted immediately; for those who flew to the east, some attempted to advance their rest–activity cycle while others maintained home‐based activity profiles. The indices indicated that the activity profile was disrupted more in those pilots who attempted to advance their rest–activity cycle. We conclude that objective estimates of the disruption caused to the rest–activity cycle and the circadian system can be obtained by suitable analysis of the activity record.     

Connecting the nucleus to the cytoskeleton by SUN–KASH bridges across the nuclear envelope

1. Download : Download high-res image (143KB)
2. Download : Download full-size image

     

Back to the future with the AGP–Ca2+ flux capacitor

Background

Arabinogalactan proteins (AGPs) are ubiquitous in green plants. AGPs comprise a widely varied group of hydroxyproline (Hyp)-rich cell surface glycoproteins (HRGPs). However, the more narrowly defined classical AGPs massively predominate and cover the plasma membrane. Extensive glycosylation by pendant polysaccharides O-linked to numerous Hyp residues like beads of a necklace creates a unique ionic compartment essential to a wide range of physiological processes including germination, cell extension and fertilization. The vital clue to a precise molecular function remained elusive until the recent isolation of small Hyp–arabinogalactan polysaccharide subunits; their structural elucidation by nuclear magentic resonance imaging, molecular simulations and direct experiment identified a 15-residue consensus subunit as a β-1,3-linked galactose trisaccharide with two short branched sidechains each with a single glucuronic acid residue that binds Ca²⁺ when paired with its adjacent sidechain.

Scope

AGPs bind Ca²⁺ (K_d ∼ 6 μm) at the plasma membrane (PM) at pH ∼5·5 but release it when auxin-dependent PM H⁺-ATPase generates a low periplasmic pH that dissociates AGP–Ca²⁺ carboxylates (pk_a ∼3); the consequential large increase in free Ca²⁺ drives entry into the cytosol via Ca²⁺ channels that may be voltage gated. AGPs are thus arguably the primary source of cytosolic oscillatory Ca²⁺ waves. This differs markedly from animals, in which cytosolic Ca²⁺ originates mostly from internal stores such as the sarcoplasmic reticulum. In contrast, we propose that external dynamic Ca²⁺ storage by a periplasmic AGP capacitor co-ordinates plant growth, typically involving exocytosis of AGPs and recycled Ca²⁺, hence an AGP–Ca²⁺ oscillator.

Conclusions

The novel concept of dynamic Ca²⁺ recycling by an AGP–Ca²⁺ oscillator solves the long-standing problem of a molecular-level function for classical AGPs and thus integrates three fields: AGPs, Ca²⁺ signalling and auxin. This accounts for the involvement of AGPs in plant morphogenesis, including tropic and nastic movements.     

Estimation of the Parameters for Tremograms According to the Eskov–Zinchenko Effect

The features of the chaotic dynamics of parameters of the neuromuscular system (tremors) were studied using conventional and novel biological methods based on a multidimensional phase-space representation. The dynamics of involuntary micromovements of limbs (finger tremor) both in the relaxation phase (F = 0) and under static load (F = 3N) was manifested in a change in the number of “coincidences” of randomly selected sample pairs (k) of matrices (15 × 15) in paired comparison of tremograms, which demonstrated the global statistical instability of the samples (statistical distribution functions f(x), spectral densities of signals, and autocorrelation A(t)). The samples that result from one experiment cannot be randomly repeated in the next experiment (with the same homeostasis). This represents a quantitative measure of the Eskov–Zinchenko effect in the analysis of chaotically changing statistical distribution functions of tremogram samples. In this paper, the use of quasi-attractor parameters of tremograms (their areas) is proposed to represent changes in the neuromuscular system when passing from one homeostasis to another (G₁ ≠ G₂).

     

Cyr61/CCN1 Displays High-Affinity Binding to the Somatomedin B 1–44 Domain of Vitronectin

Background

Cyr61 is a member of the CCN (Cyr61, connective tissue growth, NOV) family of extracellular-associated (matricellular) proteins that present four distinct functional modules, namely insulin-like growth factor binding protein (IGFBP), von Willebrand factor type C (vWF), thrombospondin type 1 (TSP), and C-terminal growth factor cysteine knot (CT) domain. While heparin sulphate proteoglycans reportedly mediate the interaction of Cyr61 with the matrix and cell surface, the role of other extracellular associated proteins has not been revealed.

Methods and Findings

In this report, surface plasmon resonance (SPR) experiments and solid-phase binding assays demonstrate that recombinant Cyr61 interacts with immobilized monomeric or multimeric vitronectin (VTNC) with K_D in the nanomolar range. Notably, the binding site for Cyr61 was identified as the somatomedin B domain (SMTB ^1–44) of VTNC, which mediates its interaction with PAI-1, uPAR, and integrin αvβ3. Accordingly, PAI-1 outcompetes Cyr61 for binding to immobilized SMTB ^1–44, and Cyr61 attenuates uPAR-mediated U937 adhesion to VTNC. In contrast, isothermal titration calorimetry shows that Cyr61 does not display high-affinity binding for SMTB ^1-44 in solution. Nevertheless, competitive ELISA revealed that multimeric VTNC, heat-modified monomeric VTNC, or SMTB ^1–44 at high concentrations attenuate Cyr61 binding to immobilized VTNC, while monomeric VTNC was ineffective. Therefore, immobilization of VTNC exposes cryptic epitopes that recognize Cyr61 with high affinity, as reported for a number of antibodies, β-endorphin, and other molecules.

Conclusions

The finding that Cyr61 interacts with the SMTB ^1–44 domain suggests that VTNC represent a point of anchorage for CCN family members to the matrix. Results are discussed in the context of the role of CCN and VTNC in matrix biology and angiogenesis.     

From the inverse density–area relationship to the minimum patch size of a host–parasitoid system

The minimum amount of suitable habitat (MASH) is an important concept in conservation biological control. Two methods for estimating the MASH have been proposed by McCoy and Mushinsky based on an inverse density–area relationship. Using data of the population densities of aphid host–parasitoid–hyperparasitoid collected from wheat fields of different habitat sizes, we argued that the inverse density–area relationship may be an artifact. Significant correlations between population densities and patch sizes from all three trophic levels were found once the population density had been log-transformed. We could not obtain the same results if the population density had not been log-transformed. We estimated that the MASH for the aphid M. avena, S. graminum, A. avenae, A. gifuensis, P. aphidis, and Alloxysta sp. were 246, 246, 479, 495, 949, and 835 m² according to the methods of McCoy and Mushinsky. The scale-dependence and the systematic spatial variations of the host–parasitoid interaction suggests that we can achieve an optimal effect of biological control by manipulating the habitat patch sizes, although not based on the inverse density–area relationship.     

A data-driven framework to model the organism–environment system

Organisms modify their development and function in response to the environment. At the same time, the environment is modified by the activities of the organism. Despite the ubiquity of such dynamical interactions in nature, it remains challenging to develop models that accurately represent them, and that can be fitted using data. These features are desirable when modeling phenomena such as phenotypic plasticity, to generate quantitative predictions of how the system will respond to environmental signals of different magnitude or at different times, for example, during ontogeny. Here, we explain a modeling framework that represents the organism and environment as a single coupled dynamical system in terms of inputs and outputs. Inputs are external signals, and outputs are measurements of the system in time. The framework uses time-series data of inputs and outputs to fit a nonlinear black-box model that allows to predict how the system will respond to novel input signals. The framework has three key properties: it captures the dynamical nature of the organism–environment system, it can be fitted with data, and it can be applied without detailed knowledge of the system. We study phenotypic plasticity using in silico experiments and demonstrate that the framework predicts the response to novel environmental signals. The framework allows us to model plasticity as a dynamical property that changes in time during ontogeny, reflecting the well-known fact that organisms are more or less plastic at different developmental stages.     

Regional assignment of the human C1-inhibitor gene to 11q11–q13.1

Summary In situ hybridisation using a biotinylated 1.8kb human cDNA clone in both normal and structurally abnormal chromosomes supports regional localisation of the gene for human C1-inhibitor to chromosome 11q11-q13.11.     

GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3–CA1 Circuitry in the Hippocampus

During the course of development, molecular mechanisms underlying activity-dependent synaptic plasticity change considerably. At immature CA3–CA1 synapses in the hippocampus, PKA-driven synaptic insertion of GluA4 AMPA receptors is the predominant mechanism for synaptic strengthening. However, the physiological significance of the developmentally restricted GluA4-dependent plasticity mechanisms is poorly understood. Here we have used microelectrode array (MEA) recordings in GluA4 deficient slice cultures to study the role of GluA4 in early development of the hippocampal circuit function. We find that during the first week in culture (DIV2–6) when GluA4 expression is restricted to pyramidal neurons, loss of GluA4 has no effect on the overall excitability of the immature network, but significantly impairs synchronization of the CA3 and CA1 neuronal populations. In the absence of GluA4, the temporal correlation of the population spiking activity between CA3–CA1 neurons was significantly lower as compared to wild-types at DIV6. Our data show that synapse-level defects in transmission and plasticity mechanisms are efficiently compensated for to normalize population firing rate at the immature hippocampal network. However, lack of the plasticity mechanisms typical for the immature synapses may perturb functional coupling between neuronal sub-populations, a defect frequently implicated in the context of developmentally originating neuropsychiatric disorders.

     

Molecular Simulation to Aid in the Understanding of the Aβ(1–42) Peptide of Alzheimer's Disease

Abstract

The Aβ(1–42) peptide of Alzheimer's disease was studied by molecular modeling. The coordinates of the peptide were experimentally generated from solution-NMR spectroscopy, and the conformations were energy minimized using a combination of connectivity-based iterative partial equalization of orbital electronegativity with the MM + force field.

There is a central folded domain in the Aβ peptide. This part is an apolar α-helix. The remaining residues form β-sheets. Aggregation requires that β-sheets interact by noncovalent bonding forces. The unsoluble, aggregated complexes are energetically stable and have ordered structures.

A perspective in drug research is to design compounds that inhibit the hydrophobic cores of the individual Aβ peptides, blocking so the associations between the β-strains.     

Using the NZ–DNDC model to estimate agricultural N2O emissions in the Manawatu–Wanganui region

Nitrous oxide (N₂O) emissions are difficult to quantify at regional and national scales. There is considerable spatial and temporal variability in N₂O emissions from soil, partly because of variability in the underlying biogenic processes responsible for soil N₂O production. The process-based NZ–DNDC (New Zealand Denitrification-Decomposition) model was used, with georeferenced input data on soils, climate and land use, to map and predict net N₂O emissions from farming in the Manawatu–Wanganui region. The Manawatu–Wanganui region has a temperate, maritime climate and the major agricultural land use is pastoral grazing. We created databases of regional soil, climate and farm management information from various available data sources including national databases of climate, soil type and land use, and national agricultural production statistics. The error introduced by upscaling the model was assessed by comparing results using measured site data with the corresponding predictions using the regional approximations. We also examined the effect of climate conditions by rerunning the 2003 simulation using the climate data for the years ended June 1990 and 2004. The modelled net N₂O emissions for this region for the year ended June 2003 were 4.6?±?1.5 Gg N₂O–N per year. The total fertiliser and excretal N inputs for the region were approximately 224,140 tonnes, so the percentage emitted as N₂O was 2.0?±?0.7%. The modelled net N₂O emissions for the region for the year ended June 1990 were 3.8?±?2.1 Gg N₂O–N per year, indicating annual net N₂O emissions in the Manawatu–Wanganui region between 1990 and 2003 had increased by 0.8?±?0.6 Gg N₂O–N (an increase of about 20%). This change can be attributed to both changes in weather conditions and land use and farm management between 1990 and 2003.     

Farewell to the Lose–Lose Reality of Policing Plant Imports

In an age of free international shipments of mail-ordered seeds and plants, more policing will not stop the global migration of hitchhiking pests. The solution is in a preemptive response based on an internationally coordinated genomic deployment of global biodiversity in the largest breeding project since the “Garden of Eden.” This plan will enrich the narrow genetic basis of annual and perennial plants with adaptations to changing environments and resistances to the pests of the future.

“Plan for what is difficult while it is easy; do what is great while it is small.”—Sun Tzu, The Art of War

When 182 countries become party to a common cause, it is reason to rejoice. Such an opportunity was provided when the Food and Agriculture Organization of the United Nations (FAO) approved the International Plant Protection Convention (IPPC) on December 6, 1951, with the objective of developing and implementing international phytosanitary standards to reduce the risks associated with the spread of plant pests to agriculture and natural ecosystems [1]. Over the years, the IPPC has been amended to enforce safer trade of plants by preventing the entry and spread of new pests. This led to the establishment of dedicated government agencies, usually associated with the ministries of agriculture, which are responsible for inspecting and policing against the entry of pests. These agencies have grown tremendously over the years because their noble mission is simply to explain to the “want to do good” elected officials who are responsible for the allocation of funds. However, the IPPC is currently implementing a losing defensive strategy, for which a scientific alternative based on a broad view of our interconnected global reality is presented below.     

Predator overcomes the Allee effect due to indirect prey–taxis

A mathematical model for spatiotemporal dynamics of prey–predator system was studied by means of linear analysis and numerical simulations. The model is a system of PDEs of taxis–diffusion–reaction type, accounting for the ability of predators to detect the locations of higher prey density, which is formalized as indirect prey–taxis, according to hypothesis that the taxis stimulus is a substance being continuously emitted by the prey, diffusing in space and decaying with constant rate in time (e.g. odour, pheromone, exometabolit). The local interactions of the prey and predators are described by the classical Rosenzweig – MacArthur system, which is modified in order to take into account the Allee effect in the predator population. The boundary conditions determine the absence of fluxes of population densities and stimulus concentration through the habitat boundaries. The obtained results suggest that the prey–taxis activity of the predator can destabilize both the stationary and periodic spatially-homogeneous regimes of the species coexistence, causing emergence of various heterogeneous patterns. In particular, it is demonstrated that formation of local dense aggregations induced by prey–taxis allows the predators to overcome the Allee effect in its population growth, avoiding the extinction that occurs in the model in the absence of spatial effects.     

Positions of the cytoplasmic end of BK α S0 helix relative to S1–S6 and of β1 TM1 and TM2 relative to S0–S6

The large-conductance, voltage- and Ca²⁺-gated K⁺ (BK) channel consists of four α subunits, which form a voltage- and Ca²⁺-gated channel, and up to four modulatory β subunits. The β1 subunit is expressed in smooth muscle, where it slows BK channel kinetics and shifts the conductance–voltage (G-V) curve to the left at [Ca²⁺] > 2 µM. In addition to the six transmembrane (TM) helices, S1–S6, conserved in all voltage-dependent K⁺ channels, BK α has a unique seventh TM helix, S0, which may contribute to the unusual rightward shift in the G-V curve of BK α in the absence of β1 and to a leftward shift in its presence. Such a role is supported by the close proximity of S0 to S3 and S4 in the voltage-sensing domain. Furthermore, on the extracellular side of the membrane, one of the two TM helices of β1, TM2, is adjacent to S0. We have now analyzed induced disulfide bond formation between substituted Cys residues on the cytoplasmic side of the membrane. There, in contrast, S0 is closest to the S2–S3 loop, from which position it is displaced on the addition of β1. The cytoplasmic ends of β1 TM1 and TM2 are adjacent and are located between the S2–S3 loop of one α subunit and S1 of a neighboring α subunit and are not adjacent to S0; i.e., S0 and TM2 have different trajectories through the membrane. In the absence of β1, 70% of disulfide bonding of W43C (S0) and L175C (S2–S3) has no effect on V₅₀ for activation, implying that the cytoplasmic end of S0 and the S2–S3 loop move in concert, if at all, during activation. Otherwise, linking them together in one state would obstruct the transition to the other state, which would certainly change V₅₀.     

Evolution of host resistance to parasite infection in the snail–schistosome–human system

The evolutionary strategies that emerge within populations can be dictated by numerous factors, including interactions with other species. In this paper, we explore the consequences of such a scenario using a host-parasite system of human concern. By analyzing the dynamical behaviors of a mathematical model we investigate the evolutionary outcomes resulting from interactions between Schistosoma mansoni and its snail and human hosts. The model includes two types of snail hosts representing resident and mutant types. Using this approach, we focus on establishing evolutionary stable strategies under conditions where snail hosts express different life-histories and when drug treatment is applied to an age-structured population of human hosts. Results from this work demonstrate that the evolutionary trajectories of host-parasite interactions can be varied, and at times, counter-intuitive, based on parasite virulence, host resistance, and drug treatment.