A Morpho-Density Approach to Estimating Neural Connectivity

Neuronal signal integration and information processing in cortical neuronal networks critically depend on the organization of synaptic connectivity. Because of the challenges involved in measuring a large number of neurons, synaptic connectivity is difficult to determine experimentally. Current computational methods for estimating connectivity typically rely on the juxtaposition of experimentally available neurons and applying mathematical techniques to compute estimates of neural connectivity. However, since the number of available neurons is very limited, these connectivity estimates may be subject to large uncertainties. We use a morpho-density field approach applied to a vast ensemble of model-generated neurons. A morpho-density field (MDF) describes the distribution of neural mass in the space around the neural soma. The estimated axonal and dendritic MDFs are derived from 100,000 model neurons that are generated by a stochastic phenomenological model of neurite outgrowth. These MDFs are then used to estimate the connectivity between pairs of neurons as a function of their inter-soma displacement. Compared with other density-field methods, our approach to estimating synaptic connectivity uses fewer restricting assumptions and produces connectivity estimates with a lower standard deviation. An important requirement is that the model-generated neurons reflect accurately the morphology and variation in morphology of the experimental neurons used for optimizing the model parameters. As such, the method remains subject to the uncertainties caused by the limited number of neurons in the experimental data set and by the quality of the model and the assumptions used in creating the MDFs and in calculating estimating connectivity. In summary, MDFs are a powerful tool for visualizing the spatial distribution of axonal and dendritic densities, for estimating the number of potential synapses between neurons with low standard deviation, and for obtaining a greater understanding of the relationship between neural morphology and network connectivity.     

The first three minutes: smooth muscle contraction, cytoskeletal events, and soft glasses.

Smooth muscle exhibits biophysical characteristics and physiological behaviors that are not readily explained by present paradigms of cytoskeletal and cross-bridge mechanics. There is increasing evidence that contractile activation of the smooth muscle cell involves an array of cytoskeletal processes that extend beyond cross-bridge cycling and the sliding of thick and thin filaments. We review here the evidence suggesting that the biophysical and mechanical properties of the smooth muscle cell reflect the integrated interactions of an array of highly dynamic cytoskeletal processes that both react to and transform the dynamics of cross-bridge interactions over the course of the contraction cycle. The activation of the smooth muscle cell is proposed to trigger dynamic remodeling of the actin filament lattice within cellular microdomains in response to local mechanical and pharmacological events, enabling the cell to adapt to its external environment. As the contraction progresses, the cytoskeletal lattice stabilizes, solidifies, and forms a rigid structure well suited for transmission of tension generated by the interaction of myosin and actin. The integrated molecular transitions that occur within the contractile cycle are interpreted in the context of microscale agitation mechanisms and resulting remodeling events within the intracellular microenvironment. Such an interpretation suggests that the cytoskeleton may behave as a glassy substance whose mechanical function is governed by an effective temperature.     

Muscarinic receptor reserve and beta-adrenergic sensitivity in tracheal smooth muscle

The possibility that differences in beta-adrenergic sensitivity among canine trachealis muscles contracted with different contractile agonists are related to differences in the receptor-occupancy characteristics of the contractile agonists was investigated. Relaxation to isoproterenol was compared in muscles contracted with the muscarinic agonists McN-A-343 and acetylcholine (ACh). The apparent dissociation constant (pKB) values for the M1-antagonist, pirenzepine, against ACh (6.96 +/- 0.18) and McN-A-343 (6.84 +/- 0.08) were similar. The pKB values for the M3-antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) against ACh (8.76 +/- 0.13) and McN-A-343 (8.71 +/- 0.10) were also similar, suggesting that these agonists were activating the same subtype of muscarinic receptor, probably M3. However, the contractile response to ACh was associated with a greater receptor reserve than that for McN-A-343. Isoproterenol relaxed muscles contracted with McN-A-343 much more effectively than those contracted with an equieffective concentration of ACh. The results suggest that the relative resistance of ACh-induced contractions to relaxation by isoproterenol may not be an inherent quality of muscarinic receptor stimulation. The large receptor reserve available to ACh may act to buffer the contractile response from the inhibitory effects of beta-adrenergic stimulation. Alternatively, ACh may be able to initiate subcellular mechanisms that are unavailable to agonists of lower efficacy.     

A high-powered replication study finds no effect of starting or stopping hormonal contraceptive use on relationship quality

A number of recent studies have implicated that incongruent use of hormonal contraceptives (HCs) negatively affects various aspects of women's romantic relationships. It has been suggested that women with incongruent HC use (a discrepancy in HC use status between when they first met their current partner and the time of study participation) report less sexual satisfaction and higher jealousy scores compared to women with congruent HC use. A similar effect has also been hypothesized for general relationship satisfaction, and recent findings suggest that the association between HC incongruency and women's general relationship satisfaction is moderated by third-party ratings of facial attractiveness of the women's male partners. Using a large convenience sample (N = 948) of Finnish women, we attempted to replicate previously reported findings but found no support for the HC congruency hypothesis, despite excellent statistical power (≥98.7%) to detect previously reported effect sizes. Instead, after dividing our sample into four groups based on HC congruency/incongruency, we found that the largest differences in jealousy, sexual satisfaction, and relationship satisfaction scores tended to be found between women who were consistent HC users and consistent non-users (i.e., between women with different kinds of congruent HC use). We also detected a significant main effect of current HC use on jealousy. We conclude that HC congruency effects reported in previous studies may have spuriously arisen from unequal distributions of current HC users within congruent and incongruent HC user groups.     

Nanocrystalline SrS:Ce3+ system for the generation of white light‐emitting diodes

Nanocrystalline SrS phosphors doped with Ce³⁺ ions at different concentrations (0.5, 1, 1.5 and 2 mol%) are synthesized via the solid‐state diffusion method (SSDM), which is suitable for the large‐scale production of phosphors in industrial applications. The as‐prepared samples are characterized using an X‐ray diffraction (XRD) technique, field emission scanning electron microscopy (FESEM), high‐resolution transmission electron microscopy (HRTEM) and energy‐dispersive X‐ray (EDX) analysis. The optical properties of these phosphors are analyzed using reflectance spectra, photoluminescence spectra and afterglow decay curves. The cubic structure of the SrS phosphor is confirmed by XRD analysis and the crystallite size calculated by Scherer's formula using XRD data shows the nanocrystalline nature of the phosphors. No phase change is observed with increasing concentrations of Ce³⁺ ions. The surface morphology of the prepared phosphors is determined by FESEM, which shows a sphere‐like structure and good connectivity of the grains. The authenticity of the formation of nanocrystalline phosphors is examined by HRTEM analysis. Elemental compositional information for the prepared phosphors is gathered by EDX analysis. Photoluminescence studies reveal that the emission spectra of the prepared phosphor shows broad band emission centered at 458 and 550 nm due to the transition of electrons from the 5d → 4f energy levels. The afterglow decay characteristics of different as‐synthesized SrS:Ce³⁺ nanophosphors are conceptually described. Copyright © 2016 John Wiley & Sons, Ltd.     

A new case of fish-eating in Japanese macaques: implications for social constraints on the diffusion of feeding innovation

This is the first detailed report of social factors affecting fish-eating in Japanese macaques under natural circumstances. We video-recorded a complete event of fish eating, involving a new fish food species for the monkeys on Koshima island. Following the discovery of a large beached sea bass by a peripheral male, we observed a total of 16 individuals feeding on the fish in turns, and interacting around it. The rank order of access to the fish was mainly explained by the spatial position of group members, whereas dominance determined how long the fish was monopolized. Although limited, the tolerated presence of close-bystanders while feeding was affected by kinship and affiliation. Genealogic data suggested that fish-eating behavior was well maintained in terms of maternal lineages. This report should contribute to a better understanding of how social features may constrain the long-term diffusion of feeding innovations in free-ranging primate groups.     

Integrin-linked kinase regulates N-WASp-mediated actin polymerization and tension development in tracheal smooth muscle

The contractile stimulation of smooth muscle tissues stimulates the recruitment of proteins to membrane adhesion complexes and the initiation of actin polymerization. We hypothesized that integrin-linked kinase (ILK), a beta-integrin-binding scaffolding protein and serine/threonine kinase, and its binding proteins, PINCH, and alpha-parvin may be recruited to membrane adhesion sites during contractile stimulation of tracheal smooth muscle to mediate cytoskeletal processes required for tension development. Immunoprecipitation analysis indicted that ILK, PINCH, and alpha-parvin form a stable cytosolic complex and that the ILK.PINCH.alpha-parvin complex is recruited to integrin adhesion complexes in response to acetylcholine (ACh) stimulation where it associates with paxillin and vinculin. Green fluorescent protein (GFP)-ILK and GFP-PINCH were expressed in tracheal muscle tissues and both endogenous and recombinant ILK and PINCH were recruited to the membrane in response to ACh stimulation. The N-terminal LIM1 domain of PINCH binds to ILK and is required for the targeting of the ILK-PINCH complex to focal adhesion sites in fibroblasts during cell adhesion. We expressed the GFP-PINCH LIM1-2 fragment, consisting only of LIM1-2 domains, in tracheal smooth muscle tissues to competitively inhibit the interaction of ILK with PINCH. The PINCH LIM1-2 fragment inhibited the recruitment of endogenous ILK and PINCH to integrin adhesion sites and prevented their association of ILK with beta-integrins, paxillin, and vinculin. The PINCH LIM1-2 fragment also inhibited tension development, actin polymerization, and activation of the actin nucleation initiator, N-WASp. We conclude that the recruitment of the ILK.PINCH.alpha-parvin complex to membrane adhesion complexes is required to initiate cytoskeletal processes required for tension development in smooth muscle.     

Activation of vinculin induced by cholinergic stimulation regulates contraction of tracheal smooth muscle tissue

Vinculin localizes to membrane adhesion junctions where it links actin filaments to the extracellular matrix by binding to the integrin-binding protein talin at its head domain (Vh) and to actin filaments at its tail domain (Vt). Vinculin can assume an inactive (closed) conformation in which Vh and Vt bind to each other, masking the binding sites for actin and talin, and an active (open) conformation in which the binding sites for talin and actin are exposed. We hypothesized that the contractile activation of smooth muscle tissues might regulate the activation of vinculin and thereby contribute to the regulation of contractile tension. Stimulation of tracheal smooth muscle tissues with acetylcholine (ACh) induced the recruitment of vinculin to cell membrane and its interaction with talin and increased the phosphorylation of membrane-localized vinculin at the C-terminal Tyr-1065. Expression of recombinant vinculin head domain peptide (Vh) in smooth muscle tissues, but not the talin-binding deficient mutant head domain, VhA50I, inhibited the ACh-induced recruitment of endogenous vinculin to the membrane and the interaction of vinculin with talin and also inhibited vinculin phosphorylation. Expression of Vh peptide also inhibited ACh-induced smooth muscle contraction and inhibited ACh-induced actin polymerization; however, it did not affect myosin light chain phosphorylation, which is necessary for cross-bridge cycling. Inactivation of RhoA inhibited vinculin activation in response to ACh. We conclude that ACh stimulation regulates vinculin activation in tracheal smooth muscle via RhoA and that vinculin activation contributes to the regulation of active tension by facilitating connections between actin filaments and talin-integrin adhesion complexes and by mediating the initiation of actin polymerization.     

Production of haploids and doubled haploids in oil palm

Background

Studies on host-pathogen interactions in a range of pathosystems have revealed an array of mechanisms by which plants reduce the efficiency of pathogenesis. While R-gene mediated resistance confers highly effective defense responses against pathogen invasion, quantitative resistance is associated with intermediate levels of resistance that reduces disease progress. To test the hypothesis that specific loci affect distinct stages of fungal pathogenesis, a set of maize introgression lines was used for mapping and characterization of quantitative trait loci (QTL) conditioning resistance to Setosphaeria turcica, the causal agent of northern leaf blight (NLB). To better understand the nature of quantitative resistance, the identified QTL were further tested for three secondary hypotheses: (1) that disease QTL differ by host developmental stage; (2) that their performance changes across environments; and (3) that they condition broad-spectrum resistance.

Results

Among a set of 82 introgression lines, seven lines were confirmed as more resistant or susceptible than B73. Two NLB QTL were validated in BC₄F₂ segregating populations and advanced introgression lines. These loci, designated qNLB1.02 and qNLB1.06, were investigated in detail by comparing the introgression lines with B73 for a series of macroscopic and microscopic disease components targeting different stages of NLB development. Repeated greenhouse and field trials revealed that qNLB1.06 _Tx303 (the Tx303 allele at bin 1.06) reduces the efficiency of fungal penetration, while qNLB1.02 _B73 (the B73 allele at bin 1.02) enhances the accumulation of callose and phenolics surrounding infection sites, reduces hyphal growth into the vascular bundle and impairs the subsequent necrotrophic colonization in the leaves. The QTL were equally effective in both juvenile and adult plants; qNLB1.06 _Tx303 showed greater effectiveness in the field than in the greenhouse. In addition to NLB resistance, qNLB1.02 _B73 was associated with resistance to Stewart's wilt and common rust, while qNLB1.06 _Tx303 conferred resistance to Stewart's wilt. The non-specific resistance may be attributed to pleiotropy or linkage.

Conclusions

Our research has led to successful identification of two reliably-expressed QTL that can potentially be utilized to protect maize from S. turcica in different environments. This approach to identifying and dissecting quantitative resistance in plants will facilitate the application of quantitative resistance in crop protection.