Nonuniform distribution of glucosinolates in Arabidopsis thaliana leaves has important consequences for plant defense

The spatial distribution of plant defenses within a leaf may be critical in explaining patterns of herbivory. The generalist lepidopteran larvae, Helicoverpa armigera (the cotton bollworm), avoided the midvein and periphery of Arabidopsis thaliana rosette leaves and fed almost exclusively on the inner lamina. This feeding pattern was attributed to glucosinolates because it was not evident in a myrosinase mutant that lacks the ability to activate glucosinolate defenses by hydrolysis. To measure the spatial distribution of glucosinolates in A. thaliana leaves at a fine scale, we constructed ion intensity maps from MALDI-TOF (matrix assisted laser desorption/ionization-time of flight) mass spectra. The major glucosinolates were found to be more abundant in tissues of the midvein and the periphery of the leaf than the inner lamina, patterns that were validated by HPLC analyses of dissected leaves. In addition, there were differences in the proportions of the three major glucosinolates in different leaf regions. Hence, the distribution of glucosinolates within the leaf appears to control the feeding preference of H. armigera larvae. The preferential allocation of glucosinolates to the periphery may play a key role in the defense of leaves by creating a barrier to the feeding of chewing herbivores that frequently approach leaves from the edge.     

Nanovehicular intracellular delivery systems

This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood-brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list "elementary" phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach.     

Shape optimization and characterization of polysaccharide beads prepared by ionotropic gelation

The shape of drug loaded polysaccharide beads produced by ionotropic gelation has been optimized, with the aim of producing spherical beads suitable for further technological operations, such as coating. The optimization was performed on a model system sodium alginate/theophylline by inclusion of various fillers. Incorporation of excipients markedly influenced the morphological characteristics of the beads. The undesired irregular shape of beads caused by incorporation of the drug could only be improved by incorporating a combination of polycarbophil (PK) and polyvinylpyrrolidone (PVP). The spherical shape of these beads was stabilized mechanically by numerous air bubbles trapped inside the beads, which prevented the collapse of the beads during drying. The optimized method was shown to be applicable to a target system of pectin and an anti-inflammatory drug, LK-423.     

Opposing effects of actin signaling and LFA‐1 on establishing the affinity threshold for inducing effector T‐cell responses in mice

Mature CD8⁺ T cells use a narrow antigen affinity threshold to generate tissue‐infiltrating cytotoxic effector T cells and induce autoimmune pathology, but the mechanisms that establish this antigen affinity threshold are poorly understood. Only antigens with affinities above the threshold induce stable contacts with APCs, polarization of a T cell, and asymmetric T‐cell division. Previously published data indicate that LFA‐1 inside‐out signaling might be involved in establishing the antigen affinity threshold. Here, we show that subthreshold antigens weakly activate all major distal TCR signaling pathways. Low‐affinity antigens are more dependent on LFA‐1 than suprathreshold antigens. Moreover, augmenting the inside‐out signaling by hyperactive Rap1 does not increase responses to the subthreshold antigens. Thus, LFA‐1 signaling does not contribute to the affinity‐based antigen discrimination. However, we found that subthreshold antigens do not induce actin rearrangement toward an APC, mediated by Rho‐family GTPases, Cdc42, and Rac. Our data suggest that Rac and Cdc42 contribute to the establishment of the antigen affinity threshold in CD8⁺ T cells by enhancing responses to high‐affinity antigens, or by reducing the responses to low‐affinity antigens.     

Cytometric analysis of cell suspension generated by cavitron ultrasonic surgical aspirator in pediatric brain tumors

Journal of Neuro-Oncology - The aim of this study was to test the possibility of using specimens obtained by a cavitron ultrasonic surgical aspirator (CUSA) in flow and mass cytometry...     

Tremor severity in Parkinson's disease and cortical changes of areas controlling movement sequencing: A preliminary study

There remains much to learn about the changes in cortical anatomy that are associated with tremor severity in Parkinson's disease (PD). For this reason, we used a combination of structural neuroimaging to measure cortical thickness and neurophysiological studies to analyze whether PD tremor was associated with cortex integrity. Magnetic resonance imaging and neurophysiological assessment were performed in 13 nondemented PD patients (9 women, 69.2%) with a clearly tremor‐dominant phenotype. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis software. Assessment of tremor was performed by means of high‐density surface electromyography (hdEMG) and inertial measurement units (IMUs). Individual motor unit discharge patterns were identified from surface hdEMG and tremor metrics quantifying motor unit synchronization from IMUs. Increased motor unit synchronization (i.e., more severe tremor) was associated with cortical changes (i.e., atrophy) in wide‐spread cortical areas, including caudal middle frontal regions bilaterally (dorsal premotor cortices), left inferior parietal lobe (posterior parietal cortex), left lateral orbitofrontal cortex, cingulate cortex bilaterally, left posterior and transverse temporal cortex, and left occipital lobe, as well as reduced left middle temporal volume. Given that the majority of these areas are involved in controlling movement sequencing, our results support Albert's classic hypothesis that PD tremor may be the result of an involuntary activation of a program of motor behavior used in the genesis of rapid voluntary alternating movements.