Secretory traffic triggers the formation of tubular continuities across Golgi sub-compartments

The organization of secretory traffic remains unclear, mainly because of the complex structure and dynamics of the secretory pathway. We have thus studied a simplified system, a single synchronized traffic wave crossing an individual Golgi stack, using electron tomography. Endoplasmic-reticulum-to-Golgi carriers join the stack by fusing with cis cisternae and induce the formation of intercisternal tubules, through which they redistribute their contents throughout the stack. These tubules seem to be pervious to Golgi enzymes, whereas Golgi vesicles are depleted of both enzymes and cargo. Cargo then traverses the stack without leaving the cisternal lumen. When cargo exits the stack, intercisternal connections disappear. These findings provide a new view of secretory traffic that includes dynamic intercompartment continuities as key players.     

Peptide inhibitors against herpes simplex virus infections

Herpes simplex virus (HSV) is a significant human pathogen causing mucocutaneous lesions primarily in the oral or genital mucosa. Although acyclovir (ACV) and related nucleoside analogs provide successful treatment, HSV remains highly prevalent worldwide and is a major cofactor for the spread of human immunodeficiency virus. Encephalitis, meningitis, and blinding keratitis are among the most severe diseases caused by HSV. ACV resistance poses an important problem for immunocompromised patients and highlights the need for new safe and effective agents; therefore, the development of novel strategies to eradicate HSV is a global public health priority. Despite the continued global epidemic of HSV and extensive research, there have been few major breakthroughs in the treatment or prevention of the virus since the introduction of ACV in the 1980s. A therapeutic strategy at the moment not fully addressed is the use of small peptide molecules. These can be either modeled on viral proteins or derived from antimicrobial peptides. Any peptide that interrupts protein–protein or viral protein–host cell membrane interactions is potentially a novel antiviral drug and may be a useful tool for elucidating the mechanisms of viral entry. This review summarizes current knowledge and strategies in the development of synthetic and natural peptides to inhibit HSV infectivity. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Running as fast as it can: How spiking dynamics form object groupings in the laminar circuits of visual cortex

How spiking neurons cooperate to control behavioral processes is a fundamental problem in computational neuroscience. Such cooperative dynamics are required during visual perception when spatially distributed image fragments are grouped into emergent boundary contours. Perceptual grouping is a challenge for spiking cells because its properties of collinear facilitation and analog sensitivity occur in response to binary spikes with irregular timing across many interacting cells. Some models have demonstrated spiking dynamics in recurrent laminar neocortical circuits, but not how perceptual grouping occurs. Other models have analyzed the fast speed of certain percepts in terms of a single feedforward sweep of activity, but cannot explain other percepts, such as illusory contours, wherein perceptual ambiguity can take hundreds of milliseconds to resolve by integrating multiple spikes over time. The current model reconciles fast feedforward with slower feedback processing, and binary spikes with analog network-level properties, in a laminar cortical network of spiking cells whose emergent properties quantitatively simulate parametric data from neurophysiological experiments, including the formation of illusory contours; the structure of non-classical visual receptive fields; and self-synchronizing gamma oscillations. These laminar dynamics shed new light on how the brain resolves local informational ambiguities through the use of properly designed nonlinear feedback spiking networks which run as fast as they can, given the amount of uncertainty in the data that they process.     

Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis

Introduction  

Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis.     

HisE11 and HisF8 Provide Bis-histidyl Heme Hexa-coordination in the Globin Domain of Geobacter sulfurreducens Globin-coupled Sensor

Among heme-based sensors, recent phylogenomic and sequence analyses have identified 34 globin coupled sensors (GCS), to which an aerotactic or gene-regulating function has been tentatively ascribed. Here, the structural and biochemical characterization of the globin domain of the GCS from Geobacter sulfurreducens (GsGCS¹⁶²) is reported. A combination of X-ray crystallography (crystal structure at 1.5 Å resolution), UV-vis and resonance Raman spectroscopy reveals the ferric GsGCS¹⁶² as an example of bis-histidyl hexa-coordinated GCS. In contrast to the known hexa-coordinated globins, the distal heme-coordination in ferric GsGCS¹⁶² is provided by a His residue unexpectedly located at the E11 topological site. Furthermore, UV-vis and resonance Raman spectroscopy indicated that ferrous deoxygenated GsGCS¹⁶² is a penta-/hexa-coordinated mixture, and the heme hexa-to-penta-coordination transition does not represent a rate-limiting step for carbonylation kinetics. Lastly, electron paramagnetic resonance indicates that ferrous nitrosylated GsGCS¹⁶² is a penta-coordinated species, where the proximal HisF8-Fe bond is severed.     

Systematic consideration of floral microcharacters of the South American genus Chrysolaena (Vernonieae,Asteraceae)

Floral microcharacters of the genus Chrysolaena H. Rob. (Vernonieae, Asteraceae) were analysed in detail for the first time in order to evaluate the taxonomic position of conflictive species in the group. The results were also compared with studies carried out in species of related genera. In addition to distinctive microcharacters previously studied in some species of the genus, other characters such as trichome types of the corolla, style, anthers and cypselae have been analysed for the first time. The presence of glandular apical appendage and cypselae are common characteristics among species Chrysolaena. In addition to these, this study shows that presence of glands on the style and corollas is another consistent characteristic in the genus. However, the absence of basal stylar node would not be a diagnostic character since this varies widely among species. The results indicate that most of the microcharacters of Chrysolaena analysed are quite consistent in the genus, but they are no more consistent than the pollen morphology (type 'C') and chromosome base number (x = 10). Until now, these last two features would be most useful for separating Chrysolaena from the related genera Lessingianthus and Lepidaploa. At species level, the results show that related species can be distinguished by the different combinations of floral microcharacters. The value of microcharacters could be increased if they are combined with other morphological, cytological, and palynological data.     

Marked Increase in PROP Taste Responsiveness Following Oral Supplementation with Selected Salivary Proteins or Their Related Free Amino Acids

The genetic predisposition to taste 6-n-propylthiouracil (PROP) varies among individuals and is associated with salivary levels of Ps-1 and II-2 peptides, belonging to the basic proline-rich protein family (bPRP). We evaluated the role of these proteins and free amino acids that selectively interact with the PROP molecule, in modulating bitter taste responsiveness. Subjects were classified by their PROP taster status based on ratings of perceived taste intensity for PROP and NaCl solutions. Quantitative and qualitative determinations of Ps-1 and II-2 proteins in unstimulated saliva were performed by HPLC-ESI-MS analysis. Subjects rated PROP bitterness after supplementation with Ps-1 and II-2, and two amino acids (L-Arg and L-Lys) whose interaction with PROP was demonstrated by ¹H-NMR spectroscopy. ANOVA showed that salivary levels of II-2 and Ps-1 proteins were higher in unstimulated saliva of PROP super-tasters and medium tasters than in non-tasters. Supplementation of Ps-1 protein in individuals lacking it in saliva enhanced their PROP bitter taste responsiveness, and this effect was specific to the non-taster group.¹H-NMR results showed that the interaction between PROP and L-Arg is stronger than that involving L-Lys, and taste experiments confirmed that oral supplementation with these two amino acids increased PROP bitterness intensity, more for L-Arg than for L-Lys. These data suggest that Ps-1 protein facilitates PROP bitter taste perception and identifies a role for free L-Arg and L-Lys in PROP tasting.