An immunocytochemical,histochemical and ultrastructural study of the nervous system of the tapeworm <Emphasis Type="Italic">Cyathocephalus truncatus</Emphasis> (Cestoda,Spathebothriidea)

This study is the first detailed study of the organisation of the neuromuscular system of Cyathocephalus truncatus (Cestoda, Spathebothriidea). Five techniques have been used: (1) immunocytochemistry, (2) staining with TRITC-conjugated phalloidin, (3) NADPHdiaphorase histochemistry, (4) confocal scanning laser microscopy and (5) transmission electron microscopy. The patterns of nerves immunoreactive (IR) to antibodies towards serotonin (5-HT) and the invertebrate neuropeptide FMRFamide are described in relation to the musculature. The patterns of NADPHdiaphorase positive nerves and 5-HT-IR nerves are compared. The fine structure of the nervous system (NS) is described. The organisation of NS in the non-segmented, polyzoic C. truncatus differs clearly from that in the non-segmented, monozoic Caryophyllaeus laticeps and shows distinct similarities with the NS in pseudophyllidean cestodes. This supports the hypothesis that taxon Caryophyllidea and Spatheobothriidea form independent lineages within Eucestoda.     

MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors

A recurring challenge for brain pathologists is to diagnose whether a brain malignancy is a primary tumor or a metastasis from some other tissue. The accurate diagnosis of brain malignancies is essential for selection of proper treatment. MicroRNAs are a class of small non-coding RNA species that regulate gene expression; many exhibit tissue-specific expression and are misregulated in cancer. Using microRNA expression profiling, we found that hsa-miR-92b and hsa-miR-9/hsa-miR-9* are over-expressed, specifically in brain primary tumors, as compared to primary tumors from other tissues and their metastases to the brain. By considering the expression of only these two microRNAs, it is possible to distinguish between primary and metastatic brain tumors with very high accuracy. These microRNAs thus represent excellent biomarkers for brain primary tumors. Previous reports have found that hsa-miR-92b and hsa-miR-9/hsa-miR-9* are expressed more strongly in developing neurons and brain than in adult brain. Thus, their specific over-expression in brain primary tumors supports a functional role for these microRNAs or a link between neuronal stem cells and brain tumorigenesis.     

Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2

Clathrin-mediated synaptic vesicle (SV) recycling involves the spatiotemporally controlled assembly of clathrin coat components at phosphatidylinositiol (4, 5)-bisphosphate [PI(4,5)P₂]-enriched membrane sites within the periactive zone. Such spatiotemporal control is needed to coordinate SV cargo sorting with clathrin/AP2 recruitment and to restrain membrane fission and synaptojanin-mediated uncoating until membrane deformation and clathrin coat assembly are completed. The molecular events underlying these control mechanisms are unknown. Here we show that the endocytic SH3 domain-containing accessory protein intersectin 1 scaffolds the endocytic process by directly associating with the clathrin adaptor AP2. Acute perturbation of the intersectin 1-AP2 interaction in lamprey synapses in situ inhibits the onset of SV recycling. Structurally, complex formation can be attributed to the direct association of hydrophobic peptides within the intersectin 1 SH3A-B linker region with the “side sites” of the AP2 α- and β-appendage domains. AP2 appendage association of the SH3A-B linker region inhibits binding of the inositol phosphatase synaptojanin 1 to intersectin 1. These data identify the intersectin-AP2 complex as an important regulator of clathrin-mediated SV recycling in synapses.     

Body mass index moderates gaze orienting biases and pupil diameter to high and low calorie food images

The primary goal of this study was to examine eye gaze behavior to different kinds of food images in individuals differing in BMI status. Eye-tracking methods were used to examine gaze and pupil responses while normal weight and overweight women freely viewed pairs of different food images: high calorie sweet foods, high calorie savory foods, and low calorie foods. Self-report measures of hunger, state and trait cravings, and restrained eating were also obtained. Results revealed orienting biases to low calorie foods and decreases in pupil diameter to high calorie sweet foods relative to low calorie foods in the overweight group. Groups did not differ in the average amount of time spent gazing at the different image types. Furthermore, increased state cravings were associated with larger pupil diameters to high calorie savory foods, especially in individuals with lower BMIs. In contrast, restrained eating scores were associated with a decreased orienting bias to high calorie sweet foods in the high BMI group. In conclusion, BMI status appears to influence gaze parameters that are less susceptible to cognitive control. Results suggest that overweight individuals, especially those who diet, have negative implicit attitudes toward high calorie foods, especially sweets.     

Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis

The role of activated microglia (MG) in demyelinating neurodegenerative diseases such as multiple sclerosis is controversial. Here we show that high, but not low, levels of IFN-gamma (a cytokine associated with inflammatory autoimmune diseases) conferred on rodent MG a phenotype that impeded oligodendrogenesis from adult neural stem/progenitor cells. IL-4 reversed the impediment, attenuated TNF-alpha production, and overcame blockage of IGF-I production caused by IFN-gamma. In rodents with acute or chronic EAE, injection of IL-4-activated MG into the cerebrospinal fluid resulted in increased oligodendrogenesis in the spinal cord and improved clinical symptoms. The newly formed oligodendrocytes were spatially associated with MG expressing MHC class II proteins and IGF-I. These results point to what we believe to be a novel role for MG in oligodendrogenesis from the endogenous stem cell pool.     

Controlled Support MEG imaging

In this paper, we present a novel approach to imaging sparse and focal neural current sources from MEG (magnetoencephalography) data. Using the framework of Tikhonov regularization theory, we introduce a new stabilizer that uses the concept of controlled support to incorporate a priori assumptions about the area occupied by focal sources. The paper discusses the underlying Tikhonov theory and its relationship to a Bayesian formulation which in turn allows us to interpret and better understand other related algorithms.     

Identification and characterization of bacterial pathogens causing bloodstream infections by DNA microarray

Bloodstream infections are potentially life-threatening and require rapid identification and antibiotic susceptibility testing of the causative pathogen in order to facilitate specific antimicrobial therapy. We developed a prototype DNA microarray for the identification and characterization of three important bacteremia-causing species: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The array consisted of 120 species-specific gene probes 200 to 800 bp in length that were amplified from recombinant plasmids. These probes represented genes encoding housekeeping proteins, virulence factors, and antibiotic resistance determinants. Evaluation with 42 clinical isolates, 3 reference strains, and 13 positive blood cultures revealed that the DNA microarray was highly specific in identifying S. aureus, E. coli, and P. aeruginosa strains and in discriminating them from closely related gram-positive and gram-negative bacterial strains also known to be etiological agents of bacteremia. We found a nearly perfect correlation between phenotypic antibiotic resistance determined by conventional susceptibility testing and genotypic antibiotic resistance by hybridization to the S. aureus resistance gene probes mecA (oxacillin-methicillin resistance), aacA-aphD (gentamicin resistance), ermA (erythromycin resistance), and blaZ (penicillin resistance) and the E. coli resistance gene probes blaTEM-106 (penicillin resistance) and aacC2 (aminoglycoside resistance). Furthermore, antibiotic resistance and virulence gene probes permitted genotypic discrimination within a species. This novel DNA microarray demonstrates the feasibility of simultaneously identifying and characterizing bacteria in blood cultures without prior amplification of target DNA or preidentification of the pathogen.