The complex role of B7 molecules in tumor immunology

T-cell activation requires the interaction of the T-cell receptor with a cognate major histocompatibility complex (MHC)-peptide complex. Initiated by antigen engagement, the adaptive immune response is orchestrated by a complex balance between stimulatory and inhibitory signals that are predominantly controlled by members of the B7 family. Here, we review the current knowledge on B7 family members concerning their constitutive and regulated expression, modulation of the immune response and their role in the evasion of host immune surveillance. We also discuss recent therapeutic strategies that aim to improve immune-cell recognition of tumors and induce tolerance to autoreactive immune responses in normal tissues by manipulating B7 functions.     

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.     

Neuropharmacology and behavior in planarians: translations to mammals

Planarians are the simplest animals to exhibit a body plan common to all vertebrates and many invertebrates, characterized by bilateral rather than radial symmetry, dorsal and ventral surfaces, and a rostrocaudal axis with a head and a tail, including specialized sense organs and an aggregate of nerve cells in the head. Neurons in planarian more closely resemble those of vertebrates than those of advanced invertebrates, exhibiting typical vertebrate features of multipolar shape, dendritic spines with synaptic boutons, a single axon, expression of vertebrate-like neural proteins, and relatively low spontaneously generated electrical activity. Here we report the most relevant contribution to the knowledge of the neuropharmacology of planarians, with particular reference to the behavioral consequences of the exposure to drugs acting on neural transmission. Neurochemical and histochemical data indicate the presence of several neurotransmitter-receptor systems in planarians. Moreover, a variety of experimental studies characterized specific behavioral patterns of these animals following the exposure to drugs acting on neural transmission. There is also evidence of the interactions between discrete neurotransmitter-receptor systems in modulating behavior in planarians. Finally, the model has proved efficacy for investigating the neurotoxicology of the dopamine neurons, and for the initial screening of the neuroprotective potential of drugs. In conclusion, these findings indicate that interactions between discrete neurotransmitter-receptor systems occur very early along phylogeny, although they may have evolved from very fundamental behaviors, such as motor activity in planarian, to more complex and integrated functions in vertebrates.     

Tritium radiolabelling of PB28, a potent sigma-2 receptor ligand: pharmacokinetic and pharmacodynamic characterization

A potent sigma-2 receptor ligand, known as PB28, was tritium radiolabelled and biologically evaluated. The results showed that [(3)H]PB28 and the corresponding unlabelled PB28 had superimposed pharmacodynamic properties. This radioligand appears as a potential candidate for receptor binding and in living cells assays.     

Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease

While the neuropathology of kuru is well defined, there are few data concerning the distribution of disease-related prion protein in peripheral tissues. Here we report the investigation of brain and peripheral tissues from a kuru patient who died in 2003. Neuropathological findings were compared with those seen in classical (sporadic and iatrogenic) Creutzfeldt-Jakob disease (CJD) and variant CJD (vCJD). The neuropathological findings of the kuru patient showed all the stereotypical changes that define kuru, with the occurrence of prominent PrP plaques throughout the brain. Lymphoreticular tissue showed no evidence of prion colonization, suggesting that the peripheral pathogenesis of kuru is similar to that seen in classical CJD rather than vCJD. These findings now strongly suggest that the characteristic peripheral pathogenesis of vCJD is determined by prion strain type alone rather than route of infection.     

Agroinfiltration of grapevine leaves for fast transient assays of gene expression and for long-term production of stable transformed cells

Agrobacterium-mediated transient assays for the analysis of gene function are used as alternatives to genetic complementation and stable plant transformation. Although such assays are routinely performed in several plant species, they have not yet been successfully applied to grapevines. We explored genetic background diversity of grapevine cultivars and performed agroinfiltration into in vitro cultured plants. By combining different genotypes and physiological conditions, we developed a protocol for efficient transient transformations of selected grapevine cultivars. Among the four cultivars analyzed, Sugraone and Aleatico exhibited high levels of transient transformation. Transient expression occurred in the majority of cells within the infiltrated tissue several days after agroinfiltration and, in a few cases, it later spread to a larger portion of the leaf. Three laboratory strains of Agrobacterium tumefaciens with different virulence levels were used for agroinfiltration assays on grapevine plants. This method promises to be a powerful tool to perform subcellular localization analyses. Grapevine leaf tissues were transformed with fluorescent markers targeted to cytoplasm (free GFP and mRFP1), endoplasmatic reticulum (GFP::HDEL), chloroplast (GAPA1::YFP) and mitochondria (β::GFP). Confocal microscope analyses demonstrated that these subcellular compartments could be easily visualized in grapevine leaf cells. In addition, from leaves of the Sugraone cultivar agroinfiltrated with endoplasmic reticulum-targeted GFP-construct, stable transformed cells were obtained that show the opportunity to convert a transiently transformed leaf tissue into a stably transformed cell line. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comparing sleep-loss sleepiness and sleep inertia: lapses make the difference

To compare the behavioral effects of sleep-loss sleepiness (performance impairment due to sleep loss) and sleep inertia (period of impaired performance that follows awakening), mean response latencies and number of lapses from a visual simple reaction-time task were analyzed. Three experimental conditions were designed to manipulate sleepiness and sleep-inertia levels: uninterrupted sleep, partial sleep reduction, and total sleep deprivation. Each condition included two consecutive nights (the first always a night of uninterrupted sleep, and the second either a night of uninterrupted sleep, a night when sleep was reduced to 3 h, or a night of total sleep deprivation), as well as two days in which performance was assessed at 10 different time points (08:00, 08:30, 09:00, 09:30, 10:00, 11:00, 14:00, 17:00, 20:00, and 23:00 h). From 08:00 to 09:00 h, reaction times in the partial sleep-reduction and total sleep-deprivation conditions were at a similar level and were slower than those observed in the uninterrupted sleep condition. In the same time period, the frequency of lapses in the total sleep-deprivation condition was higher than in the partial sleep-reduction condition, while this latter condition never differed from the uninterrupted sleep condition. The results indicate that both sleep inertia and sleep-loss sleepiness lead to an increase in response latencies, but only extreme sleepiness leads to an increase in lapse frequency. We conclude that while reaction times slow as a result of both sleep inertia and sleep-loss sleepiness, lapses appear to be a specific feature of sleep-loss sleepiness.     

Comparison of two different actigraphs with polysomnography in healthy young subjects

The present study aimed to compare two commercially available actigraphs, with a concurrent polysomnographic (PSG) recording. Twelve healthy volunteers (six women; age range 19-28 yrs) simultaneously wore the Basic Mini-Motionlogger^® and Actiwatch^® for seven overnight polysomnographic recordings. Comparisons of the following sleep measures were focused on: sleep onset latency (SOL), total sleep time, wake after sleep onset, and sleep efficiency. Both devices underestimated SOL in comparison to PSG, but they had similar performance compared to PSG for the other sleep measures. A limit of the study is that the results can be only generalized to healthy young subjects.