Priming illusory words: an ERP approach

Repetition blindness (RB) was used to investigate whether illusory words emerge at a lexical-perceptual or a semantic-reconstructional level. Illusory words were evoked by the rapid serial visual presentation (RSVP) of two real words and a word fragment. The initial words share the same string of letters ("CREEP"-"SHEEP"), producing a free-floating word fragment ("SH"). This fragment is likely to be linked to a subsequently presented fragment ("IFT") if both combine to a meaningful word ("SHIFT"). The processing level of the illusions was probed by prime words preceding the RSVP sequence which were semantically related or unrelated to the second real word or to the illusion. Behavioural and electrophysiological correlates of the semantic priming effect were recorded in 14 subjects. Real words related to the prime were perceived more frequently, and evoked widespread N400-like effect in the event-related brain potentials (ERPs). An ERP effect of the same polarity was obtained for illusory words, however, its latency was delayed and the topographical distribution was restricted to left posterior electrode positions. These differences suggest that priming might affect real and illusory words at different levels of word processing: access to real words is facilitated at a semantic level, whereas lexical activation apparently accompanies the generation of illusory words.     

Overexpression/amplification of HER-2/neu is uncommon in hepatocellular carcinoma

Background： Hepatocellular carcinoma （HCC） is one of the most prevalent fatal cancers in the world. Despite advances in early diagnosis and improvements in surgical techniques, the survival of patients with HCC even after resection is poor because of the high incidence of recurrences. Therefore, the identification of prognostic factors may be helpful in the development of new treatment protocols. Aims： To investigate HER-2/neu status in HCC by immunohistochemistry （IHC） and fluorescence in situ hybridisation （FISH）, and to explore the possibility of using trastuzumab in the treatment of HCC. Methods.. Eight hundred and sixty eight surgical samples from patients with primary HCC were examined for their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The correlations between HER-2/neu overexpression and clinicopathological characteristics were analysed statistically. Results： HER-2/neu overexpression was detected in 21 （2.42%） of the 868 primary HCCs. Only one specimen showed HER-2/neu gene amplification by FISH. No significant associations were found between HER-2/neu overexpression and the clinicopathological parameters. Conclusions： There is a low frequency of HER-2/neu overexpression/amplification in HCC. There appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti-HER-2/neu trastuzumab treatment in patients with HCC.     

Functional organization of auditory cortex in the Mongolian gerbil (Meriones unguiculatus). IV. Connections with anatomically characterized subcortical structures

The subcortical connections of the four tonotopically organized fields of the auditory cortex of the Mongolian gerbil, namely the primary (AI), the anterior (AAF), the dorsoposterior (DP) and the ventroposterior field (VP), were studied predominantly by anterograde transport of biocytin injected into these fields. In order to allow the localization of connections with respect to subdivisions of subcortical auditory structures, their cyto-, fibre- and chemoarchitecture was characterized using staining methods for cell bodies, myelin and the calcium-binding protein parvalbumin. Each injected auditory cortical field has substantial and reciprocal connections with each of the three subdivision of the medial geniculate body (MGB), namely the ventral (MGv), dorsal (MGd) and medial division (MGm). However, the relative strengths of these connections vary: AI is predominantly connected with MGv, AAF with MGm and MGv, and DP and VP with MGd and MGv. The connections of at least AI and MGv are topographic: injections into caudal low-frequency AI label laterorostral portions of MGv, whereas injections into rostral high-frequency AI label mediocaudal portions of MGv. All investigated auditory fields send axons to the suprageniculate, posterior limitans, laterodorsal and lateral posterior thalamic nuclei, with strongest projections from DP and VP, as well as to the reticular and subgeniculate thalamic nuclei. AI, AAF, DP and VP project to all three subdivisions of the inferior colliculus, namely the dorsal cortex, external cortex and central nucleus ipsilaterally and to the dorsal and external cortex contralaterally. They also project to the deep and intermediate layers of the ipsilateral superior colliculus, with strongest projections from DP and VP to the lateral and basolateral amygdaloid nuclei, the caudate putamen, globus pallidus and the pontine nuclei. In addition, AAF and particularly DP and VP project to paralemniscal regions around the dorsal nucleus of the lateral lemniscus (DNLL), to the DNLL itself and to the rostroventral aspect of the superior olivary complex. Moreover, DP and VP send axons to the dorsal lateral geniculate nucleus. The differences with respect to the existence and/or relative strengths of subcortical connections of the examined auditory cortical fields suggest a somewhat different function of each of these fields in auditory processing.     

A multivalent HIV-vaccine: development of a plasmid DNA for the expression of HIV envelope glycoproteins with hypervariable V3-loop domains

The third hypervariable (V3) loop of the HIV-1 envelope glycoprotein gp120 plays an essential role in the process of viral entry. It contributes to the tropism, coreceptor usage and immune-escape of the virus. We generated a monovalent plasmid DNA and demonstrated the expression of HIV-1 clade B subtype NL4-3 gp120 and gp160 in comparison to a multivalent plasmid DNA encoding for a variety of V3-variants. In contrast to the membrane-anchored gp160, preliminary data demonstrate the monovariant gp120 is expressed in and presented on a human dendritic cell (DC) line, due to a HIVenv-specific re-stimulation of na?ve T-cells detected by IFNgamma-ELISPOT assay.     

Heparin binding sites on Ross River virus revealed by electron cryo-microscopy

Cell surface glycosaminoglycans play important roles in cell adhesion and viral entry. Laboratory strains of two alphaviruses, Sindbis and Semliki Forest virus, have been shown to utilize heparan sulfate as an attachment receptor, whereas Ross River virus (RRV) does not significantly interact with it. However, a single amino acid substitution at residue 218 in the RRV E2 glycoprotein adapts the virus to heparan sulfate binding and expands the host range of the virus into chicken embryo fibroblasts. Structures of the RRV mutant, E2 N218R, and its complex with heparin were determined through the use of electron cryo-microscopy and image reconstruction methods. Heparin was found to bind at the distal end of the RRV spikes, in a region of the E2 glycoprotein that has been previously implicated in cell-receptor recognition and antibody binding.     

Diagnostic findings in endoscopic screening of superficial colorectal neoplasia: results from a prospective study

BACKGROUND: A prospective study was carried out to clarify the efficacy of an endoscopic screening program for detecting superficial colorectal neoplasias by color changes such as faint redness or discoloration, which have been described as a key finding of these lesions in the literature. METHODS: We enrolled 716 consecutive cases in this study, but more than half of them did not reveal any abnormalities colonoscopically. RESULTS: Of the 716 cases, 48 (7%) were examined by magnifying colonoscopy with a dye spraying technique, following the detection of superficial color changes. Sixteen neoplastic lesions (in 16 cases) were detected among the 48 cases and the detection rate was calculated as 2.2% (16/716) in the total number of cases and 33% (16/48) in those showing color abnormalities. Histologically, all of the 16 were adenomas. These neoplastic lesions were most frequent (52%; 11/21) in those showing faint redness in an oval shape, whereas 14 (94%) of the 15 lesions were non-specific in those showing faint redness with unclear margin. CONCLUSIONS: These results may confirm the diagnostic utility of color abnormality, particularly faint redness in an oval shape, for endoscopic screening of superficial colorectal neoplasias.      

Choline deficiency selects for resistance to p53-independent apoptosis and causes tumorigenic transformation of rat hepatocytes

The mechanisms which drive initiated cells to progress to form carcinomas are poorly understood. CWSV-1 rat hepatocytes, in which p53 protein is inactivated by SV40 large T antigen, respond by inducing p53- independent apoptosis when acutely switched to medium containing low choline (16% apoptotic at 48 h in 5 microM choline) as compared with controls (1% apoptotic at 48 h in 70 microM choline). The rate of apoptosis was inversely correlated with cellular phosphatidylcholine content. Choline deficiency (CD)-induced apoptosis is probably mediated by TGFbeta1 and reactive oxygen species, since immunoneutralization of TGFbeta1 in the medium or treatment with N-acetylcysteine (an antioxidant) or addition of neocuproine (a transition metal chelator) prevented CD-induced apoptosis. CWSV-1 hepatocytes could be gradually adapted to survive in 5 microM choline. CD-adapted cells had increased membrane phosphatidylcholine concentrations (compared with acute CD cells). Adapted cells acquired relative resistance to CD-induced apoptosis (7% of adapted cells compared with 19% of non-adapted cells were apoptotic at 48 h in 5 microM choline). They also became relatively resistant to another p53-independent form of apoptosis (TGFbeta1-induced). CD-adapted hepatocytes developed increased capability for anchorage-independent growth and formed tumors when transplanted into nude mice; passage-matched control hepatocytes did not possess these properties. Cell transformation was dependent on exposure to the selective pressure of CD apoptosis, as we observed that when CD apoptosis was inhibited with an antioxidant during adaptation, cells did not become anchorage independent. Acquisition by p53- deficient cells of resistance to p53-independent inducers of apoptosis (CD, TGFbeta1 and reactive oxygen species) may leave cells without another important apoptotic defensive barrier and may be responsible for the progression of initiated cells to frank carcinomas.