pMel17 is recognised by monoclonal antibodies NKI-beteb, HMB-45 and HMB-50 and by anti-melanoma CTL.

Recently, we cloned the cDNA encoding the melanocyte lineage-specific antigen gp100 and demonstrated that gp100 is recognised by three different monoclonal antibodies (MAbs) used to diagnose malignant melanoma. In addition, we showed that tumour-infiltrating lymphocytes (TIL 1200) from a melanoma patient reacted specifically with cells transfected with the gp100 cDNA. Molecular characterisation of the gp100 cDNA revealed that the gp100 antigen is highly homologous, but not identical, to another melanocyte-specific protein, pMel17. Here, we report that cells transfected with pMel17 cDNA also react with all three MAbs used to diagnose malignant melanoma, NKI-beteb, HMB-45 and HMB-50. Moreover, pMel17 transfectants are specifically lysed by TIL1200. These data demonstrate that antigenic processing of both gp100 and pMel17 give rise to peptides seen by anti-melanoma cytotoxic T lymphocytes (CTL) and are therefore potential targets for immunotherapy of malignant melanoma

An inducible CiliaGFP mouse model for in vivo visualization and analysis of cilia in live tissue

BACKGROUND: Cilia are found on nearly every cell type in the mammalian body, and have been historically classified as either motile or immotile. Motile cilia are important for fluid and cellular movement; however, the roles of non-motile or primary cilia in most tissues remain unknown. Several genetic syndromes, called the ciliopathies, are associated with defects in cilia structure or function and have a wide range of clinical presentations. Much of what we know about the formation and maintenance of cilia comes from model systems like C. elegans and Chalmydomonas. Studies of mammalian cilia in live tissues have been hampered by difficulty visualizing them. RESULTS: To facilitate analyses of mammalian cilia function we generated an inducible Cilia(GFP) mouse by targeting mouse cDNA encoding a cilia-localized protein somatostatin receptor 3 fused to GFP (Sstr3::GFP) into the ROSA26 locus. In this system, Sstr3::GFP is expressed from the ubiquitous ROSA26 promoter after Cre mediated deletion of an upstream Neo cassette flanked by lox P sites. Fluorescent cilia labeling was observed in a variety of live tissues and after fixation. Both cell-type specific and temporally regulated cilia labeling were obtained using multiple Cre lines. The analysis of renal cilia in anesthetized live mice demonstrates that cilia commonly lay nearly parallel to the apical surface of the tubule. In contrast, in more deeply anesthetized mice the cilia display a synchronized, repetitive oscillation that ceases upon death, suggesting a relationship to heart beat, blood pressure or glomerular filtration. CONCLUSIONS: The ability to visualize cilia in live samples within the Cilia(GFP) mouse will greatly aid studies of ciliary function. This mouse will be useful for in vivo genetic and pharmacological screens to assess pathways regulating cilia motility, signaling, assembly, trafficking, resorption and length control and to study cilia regulated physiology in relation to ciliopathy phenotypes

Conversational correlates of children's acquisition of mental verbs and a theory of mind

The purpose of this study was to conduct a detailed examination of the ways mothers use mental verbs in conversations with three- and four-year-old children, and to link these usages to the children's developing understanding of mental verbs and a theory of mind. Sixty three- and four-year-olds, either attending preschool (PS) or not (NPS) were given tasks assessing mental verb distinctions and false belief. Their mothers' mental verb use was coded for (a) frequency, (b) type of utterance, (c) type of subordinate clause, (d) the person of the subject of the verb, and (e) the certainty of think. Within the three-year-olds, the NPS children performed significantly better on the mental verb comprehension task; moreover, compared to the PS mothers, the NPS mothers were found to use: (1) less statements and more questions, (2) less first person utterances and more second person utterances, and (3) think in its `very certain' form less often. In regression analyses, children's mental verb and false belief performance were positively predicted by maternal mental verb 1) questions, and 2) single clause utterances; the children's performance was negatively predicted by statements. These findings indicate how maternal input has the potential to promote or hinder children's understanding of the mind.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Correlation of enhanced thrombospondin-1 expression, TGF-β signalling and proteinuria in human type-2 diabetic nephropathy

Background. Activation of the thrombospondin-1 (TSP-1)-TGF-β pathway by glucose and the relevance of TSP-1-dependent activation of TGF-β for renal matrix expansion, renal fibrosis and sclerosis have previously been demonstrated by our group in in vivo and in vitro studies

Acquired Epidermodysplasia Verruciformis Due to Multiple and Unusual HPV Infection Among Vertically-Infected, HIV-Positive Adolescents in Zimbabwe

We have characterized the EV-like dermatosis of acquired HIV in 4 adolescents. Multiple HPV types were isolated in skin tissue samples, including β-HPV, but also high levels of HPV 1 and 2. ARV did not improve the EV eruption

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Genotype-phenotype correlations among BRCA1 4153delA and 5382insC mutation carriers from Latvia

<p>Abstract</p> <p>Background</p> <p>Mutations in the high penetrance breast and ovarian cancer susceptibility gene <it>BRCA1 </it>account for a significant percentage of hereditary breast and ovarian cancer cases. Genotype-phenotype correlations of <it>BRCA1 </it>mutations located in different parts of the <it>BRCA1 </it>gene have been described previously; however, phenotypic differences of specific <it>BRCA1 </it>mutations have not yet been fully investigated. In our study, based on the analysis of a population-based series of unselected breast and ovarian cancer cases in Latvia, we show some aspects of the genotype-phenotype correlation among the <it>BRCA1 </it>c.4034delA (4153delA) and c.5266dupC (5382insC) founder mutation carriers.</p> <p>Methods</p> <p>We investigated the prevalence of the <it>BRCA1 </it>founder mutations c.4034delA and c.5266dupC in a population-based series of unselected breast (n = 2546) and ovarian (n = 795) cancer cases. Among the <it>BRCA1 </it>mutation carriers identified in this analysis we compared the overall survival, age at diagnosis and family histories of breast and ovarian cancers.</p> <p>Results</p> <p>We have found that the prevalence of breast and ovarian cancer cases (breast: ovarian cancer ratio) differs significantly among the carriers of the c.5266dupC and c.4034delA founder mutations (OR = 2.98, 95%CI = 1.58 to 5.62, P < 0.001). We have also found a difference in the prevalence of breast and ovarian cancer cases among the 1^stand 2^nddegree relatives of the c.4034delA and c.5266dupC mutation carriers. In addition, among the breast cancer cases the c.4034delA mutation has been associated with a later age of onset and worse clinical outcomes in comparison with the c.5266dupC mutation.</p> <p>Conclusions</p> <p>Our data suggest that the carriers of the c.4034delA and c.5266dupC founder mutations have different risks of breast and ovarian cancer development, different age of onset and prognosis of breast cancer.</p

L’insediamento a bifacciali di Guado San Nicola (Monteroduni, Molise, Italia)

La monografia rappresenta un compendio di lavori specialistici sul sito paleolitico di Guado San Nicola a Monteroduni (Molise, Italia), oggetto di ricerche sistematiche ed indagini interdisciplinari inaugurate nell’area a partire dal 2000 dall'Università degli Studi di Ferrara. Il sito, ascrivibile al MIS 10/11, costituisce un tassello importante nell’ambito della ricostruzione del quadro del popolamento umano della penisola italiana e dell’intero bacino del Mediterraneo, alla luce delle considerazioni crono-stratigrafiche, della ricchezza della documentazione e della presenza di elementi innovativi dal punto di vista culturale quali la padronanza del metodo Levallois e l’uso di percussori in palchi di cervo

Identity and destination branding among residents: How does brand self-congruity influence brand attitude and ambassadorial behavior?

Residents of a particular destination are potentially the largest and most powerful stakeholders of destination brands. However, the basis of residents' attitudes toward destination branding is not widely understood. In this study, it is proposed that selfcongruity (the degree of match between the perceived self and perceived brand identity) is a possible antecedent of these attitudes. We empirically demonstrate that brand self‐congruity is a likely indicator of destination brand attitude and that subsequent ambassadorial behavior among residents is probable. Implications for practitioners and future research opportunities are finally suggested