Direct comparison of a radioiodinated intact chimeric anti-CEA MAb with its F(ab')2 fragment in nude mice bearing different human colon cancer xenografts.

Tumour localisation and tumour to normal tissue ratios of a chimeric anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), in intact form and as an F(ab')2 fragment labelled with 125I and 131I, were compared in groups of nude mice bearing four different colon cancer xenografts, T380, Co112 or LoVo, of human origin, or a rat colon cancer transfected with human CEA cDNA, called '3G7'. For each tumour, three to four mice per time point were analysed 6, 12, 24, 48 and 96 h after MAb injection. In the different tumours, maximal localisation of intact MAb was obtained at 24 to 48 h, and of F(ab')2 fragment 12 to 24 h after injection. Among the different tumours, localisation was highest with colon cancer T380, with 64% of the injected dose per gram (% ID/g) for the intact MAb and 57% for its F(ab')2 fragment, while in the three other tumours, maximal localisation ranged from 14 to 22% ID g-1 for the intact MAb and was about 11% for the F(ab')2. Tumour to normal tissue ratios of intact MAb increased rapidly until 24 h after injection and remained stable or showed only a minor increase thereafter. In contrast, for the F(ab')2 fragment, the tumour to normal tissue ratios increased steadily up to 4 days after injection reaching markedly higher values than those obtained with intact MAb. For the four different xenografts, tumour to blood ratios of F(ab')2 were about 2, 3 and 5 to 16 times higher than those of intact antibodies at 12, 24 and 96 h after injection, respectively.

Yeast vacuoles fragment in an asymmetrical two-phase process with distinct protein requirements.

Yeast vacuoles fragment and fuse in response to environmental conditions, such as changes in osmotic conditions or nutrient availability. Here we analyze osmotically induced vacuole fragmentation by time-lapse microscopy. Small fragmentation products originate directly from the large central vacuole. This happens by asymmetrical scission rather than by consecutive equal divisions. Fragmentation occurs in two distinct phases. Initially, vacuoles shrink and generate deep invaginations that leave behind tubular structures in their vicinity. Already this invagination requires the dynamin-like GTPase Vps1p and the vacuolar proton gradient. Invaginations are stabilized by phosphatidylinositol 3-phosphate (PI(3)P) produced by the phosphoinositide 3-kinase complex II. Subsequently, vesicles pinch off from the tips of the tubular structures in a polarized manner, directly generating fragmentation products of the final size. This phase depends on the production of phosphatidylinositol-3,5-bisphosphate and the Fab1 complex. It is accelerated by the PI(3)P- and phosphatidylinositol 3,5-bisphosphate-binding protein Atg18p. Thus vacuoles fragment in two steps with distinct protein and lipid requirements.

Adding similarity-based reasoning capabilities to a Horn fragment of possibilistic logic with fuzzy constants

PLFC is a first-order possibilistic logic dealing with fuzzy constants and fuzzily restricted quantifiers. The refutation proof method in PLFC is mainly based on a generalized resolution rule which allows an implicit graded unification among fuzzy constants. However, unification for precise object constants is classical. In order to use PLFC for similarity-based reasoning, in this paper we extend a Horn-rule sublogic of PLFC with similarity-based unification of object constants. The Horn-rule sublogic of PLFC we consider deals only with disjunctive fuzzy constants and it is equipped with a simple and efficient version of PLFC proof method. At the semantic level, it is extended by equipping each sort with a fuzzy similarity relation, and at the syntactic level, by fuzzily “enlarging” each non-fuzzy object constant in the antecedent of a Horn-rule by means of a fuzzy similarity relation.

Un nou fragment del sepulcre de Ramon Folc VI de Cardona del monestir de Poblet

En el present article donem a conèixer un fragment del sepulcre de Ramon Folc VI de Cardona (†1320), conegut com el Prohom Vinculador, que es troba al braç meridional del transsepte de l’església del monestir de Poblet. El fragment fou subhastat a Barcelona el març del 2008 i fou adquirit per la Generalitat de Catalunya, que el diposità al Museu de Lleida: diocesà i comarcal. La peça sortia a la venda amb un possible origen pobletana procedent de la tradició antiquària, ja que havia estat propietat del pintor i il·lustrador modernista Alexandre de Riquer (1856-1920), de qui sabem que va extreure materials del monestir, a la vegada que és coneguda la seva faceta de col·leccionista i marxant d’art i antiguitats. Finalment, aquesta procedència s’ha pogut corroborar en descobrir-se que el fragment subhastat era un dels membra disjecta de l’esmentat sepulcre. Avui el fragment es troba pendent de ser restituït al Monestir de Poblet.

The striatal long noncoding RNA Abhd11os is neuroprotective against an N-terminal fragment of mutant huntingtin in vivo.

A large number of gene products that are enriched in the striatum have ill-defined functions, although they may have key roles in age-dependent neurodegenerative diseases affecting the striatum, especially Huntington disease (HD). In the present study, we focused on Abhd11os, (called ABHD11-AS1 in human) which is a putative long noncoding RNA (lncRNA) whose expression is enriched in the mouse striatum. We confirm that despite the presence of 2 small open reading frames (ORFs) in its sequence, Abhd11os is not translated into a detectable peptide in living cells. We demonstrate that Abhd11os levels are markedly reduced in different mouse models of HD. We performed in vivo experiments in mice using lentiviral vectors encoding either Abhd11os or a small hairpin RNA targeting Abhd11os. Results show that Abhd11os overexpression produces neuroprotection against an N-terminal fragment of mutant huntingtin, whereas Abhd11os knockdown is protoxic. These novel results indicate that the loss lncRNA Abhd11os likely contribute to striatal vulnerability in HD. Our study emphasizes that lncRNA may play crucial roles in neurodegenerative diseases.

Scrfl restriction fragment length polymorphism at the D7S23 locus (probe pKM.19), closely linked to cystic fibrosis

Source/Description: pKM.19 is a 1.0 kb EcoRI genomic fragment in pUC13 (ref. 1,2). pPl was isolated independently but contains the same fragment as pKM.19 (ref. 3)...