Transforming growth factor β1 induces mitogenesis in fetal rat brown adipocytes

The presence of transforming growth factor β₁ (TGF-β₁) for 24 or 48 h stimulated DNA synthesis, the percentage of cells in the S + G₂/M phases of the cell cycle, and cell number, as compared to quiescent cells. The mitogenic capacity of TGF-β₁ (1 pM) was similar to that shown by 10% fetal calf serum (FCS). TGF-β₁ for 48 h increased by 5-fold the percentage of cells containing (³H)thymidine-labeled nuclei as compared to quiescent cells. In addition, single fetal brown adipocytes, showing their typical multilocular fat droplets phenotype, become positive for (³H)thymidine-labeled nuclei in response to TGF-β₁. Moreover, TGF-β₁ induced the mRNA expression of a complete set of proliferation-related genes, such as c-fos (30 min), c-myc and β-actin (2 h), and H-ras, cdc2 kinase, and glucose 6-phosphate dehydrogenase (G6PD) at 4 and 8 h, as compared to quiescent cells. Concurrently, TGF-β₁ for 12 h increased the protein content of proliferating cellular nuclear antigen (PCNA) by 6-fold and p21-ras by 2-fold. Although our results demonstrate that TGF-β₁ induces the expression of very early genes related to cell proliferation, TGF-β₁ could be acting either as a mitogen or as a survival factor to induce proliferation in fetal brown adipocytes. © 1996 Wiley-Liss, Inc.     

Cancer induction by restriction of oncogene expression to the stem cell compartment

In human cancers, all cancerous cells carry the oncogenic genetic lesions. However, to elucidate whether cancer is a stem cell-driven tissue, we have developed a strategy to limit oncogene expression to the stem cell compartment in a transgenic mouse setting. Here, we focus on the effects of the BCR-ABLp210 oncogene, associated with chronic myeloid leukaemia (CML) in humans. We show that CML phenotype and biology can be established in mice by restricting BCR-ABLp210 expression to stem cell antigen 1 (Sca1)⁺ cells. The course of the disease in Sca1-BCR-ABLp210 mice was not modified on STI571 treatment. However, BCR-ABLp210-induced CML is reversible through the unique elimination of the cancer stem cells (CSCs). Overall, our data show that oncogene expression in Sca1⁺ cells is all that is required to fully reprogramme it, giving rise to a full-blown, oncogene-specified tumour with all its mature cellular diversity, and that elimination of the CSCs is enough to eradicate the whole tumour.     

Effects of nutrients and fish on periphyton and plant biomass across a European latitudinal gradient

Replicated, factorial mesocosm experiments were conducted across Europe to study the effects of nutrient enrichment and fish density on macrophytes and on periphyton chlorophyll a (chl-a) with regard to latitude. Periphyton chl-a densities and plant decline were significantly related to nutrient loading in all countries. Fish effects were significant in a few sites only, mostly because of their contribution to the nutrient pool. A saturation-response type curve in periphyton chl-a with nutrients was found, and northern lakes achieved higher densities than southern lakes. Nutrient concentration and phytoplankton chl-a necessary for a 50% plant reduction followed a latitudinal gradient. Total phosphorus values for 50% plant disappearance were similar from Sweden (0.27 mg L⁻¹) to northern Spain (0.35 mg L⁻¹), but with a sharp increase in southern Spain (0.9 mg L⁻¹). Planktonic chl-a values for 50% plant reduction increased monotonically from Sweden (30 μg L⁻¹) to València (150 μg L⁻¹). Longer plant growing-season, higher light intensities and temperature, and strong water-level fluctuations characteristic of southern latitudes can lead to greater persistence of macrophyte biomass at higher turbidities and nutrient concentration than in northern lakes. Results support the evidence that latitudinal differences in the functioning of shallow lakes should be considered in lake management and conservation policies.     

Multivariate palaeoecological analysis of a late quaternary small mammal succession from North Bulgaria

The basic assumption of the analysis is that the stratigraphical change of relative abundance of the small mammal species is a phenomenon due to a certain number of environmental factors. In order to reveal these factors and to make some palaeoclimatic reconstructions the following approaches have been used: 1. Analysis of intrinsic structure of the initial data by using principal component analysis (PCA)—delimitation of recurrent groups of species and ordination of assemblages; 2. Extension backward in time of known ecological preference of taxa, forming a particular recurrent group; 3. Comparison of the results with the analysis of assemblages from “known”; (Holocene) environment. On the basis of ecological appearance of particular recurrent groups it is assumed that the main factors are temperatures and effective moisture. The reconstructed values for these environmental factors obtained on the basis of the Holocene recurrent groups of small mammals shows similarity to the recent climate in the area.     

Discovery and optimization of orally active cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors

The synthesis, SAR, binding affinities and pharmacokinetic profiles are described for a series of cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors discovered by high throughput screening. Compounds show high levels of ex vivo target engagement in mouse plasma 20 h post oral dose.     

Particular universalisms: North African immigrants respond to French racism

This article examines how ordinary victims of racism rebut racist beliefs communicated to them by the mass media and encountered in daily life. We describe the rhetorical devices that North African immigrant men in France use to respond to French racism, drawing on thirty in-depth interviews conducted with randomly selected blue-collar immigrants residing in the Paris suburbs. We argue that while French anti-racist rhetorics, both elite and popular, draw on universalistic principles informed by the Enlightenment as well as French Republican ideals, North African immigrants rebut racism by drawing instead on their daily experience and on a 'particular universalism', i.e. a moral universalism informed by Islam. Their arguments frequently centre on claims of equality or similarity between all human beings, or between North Africans and the French. Available cultural repertoires and the structural positions of immigrants help to account for the rhetorical devices that immigrants use to rebut racism.     

UV-B-induced damage and photoreactivation in three species of Boeckella (Copepoda, Calanoida)

Solar ultraviolet (UV) radiation poses a threat to most livingorganisms. Aquatic organisms have evolved three basic mechanismsto cope with harmful levels of radiation. Two mechanisms, avoidance(e.g. vertical migration) and photoprotection (e.g. productionof photoprotective compounds that act as filters, antioxidants,etc.), serve to minimize the dose of UV radiation that reachesthe organism's vital structures (DNA, membranes, etc.). Thethird mechanism, repair (e.g. dark repair mechanisms, such asnucleotide excision repair; or photoreactivation mechanisms,such as photoenzymatic repair), serves to repair the damagefollowing UV exposure. Here, we compare the vulnerability toUV-B radiation of three copepod species (Boeckella brevicaudata,Boeckella gibbosa, and Boeckella gracilipes) that occur in lakesthat differ in UV-B penetration and depth. Our aim was to gaininsight into the significance of each of the three mechanismsin different UV-B environments. Results from a 3-day ‘insitu’ incubation in ultra-oligotrophic Lake Toncek showedthat B.gracilipes is highly vulnerable to UV-B and UV-A radiation.In contrast, virtually no mortality was observed in B.gibbosaand B.brevicaudata during the same period. In order to discriminatethe contribution of photoprotection and photoreactivation, thethree species were subsequently exposed in the laboratory toan artificial source of UV-B radiation, both in the presenceand absence of visible radiation (recovery radiation). The photoprotectionpotential (i.e. resistance to UV-B in the absence of recoveryradiation) of B.gracilipes and B.gibbosa was lower than thatof B.brevicaudata. On the other hand, photoreactivation (higherresistance to UV-B in the presence of recovery radiation) wasobserved in B.brevicaudata and B.gibbosa, but not in B.gracilipes.To cope with damaging UV-B levels in nature, B.gracilipes dependsexclusively on the attenuation by the external media (i.e. avoidance).Although B.gibbosa tends to avoid the surface waters of lakes,it also occurs in shallow transparent pools. Most likely itsability to survive in these shallow, high UV environments isdue to its photoreactivation potential. Finally, despite itsoccurrence in highly turbid lakes, B.brevicaudata seems extremelywell suited to cope with UV-B radiation thanks to a combinationof photoreactivation and photoprotection.     

Two new species of <Emphasis Type="Italic">Parspina</Emphasis> Pearse, 1920 (Digenea: Cryptogonimidae) from freshwater fishes (Gymnotiformes) of the Paraná River basin in Argentina

Two new species of the cryptogonimid genus Parspina Pearse, 1920 are described from gymnotiform fishes of the Paraná River basin, P. carapo n. sp. from the banded knifefish Gymnotus carapo Linnaeus and P. virescens n. sp. from the glass knifefish Eigenmannia virescens (Valenciennes). Parspina carapo differs from P. virescens in the number of oral spines (32–39 vs 30–33) and their length (28–47 vs 16–28 μm), the distribution of tegumental spines and their anchorage, the types of sensory papillae on the body surface (three vs two types), the extent of body length posterior to the caeca (5 vs 13% of the total body length), the dimensions of the pars prostatica (52 × 34 vs 24 × 10 μm), and in the absence of a gonotyl (vs presence). Both P. carapo and P. virescens differ from P. bagre Pearse, 1920 and P. argentinensis (Szidat, 1954) in the number of oral spines (20–21 and 21–28 in the latter pair) and their length (28–32 and 35–60 μm), and in total body length. Additionally, the two new species differ from P. argentinensis in the arrangement of the vitelline follicles (one continuous band vs two groups on each side of the body) and in having a smaller pars prostatica (149 × 49 μm in the latter). Parspina carapo is the fifth intestinal helminth found in G. carapo, and P. virescens is the first found in E. virescens.     

Cyclooxygenase-2 deficiency leads to intestinal barrier dysfunction and increased mortality during polymicrobial sepsis

Sepsis remains the leading cause of death in critically ill patients, despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase (COX)-2 is highly upregulated in the intestine during sepsis, and we hypothesized that it may be critical in the maintenance of intestinal epithelial barrier function during peritonitis-induced polymicrobial sepsis. COX-2(-/-) and COX-2(+/+) BALB/c mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398, PGD(2), or vehicle and stimulated with cytokines. COX-2(-/-) mice developed exaggerated bacteremia and increased mortality compared with COX-2(+/+) mice following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype, suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia following CLP. Absence of COX-2 significantly increased epithelial permeability of the ileum and reduced expression of the tight junction proteins zonula occludens-1, occludin, and claudin-1 in the ileum following CLP. Furthermore, PGD(2) attenuated cytokine-induced hyperpermeability and zonula occludens-1 downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence of COX-2 is associated with enhanced intestinal epithelial permeability and leads to exaggerated bacterial translocation and increased mortality during peritonitis-induced sepsis. Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis.     

The relation of the microglia with the pericytes in the cat cerebral cortex

Summary Capillaries, pericytes and microglial cells in layer I of the cerebral cortex of normal adult cats have been studied with electron microscopy. The data obtained in this study show that pericytes are cells which are able to transform themselves into microglial cells by virtue of an activation process in which the astrocytic neuroglia appears to play a decisive role. By virtue of its structure, its mesodermic origin and its function the microglia has to be distinguished clearly from the astrocytic neuroglia and the oligodendroglia.This study was partly supported by a grant from the Seguridad Social, Instituto Nacional de Previsión.