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This paper investigates the usefulness of two mitochondrial genes (16S rRNA and cytochrome b) to solve taxonomical difficulties within the genus Hylomyscus and to infer its evolutionary history. Both genes proved to be suitable molecular markers for diagnosis of Hylomyscus species. Nevertheless the resolving powers of these two genes differ, and with both markers (either analyzed singly or in combination), some nodes remain unresolved. This is probably related to the fact that the species emerged during a rapid diversification event that occurred 2-6 Myr ago (4-5 Myr ago for most divergence events). Our molecular data support the recognition of an "aeta" group, while the "alleni" and "parvus" groups are not fully supported. Based on tree topology and genetic divergence, two taxa generally recognized as subspecies should be elevated at the species level (H. simus and H. cf kaimosae). H. stella populations exhibit ancient haplotype segregation that may represent currently unrecognized allopatric species. The existence of cryptic species within H. parvus is questioned. Finally, three potentially new species may occur in West Central Africa. The Congo and Oubangui Rivers, as well as the Volta and Niger Rivers and/or the Dahomey gap could have formed effective barriers to Hylomyscus species dispersal, favoring their speciation in allopatry. The pronounced shifts in African climate during the late Pliocene and Miocene, which resulted in major changes in the distribution and composition of the vegetation, could have promoted speciation within the genus (refuge theory). Future reports should focus on the geographic distribution of Hylomyscus species in order to get a better understanding of the evolutionary history of the genus.

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African mole-rats are subterranean Hystricomorph rodents, distributed widely throughout sub-Saharan Africa, and displaying a range of social and reproductive strategies from solitary dwelling to the 'insect-like' sociality of the naked mole-rat, Heterocephalus glaber. Both molecular systematic studies of Rodentia and the fossil record of bathyergids indicate an ancient origin for the family. This study uses an extensive molecular phylogeny and mitochondrial cytochrome b and 12s rRNA molecular clocks to examine in detail the divergence times, and patterns of speciation of the five extant genera in the context of rift valley formation in Africa. Based on a value of 40-48 million years ago (Myr) for the basal divergence of the family (Heterocephalus), we estimate divergence times of 32-40 Myr for Heliophobius, 20-26 Myr for Georychus/Bathyergus and 12-17 Myr for Cryptomys, the most speciose genus. While early divergences may have been independent of rifting, patterns of distribution of later lineages may have been influenced directly by physical barriers imposed by the formation of the Kenya and Western Rift, and indirectly by accompanying climatic and vegetative changes. Rates of chromosomal evolution and speciation appear to vary markedly within the family. In particular, the genus Cryptomys appears to have undergone an extensive radiation and shows the widest geographical distribution. Of the two distinct clades within this genus, one exhibits considerable karyotypic variation while the other does not, despite comparatively high levels of sequence divergence between some taxa. These different patterns of speciation observed both within the family and within the genus Cryptomys may have been a result of environmental changes associated with rifting.

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The African rats of the genus Arvicanthis have been widely studied during recent years to clarify species boundaries and phylogenetic relationships. The wide chromosomal variability of the genus has been highlighted in several studies, with each accepted species characterised by its individual karyotypes and others being revealed as cryptic species. In the present paper we report the karyotype and the C- and G-banding patterns of the two species A. nairobae and A. neumanni from seven localities of Tanzania, an area of the range poorly studied. The two karyotypes were compared to that of A. niloticus, which is considered to be primitive. The karyotype of A. neumanni is characterised by 2n = 53-54 and NFa = 62. This karyotypic variability depends on a widespread Robertsonian polymorphism. The karyotype of A. nairobae shows 2n = 62 and NFa = 78; it diverges from that of A. niloticus through one reciprocal translocation, five inversions and three heterochromatic additions. The comparison with the karyotypes of other species of the genus showed that A. neumanni belongs to the east African lineage (with A. abyssinicus, A. blicki, A. niloticus), while A. nairobae is closer to the central and the west African representatives which were all previously under the name of A. niloticus (ANI-2, ANI-3, ANI-4). The distribution of A. nairobae in east Africa opens new scenarios in the biogeographical pattern of evolution of the genus.

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The authors previously reported that one of the cAMP-response elements (CREs) of the human beta3-AR gene, beta3CRE2, interacts with a nuclear factor which is distinct from CREB/ATF family. We named this factor WATSF-1 (white adipose tissue specific factor-1) since it is preferentially expressed in WAT. In this work, we have shown the absence of DNA binding or transcriptional activity of this factor in several non-adipose cells tested. By computer analysis, beta3CRE2 was found to constitute an octameric element that is highly homologous to the binding site for some members of the nuclear hormone receptor superfamily. Using the response elements of other adipocyte-specific nuclear receptors as competitors, a 'cross-talk' between WATSF-1 and these response elements has been demonstrated. However, the affinity of WATSF-1 for these response elements differs from that for beta3CRE2 (self), implying that WATSF-1 is distinct from these adipocyte-specific nuclear receptors. Furthermore the DNA-binding activity of WATSF-1 was shown to be enhanced by phosphatase treatment, suggesting that phosphorylation may play an important role in the functional modulation of this factor. In an effort to prove that it is indeed an adipocyte-specific factor, we used 3T3-L1 cells, a cellular model of WAT, that can undergo differentiation into adipocytes. The DNA binding and transcriptional activity of this factor appeared during differentiation of the cells. Taken together, these results demonstrate that WATSF-1 is a putative white adipocyte-specific nuclear orphan receptor induced during adipogenesis and is a transcriptional activator through one of the CREs of the human beta3-AR gene. Targeting this factor may be a novel therapeutic approach to stimulation of the beta3-AR signal transduction pathway in adipose tissues.

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Ecology has long been troubled by the controversy over how populations are regulated. Some ecologists focus on the role of environmental effects, whereas others argue that density-dependent feedback mechanisms are central. The relative importance of both processes is still hotly debated, but clear examples of both processes acting in the same population are rare. Key-factor analysis (regression of population changes on possible causal factors) and time-series analysis are often used to investigate the presence of density dependence, but such approaches may be biased and provide no information on actual demographic rates. Here we report on both density-dependent and density-independent effects in a murid rodent pest species, the multimammate rat Mastomys natalensis (Smith, 1834), using statistical capture-recapture models. Both effects occur simultaneously, but we also demonstrate that they do not affect all demographic rates in the same way. We have incorporated the obtained estimates of demographic rates in a population dynamics model and show that the observed dynamics are affected by stabilizing nonlinear density-dependent components coupled with strong deterministic and stochastic seasonal components.

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OBJECTIVE: R 75,231, a potent and specific nucleoside transport inhibitor, largely prevents cardiac damage and death in catecholamine challenged rabbits. The major biochemical effect of nucleoside transport inhibition in ischaemic and reperfused myocardium is a prolonged accumulation of adenosine. The cardioprotection by R 75,231 may be explained if it can be shown that endogenous adenosine plays a role in catecholamine cardiotoxicity and if nucleoside transport inhibition is required for the cardioprotective effect of R 75,231. METHODS: Several groups of rabbits were infused with catecholamines until death. Changes in survival with time of infusion by coinfusion of aminophylline and/or treatment with R 75,231 and its two stereoenantiomers were assessed. RESULTS: Treatment with R 75,231 postponed the time to reach 50% mortality threefold after challenge with adrenaline or noradrenaline. Draflazine, the (-)-enantiomer of R 75,231, was also effective, whereas the (+)-enantiomer, which is devoid of any effect on the transporter, was not cardioprotective. The cardioprotective effect of R 75,231 was dependent on the extent and duration of ex vivo inhibition of the transporter in blood. Co-infusion of aminophylline with adrenaline significantly accelerated the rate of mortality. CONCLUSIONS: Nucleoside transport inhibition is the major, if not the only, determinant for efficacy of R 75,231 and draflazine as cardioprotective agents. Taken together with the evidence for a role of endogenous adenosine, the benefit from nucleoside transport inhibition in this model may be the result of prolonged accumulation of endogenous adenosine.

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The effect of a potent and specific nucleoside transport inhibitor, R 75,231, on catecholamine-induced cardiac toxicity has been studied in rabbits. Epinephrine (1 mg/kg) or norepinephrine (2.5 mg/kg) subcutaneously were lethal in 25 (42%) of 60 control animals, while survivors showed major myocardial damage, as judged from high plasma lactate dehydrogenase (LDH) and its myocardial isoenzyme (LDH1) after 24 h. When a low dose of R 75,231 (0.1 mg/kg) was given intravenously either 1 h before or 1 h after the catecholamine insult, only 1 of 60 animals died. The plasma total LDH and the LDH1 myocardial isoenzyme were low in these animals compared with untreated survivors. Studies ex vivo on isolated perfused hearts confirmed that with treatment using R 75,231, there was both left ventricular nucleoside retention and functional preservation after in vivo exposure of the animals to epinephrine. R 75,231 did not affect the peripheral venous hyperglycemic response to epinephrine. Nucleoside transport inhibition offers a new approach to the prevention and treatment of several cardiac disorders characterized by a pathogenic effect of catecholamines.

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Adenosine (ADO) has a pharmacological profile which makes it an interesting 'drug' to handle many of the problems arising with ischemia and reperfusion. In human blood, however, it is rapidly taken up by the red blood cells and metabolized to inactive inosine and hypoxanthine. This transporter-mediated uptake can be specifically inhibited in vitro by a few drugs, known as nucleoside transport inhibitors. It has been reported that ADO can inhibit platelet aggregation in whole blood in the presence of dipyridamole, and it is well-known that ADO can inhibit the respiratory burst of purified neutrophils induced by certain stimuli. We investigated the effect of some of these drugs on the ADO-mediated inhibition of the fMLP-induced respiratory burst in neutrophils (as measured by lucigenin-enhanced luminescence), in undiluted whole blood. The combination of R 75,231 (a newly developed analog of mioflazine, with unique pharmacokinetic properties, for details see with ADO (0.1 microM) inhibited the luminescence by 40 +/- 4% (n = 10), while either R 75,231 or ADO alone did not affect the response to fMLP. In the presence of ADO (1 microM), R 75,231 (EC50 = 1.9 +/- 0.3 x 10(-7) M) (n = 3) was almost as potent as dilazep (EC50 = 1.1 +/- 0.2 x 10(-7) M) (n = 3), but far more potent than dipyridamole (EC50 = 1.2 +/- 0.2 x 10(-6) M) (n = 3). The present data show that ADO can inhibit PMN-activation in whole blood in the presence of R 75,231 or of other nucleoside transport inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

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The diffusion coefficients of [3H] water, urea, benzoic acid, antipyrine, aminopyrine, alpha-methyl-glucoside, L-phenylalanine and of hydrogen ions were measured at 38 degrees C in native mucus gel from rat small intestine. The diffusion in the gel was reduced to 37-53% (for hydrogen ions to 7%) compared with buffer solution. In addition, the buffering capacity of the gel retarded the permeation of hydrogen ions before a steady state flux was attained. A model calculation revealed that in the preparation a gel layer of 80 microns thickness represents 23% of the total permeation resistance for substances with high epithelial permeability. The aqueous part of the pre-epithelial diffusion resistance amounts to 77% of the total resistance.

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Small mammals were screened for the presence of antibodies to Hantaan virus (HTN) and Hantavirus (HV) antigen in Belgium. Antibody and antigen-positive animals were found in different parts of the country. One insectivore and five rodent species were found positive. The highest prevalence of infection was found in the bank vole (Clethrionomys glareolus). A relation between infected animals and wet habitats was observed. It was obvious that in bank vole the likelihood of infection increased with age.

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