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Segmental identity of structures located in the hindbrain and branchial arches of vertebrates are determined, at least in part, through the action of Hox paralog group 2 (PG2) genes. Despite an overall similarity in their function during development, Hox PG2 genes from evolutionarily divergent lineages have distinctly different spatio-temporal expression patterns, particularly in comparisons between actinopterygians and sarcopterygians. Results from our laboratory, including the cloning and expression analysis of an unprecedented three Hox PG2 genes (Hoxa2a, a2b, and b2a) from Morone saxatilis (striped bass), show that the trans-orthologs Hoxa2a and a2b are differentially expressed in both rhombomeres and branchial arch tissue whereas their paralogs expression (Hoxb2a) is restricted solely to the rhombomeres. The pattern of Hox PG2 expression documented for M. saxatilis contrasts sharply with that of Danio rerio (zebrafish) and mammals but appears to be similar to that of Gallus gallus (chicken). Our results indicate that while the Hox PG2 gene complement in actinopterygians is greater than that of sarcopterygians, expression patterns in these two major vertebrate lineages are similarly divergent, indicative that an increased number of genes does not lead to concordant increases in expression pattern divergence. Our results also reveal a considerable plasticity in the Hox gene-related evolutionary developmental specification of vertebrate hindbrain and branchial arch structures, at least some of which may underlie the variation in morphology observed in these divergent organisms.

The well conserved family of Hox genes code for transcription factors that are active regulators of segmental identity along the anterior-posterior axis in developing embryos. This activity is reportedly seen in the AP axis of the developing digestive tract in chick and mouse where Hox genes exhibit patterns of expression specific to the region of the gut. In the hindgut, the expression of Abd-B-like genes (paralogs 913) seems to be restricted in the mesoderm during differentiation where conducive signaling directs the epithelial transition of the endoderm. Here we investigate the expression of the Abd-B-like genes in the human colon adenocarcinoma cell line Caco-2, which is a well defined model for enterocyte differentiation. RT-PCR and Northern Blot results show differential expression of HoxD10, HoxC12, HoxB13 and HoxD13 when evaluated before and after differentiation. Transcripts for HoxD13 are present during exponential growth but not after differentiation, while HoxC12, HoxD10 and HoxB13 show an increase in transcripts post differentiation. Functional studies will further clarify these genes as potential regulators of proliferation and/or differentiation within this cell model. This work was supported by the American Cancer Society, Institutional Research Grant ECU 5-89812.

We developed a computational method for the identification of putative cis-regulatory elements, which incorporates a direct measure of the effects of selection as a determinant in non-protein coding sequence evolution. As such, the method provides a biologically relevant framework for comparisons of non-protein coding sequence evolution. Comparisons of orthologous HoxA, Aa and Ab cluster paralogous group 2 intergenic and intron-related sequences from Mus muscu/us(mouse), Homo sapiens (humans), Heterodontus francisci (horn shark), Polypterus senegalus (bichir), Danio rerio (zebrafish), Oreochromis niloticus (Nile tilapia), Morone saxatilis (striped bass), and Takifugu rubripes (Japanese pufferfish) revealed three sequence domains that are under purifying selection in all the species and on both clusters, indicative that these three regions likely represent fundamental regulatory control elements of HoxA cluster paralogous group 2 genes in their common gnathostome ancestor. Detailed analysis of one of these three domains using both Mus musculus and Morone saxatilis HoxA paralogous group 2 regions as the index for comparisons demonstrated the presence of four general gnathostome elements, one general actinopterygian element, two general teleost elements and a host of mammalian and perciform-specific elements. The results also showed the partitioning of cis-regulatory elements between the actinopterygian HoxAa and Ab clusters relative to the inferred ancestral gnathostome HoxA cluster. Overall, our results indicate that the evolution of Hox paralogous group 2 cis-regulatory regions is dominated by the evolution of novel lineage-specific elements superimposed on a framework of shared common ancestral elements.

Abstract: Pneumocystis jiroveci pneumonia is a classic opportunist infection affecting AIDS patients. However it is less frequent since systematic prophylaxis and antiretroviral therapies. Treatment resistance is rare in France. We report the case of a severe Pneumocystis jiroveci pneumonia with treatment resistance to standard treatment and fatal outcome. The different causes of treatment resistance, notably the role of CMV co-infection, were reviewed and discussed. [Copyright &y& Elsevier]

Trophic changes of the exocrine pancreas after in vivo gastrin (G)/CCK treatment are well documented but up to now the study of the mechanisms involved is restricted by the lack of a suitable in vitro model. Nevertheless the in vivo trophic effect induced by gastrin/CCK peptides has been associated with an increase of ornithine decarboxylase (ODC) activity. In the present work, using the AR42J cell line in which CCK receptors and stimulation of amylase release by CCK peptides has already been demonstrated, we investigated the presence of gastrin binding sites and the possible modulation of proliferation by an inhibitor of ODC activity. 125I-BH-G17ns binding is saturable, reversible and specific. Potencies of the different analogues tested are G17ns greater than CCK8 greater than CCK8ns greater than or equal to G6s greater than G/CCK4. Furthermore dBt cGMP, a non-peptide antagonist for CCK receptors, does not compete for gastrin binding. This indicates the existence of a subclass of gastrin binding sites. Difluoromethyl ornithine (DFMO) (1 mM), an irreversible inhibitor of ODC, inhibits cell growth from day 3 up to day 7. This growth inhibition is dose dependent and closely related to an intracellular polyamine modulation. Putrescine and spermidine levels fell under detectable values while spermine levels increased. All these data suggest that this cell line could be a useful in vitro model to study the mechanisms of gastrin induced growth control. [ABSTRACT FROM PUBLISHER]