Evolutionary History of the Grey-Faced Sengi,Rhynchocyon udzungwensis,from Tanzania: A Molecular and Species Distribution Modelling Approach

Rhynchocyon udzungwensis is a recently described and poorly understood sengi (giant elephant-shrew) endemic to two small montane forests in Southern Tanzania, and surrounded in lower forests by R. cirnei reichardi. In this study, we investigate the molecular genetic relationship between R. udzungwensis and R. c. reichardi, and the possible role that shifting species distributions in response to climate fluctuations may have played in shaping their evolutionary history. Rhynchocyon udzungwensis and R. c. reichardi individuals were sampled from five localities for genetic analyses. Three mitochondrial and two nuclear loci were used to construct species trees for delimitation and to determine whether introgression was detectable either from ancient or ongoing hybridization. All species-tree results show R. udzungwensis and R. c. reichardi as distinct lineages, though mtDNA shows evidence of introgression in some populations. Nuclear loci of each species were monophyletic, implying introgression is exclusively historical. Because we found evidence of introgression, we used distribution data and species distribution modelling for present, glacial, and interglacial climate cycles to predict how shifting species distributions may have facilitated hybridization in some populations. Though interpretations are affected by the limited range of these species, a likely scenario is that the mtDNA introgression found in eastern mid-elevation populations was facilitated by low numbers of R. udzungwensis that expanded into lowland heavily occupied R. c. reichardi areas during interglacial climate cycles. These results imply that relationships within the genus Rhynchocyon may be confounded by porous species boundaries and introgression, even if species are not currently sympatric.     

Intestinal transport of thiamin and thiamin monophosphate in rat everted jejunal sacs: a comparative study using some potential inhibitors

Rat everted jejunal sacs were incubated for 15 and 30 min at 37 degrees C in oxygenated Krebs-Henseleit buffer, pH 7.4, containing 0.2 microM [3H]-thiamin (3H-T) or [3H]-thiamin monophosphate (3H-TMP) with and without 10 mM 1-phenylalanine (PAL) or 2.5 mM levamisole (LEV). The concentrations of 3H-T and its phosphoesters in sac wall and serosal fluid were determined by a radiometric method after electrophoretic separation. In separate experiments, thiamin pyrophosphokinase (TPKase) and thiamin pyrophosphatase (TPPase) activities were determined in mucosal scrapings, with and without PAL or LEV, by using a radiometric and a colorimetric method, respectively. 3H-TMP was transported partly unchanged by an active mechanism similarly to 3H-T, but less efficiently. During transport, 3H-TMP was also enzymatically transformed to thiamin (T) and thiamin pyrophosphate, which accumulated in the tissue. In the serosal fluid, the concentration of 3H-TMP exceeded that of 3H-T. Presence of PAL or LEV with 3H-T or 3H-TMP in the incubation medium reduced the serosal transport and the tissue content of T compounds. LEV caused a dose-dependent inhibition of TPKase without affecting TPPase, whereas PAL inhibited both activities to about the same extent. These results indicate that the transport of TMP involves a number of different processes similar to those responsible for T transport. The effects of PAL and LEV underline the importance of phosphorylation-dephosphorylation coupling.     

Great Apes in the Giardino Zoologico of Rome (1910-1998): An Overview

This work reviews nearly 90 years of ape keeping and housing at the Giardino Zoologico in Rome, and offers an overview of the scientific research carried out on these primates. It may thus contribute to a better historical knowledge of primate zoo management in Italy. Furthermore, particular attention is paid to morphological aspects in orangutan physical development that should deserve further research.     

Citrus Allergy from Pollen to Clinical Symptoms

Allergy to citrus fruits is often associated with pollinosis and sensitization to other plants due to a phenomenon of cross-reactivity. The aims of the present study were to highlight the cross-reactivity among citrus and the major allergenic pollens/fruits, throughout clinical and molecular investigations, and to evaluate the sensitization frequency to citrus fruits in a population of children and adults with pollinosis. We found a relevant percentage of sensitisation (39%) to citrus fruits in the patients recruited and in all of them the IgE-mediated mechanism has been confirmed by the positive response to the prick-to-prick test. RT-PCR experiments showed the expression of Cit s 1, Cit s 3 and a profilin isoform, already described in apple, also in Citrus clementine pollen. Data of multiple sequence alignments demonstrated that Citrus allergens shared high percentage identity values with other clinically relevant species (i.e. Triticum aestivum, Malus domestica), confirming the possible cross-allergenicity citrus/grasses and citrus/apple. Finally, a novelty of the present work has been the expression of two phospholipaseA2 isoforms (PLA2 α and β) in Citrus as well as in Triticum pollens; being PLA2 able to generate pro-inflammatory factors, this enzyme could participate in the activation of the allergenic inflammatory cascade.     

Cost-Utility Analysis of Lopinavir/Ritonavir versus Atazanavir + Ritonavir Administered as First-Line Therapy for the Treatment of HIV Infection in Italy: From Randomised Trial to Real World

Objective

To estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment.

Design

With this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r.

Methodology

A Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer’s perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature.

Results

The average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2.

Conclusions

Using real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV.     

A Novel Ion Channel Formed by Interaction of TRPML3 with TRPV5

TRPML3 and TRPV5 are members of the mucolipin (TRPML) and TRPV subfamilies of transient receptor potential (TRP) cation channels. Based on sequence similarities of the pore forming regions and on structure-function evidence, we hypothesized that the pore forming domains of TRPML and TRPV5/TRPV6 channels have similarities that indicate possible functional interactions between these TRP channel subfamilies. Here we show that TRPML3 and TRPV5 associate to form a novel heteromeric ion channel. This novel conductance is detectable under conditions that do not activate either TRPML3 or TRPV5. It has pharmacological similarity with TRPML3 and requires functional TRPML3 as well as functional TRPV5. Single channel analyses revealed that TRPML3 and TRPV5 heteromers have different features than the respective homomers, and furthermore, that they occur in potentially distinct stoichiometric configurations. Based on overlapping expression of TRPML3 and TRPV5 in the kidney and the inner ear, we propose that TRPML3 and TRPV5 heteromers could have a biological function in these organs.