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Endothelin isoforms and the response to myocardial stretch

Endothelin isoforms and the response to myocardial stretch Ennis, Irene Lucia; Garciarena, Carolina Denis; Perez, Nestor Gustavo; Dulce, Raul; Camilion, Maria Cristina; Cingolani, Horacio Eugenio Myocardial stretch elicits a biphasic increase in developed force with a first rapid force response and a second slow force response (SFR). The rapid phase is due to an increase in myofilament Ca(2+) responsiveness; the SFR, analyzed here, is ascribed to a progressive increase in Ca(2+) transients. Experiments were performed in cat papillary muscles to further elucidate the signaling pathway underlying the SFR. Although the SFR was diminished by BQ-123, a similar endothelin (ET)-1-induced increase in force was not affected: 23 +/- 2 vs. 23 +/- 3% (not significant). Instead, BQ-123 suppressed the contractile effects of ET-2 or ET-3 (21 +/- 2 and 25 +/- 3% vs. -1 +/- 1 and -7 +/- 3% respectively, P < 0.05), suggesting that ET-2 or ET-3, but not ET-1, was involved in the SFR. Each isoform activated the Na(+)/H(+) exchanger (NHE-1), increasing intracellular Na(+) concentration by 2.0 +/- 0.1, 2.3 +/- 0.1, and 2.1 +/- 0.4 mmol/l for ET-1, ET-2, and ET-3, respectively (P < 0.05). The NHE-1 inhibitor HOE-642 prevented the increases in force and intracellular Na(+) concentration induced by all the ET isoforms, but only ET-2 and ET-3 effects were sensitive to BQ-123. Real-time RT-PCR measurements of prepro-ET-1, -ET-2, and -ET-3 were performed before and 5, 15, and 30 min after stretch. No changes in ET-1 or ET-2, but an increase of approximately 60% in ET-3, mRNA after 15 min of stretch were detected. Stretch-induced ET-3 mRNA upregulation and its mechanical counterpart were suppressed by AT(1) receptor blockade with losartan. These data suggest a role for AT(1)-mediated ET-3 released in the early activation of NHE-1 that follows myocardial stretch.

Identifying variable gamma-ray sources through radio observations

Identifying variable gamma-ray sources through radio observations Paredes, Josep Maria; Martí, Josep; Torres, Diego F.; Romero, Gustavo Esteban; Combi, Jorge Ariel; Bosch Ramon, Valentí; García Sánchez, J. We present preliminary results of a campaign undertaken with different radio interferometers to observe a sample of the most variable unidentified EGRET sources. We expect to detect which of the possible counterparts of the γ -ray sources (any of the radio emitters in the field) varies in time with similar timescales as the γ -ray variation. If the γ -rays are produced in a jet-like source, as we have modelled theoretically, synchrotron emission is also expected at radio wavelengths. Such radio emission should appear variable in time and correlated with the γ -ray variability.

Galectin-1 as a potential cancer target

Galectin-1 as a potential cancer target Rabinovich, Gabriel Adrián Galectins are a family of structurally related carbohydrate-binding proteins, which are defined by their affinity for poly-N-acetyllactosamine-enriched glycoconjugates and sequence similarities in the carbohydrate recognition domain. Galectin-1, a member of this family, contributes to different events associated with cancer biology, including tumour transformation, cell cycle regulation, apoptosis, cell adhesion, migration and inflammation. In addition, recent evidence indicates that galectin-1 contributes to tumour evasion of immune responses. Given the increased interest of tumour biologists and clinical oncologists in this field and the potential use of galectins as novel targets for anticancer drugs, we summarise here recent advances about the role of galectin-1 in different events of tumour growth and metastasis.

Histological events during in vitro rooting of Nothofagus nervosa (Fagaceae)

Histological events during in vitro rooting of Nothofagus nervosa (Fagaceae) Martínez Pastur, Guillermo José; Arena, Miriam Elisabet; Hernandez, Luis Francisco; Curvetto, Nestor Raul; Eliasco, Eleonora In vitro rooting protocols were previously performed on Nothofagus nervosa to optimise the culture medium and environmental conditions. A qualitative and quantitative tissue differentiation study during adventitious rooting in N. nervosa under different light/dark conditions was carried out to increase knowledge of the rhizogenesis process in shoots. The histological events through the rooting period were consistent with the proposed biochemical markers (peroxidases, tissue nutrient contents, polyamines, flavonoids). Development of parenchymatic tissues, shown by the staining pattern of the cell contents, and cambium activity were the best tissues to define the rooting phases. Knowledge of the histological changes could be used to optimise a protocol for micro‐propagation improving timing, quantity, and quality of roots, which would positively affect the survival rate during hardening.

GABAB1 knock-out mice reveals alteration in prolactin levels, gonadotropin axis and reproductive function

GABAB1 knock-out mice reveals alteration in prolactin levels, gonadotropin axis and reproductive function Catalano, Paolo Nicolás; Bonaventura, Maria Marta; Silveyra, Patricia; Bettler, Bernhard; Libertun, Carlos; Lux, Victoria Adela R. gamma-Aminobutyric acid (GABA) has been implicated in the control of hypophyseal functions. We evaluated whether the constitutive loss of functional GABA(B) receptors in GABA(B1) knockout (GABA(B1)(-/-)) mice alters hormonal levels, under basal and stimulated conditions, and reproductive function. The serum hormone levels were measured by radioimmunoassay, the estrous cyclicity was evaluated by vaginal lavages, and the mating behavior was determined by the presence of vaginal plugs. A moderate hyperprolactinemic condition was observed, in which prolactin increase and thyroid-stimulating hormone decrease were similar between genotypes. Basal luteinizing hormone (LH), follicle-stimulating hormone, thyroid-stimulating hormone, and growth hormone levels were similar between genotypes in each sex. Analysis of the gonadotropin axis revealed no differences in puberty onset between female genotypes. In con trast, the estrous cyclicity was significantly disrupted in GABA(B1)(-/-) female mice, showing significantly extended periods in estrus and shortened periods in proestrus. Reproduction was significantly compromised in GABA(B1)(-/-) females, with a significantly lower proportion of mice (37.5%) getting pregnant during the first 30 days of mating as compared with wild-type controls (87.5%). Moreover, only 14% of vaginal plug positive GABA(B1)(-/-) females had successful pregnancies as compared with 75% in the controls. In addition, the postovariectomy LH rise was significantly advanced in GABA(B1)(-/-) mice, while the response to estradiol feedback was similar in both genotypes. In conclusion, our endocrine analysis of GABA(B1)(-/-) mice reveals that GABA(B) receptors are involved in the regulation of basal prolactin titers. Moreover, the hypothalamic-hypophyseal-ovarian axis is seriously disturbed, with alterations in cyclicity, postcastration LH increase, and fertility indexes. The molecular mechanism underlying these hormonal disturbances remains to be addressed.

Design of photocatalytic reactors made easy by considering the photons as immaterial reactants

Design of photocatalytic reactors made easy by considering the photons as immaterial reactants Camera Roda, Giovanni; Santarelli, Francesco; Martin, Carlos Alberto While it is quite obvious that photons have an essential role in photochemical and photocatalytic processes, it is not simple to analyse the radiation process. A simple approach is presented on the assumption that photons can be treated as immaterial reactants. It is then possible to evaluate the radiation process in terms of parameters such as conversion, selectivity and yield, which are common in the conventional reaction engineering, and of an additional parameter, a volume efficiency factor, which accounts for the exploitation of the reaction volume as the result of the inevitable attenuation of the radiation in the transport through the participating medium. Attention has also been focused on the validation of kinetic data when, as it is usually done, they are interpreted in terms of volume averages. Finally, guidelines have been prepared to support preliminary phases of analysis and/or design of a photocatalytic reactor.

Linear combination of atomic orbitals calculation of the Auger neutralization rate of He on Al (111), Al (100) and Al (110) surfaces

Linear combination of atomic orbitals calculation of the Auger neutralization rate of He on Al (111), Al (100) and Al (110) surfaces Valdés, Diego; Goldberg, Edith Catalina; Blanco, J. M.; Monreal, R. C. We develop a theory of the Auger neutralization rate of ions on solid surfaces in which the matrix elements for the transition are calculated by means of a linear combination of atomic orbitals technique. We apply the theory to the calculation of the Auger rate of He+ on unreconstructed Al(111), (100), and (110) surfaces, assuming He+ to approach these surfaces on high symmetry positions and compare them with the results of the jellium model. Although there are substantial differences between the Auger rates calculated with both kinds of approaches, those differences tend to compensate when evaluating the integral along the ion trajectory and, consequently, are of minor influence in some physical magnitudes like the ion survival probability for perpendicular energies larger than 100 eV. We find that many atoms contribute to the Auger process and small effects of lateral corrugation are registered.

Diffuse component spectra of solar active regions at submillimeter wavelengths

Diffuse component spectra of solar active regions at submillimeter wavelengths Silva, Adriana V. R.; Laganá, Tatiana F.; Castro, C. Guillermo Gimenez de; Kaufmann, Pierre; Costa, Joaquim E. R.; Levato, H.; Rovira, Marta Graciela Solar maps at 212 and 405 GHz obtained by the Solar Submillimetric Telescope (SST) show regions of enhanced brightness temperature, which coincide with the location of active regions. A statistical study of the radio emission from these active regions was performed for the first time at such high frequencies during 23 days on June and July 2002, when the atmospheric opacity was low. The brightest regions on the maps were chosen for this study, where the brightness excess observed varies from 3 to 20% above quiet Sun levels (i.e., 200–1000 K) at both wavelengths. Sizes of the regions of enhanced emission calculated at half the maximum value were estimated to be between 2′ and 7′. These sizes agree with observed sizes of active regions at other wavelengths such as Hα and ultraviolet. An important result is that the flux density spectra of all sources increase toward submillimeter frequencies, yielding flux density spectral index with an average value of 2.0. The flux density of the active region sources were complemented with that from maps at 17 and 34 GHz from the Nobeyama Radio Heliograph. The resulting spectra at all four frequencies were fit considering the flux density to be due to thermal bremsstrahlung from the active region. In the calculations, the source radius was assumed to be the mean of the measured values at 212 and 405 K. The effective temperatures of the radio emitting source, assumed homogeneous, obtained from this fit were 0.6–2.9 × 104 K, for source diameters of 2′–7′.

Self-induced decoherence and the classical limit of quantum mechanics

Self-induced decoherence and the classical limit of quantum mechanics Castagnino, Mario Alberto G. J.; Lombardi, Olimpia Iris In this paper we argue that the emergence of the classical world from the underlying quantum reality involves two elements: self‐induced decoherence and macroscopicity. Self‐induced decoherence does not require the openness of the system and its interaction with the environment: a single closed system can decohere when its Hamiltonian has continuous spectrum. We show that, if the system is macroscopic enough, after self‐induced decoherence it can be described as an ensemble of classical distributions weighted by their corresponding probabilities. We also argue that classicality is an emergent property that arises when the behavior of the system is described from an observational perspective.

Angular dispersion of protons passing through thin metallic films

Angular dispersion of protons passing through thin metallic films Archubi, Claudio Darío; Denton, C.; Eckardt, J. C.; Lantschner, G. H.; Arista, N. R.; Valdés, J.; Ferrón, J. The angular distributions of protons after traversing thin polycrystalline Al targets (∼15 nm) with an incident energy of 10 keV have been measured and an analysis of the targets by means of transmission electron microscopy (TEM) techniques has been made. The separate influence of the different crystal characteristics and defects has been evaluated by numerical simulation considering the interaction of the ion with all the nearest neighboring atoms simultaneously. In the analysis we included the evaluation of the effects of lattice vibrations, oxide layers and foil roughness on the angular distributions. Previous experimental data in monocrystalline and polycrystalline Au targets has also been analyzed. For a consistency check a comparison with the results of the MARLOWE code for the simpler case of proton channeling in 〈1 0 0〉 Al has been performed. As in the case of Au, the present results indicate that the experiments can be explained in terms of a modified Moliere potential, and confirm the critical influence of crystal characteristics, in this case the amorphous oxide layer on the surface and the thermal vibration of the lattice atoms.

Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission.

Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission. Matarrese, Paola; Tinari, Antonella; Mormone, Elisabetta; Bianco, German Ariel; Toscano, Marta Alicia; Ascione, Barbara; Rabinovich, Gabriel Adrián; Malorni, Walter Galectins have emerged as a novel family of immunoregulatory proteins implicated in T cell homeostasis. Recent studies showed that galectin-1 (Gal-1) plays a key role in tumor-immune escape by killing antitumor effector T cells. Here we found that Gal-1 sensitizes human resting T cells to Fas (CD95)/caspase-8-mediated cell death. Furthermore, this protein triggers an apoptotic program involving an increase of mitochondrial membrane potential and participation of the ceramide pathway. In addition, Gal-1 induces mitochondrial coalescence, budding, and fission accompanied by an increase and/or redistribution of fission-associated molecules h-Fis and DRP-1. Importantly, these changes are detected in both resting and activated human T cells, suggesting that Gal-1-induced cell death might become an excellent model to analyze the morphogenetic changes of mitochondria during the execution of cell death. This is the first association among Gal-1, Fas/Fas ligand-mediated cell death, and the mitochondrial pathway, providing a rational basis for the immunoregulatory properties of Gal-1 in experimental models of chronic inflammation and cancer.

El agua en la Produccion de cultivos extensivos: III. Impacto de las practicas de manejo sobre la eficiencia de uso del agua

El agua en la Produccion de cultivos extensivos: III. Impacto de las practicas de manejo sobre la eficiencia de uso del agua Micucci, Federico; Alvarez, Carina Rosa El agua es el factor más limitante en la producción de cultivos extensivos en secano en la región pampeana argentina y en muchas otras regiones del mundo. Por lo tanto, debemos saber producir haciendo un uso eficiente del recurso más escaso, el agua. El objetivo de este artículo es brindar algunos conceptos básicos relacionados con la eficiencia de uso del agua (EUA) y las prácticas de manejo que la mejoran. Para ello es necesario conocer cuales son los componentes de la EUA posibles de modificar y como las prácticas agronómicas pueden afectarla.

Sunflower chlorotic mottle virus in compatible interactions with sunflower: ROS generation and antioxidant response

Sunflower chlorotic mottle virus in compatible interactions with sunflower: ROS generation and antioxidant response Arias, Maria Cecilia; Luna, Celina Mercedes; Rodríguez, Marianela; Lenardon, Sergio Luis; Taleisnik, Edith Sunflower chlorotic mottle virus (SuCMoV) is a recently described potyvirus that causes systemic infections in sunflower plants leading to chlorotic mottling and important growth reductions and yield losses. Oxidative damage is expressed after symptom development in this host-pathogen combination. The involvement of antioxidant enzyme activities in disease susceptibility was studied in two sunflower lines differing in the intensity and rate of development of SuCMoV infections: L2 is more susceptible than L33. A transient superoxide production peak was detected in leaves of both lines before symptom development. H2O2 accumulation increased before symptom expression in infected plants of L33 but in L2 such increase was registered only after symptoms became evident. In healthy plants of both lines, superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) showed similar activity levels. In inoculated plants of line L2, but not in L33, SOD and CAT activities increased significantly before the appearance of symptoms, and APX increases were detected later. A 1 mM SA treatment effectively decreased SuCMoV accumulation in plants of L2 but it did not affect it in L33. This treatment increased H2O2 accumulation and prevented the increase in antioxidant enzyme activities in infected plants of L2. It is suggested that increases in antioxidant enzyme activities interrupted the signals generated by the increase in ROS, which may have otherwise triggered defence reactions in the host and thus, resulted in a compatible interaction.

Scanning electron microscopy of Chordodes moutoni Camerano, 1895 (Gordiida, Nematomorpha)

Scanning electron microscopy of Chordodes moutoni Camerano, 1895 (Gordiida, Nematomorpha) Zanca, Fernanda Mariel; De Villalobos, Cristina Taxonomic characters of both male and female horse-hair worms Chordodes moutoni Camerano, 1895 (Nematomorpha) are re-described using scanning electron microscopy. The features are compared with the original description. C. moutoni cuticle has five different areolar types in male while female have six types of areoles. The crowned areoles, characteristic of Chordodes, are surrounded by other areoles forming pairs or clusters. Sexual dimorphism was found in the cuticular pattern, the female showing two different types of crowned areoles with distinct distribution pattern while the male has only one type of crowned areoles. These data are compared to other Chordodes species that have been studied.

Neuronal differentiation in the adult hippocampus recapitulates embryonic development

Neuronal differentiation in the adult hippocampus recapitulates embryonic development Esposito, Maria Soledad; Piatti, Veronica del Carmen; Laplagne, Diego Andres; Morgenstern, Nicolás Andrés; Ferrari, Carina Cintia; Pitossi, Fernando Juan; Schinder, Alejandro Fabián In the adult hippocampus and olfactory bulb, neural progenitor cells generate neurons that functionally integrate into the existing circuits. To understand how neuronal differentiation occurs in the adult hippocampus, we labeled dividing progenitor cells with a retrovirus expressing green fluorescent protein and studied the morphological and functional properties of their neuronal progeny over the following weeks. During the first week neurons had an irregular shape and immature spikes and were synaptically silent. Slow GABAergic synaptic inputs first appeared during the second week, when neurons exhibited spineless dendrites and migrated into the granule cell layer. In contrast, glutamatergic afferents were detected by the fourth week in neurons displaying mature excitability and morphology. Interestingly, fast GABAergic responses were the latest to appear. It is striking that neuronal maturation in the adult hippocampus follows a precise sequence of connectivity (silent → slow GABA → glutamate → fast GABA) that resembles hippocampal development. We conclude that, unlike what is observed in the olfactory bulb, the hippocampus maintains the same developmental rules for neuronal integration through adulthood.

Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level; a study on hCG overexpressing transgenic mice

Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level; a study on hCG overexpressing transgenic mice Ahtianen, Petteri; Rulli, Susana Beatriz; Shariatmadari, Ramin; Pelliniemi, Lauri J.; Toppari, Jorma; Poutanen, Matti; Huhtaniemi, Ilpo T. We have previously demonstrated that male transgenic (TG) mice overexpressing human chorionic gonadotropin (hCG+) develop reproductive organ defects, but no tumors, in adult age. In this study, the effects of persistently elevated hCG were followed in TG males between day 5 postpartum and adulthood. Leydig cell (LC) adenomas were found in prepubertal mice, most prominently at the age of 10 days, but not in adult age. Serum testosterone concentrations were significantly increased in TG males at all ages studied. The phenotype of the prepubertal hCG+ males resembled that found in boys upon expression of constitutively activating luteinizing hormone (LH) receptor mutations. The temporal expression patterns of the fetal LC marker gene, thrombospondin 2, and those of adult LCs, hydroxysteroid dehydrogenase-6, delta5-3-beta and prostaglandin D synthase, were similar in wild-type and hCG+ males. Hence, the postnatal adenomas resemble functionally fetal LCs, and only these cells are susceptible to hCG-induced tumorigenesis. Our findings demonstrate a novel intriguing difference between the fetal and adult LC populations and provide further insight into the potential tumorigenic effects of gonadotropins.

Diversity of rhizobia isolated from an agricultural soil in Argentina based on carbon utilization and effects of herbicides on growth

Diversity of rhizobia isolated from an agricultural soil in Argentina based on carbon utilization and effects of herbicides on growth Zabaloy, Maria Celina; Gomez, Marisa Anahi Seventy-six rhizobial isolates belonging to four different genera were obtained from root nodules of several legumes (Vicia sativa, Vicia faba, Medicago sativa, Melilotus sp., Glycine max and Lotus corniculatus). The action of five commonly used herbicides (2,4-dichlorophenoxyacetic acid [2,4-D], glyphosate [GF], dicamba, atrazine and metsulfuron-methyl), on the growth of rhizobial strains was assessed. Subsequently, GF and 2,4-D were tested in a minimum broth as C and energy sources for twenty tolerant strains. The ability of these strains to metabolize different carbon sources was studied in order to detect further differences among them. Tolerance of the bacteria to agrochemicals varied; 2,4­-D and GF in solid medium inhibited and diminished growth, respectively, in slow-growing rhizobial strains. Among slow-growing strains we detected Bradyrhizobium sp. SJ140 that grew well in broth+GF as the sole C and energy source. No strain was found which could use 2,4-D as sole C source. The twenty strains studied exhibited different patterns of C sources utilization. Cluster analysis revealed three groups, corresponding to four genera of rhizobia: Rhizobium (group I), Sinorhizobium (group II) and Mesorhizobium-Bradyrhizobium (group III). On the basis of the results obtained on responses to herbicides and C sources utilization by the isolates investigated, it was possible to differentiate them at the level of strains. These results evidenced a considerable diversity in rhizobial populations that has not been previously described for Argentinean soils, and suggested a physiological potential to use natural and xenobiotic C sources.

Analysis of the use of voltammetric results as a steady state approximation to evaluate kinetic parameters of the hydrogen evolution reaction

Analysis of the use of voltammetric results as a steady state approximation to evaluate kinetic parameters of the hydrogen evolution reaction Marozzi, Carlos Alberto; Canto, Mario Ruben; Costanza, Vicente; Chialvo, Abel Cesar The use of the voltammetric response jvol(η) of a potentiodynamic sweep at a slow scan rate vs in place of a steady state polarization curve jss(η) for the determination of the kinetic parameters of the hydrogen evolution reaction is analyzed. It is proposed to consider jvol(η, vs) ∼= jss(η) when the condition 0.99 ≤ jvol(η, vs)/jss(η) ≤ 1.01 is verified in the overpotentials range η≤−0.05V. It has been also established a simple relationship between the maximum admissible scan rate vmax s and the equilibrium polarization resistance Rp. Finally, the application of this criterion on different electrodes is described and discussed.

Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep

Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep Sanchez Bruni, Sergio Fabian; Jones, Douglas G.; Small, John; McKellar, Quintin A. This study compared pharmacokinetic (PK) profiles in sheep dosed intravenously with three different concentrations of oxfendazole (OFZ).  An in vitro plasma OFZ dissolution study provided additional information on plasma saturation.  For the PK study, 18 adult, parasite-free, female Suffolk cross sheep, allocated into three groups (n=6), were treated intravenously, at a dose rate of 5mg/kg bodyweight, with aqueous solutions containing at 4, 8 or 16% OFZ.  Plasma drug concentrations were measured, for up to 72 hours post-treatment, by a validated high performance liquid chromatography (HPLC) method with UV detection.  OFZ and fenbendazole sulphone (FBZSO2) were the main metabolites detected in all three experimental groups. In animals given the 4% solution, OFZ depleted according to a biexponential concentration vs. time curve.  In contrast, those given 8 or 16% preparations produced atypical curves fitted by monoexponential equations. No statistically significant differences in area under concentration-time curves (AUC) were observed, but concentration-dependent differences in distribution and mean residence time (MRT) were evident.  Compared with 4% OFZ, animals treated with 8 and 16% formulations had slower half-lives of metabolite formation,and lower AUC’s, suggesting that OFZ sulphonation may have been modified.  In vitro there was evidence of plasma saturation and precipitation associated with 8 and 16% OFZ preparations.  It is concluded that differences in PK profiles, in vivo, may have been related to inadequate dissolution and/or tissue drug precipitation.

Impact of the Placental Cytokine-Chemokine Balance on Regulation of Cell-Cell Contact-Induced Human Immunodeficiency Virus Type 1 Translocation across a Trophoblastic Barrier In Vitro

Impact of the Placental Cytokine-Chemokine Balance on Regulation of Cell-Cell Contact-Induced Human Immunodeficiency Virus Type 1 Translocation across a Trophoblastic Barrier In Vitro Derrien, Muriel; Faye, Albert; Dolcini, Guillermina Laura; Chaouat, Gérard; Barré Sinoussi, Françoise; Menu, Elisabeth Cells constituting the placental barrier secrete soluble factors that may participate in controlling human immunodeficiency virus type 1 (HIV-1) transmission from the mother to the fetus. In this study, we asked whether placental soluble factors (PSF) could limit cell-cell contact inducing HIV-1 production that occurs after inoculation of HIV-1-infected peripheral blood mononuclear cells (HIV-1+ PBMCs) onto trophoblast-derived BeWo cells grown as tight and polarized barriers in a two-chamber system. The activity of recombinant chemokines and cytokines expressed by placental tissue and of factors secreted by either early or term placentae of HIV-1-negative women, was analyzed. We identified chemokines (RANTES and MIP-1beta) and cytokines (tumor necrosis factor alpha and interleukin-8) that decreased and increased, respectively, viral production in trophoblast barrier cells inoculated with HIV-1+ PBMCs. Unexpectedly, factors secreted by either early or term placentae of HIV-1-negative women enhanced viral production. Nevertheless, the same PSF did not favor infection of trophoblastic barriers with cell-free HIV-1 and strongly reduced viral production in PBMCs infected with cell-free HIV-1. Moreover, PSF contained chemokines (RANTES and MIP-1beta) and a cytokine, leukemia inhibitory factor, exhibiting a strong anti-HIV-1 activity in our model of cell-to-cell infection. Together these data suggested that at the maternal interface the global activity of PSF is related to the synergistic action of several soluble factors with a balance in favor of an enhancing activity on the passage of viruses across the trophoblast barrier. This could explain the presence of viral sequences in trophoblasts in all placentae of HIV-1-infected women.

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