Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new “B2” configuration of the RA-6 nuclear reactor

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new “B2” configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in “B1” experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94–96%) than in control (16%) and BO groups (9–38%), and did not differ significantly from the “B1” results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.     

Pattern of natural introgression in a <Emphasis Type="Italic">Nothofagus</Emphasis> hybrid zone from South American temperate forests

Interspecific gene flow is a common phenomenon in Nothofagaceae species; however, the dynamics of introgression in hybrid zones remains largely unknown. We focused on two ecologically and morphologically different Nothofagus species from Patagonia, Nothofagus nervosa and Nothofagus obliqua. In a natural hybrid zone, we established two plots 280 m apart in altitude (ca. 1.9 °C difference in mean temperature), and two subplots which captured microsite variation (abundance and spatial distribution of species and predominance of wind direction). We used intensive sampling of individuals (2055, including adults and regeneration) and molecular genotyping of 6 highly species-specific nuclear microsatellites for the identification and classification of hybrids, based on estimates of ancestry and interclass heterozygosity. We evaluated the relative contribution of our sampling effects to variation in hybrid incidence and direction of introgression using generalized linear mixed effects models. We determined that introgressive hybridization occurs at a global rate of 7.8% and that variation was mostly explained by plots (frequency at low altitude was approximately twice that found at high altitude), while it was less influenced by subplots. The high altitude plot was dominated by late-generation backcrosses to N. obliqua (asymmetric bimodality), whereas the low altitude plot consisted of intermediate hybrids (unimodality) and showed asymmetry for introgression between subplots. Differences were not detected between adults and regeneration, suggesting early-acting reproductive isolating barriers. F1 hybrids occur at a global frequency of 3.8%, and are fertile, as the detection of first- and late-generation hybrids indicates.     

The role of macroinvertebrates for conservation of freshwater systems

Freshwater ecosystems are the most threatened ecosystems worldwide. Argentinian‐protected areas have been established mainly to protect vertebrates and plants in terrestrial ecosystems. In order to create a comprehensive biodiverse conservation plan, it is crucial to integrate both aquatic and terrestrial systems and to include macroinvertebrates. Here, we address this topic by proposing priority areas of conservation including invertebrates, aquatic ecosystems, and their connectivity and land uses. Location: Northwest of Argentina. We modeled the ecological niches of different taxa of macroinvertebrates such as Coleoptera, Ephemeroptera, Hemiptera, Megaloptera, Lepidoptera, Odonata, Plecoptera, Trichoptera, Acari, and Mollusca. Based on these models, we analyzed the contribution of currently established protected areas in the conservation of the aquatic biodiversity and we propose a spatial prioritization taking into account possible conflict regarding different land uses. Our analysis units were the real watersheds, to which were added longitudinal connectivity up and down the rivers. A total of 132 species were modeled in the priority area analyses. The analysis 1 showed that only an insignificant percentage of the macroinvertebrates distribution is within the protected areas in the North West of Argentina. The analyses 2 and 3 recovered similar values of protection for the macroinvertebrate species. The upper part of Bermejo, Salí‐Dulce, San Francisco, and the Upper part of Juramento basins were identified as priority areas of conservation. The aquatic ecosystems need special protection and 10% or even as much as 17% of land conservation is insufficient for species of macroinvertebrates. In turn the protected areas need to combine the aquatic and terrestrial systems and need to include macroinvertebrates as a key group to sustain the biodiversity. In many cases, the land uses are in conflict with the conservation of biodiversity; however, it is possible to apply the connectivity of the watersheds and create multiple‐use modules.     

Coalescing red algae exhibit noninvasive,reversible chimerism

Chimerism is produced by the somatic fusion of two or more genetically distinct conspecific individuals. In animals, the main cost of fusion is competition between genetically different cell lineages and the probability of original cell line replacement by more competitive invasive lines, which limits its natural frequency (3%–5%). In red and brown seaweeds, chimerism is widespread (27%–53%), seemingly without the negative outcomes described for animals. The rigidity of cell walls in macroalgae prevents cell motility and invasions. In addition, in moving waters, most somatic fusions involve the holdfast. Histological observations in laboratory‐built bicolor macroalgal chimeras indicated that upright axes emerge from the base of plants by proliferation and vertical growth of discrete cell groups that include one or just a few of the cell lineages occurring in the holdfasts. Laboratory experiments showed growth competition between cell lineages, thus explaining lineage segregation during growth along originally chimeric erect axes. Genotyping of the axes showed more heterogeneous tissues basally, but apically more homogeneous ones, generating a vertical gradient of allele abundance and diversity. The few chimeric primary branches produced, eventually became homogenous after repeated branching. Therefore, coalescing macroagae exhibit a unique pattern of post‐fusion growth, with the capacity to reverse chimerism. This pattern is significantly different from those in animals and land plants, suggesting chimerism is a biologically heterogeneous concept.     

Species complex delimitation and patterns of population structure at different geographic scales in Neotropical silver catfish (<Emphasis Type="Italic">Rhamdia</Emphasis>: Heptapteridae)

The Neotropical catfish genus Rhamdia inhabits rivers and lakes from Mexico to Argentina. Previous studies have found that the taxonomy of this genus, as well as that of R. quelen, remains controversial. The present study aims to contribute to the understanding of Rhamdia systematics by delimiting putative species, and to elucidate the pattern of genetic differentiation of Rhamdia at different geographic levels within the cis-andean region. Species boundaries were defined by Generalized Mixed Yule Coalescent and Automatic Barcode Gap Discovery methods, and by phylogenetic analyses of cytochrome b (cyt b) sequences. Moreover, we performed phylogeographic analyses based on cyt b sequences and microsatellite markers. Patterns of differentiation were analyzed at three nested geographic levels: in the main cis-andean basins (macrogeographic scale); in the second major Neotropical basin system (mesogeographic scale), which encompasses La Plata basin, Patos-Merin basin, and the coastal lagoons draining to SW Atlantic Ocean; and finally, in the three most important coastal lagoons for artisanal fisheries in Uruguay (microgeographic scale). Sixteen species were found within Rhamdia, divided into two clades (cis- and trans-andean clades), each composed of eight putative species. Cis-andean Rhamdia species have probably diverged due to vicariance events occurring between and within basins since late Miocene-Pleistocene. Microgeographic scale analysis based on cyt b and microsatellite data revealed a high genetic structuring among the studied coastal lagoons. Mitochondrial and microsatellite markers enabled to identify three different populations, corresponding to the three coastal lagoons analyzed, which would have diverged recently and could be considered as different Management Units.     

Rainfall reduction impacts rhizosphere biogeochemistry in eucalypts grown in a deep Ferralsol in Brazil

Plant and Soil - Comparing root functioning under contrasting rainfall regimes can help assessing the capacity of plant species to cope with more intense and frequent drought predicted under...     

Atorvastatin modifies the protein profile of circulating human monocytes after an acute coronary syndrome

Aggressive treatment with high‐dose atorvastatin reduces more effectively the incidence of cardiovascular events than moderate statin therapy. The mechanism of this benefit has not been fully elucidated. In order to know the potential effects of statin treatment on the protein expression of circulating monocytes in acute coronary syndrome (ACS) patients, a proteomic analysis of these cells was carried out by 2‐DE and MS. Twenty‐five patients with non‐ST‐elevation acute coronary syndrome (NSTEACS) were randomized, the fourth day after admission, to receive ATV 80 mg/dL (n = 14) or conventional treatment (CT) (n = 11), for two months. Blood was withdrawn at the end of the treatment, and monocytes were extracted for proteomic analysis and their protein expression patterns determined. Age, sex, total cholesterol, LDL, HDL, triglycerides, body mass index, presence of hypertension, diabetes, and smoking status were not significantly different between the two groups of patients. The expression of 20 proteins was modified by intensive ATV. Among the most relevant results stand out the normalization by intensive ATV treatment of the expression of proteins that modulate inflammation and thrombosis such as protein disulfide isomerase ER60 (PDI), Annexin I, and prohibitin, or that have other protective effects as HSP‐70. Thus, this approach shed light at the molecular level of the beneficial mechanisms of anti‐atherothrombotic drugs.     

Isolation and selection of native microorganisms for the aerobic treatment of simulated dairy wastewaters

Milk fat/protein degrading microorganisms were isolated from different locations of a dairy wastewater treatment system with the goal of developing an inoculum for bioaugmentation strategies. Eight isolates, identified by 16S rRNA gene sequence analysis as belonging to the genera Bacillus, Pseudomonas, and Acinetobacter, were tested for their ability to remove COD and protein from a milk-based medium (3000 mg/L COD) and compared to a commercial bioaugmentation inoculum. The Acinetobacter isolate exhibited a pellet-type growth in liquid culture, a property that could potentially aid in the separation of microbes and liquid phase following treatment. Based on the individual degradation capacity and growth behavior of the isolates, three microorganisms were further selected and tested together. This consortium exhibited a COD removal similar to the commercial inoculum (57% and 63%, respectively), but higher protein (consortium: 93%; commercial inoculum: 54%), and fat removals (consortium: 75%; commercial inoculum: 38%).     

Productive infection of Piscirickettsia salmonis in macrophages and monocyte‐like cells from rainbow trout,a possible survival strategy

Piscirickettsia salmonis is the etiologic agent of the salmonid rickettsial septicemia (SRS), an endemic disease which causes significant losses in salmon production. This intracellular bacterium is normally cultured in salmonid epithelial cell lines inducing characteristic cytopathic effects (CPEs). In this study we demonstrate that P. salmonis is able to infect, survive, replicate, and propagate in the macrophages/monocytes cell line RTS11 derived from rainbow trout spleen, without inducing the characteristic CPEs and the host cells showing the same expression levels as non‐infected control cell. On the other hand, bacteria were capable of expressing specific proteins within infected cells. Infected macrophages cease proliferation and a fraction of them detached from the plate, transform to non‐adhesive, monocyte‐like cells with proliferative activity. Productive infection of P. salmonis into salmonid macrophage/monocyte cells in culture provides an excellent model for the study of host–pathogen interactions, almost unknown in the case of P. salmonis. Our results suggest that the infection of cells from the salmonid innate immune system without inducing an important cell death response should lead to the persistence of the bacteria and consequently their dissemination to other tissues, favoring the evasion of the first line of defense against pathogens. J. Cell. Biochem. 108: 631–637, 2009. © 2009 Wiley‐Liss, Inc.