Expansion of CD11b+Ly6G+Ly6Cint cells driven by medroxyprogesterone acetate in mice bearing breast tumors restrains NK cell effector functions

The progesterone analog medroxyprogesterone acetate (MPA) is widely used as a hormone replacement therapy in postmenopausal women and as contraceptive. However, prolonged administration of MPA is associated with increased incidence of breast cancer through ill-defined mechanisms. Here, we explored whether exposure to MPA during mammary tumor growth affects myeloid-derived suppressor cells (MDSCs; CD11b⁺Gr-1⁺, mostly CD11b⁺Ly6G⁺Ly6C^int and CD11b⁺Ly6G^?Ly6C^high cells) and natural killer (NK) cells, potentially restraining tumor immunosurveillance. We used the highly metastatic 4T1 breast tumor (which does not express the classical progesterone receptor and expands MDSCs) to challenge BALB/c mice in the absence or in the presence of MPA. We observed that MPA promoted the accumulation of NK cells in spleens of tumor-bearing mice, but with reduced degranulation ability and in vivo cytotoxic activity. Simultaneously, MPA induced a preferential expansion of CD11b⁺Ly6G⁺Ly6C^int cells in spleen and bone marrow of 4T1 tumor-bearing mice. In vitro, MPA promoted nuclear mobilization of the glucocorticoid receptor (GR) in 4T1 cells and endowed these cells with the ability to promote a preferential differentiation of bone marrow cells into CD11b⁺Ly6G⁺Ly6C^int cells that displayed suppressive activity on NK cell degranulation. Sorted CD11b⁺Gr-1⁺ cells from MPA-treated tumor-bearing mice exhibited higher suppressive activity on NK cell degranulation than CD11b⁺Gr-1⁺ cells from vehicle-treated tumor-bearing mice. Thus, MPA, acting through the GR, endows tumor cells with an enhanced capacity to expand CD11b⁺Ly6G⁺Ly6C^int cells that subsequently display a stronger suppression of NK cell-mediated anti-tumor immunity. Our results describe an alternative mechanism by which MPA may affect immunosurveillance and have potential implication in breast cancer incidence.     

Ithyoclinostomum yamagutii n. sp. (Digenea: Clinostomidae) in the great blue heron Ardea herodias L. (Aves: Ardeidae) from Mississippi,USA

With only six recognised genera, the family Clinostomidae Lühe, 1901 remains a global research interest of parasitologists and ecologists. Recent efforts have focused on providing molecular data to investigate species diversity, elucidate life-cycles, and make inferences on the group’s evolutionary history. Of the clinostomid genera, the monotypic Ithyoclinostomum Witenberg, 1926 has remained more enigmatic compared to the commonly encountered Clinostomum Leidy, 1856. Recent morphological and molecular evidence from metacercariae suggests a second Ithyoclinostomum species may exist in freshwater cichlids in Central America and Mexico. In a recent survey of great blue herons Ardea herodias L. from commercial catfish production farms in Mississippi, USA, two specimens of an abnormally large (> 20 mm) clinostomid were encountered in the oesophagus of a single bird. These specimens were identified as an Ithyoclinostomum sp. morphologically distinct from the only nominal species Ithyoclinostomum dimorphum (Diesing, 1850). Using morphological and molecular data these adult specimens were confirmed as conspecific with the larval metacercariae previously described from Central America and Mexico and represent the novel species, Ithyoclinostomum yamagutii n. sp.

     

Imaging plant responses to water deficit using electrical resistivity tomography

Background and aims

Monitoring root water uptake dynamics under water deficit (WD) conditions in fields are crucial to assess plant drought tolerance. In this study, we investigate the ability of Electrical Resistivity Tomography (ERT) to capture specific soil water depletion induced by root water uptake.

Methods

A combination of surface and depth electrodes with a high spatial resolution (10 cm) was used to map 2-D changes of bulk soil electrical conductivity (EC) in an agronomic trial with different herbaceous species. A synthetic experiment was performed with a mechanistic model to assess the ability of the electrode configuration to discriminate abstraction patterns due to roots. The impact of root segments was incorporated in the forward electrical model using the power-law mixing model.

Results

The time-lapse analysis of the synthetic ERT experiment shows that different root water uptake patterns can be delineated for measurements collected under WD conditions but not under wet conditions. Three indices were found (depletion amount, maximum depth, and spread), which allow capturing plant-specific water signatures based moisture profile changes derived from EC profiles. When root electrical properties were incorporated in the synthetic experiments, it led to the wrong estimation of the amount of water depletion, but a correct ranking of plants depletion depth. When applied to the filed data, our indices showed that Cocksfoot and Ryegrass had shallower soil water depletion zones than white clover and white clover combined with Ryegrass. However, in terms of water depletion amount, Cocksfoot consumed the largest amount of water, followed by White Clover, Ryegrass+White Clover mixture, and Ryegrass.

Conclusion

ERT is a well-suited method for phenotyping root water uptake ability in field trials under WD conditions.

     

Metabolic rate and genomic GC: what we can learn from teleost fish

Teleosts are a highly diverse group of animals occupying all kind of aquatic environment. Data on routine mass specific metabolic rate were re-examined correcting them for the Boltzmann's factor. Teleostean fish were grouped in five broad groups, corresponding to major environmental classifications: polar, temperate, sub-tropical, tropical and deep-water. The specific routine metabolic rate, temperature-corrected using the Boltzmann's factor (MR), and the average base composition of genomes (GC%) were calculated in each group. Fish of the polar habitat showed the highest MR. Temperate fish displayed a significantly higher MR than tropical fish, which had the lowest average value. These results were apparently in agreement with the cold adaptation hypothesis. In contrast with this hypothesis, however, the MR of fish living in deep-water environment turned out to be not significantly different from that of fish living in tropical habitats. Most probably, the amount of oxygen dissolved in the water directly affects MR adaptation. Regarding the different habitats, the genomic GC levels showed a decreasing trend similar to that of MR. Indeed, both polar and temperate fish showed a GC level significantly higher than that of both sub-tropical and tropical fish. Plotting the genomic GC levels versus the MR a significant positive correlation was found, supporting the hypothesis that metabolic rate can explain not only the compositional transition mode (e.g. amphibian/mammals), but also the compositional shifting mode (e.g. fish/fish) of evolution observed for vertebrate genomes.     

New 1,2,3,9-tetrahydro-4H-carbazol-4-one derivatives: analogues of HEAT as ligands for the alpha1-adrenergic receptor subtypes

With the aim to develop new ligands able to discriminate among the three subtypes of alpha1-adrenergic receptors (alpha1A-AR, alpha1B-AR, and alpha1D-AR), a series of new 1,2,3,9-tetrahydro-4H-carbazol-4-ones bearing a 3-[[[2-(4-hydroxyphenyl)ethyl]amino]methyl] or a 3-[[4-(2-substitutedphenyl)piperazin-1-yl]methyl] side chain were synthesized. The general structure of the new compounds is reminiscent of HEAT and RN5, two potent alpha1-AR antagonists which show high affinities for all three alpha1-AR subtypes. Some derivatives in which one ring of the tetrahydrocarbazolone system was opened were also prepared. Compounds were tested in radioligand binding assays on human cloned alpha1A-AR, alpha1B-AR, and alpha1D-AR subtypes stably expressed in HEK293 cells. They showed moderate to good affinities, although their selectivity among the receptor subtypes hardly reached one order of magnitude.     

The ruddy duck Oxyura jamaicensis in Europe: natural colonization or human introduction?

Native to North America, ruddy ducks Oxyura jamaicensis now occur in 21 countries in the western Palaearctic (including Iceland) and their expanding population threatens the native white-headed duck, Oxyura leucocephala, through hybridization and possibly competition for food and nest sites. We used mitochondrial DNA sequences and nuclear microsatellites to test whether the European ruddy duck population is descended solely from the captive population in the UK, which traces to seven individuals imported from the USA in 1948, or, alternatively, has been augmented by natural dispersal of birds from North America. Limited genetic diversity in the European population is consistent with a founder population as small as seven birds. In addition, shifts in allele frequencies at several loci, presumably due to genetic drift in the founding population, result in significant differentiation between the European and North American populations. Despite the recent separation of these populations, almost all individuals could be unambiguously assigned based on their composite genotypes, to one of two distinct populations, one comprising all of the European ruddy ducks we sampled (including those from Iceland and captive birds in the UK) and the other comprising all North American samples. Our results confirm that the European ruddy duck population is likely to derive solely from the captive population in the UK and we find no evidence of recent arrivals from North America or of admixture between ruddy ducks from Europe and North America.     

Genetic diversity, population structure, effective population size and demographic history of the Finnish wolf population

The Finnish wolf population (Canis lupus) was sampled during three different periods (1996-1998, 1999-2001 and 2002-2004), and 118 individuals were genotyped with 10 microsatellite markers. Large genetic variation was found in the population despite a recent demographic bottleneck. No spatial population subdivision was found even though a significant negative relationship between genetic relatedness and geographic distance suggested isolation by distance. Very few individuals did not belong to the local wolf population as determined by assignment analyses, suggesting a low level of immigration in the population. We used the temporal approach and several statistical methods to estimate the variance effective size of the population. All methods gave similar estimates of effective population size, approximately 40 wolves. These estimates were slightly larger than the estimated census size of breeding individuals. A Bayesian model based on Markov chain Monte Carlo simulations indicated strong evidence for a long-term population decline. These results suggest that the contemporary wolf population size is roughly 8% of its historical size, and that the population decline dates back to late 19th century or early 20th century. Despite an increase of over 50% in the census size of the population during the whole study period, there was only weak evidence that the effective population size during the last period was higher than during the first. This may be caused by increased inbreeding, diminished dispersal within the population, and decreased immigration to the population during the last study period.