Transfer of the Nonmatch-to-Goal rule in Monkeys across Cognitive Domains

To solve novel problems, it is advantageous to abstract relevant information from past experience to transfer on related problems. To study whether macaque monkeys were able to transfer an abstract rule across cognitive domains, we trained two monkeys on a nonmatch-to-goal (NMTG) task. In the object version of the task (O-NMTG), the monkeys were required to choose between two object-like stimuli, which differed either only in shape or in shape and color. For each choice, they were required to switch from their previously chosen object-goal to a different one. After they reached a performance level of over 90% correct on the O-NMTG task, the monkeys were tested for rule transfer on a spatial version of the task (S-NMTG). To receive a reward, the monkeys had to switch from their previously chosen location to a different one. In both the O-NMTG and S-NMTG tasks, there were four potential choices, presented in pairs from trial-to-trial. We found that both monkeys transferred successfully the NMTG rule within the first testing session, showing effective transfer of the learned rule between two cognitive domains.     

Structure-activity relationship study of position 4 in the urotensin-II receptor ligand U-II(4-11)

In the present study we describe the synthesis and biological evaluation of 24 analogues of the urotensin II (U-II) fragment U-II(4-11) substituted in position 4 with coded and non-coded aromatic amino acids. All of the new analogues behaved as full U-II receptor (UT) agonists. Our results indicated that aromaticity is well tolerated, size, length and chirality of the side chain are not important, while substituents with a nitrogen atom are preferred. Thus acylation of U-II(5-11) with small groups bearing nitrogen atoms could be instrumental in future studies for the identification of novel potent UT receptor ligands.     

A consistent phylogenetic backbone for the fungi

The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data-a common practice in phylogenomic analyses-introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses.     

Thermal ecology of two sympatric saxicolous lizards of the genus Phymaturus from the Payunia region (Argentina)

We evaluated the thermal biology of two sympatric saxicolous species of the genus Phymaturus, endemic from the Argentine Payunia region. Taking into account that the distributional range of Phymaturus roigorum (the largest species) is greater than the range of P. payuniae, we evaluated the habitat (type of rocks) used by these species. We recorded body temperature and operative temperatures in different habitats, and we determined the preferred body temperature in the laboratory. We compared the thermal quality of habitats occupied and not occupied by Phymaturus payuniae, and the accuracy and effectiveness of thermoregulation between species.     

Up-regulation of blood arachidonate (20:4) levels in patients with chronic obstructive pulmonary disease

Context and objective: Plasma arachidonate (20:4) levels in patients with chronic obstructive pulmonary disease (COPD) were investigated. Methods: Plasma was extracted and free fatty acids (FFAs) were separated using column chromatography and measured by fluorescence. Plasma 20:4 levels and its percentage relative to total FFA levels (%20:4) were measured in COPD (n = 18) and control (n = 20) subjects. Results and conclusions: FFA levels were lower in COPD compared with normals. However, there was a significant increase in %20:4 levels in COPD patients (GOLD stage I/II 0.9 ± 0.4%; GOLD stage III/IV 1.1 ± 0.1%) compared with control subjects (0.6 ± 0.1, p < 0.05). %20:4 is a potential biomarker for COPD.     

Sexual attraction: on the role of fungal pheromone/receptor systems (A review)

Pheromones have been detected in all fungal phylogenetic lineages. This came as a surprise, as the general role of pheromones in mate attraction was not envisioned for some fungi. Pheromones and pheromone receptor genes have been identified, however, in members of all true fungal lineages, and even for mycelia forming organisms of plant and amoeba lineages, like oomycetes and myxomycetes. The mating systems and genes governing the mating type are different in fungi, ranging from bipolar with two opposite mating types to tetrapolar mating systems (with four possible mating outcomes, only one of which leads to fertile sexual development) in homobasidioymcetes with more than 23,000 mating types occurring in nature. Pheromones and receptors specifically recognizing these pheromones have evolved with slightly different functions in these different systems. This review is dedicated to follow the evolution of pheromone/receptor systems from simple, biallelic bipolar systems to multiallelic, tetrapolar versions and to explain the slightly different functions the pheromone recognition and subsequent signal transduction cascades within the fungal kingdom. The biotechnological implications of a detailed understanding of mating systems for biological control and plant protection, in medicine, and in mushroom breeding are discussed.     

Split T cell tolerance against a self/tumor antigen: spontaneous CD4+ but not CD8+ T cell responses against p53 in cancer patients and healthy donors

Analyses of NY-ESO-1-specific spontaneous immune responses in cancer patients revealed that antibody and both CD4(+) and CD8(+) T cell responses were induced together in cancer patients. To explore whether such integrated immune responses are also spontaneously induced for other tumor antigens, we have evaluated antibody and T cell responses against self/tumor antigen p53 in ovarian cancer patients and healthy individuals. We found that 21% (64/298) of ovarian cancer patients but no healthy donors showed specific IgG responses against wild-type p53 protein. While none of 12 patients with high titer p53 antibody showed spontaneous p53-specific CD8(+) T cell responses following a single in vitro sensitization, significant p53-specific IFN-γ producing CD4(+) T cells were detected in 6 patients. Surprisingly, similar levels of p53-specific CD4(+) T cells but not CD8(+) T cells were also detected in 5/10 seronegative cancer patients and 9/12 healthy donors. Importantly, p53-specific CD4(+) T cells in healthy donors originated from a CD45RA(-) antigen-experienced T cell population and recognized naturally processed wild-type p53 protein. These results raise the possibility that p53-specific CD4(+) T cells reflect abnormalities in p53 occurring in normal individuals and that they may play a role in processes of immunosurveillance or immunoregulation of p53-related neoplastic events.     

Mesenchymal Stem Cells Promote Mammosphere Formation and Decrease E-Cadherin in Normal and Malignant Breast Cells

Introduction

Normal and malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew, referred to as stem cells, or tumor initiating cells (TIC). These cells can be enriched by growth as “mammospheres” in three-dimensional cultures.

Objective

We tested the hypothesis that human bone-marrow derived mesenchymal stem cells (MSC), which are known to support tumor growth and metastasis, increase mammosphere formation.

Results

We found that MSC increased human mammary epithelial cell (HMEC) mammosphere formation in a dose-dependent manner. A similar increase in sphere formation was seen in human inflammatory (SUM149) and non-inflammatory breast cancer cell lines (MCF-7) but not in primary inflammatory breast cancer cells (MDA-IBC-3). We determined that increased mammosphere formation can be mediated by secreted factors as MSC conditioned media from MSC spheroids significantly increased HMEC, MCF-7 and SUM149 mammosphere formation by 6.4 to 21-fold. Mammospheres grown in MSC conditioned media had lower levels of the cell adhesion protein, E-cadherin, and increased expression of N-cadherin in SUM149 and HMEC cells, characteristic of a pro-invasive mesenchymal phenotype. Co-injection with MSC in vivo resulted in a reduced latency time to develop detectable MCF-7 and MDA-IBC-3 tumors and increased the growth of MDA-IBC-3 tumors. Furthermore, E-cadherin expression was decreased in MDA-IBC-3 xenografts with co-injection of MSC.

Conclusions

MSC increase the efficiency of primary mammosphere formation in normal and malignant breast cells and decrease E-cadherin expression, a biologic event associated with breast cancer progression and resistance to therapy.