Condition-dependent sexual traits and social dominance in the house finch

Elaboration of costly sexual traits can reduce investment inother aspects of reproduction, such as parental care or intrasexualcompetition, which may lead to the evolution of alternativemating tactics. In house finches (Carpodacus mexicanus), lesselaborately ornamented (dull) males tend to dominate more elaborated(redder) males, but redder males pair earlier and invest morein parental care. This suggests that males may pursue alternativeparental or competitive tactics, depending on the elaborationof their sexual trait. Elevation of testosterone, a hormonethat is closely associated with condition in male house finches,influences dominance and sexual behaviors but is antagonisticto parental behaviors. We tested the hypothesis that the higherdominance status of dull males reflects an alternative testosterone-dependentmating tactic. First, we experimentally manipulated the testosteronelevels of captive males and measured the effect on dominancerank, and second, we measured the association of testosteroneelevation and plumage hue in free-living males. We found that,as predicted, testosterone elevation increased dominance rankin captive males. However, in free-living males, testosteronelevels were higher in redder males, suggesting that testosteroneis dissociated from dominance status under natural circumstances.This may be because the context of social interactions and thehigher motivation of dull males to access food resources havea stronger influence on the outcome of dominance interactionsthan does the physiological effects of testosterone elevation.In turn, the strong positive correlation between testosteronelevels and plumage elaboration likely reflects the common conditiondependence of these traits.     

The orphan receptor COUP-TFII regulates G2/M progression of breast cancer cells by modulating the expression/activity of p21(WAF1/CIP1), cyclin D1, and cdk2

The orphan receptors COUP-TFI and COUP-TFII play an important role in development and differentiation by activating specific genes and by modulating the activity of nuclear receptors including estrogen receptor alpha (ERalpha) and retinoic acid receptors (RARs). Previously, it was demonstrated that the expression and activity of ERalpha and RARs are lost or impaired in anti-estrogen-resistant breast cancers. Here we show that, similar to ERalpha and RARs, the expression of COUP-TFII but not COUP-TFI is reduced in approximately 30% of breast cancer cell lines. Introduction of COUP-TFII to MDA-MB-435 cells resulted in reduced growth and plating efficiency. Interestingly, COUP-TFII increased the expression of cyclin D1 and p21(WAF1/CIP1) in MDA-MB-435 cells. Although parental and COUP-TFII-transduced cells progressed through the G1-S phase at a similar rate, progression of COUP-TFII cells through the G2/M transition phase was delayed. The activity of cdk2 required for G2/M progression was reduced in COUP-TFII cells compared to parental cells. This property of COUP-TFII is distinct from that of ERalpha and RARs, which usually modulate the G1 phase of breast cancer cells. Furthermore, these results reveal an important physiological function of COUP-TFII, which correlates with its ability to induce gene expression rather than modulation of nuclear receptor activity.     

Identification of structural DNA variations in human cell cultures after long-term passage

Random amplified polymorphic DNA (RAPD) analysis was adapted for genomic identification of cell cultures and evaluation of DNA stability in cells of different origin at different culture passages. DNA stability was observed in cultures after no more than 5 passages. Adipose-derived stromal cells demonstrated increased DNA instability. RAPD fragments from different cell lines after different number of passages were cloned and sequenced. The chromosomal localization of these fragments was identified and single-nucleotide variations in RAPD fragments isolated from cell lines after 8–12 passages were revealed. Some of them had permanent localization, while most variations demonstrated random distribution and can be considered as de novo mutations.     

The expression level of luciferase within tumour cells can alter tumour growth upon in vivo bioluminescence imaging.

In vivo bioluminescence imaging is becoming a very important tool for the study of a variety of cellular and molecular events or disease processes in living systems. In vivo bioluminescence imaging is based on the detection of light emitted from within an animal. The light is generated as a product of the luciferase-luciferin reaction taking place in a cell. In this study, we implanted mice with tumour cells expressing either a high or a low level of luciferase. In vivo bioluminescence imaging was used to follow tumour progression. Repeated luciferin injection and imaging of high and low luciferase-expressing tumours was performed. While low luciferase-expressing tumours grew similarly to vector controls, growth of the high luciferase-expressing tumours was severely inhibited. The observation that a high level of luciferase expression will inhibit tumour cell growth when an animal is subjected to serial in vivo bioluminescence imaging is potentially an important factor in designing these types of studies.     

Recruitment of TRF2 to laser-induced DNA damage sites

Several lines of evidence suggest that the telomere-associated protein TRF2 plays critical roles in the DNA damage response. TRF2 is rapidly and transiently phosphorylated by an ATM-dependent pathway in response to DNA damage and this DNA damage-induced phosphoryation is essential for the DNA-PK-dependent pathway of DNA double-strand break repair (DSB). However, the type of DNA damage that induces TRF2 localization to the damage sites, the requirement for DNA damage-induced phosphorylation of TRF2 for its recruitment, as well as the detailed kinetics of TRF2 accumulation at DNA damage sites have not been fully investigated. In order to address these questions, we used an ultrafast femtosecond multiphoton laser and a continuous wave 405-nm single photon laser to induce DNA damage at defined nuclear locations. Our results showed that DNA damage produced by a femtosecond multiphoton laser was sufficient for localization of TRF2 to these DNA damage sites. We also demonstrate that ectopically expressed TRF2 was recruited to DNA lesions created by a 405-nm laser. Our data suggest that ATM and DNA-PKcs kinases are not required for TRF2 localization to DNA damage sites. Furthermore, we found that phosphorylation of TRF2 at residue T188 was not essential for its recruitment to laser-induced DNA damage sites. Thus, we provide further evidence that a protein known to function in telomere maintenance, TRF2, is recruited to sites of DNA damage and plays critical roles in the DNA damage response.     

Molecular evolution in the gnd locus of Salmonella enterica

The gnd gene, the structural gene for 6-phosphogluconate dehydrogenase, was sequenced and analyzed in 34 isolates from different serovars of the seven subspecies of Salmonella enterica to provide comparative information on the evolution in this gene, which has been studied extensively in Escherichia coli. The gene tree obtained by the neighbor- joining method in general gave separate branches for each subspecies, with the few exceptions readily explained by recombination. There is evidence of recombination involving transfer of long (more than 400 bp) and short (30-150 bp) segments of DNA. Four of the six long-segment transfers detected are at the 5' end of the gene, and in all four cases a variant of the chi sequence is located close to the recombination junction and appears to have mediated the recombination events. We suggest that in these four cases and in a fifth case with intersubspecies transfer of the whole gnd gene, the adjacent rfb (O antigen) locus may have been transferred in the same event. The estimates of the number of synonymous substitutions per synonymous site, KS, and the number of nonsynonymous substitutions per nonsynonymous site, KA, within the E. coli and S. enterica gnd genes, and also between the two species show an interesting distribution, with KS being lower toward the ends of the gene and KA in particular being lower in the first than in the second domain. In S. enterica, synonymous sites also seem to be subjected to negative selection. The ratio of KA to KS was higher within S. enterica and E. coli than between them, which may indicate that intraspecies variation is essentially between clones and that mildly deleterious mutations can be fixed within clones, which would thus raise KA within species.      

Differential use of autophagy by primary dendritic cells specialized in cross-presentation

Antigen-presenting cells survey their environment and present captured antigens bound to major histocompatibility complex (MHC) molecules. Formation of MHC-antigen complexes occurs in specialized compartments where multiple protein trafficking routes, still incompletely understood, converge. Autophagy is a route that enables the presentation of cytosolic antigen by MHC class II molecules. Some reports also implicate autophagy in the presentation of extracellular, endocytosed antigen by MHC class I molecules, a pathway termed “cross-presentation.” The role of autophagy in cross-presentation is controversial. This may be due to studies using different types of antigen presenting cells for which the use of autophagy is not well defined. Here we report that active use of autophagy is evident only in DC subtypes specialized in cross-presentation. However, the contribution of autophagy to cross-presentation varied depending on the form of antigen: it was negligible in the case of cell-associated antigen or antigen delivered via receptor-mediated endocytosis, but more prominent when the antigen was a soluble protein. These findings highlight the differential use of autophagy and its machinery by primary cells equipped with specific immune function, and prompt careful reassessment of the participation of this endocytic pathway in antigen cross-presentation.     

Radiation-induced genetic instability in vivo depends on p53 status

In response to ionizing radiation and other agents that damage DNA, the p53 tumor suppressor protein activates multiple cellular processes including cell cycle checkpoints and programmed cell death. Although loss of p53 function is associated with radiation-induced genetic instability in cell lines, it is not clear if this relationship exists in vivo. To study the role of p53 in maintenance of genetic stability in normal tissues following irradiation, we have measured mutant frequencies at the adenine phosphoribosyltransferase (Aprt) and hypothanine-guanine phosphoribosyltransferase (Hprt) loci and examined mechanisms of loss of heterozygosity (LOH) in normal T cells of p53-deficient, Aprt heterozygous mice that were subjected to whole-body irradiation with a single dose of 4Gy X-rays. The radiation-induced mutant frequency at both the Aprt and Hprt loci was elevated in cells from mice with different p53 genotypes. The radiation-induced elevation of p53-/- mice was significantly greater than that of p53+/- or p53+/+ mice and was caused by several different kinds of mutational events at the both chromosomal and intragenic levels. Most significantly, interstitial deletion, which occurs rarely in unirradiated mice, became the most common mechanism leading to LOH in irradiated p53 null mice. These observations support the idea that absence or reduction of p53 expression enhances radiation-induced tumorigenesis by increasing genetic instability at various loci, such as those for tumor suppressor genes.     

SIMPLE: implementation of recommendations from international evidence-based guidelines on caesarean sections in the Netherlands. Protocol for a controlled before and after study

Background

Caesarean section (CS) rates are rising worldwide. In the Netherlands, the most significant rise is observed in healthy women with a singleton in vertex position between 37 and 42 weeks gestation, whereas it is doubtful whether an improved outcome for the mother or her child was obtained. It can be hypothesized that evidence-based guidelines on CS are not implemented sufficiently. Therefore, the present study has the following objectives: to develop quality indicators on the decision to perform a CS based on key recommendations from national and international guidelines; to use the quality indicators in order to gain insight into actual adherence of Dutch gynaecologists to guideline recommendations on the performance of a CS; to explore barriers and facilitators that have a direct effect on guideline application regarding CS; and to develop, execute, and evaluate a strategy in order to reduce the CS incidence for a similar neonatal outcome (based on the information gathered in the second and third objectives).

Methods

An independent expert panel of Dutch gynaecologists and midwives will develop a set of quality indicators on the decision to perform a CS. These indicators will be used to measure current care in 20 hospitals with a population of 1,000 women who delivered by CS, and a random selection of 1,000 women who delivered vaginally in the same period. Furthermore, by interviewing healthcare professionals and patients, the barriers and facilitators that may influence the decision to perform a CS will be measured. Based on the results, a tailor-made implementation strategy will be developed and tested in a controlled before-and-after study in 12 hospitals (six intervention, six control hospitals) with regard to effectiveness, experiences, and costs.

Discussion

This study will offer insight into the current CS care and into the hindering and facilitating factors influencing obstetrical policy on CS. Furthermore, it will allow definition of patient categories or situations in which a tailor-made implementation strategy will most likely be meaningful and cost effective, without negatively affecting the outcome for mother and child.

Trial registration

http://www.clinicaltrials.gov: NCT01261676