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Mechanisms regulating the transition of mammary epithelial cells (MECs) to mammary stem cells (MaSCs) and to tumor-initiating cells (TICs) have not been entirely elucidated. The p53 family member, p63, is critical for mammary gland development and contains transactivation domain isoforms, which have tumor-suppressive activities, and the ΔN isoforms, which act as oncogenes. In the clinic, p63 is often used as a diagnostic marker, and further analysis of the function of TAp63 in the mammary gland is critical for improved diagnosis and patient care. Loss of TAp63 in mice leads to the formation of aggressive metastatic mammary adenocarcinoma at 9–16 months of age. Here we show that TAp63 is crucial for the transition of mammary cancer cells to TICs. When TAp63 is lost, MECs express embryonic and MaSC signatures and activate the Hippo pathway. These data indicate a crucial role for TAp63 in mammary TICs and provide a mechanism for its role as a tumor- and metastasis-suppressor in breast cancer.

Context. We have carried out a semi-automated search for planetary nebulae (PNe) in the INT photometric H-alpha survey (IPHAS) catalogue. We present the PN search and the list of selected candidates. We cross correlate the selected candidates with a number of existing infrared galactic surveys in order to gain further insight into the nature of the candidates. Spectroscopy of a subset of objects is used to estimate the number of PNe present in the entire candidate list.

Context.The study of symbiotic stars is essential to understand important aspects of stellar evolution in interacting binaries. Their observedpopulation in the Galaxy is however poorly known, and is one to three orders of magnitudes smaller than the predictedpopulation size.

Context.The Isaac Newton Telescope Photometric HαSurvey (IPHAS) is currently mapping the Northern Galactic plane reaching to $r'=20$mag with typically 1″ resolution. Hundreds of Planetary Nebulae (PNe), both point-like and resolved, are expected to be discovered. We report on the discovery of the first new PN from this survey: it is an unusual object located at a large galactocentric distance and has a very low oxygen abundance.

Caspases are the executioners of apoptosis. Although much is known about their physiological roles and structures, detailed analyses of missense mutations of caspases are lacking. As mutations within caspases are identified in various human diseases, the study of caspase mutants will help to elucidate how caspases interact with other components of the apoptosis pathway and how they may contribute to disease. DrICE is the major effector caspase in Drosophila required for developmental and stress-induced cell death. Here, we report the isolation and characterization of six de novo drICE mutants, all of which carry point mutations affecting amino acids conserved among caspases in various species. These six mutants behave as recessive loss-of-function mutants in a homozygous condition. Surprisingly, however, two of the newly isolated drICE alleles are gain-of-function mutants in a heterozygous condition, although they are loss-of-function mutants homozygously. Interestingly, they only behave as gain-of-function mutants in the presence of an apoptotic signal. These two alleles carry missense mutations affecting conserved amino acids in close proximity to the catalytic cysteine residue. This is the first time that viable gain-of-function alleles of caspases are described in any intact organism and provides a significant exception to the expectation that mutations of conserved amino acids always abolish the pro-apoptotic activity of caspases. We discuss models about how these mutations cause the gain-of-function character of these alleles.

Four soybean meals (SBM) were manufactured in a commerical solvent-extraction plant to give a much wider range in heat treatment than is usually found among commercially available SBM. The SBM were designated in ascending order of heat treatment as Under, Normal, Over and Rumen Escape. The nutritive value of the four meals was evaluated in a series of five feeding trials using 458 pigs: two performance and two diet preference trials with pigs weaned at 4 wk of age and one performance trial with growing pigs (17.4 kg initial weight were conducted). In both nursery and grower trials, there were no differences (P>.10) in performance of pigs fed the four meals. However, in the nursery trials, the severely heated meal (Rumen Escape) supported slightly lower gains (6.4%) and less desirable feed efficiency (3.5%) than the average of the other three meals. Growing pig performance was essentially the same for all meals. This suggests that older pigs either used the Rumen Escape meal more effectively than nursery pigs, or the Rumen Escape diet contained adequate digestible lysine for 17.4-kg pigs to grow optimally. In the preference studies, pigs selected between Normal- and Rumen Escape-supplemented diets. Pigs consumed 63 and 62% of the Normal diet in preference trials 1 and 2, but these differences were not significant (P>.10) due to the large variation among pens. These data suggest that the range of heat treatment normally found among commercially available SBM (Under, Normal and Over meals) has no effect on the nutritive value of the meal for swine. Pigs would be expected to perform similarly on meals with urease activity (ΔpH) of .19 to .01, trypsin inhibitor values of 5.3 to 1.6, nitrogen solubility indexes of 27.8 to 12.5% and +a Hunterlab color values of 2.9 to 7.3.

The study of human papillomavirus type 16 (HPV-16) replication has been impaired because of the lack of a cell culture system that stably maintains viral replication. Recently, cervical epithelial cell populations that stably maintain HPV-16 replicons at a copy number of approximately 1,000 per cell were derived from an HPV-16-infected patient (W12 cell clone 20863 [W12-E cells]). We used neutral/neutral and neutral/alkaline two-dimensional gel electrophoretic techniques to characterize HPV-16 DNA replication in these cells. When W12-E cells were maintained in an undifferentiated state mimicking the nonproductive stage of the life cycle, HPV-16 DNA was found to replicate primarily by theta structures in a bidirectional manner. The initiation site of HPV-16 DNA replication was mapped to approximately nucleotide 100, and the termination site was mapped to between nucleotides 3398 and 5990. To study the productive stage of HPV-16 DNA replication, W12-E cells were grown under culture conditions that promote differentiation of epithelial cell types. Under these conditions, where virus-like particles were detected, the mode of viral DNA replication changed from theta structure to what is apparently a rolling circle mode. Additionally, CIN 612-9E cells, which were derived from an HPV-31-infected patient and harbor HPV-31 extrachromosomally, exhibited the same switch in the mode of DNA replication upon induction of differentiation. These data argue that a fundamental switch in the mechanism of viral DNA replication occurs during the life cycle of the papillomavirus.

Context. Knowledge of the total population of symbiotic stars in the Galaxy is important for understanding basic aspects of stellar evolution in interacting binaries and the relevance of this class of objects in the formation of supernovae of type Ia.Aims. In a previous paper, we presented the selection criteria needed to search for symbiotic stars in IPHAS, the INT Hasurvey of the Northern Galactic plane. IPHAS gives us the opportunity to make a systematic, complete search for symbiotic stars in a magnitude-limited volume.Methods. Follow-up spectroscopy at different telescopes worldwide of a sample of sixty two symbiotic star candidates is presented.Results. Seven out of nineteen S-type candidates observed spectroscopically are confirmed to be genuine symbiotic stars. The spectral type of their red giant components, as well as reddening and distance, were computed by modelling the spectra. Only one new D-type symbiotic system, out of forty-three candidates observed, was found. This was as expected (see discussion in our paper on the selection criteria). The object shows evidence for a high density outflow expanding at a speed =65 km?s-1.?Most of the other candidates are lightly reddened classical T Tauri stars and more highly reddened young stellar objects that may be either more massive young stars of HAeBe type or classical Be stars. In addition, a few notable objects have been found, such as three new Wolf-Rayet stars and two relatively high-luminosity evolved massive stars. We also found a helium-rich source, possibly a dense ejecta hiding a WR star, which is surrounded by a large ionized nebula.Conclusions. These spectroscopic data allow us to refine the selection criteria for symbiotic stars in the IPHAS survey and, more generally, to better understand the behaviour of different Haemitters in the IPHAS and 2MASS colour-colour diagrams.

Context. Knowledge of the total population of symbiotic stars in the Galaxy is important for understanding basic aspects of stellar evolution in interacting binaries and the relevance of this class of objects in the formation of supernovae of type Ia.Aims. In a previous paper, we presented the selection criteria needed to search for symbiotic stars in IPHAS, the INT Hasurvey of the Northern Galactic plane. IPHAS gives us the opportunity to make a systematic, complete search for symbiotic stars in a magnitude-limited volume.Methods. Follow-up spectroscopy at different telescopes worldwide of a sample of sixty two symbiotic star candidates is presented.Results. Seven out of nineteen S-type candidates observed spectroscopically are confirmed to be genuine symbiotic stars. The spectral type of their red giant components, as well as reddening and distance, were computed by modelling the spectra. Only one new D-type symbiotic system, out of forty-three candidates observed, was found. This was as expected (see discussion in our paper on the selection criteria). The object shows evidence for a high density outflow expanding at a speed =65 km?s-1.?Most of the other candidates are lightly reddened classical T Tauri stars and more highly reddened young stellar objects that may be either more massive young stars of HAeBe type or classical Be stars. In addition, a few notable objects have been found, such as three new Wolf-Rayet stars and two relatively high-luminosity evolved massive stars. We also found a helium-rich source, possibly a dense ejecta hiding a WR star, which is surrounded by a large ionized nebula.Conclusions. These spectroscopic data allow us to refine the selection criteria for symbiotic stars in the IPHAS survey and, more generally, to better understand the behaviour of different Haemitters in the IPHAS and 2MASS colour-colour diagrams.

Context. Knowledge of the total population of symbiotic stars in the Galaxy is important for understanding basic aspects of stellar evolution in interacting binaries and the relevance of this class of objects in the formation of supernovae of type Ia.