Prevention of breast cancer by recapitulation of pregnancy hormone levels

At the present time, the only approved method of breast cancer prevention is use of the selective estrogen receptor modulator (SERM) tamoxifen. Many breast cancers are driven to grow by estrogen, and tamoxifen exploits this by blocking estrogen action at the estrogen receptor. A counter-intuitive and controversial approach to breast cancer prevention is administration of estrogen and progestin at an early age to achieve pregnancy levels. This approach is supported by the fact that breast cancer incidence is halved by early (≤ 20 years of age) full-term pregnancy. Moreover, it has been demonstrated in rodent models that mimicking the hormonal milieu can effectively prevent carcinogen-induced mammary cancer. In this issue of Breast Cancer Research Rajkumar and colleagues use the rodent model to further define the timing and type of hormonal therapy that is effective in preventing mammary carcinogenesis. Clearly, application of this approach in humans may be difficult, but the potential benefit is intriguing

Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network

BACKGROUND: Large-scale studies have revealed networks of various biological interaction types, such as protein-protein interaction, genetic interaction, transcriptional regulation, sequence homology, and expression correlation. Recurring patterns of interconnection, or 'network motifs', have revealed biological insights for networks containing either one or two types of interaction. RESULTS: To study more complex relationships involving multiple biological interaction types, we assembled an integrated Saccharomyces cerevisiae network in which nodes represent genes (or their protein products) and differently colored links represent the aforementioned five biological interaction types. We examined three- and four-node interconnection patterns containing multiple interaction types and found many enriched multi-color network motifs. Furthermore, we showed that most of the motifs form 'network themes' – classes of higher-order recurring interconnection patterns that encompass multiple occurrences of network motifs. Network themes can be tied to specific biological phenomena and may represent more fundamental network design principles. Examples of network themes include a pair of protein complexes with many inter-complex genetic interactions – the 'compensatory complexes' theme. Thematic maps – networks rendered in terms of such themes – can simplify an otherwise confusing tangle of biological relationships. We show this by mapping the S. cerevisiae network in terms of two specific network themes. CONCLUSION: Significantly enriched motifs in an integrated S. cerevisiae interaction network are often signatures of network themes, higher-order network structures that correspond to biological phenomena. Representing networks in terms of network themes provides a useful simplification of complex biological relationships

Attitudes toward Precision Treatment of Smoking in the Southern Community Cohort Study

Background: Precision interventions using biological data may enhance smoking treatment, yet are understudied among smokers who are disproportionately burdened by smoking-related disease. Methods: We surveyed smokers in the NCI-sponsored Southern Community Cohort Study, consisting primarily of African-American, low-income adults. Seven items assessed attitudes toward aspects of precision smoking treatment, from undergoing tests to acting on results. Items were dichotomized as favorable (5 = strongly agree/4 = agree) versus less favorable (1 = strongly disagree/2 = disagree/3 = neutral); a summary score reflecting generalized attitudes was also computed. Multivariable logistic regression tested independent associations of motivation (precontemplation, contemplation, and preparation) and confidence in quitting (low, medium, and high) with generalized attitudes, controlling for sociodemographic factors and nicotine dependence. Results: More than 70% of respondents endorsed favorable generalized attitudes toward precision medicine, with individual item favorability ranging from 64% to 83%. Smokers holding favorable generalized attitudes reported higher income and education (P \u3c 0.05). Predicted probabilities of favorable generalized attitudes ranged from 63% to 75% across motivation levels [contemplation vs. precontemplation: adjusted odds ratio (AOR) = 2.10, 95% confidence interval (CI), 1.36–3.25, P = 0.001; preparation vs. precontemplation: AOR = 1.83, 95% CI, 1.20–2.78, P = 0.005; contemplation vs. preparation: AOR = 1.15, 95% CI, 0.75–1.77, P = 0.52] and from 59% to 78% across confidence (medium vs. low: AOR = 1.91, 95% CI, 1.19–3.07, P = 0.007; high vs. low: AOR = 2.62, 95% CI, 1.68–4.10, P \u3c 0.001; medium vs. high: AOR = 0.73, 95% CI, 0.48–1.11, P = 0.14). Conclusions: Among disproportionately burdened community smokers, most hold favorable attitudes toward precision smoking treatment. Individuals with lower motivation and confidence to quit may benefit from additional intervention to engage with precision smoking treatment. Impact: Predominantly favorable attitudes toward precision smoking treatment suggest promise for future research testing their effectiveness and implementation

PTB Domain-Directed Substrate Targeting in a Tyrosine Kinase from the Unicellular Choanoflagellate Monosiga brevicollis

Choanoflagellates are considered to be the closest living unicellular relatives of metazoans. The genome of the choanoflagellate Monosiga brevicollis contains a surprisingly high number and diversity of tyrosine kinases, tyrosine phosphatases, and phosphotyrosine-binding domains. Many of the tyrosine kinases possess combinations of domains that have not been observed in any multicellular organism. The role of these protein interaction domains in M. brevicollis kinase signaling is not clear. Here, we have carried out a biochemical characterization of Monosiga HMTK1, a protein containing a putative PTB domain linked to a tyrosine kinase catalytic domain. We cloned, expressed, and purified HMTK1, and we demonstrated that it possesses tyrosine kinase activity. We used immobilized peptide arrays to define a preferred ligand for the third PTB domain of HMTK1. Peptide sequences containing this ligand sequence are phosphorylated efficiently by recombinant HMTK1, suggesting that the PTB domain of HMTK1 has a role in substrate recognition analogous to the SH2 and SH3 domains of mammalian Src family kinases. We suggest that the substrate recruitment function of the noncatalytic domains of tyrosine kinases arose before their roles in autoinhibition

First LIGO search for gravitational wave bursts from cosmic (super)strings

We report on a matched-filter search for gravitational wave bursts from cosmic string cusps using LIGO data from the fourth science run (S4) which took place in February and March 2005. No gravitational waves were detected in 14.9 days of data from times when all three LIGO detectors were operating. We interpret the result in terms of a frequentist upper limit on the rate of gravitational wave bursts and use the limits on the rate to constrain the parameter space (string tension, reconnection probability, and loop sizes) of cosmic string models.Comment: 11 pages, 3 figures. Replaced with version submitted to PR

Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target

All-sky LIGO Search for Periodic Gravitational Waves in the Early S5 Data

We report on an all-sky search with the LIGO detectors for periodic gravitational waves in the frequency range 50--1100 Hz and with the frequency's time derivative in the range -5.0E-9 Hz/s to zero. Data from the first eight months of the fifth LIGO science run (S5) have been used in this search, which is based on a semi-coherent method (PowerFlux) of summing strain power. Observing no evidence of periodic gravitational radiation, we report 95% confidence-level upper limits on radiation emitted by any unknown isolated rotating neutron stars within the search range. Strain limits below 1.E-24 are obtained over a 200-Hz band, and the sensitivity improvement over previous searches increases the spatial volume sampled by an average factor of about 100 over the entire search band. For a neutron star with nominal equatorial ellipticity of 1.0E-6, the search is sensitive to distances as great as 500 pc--a range that could encompass many undiscovered neutron stars, albeit only a tiny fraction of which would likely be rotating fast enough to be accessible to LIGO. This ellipticity is at the upper range thought to be sustainable by conventional neutron stars and well below the maximum sustainable by a strange quark star.Comment: 6 pages, 1 figur

Search for Gravitational Wave Bursts from Six Magnetars

Soft gamma repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are thought to be magnetars: neutron stars powered by extreme magnetic fields. These rare objects are characterized by repeated and sometimes spectacular gamma-ray bursts. The burst mechanism might involve crustal fractures and excitation of non-radial modes which would emit gravitational waves (GWs). We present the results of a search for GW bursts from six galactic magnetars that is sensitive to neutron star f-modes, thought to be the most efficient GW emitting oscillatory modes in compact stars. One of them, SGR 0501+4516, is likely similar to 1 kpc from Earth, an order of magnitude closer than magnetars targeted in previous GW searches. A second, AXP 1E 1547.0-5408, gave a burst with an estimated isotropic energy >10(44) erg which is comparable to the giant flares. We find no evidence of GWs associated with a sample of 1279 electromagnetic triggers from six magnetars occurring between 2006 November and 2009 June, in GW data from the LIGO, Virgo, and GEO600 detectors. Our lowest model-dependent GW emission energy upper limits for band-and time-limited white noise bursts in the detector sensitive band, and for f-mode ringdowns (at 1090 Hz), are 3.0 x 10(44)d(1)(2) erg and 1.4 x 10(47)d(1)(2) erg, respectively, where d(1) = d(0501)/1 kpc and d(0501) is the distance to SGR 0501+4516. These limits on GW emission from f-modes are an order of magnitude lower than any previous, and approach the range of electromagnetic energies seen in SGR giant flares for the first time.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyItalian Istituto Nazionale di Fisica NucleareFrench Centre National de la Recherche ScientifiqueAustralian Research CouncilCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Educacion y CienciaConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsFoundation for Fundamental Research on Matter supported by the Netherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFoundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space Administration NNH07ZDA001-GLASTCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationRussian Space AgencyRFBR 09-02-00166aIPN JPL Y503559 (Odyssey), NASA NNG06GH00G, NASA NNX07AM42G, NASA NNX08AC89G (INTEGRAL), NASA NNG06GI896, NASA NNX07AJ65G, NASA NNX08AN23G (Swift), NASA NNX07AR71G (MESSENGER), NASA NNX06AI36G, NASA NNX08AB84G, NASA NNX08AZ85G (Suzaku), NASA NNX09AU03G (Fermi)Astronom