Increased Dickkopf-1 expression in breast cancer bone metastases

The aim of this study was to determine whether Dickkopf-1 (Dkk-1) expression in breast cancer was associated with bone metastases. We first analysed Dkk-1 expression by human breast cancer cell lines that induce osteolytic or osteoblastic lesions in animals. Dickkopf-1 levels were then measured in the bone marrow aspirates of hind limbs from eight NMRI mice inoculated with breast cancer cells that induced bone metastases and 11 age-matched non-inoculated control animals. Finally, Dkk-1 was measured in the serum of 17 women with breast cancer in complete remission, 19 women with breast cancer and bone metastases, 16 women with breast cancer and metastases at non-bone sites and 16 healthy women. Only breast cancer cells that induce osteolytic lesions in animals produced Dkk-1. There was a six-fold increase in Dkk-1 levels in the bone marrow from animals inoculated with MDA-B02 cells when compared with that of control non-inoculated animals (P=0.003). Median Dkk-1 levels in the serum of patients with breast cancer and bone metastases were significantly higher than levels of patients in complete remission (P=0.016), patients with breast cancer having metastases at non-bone sites (P<0.0001) and healthy women (P=0.047), although there was a large overlap in individual levels between the different groups. In conclusion, Dkk-1 is secreted by osteolytic human breast cancer cells lines and increased circulating levels are associated with the presence of bone metastases in patients with breast cancer. Measurements of circulating Dkk-1 levels may be useful for the clinical investigation of patients with breast cancer and bone metastases

Preliminary evidence that both blue and red light can induce alertness at night

<p>Abstract</p> <p>Background</p> <p>A variety of studies have demonstrated that retinal light exposure can increase alertness at night. It is now well accepted that the circadian system is maximally sensitive to short-wavelength (blue) light and is quite insensitive to long-wavelength (red) light. Retinal exposures to blue light at night have been recently shown to impact alertness, implicating participation by the circadian system. The present experiment was conducted to look at the impact of both blue and red light at two different levels on nocturnal alertness. Visually effective but moderate levels of red light are ineffective for stimulating the circadian system. If it were shown that a moderate level of red light impacts alertness, it would have had to occur via a pathway other than through the circadian system.</p> <p>Methods</p> <p>Fourteen subjects participated in a within-subject two-night study, where each participant was exposed to four experimental lighting conditions. Each night each subject was presented a high (40 lx at the cornea) and a low (10 lx at the cornea) diffuse light exposure condition of the same spectrum (blue, λ_max= 470 nm, or red, λ_max= 630 nm). The presentation order of the light levels was counterbalanced across sessions for a given subject; light spectra were counterbalanced across subjects within sessions. Prior to each lighting condition, subjects remained in the dark (< 1 lx at the cornea) for 60 minutes. Electroencephalogram (EEG) measurements, electrocardiogram (ECG), psychomotor vigilance tests (PVT), self-reports of sleepiness, and saliva samples for melatonin assays were collected at the end of each dark and light periods.</p> <p>Results</p> <p>Exposures to red and to blue light resulted in increased beta and reduced alpha power relative to preceding dark conditions. Exposures to high, but not low, levels of red and of blue light significantly increased heart rate relative to the dark condition. Performance and sleepiness ratings were not strongly affected by the lighting conditions. Only the higher level of blue light resulted in a reduction in melatonin levels relative to the other lighting conditions.</p> <p>Conclusion</p> <p>These results support previous findings that alertness may be mediated by the circadian system, but it does not seem to be the only light-sensitive pathway that can affect alertness at night.</p

On the Origin and Trigger of the Notothenioid Adaptive Radiation

Adaptive radiation is usually triggered by ecological opportunity, arising through (i) the colonization of a new habitat by its progenitor; (ii) the extinction of competitors; or (iii) the emergence of an evolutionary key innovation in the ancestral lineage. Support for the key innovation hypothesis is scarce, however, even in textbook examples of adaptive radiation. Antifreeze glycoproteins (AFGPs) have been proposed as putative key innovation for the adaptive radiation of notothenioid fishes in the ice-cold waters of Antarctica. A crucial prerequisite for this assumption is the concurrence of the notothenioid radiation with the onset of Antarctic sea ice conditions. Here, we use a fossil-calibrated multi-marker phylogeny of nothothenioid and related acanthomorph fishes to date AFGP emergence and the notothenioid radiation. All time-constraints are cross-validated to assess their reliability resulting in six powerful calibration points. We find that the notothenioid radiation began near the Oligocene-Miocene transition, which coincides with the increasing presence of Antarctic sea ice. Divergence dates of notothenioids are thus consistent with the key innovation hypothesis of AFGP. Early notothenioid divergences are furthermore congruent with vicariant speciation and the breakup of Gondwana

Cold Physiology: Postprandial Blood Flow Dynamics and Metabolism in the Antarctic Fish Pagothenia borchgrevinki

Previous studies on metabolic responses to feeding (i.e. the specific dynamic action, SDA) in Antarctic fishes living at temperatures below zero have reported long-lasting increases and small peak responses. We therefore hypothesized that the postprandial hyperemia also would be limited in the Antarctic fish Pagothenia borchgrevinki. The proportion of cardiac output directed to the splanchnic circulation in unfed fish was 18%, which is similar to temperate fish species. Contrary to our prediction, however, gastrointestinal blood flow had increased by 88% at twenty four hours after feeding due to a significant increase in cardiac output and a significant decrease in gastrointestinal vascular resistance. While gastric evacuation time appeared to be longer than in comparable temperate species, digestion had clearly commenced twenty four hours after feeding as judged by a reduction in mass of the administered feed. Even so, oxygen consumption did not increase suggesting an unusually slowly developing SDA. Adrenaline and angiotensin II was injected into unfed fish to investigate neuro-humoral control mechanisms of gastrointestinal blood flow. Both agonists increased gastrointestinal vascular resistance and arterial blood pressure, while systemic vascular resistance was largely unaffected. The hypertension was mainly due to increased cardiac output revealing that the heart and the gastrointestinal vasculature, but not the somatic vasculature, are important targets for these agonists. It is suggested that the apparently reduced SDA in P. borchgrevinki is due to a depressant effect of the low temperature on protein assimilation processes occurring outside of the gastrointestinal tract, while the gastrointestinal blood flow responses to feeding and vasoactive substances resemble those previously observed in temperate species

TESS Delivers Five New Hot Giant Planets Orbiting Bright Stars from the Full-frame Images

We present the discovery and characterization of five hot and warm Jupiters—TOI-628 b (TIC 281408474; HD 288842), TOI-640 b (TIC 147977348), TOI-1333 b (TIC 395171208, BD+47 3521A), TOI-1478 b (TIC 409794137), and TOI-1601 b (TIC 139375960)—based on data from NASA's Transiting Exoplanet Survey Satellite (TESS). The five planets were identified from the full-frame images and were confirmed through a series of photometric and spectroscopic follow-up observations by the TESS Follow-up Observing Program Working Group. The planets are all Jovian size (RP = 1.01–1.77 RJ) and have masses that range from 0.85 to 6.33 MJ. The host stars of these systems have F and G spectral types (5595 ≤ Teff ≤ 6460 K) and are all relatively bright (9.5 1.7 RJ, possibly a result of its host star's evolution) and resides on an orbit with a period longer than 5 days. TOI-628 b is the most massive, hot Jupiter discovered to date by TESS with a measured mass of ${6.31}_{-0.30}^{+0.28}$ MJ and a statistically significant, nonzero orbital eccentricity of e = ${0.074}_{-0.022}^{+0.021}$. This planet would not have had enough time to circularize through tidal forces from our analysis, suggesting that it might be remnant eccentricity from its migration. The longest-period planet in this sample, TOI-1478 b (P = 10.18 days), is a warm Jupiter in a circular orbit around a near-solar analog. NASA's TESS mission is continuing to increase the sample of well-characterized hot and warm Jupiters, complementing its primary mission goals