Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon γ

The immunosurveillance of transformed cells by the immune system remains one of the most controversial and poorly understood areas of immunity. Gene-targeted mice have greatly aided our understanding of the key effector molecules in tumor immunity. Herein, we describe spontaneous tumor development in gene-targeted mice lacking interferon (IFN)-γ and/or perforin (pfp), or the immunoregulatory cytokines, interleukin (IL)-12, IL-18, and tumor necrosis factor (TNF). Both IFN-γ and pfp were critical for suppression of lymphomagenesis, however the level of protection afforded by IFN-γ was strain specific. Lymphomas arising in IFN-γ-deficient mice were very nonimmunogenic compared with those derived from pfp-deficient mice, suggesting a comparatively weaker immunoselection pressure by IFN-γ. Single loss of IL-12, IL-18, or TNF was not sufficient for spontaneous tumor development. A significant incidence of late onset adenocarcinoma observed in both IFN-γ– and pfp-deficient mice indicated that some epithelial tissues were also subject to immunosurveillance

Current clinical practice in disabling and chronic migraine in the primary care setting: results from the European My-LIFE anamnesis survey.

Migraine is a prevalent and disabling headache disorder that affects more than 1.04 billion individuals world-wide. It can result in reduction in quality of life, increased disability, and high socio-economic burden. Nevertheless, and despite the availability of evidence-based national and international guidelines, the management of migraine patients often remains suboptimal, especially for chronic migraine (CM) patients. My-LIFE anamnesis project surveyed 201 General practitioners (GPs) from 5 European countries (France, Germany, Italy, Spain, and the UK) with the aim of understanding chronic migraine (CM) patients' management in the primary care setting. In our survey, GPs diagnosed episodic migraine (EM) more often than CM (87% vs 61%, p < 0.001). We found that many CM patients were not properly managed or referred to specialists, in contrast to guidelines recommendations. The main tools used by primary-care physicians included clinical interview, anamnesis guide, and patient diary. Tools used at the first visit differed from those used at follow-up visits. Up to 82% of GPs reported being responsible for management of patients diagnosed with disabling or CM and did not refer them to a specialist. Even when the GP had reported referring CM patients to a specialist, 97% of them were responsible for their follow-up. Moreover, the treatment prescribed, both acute and preventive, was not in accordance with local and international recommendations. GPs reported that they evaluated the efficacy of the treatment prescribed mainly through patient perception, and the frequency of follow-up visits was not clearly established in the primary care setting. These results suggest that CM is underdiagnosed and undertreated; thereby its management is suboptimal in the primary care. There is a need of guidance in the primary care setting to both leverage the management of CM patients and earlier referral to specialists, when appropriate

On the compatibility of a flux transport dynamo with a fast tachocline scenario

The compatibility of the fast tachocline scenario with a flux transport dynamo model is explored. We employ a flux transport dynamo model coupled with simple feedback formulae relating the thickness of the tachocline to the amplitude of the magnetic field or to the Maxwell stress. The dynamo model is found to be robust against the nonlinearity introduced by this simplified fast tachocline mechanism. Solar-like butterfly diagrams are found to persist and, even without any parameter fitting, the overall thickness of the tachocline is well within the range admitted by helioseismic constraints. In the most realistic case of a time and latitude dependent tachocline thickness linked to the value of the Maxwell stress, both the thickness and its latitude dependence are in excellent agreement with seismic results. In the nonparametric models, cycle related temporal variations in tachocline thickness are somewhat larger than admitted by helioseismic constraints; we find, however, that introducing a further parameter into our feedback formula readily allows further fine tuning of the thickness variations.Comment: Accepted in Solar Physic

Reflection and Ducting of Gravity Waves Inside the Sun

Internal gravity waves excited by overshoot at the bottom of the convection zone can be influenced by rotation and by the strong toroidal magnetic field that is likely to be present in the solar tachocline. Using a simple Cartesian model, we show how waves with a vertical component of propagation can be reflected when traveling through a layer containing a horizontal magnetic field with a strength that varies with depth. This interaction can prevent a portion of the downward-traveling wave energy flux from reaching the deep solar interior. If a highly reflecting magnetized layer is located some distance below the convection zone base, a duct or wave guide can be set up, wherein vertical propagation is restricted by successive reflections at the upper and lower boundaries. The presence of both upward- and downward-traveling disturbances inside the duct leads to the existence of a set of horizontally propagating modes that have significantly enhanced amplitudes. We point out that the helical structure of these waves makes them capable of generating an alpha-effect, and briefly consider the possibility that propagation in a shear of sufficient strength could lead to instability, the result of wave growth due to over-reflection.Comment: 23 pages, 5 figures. Accepted for publication in Solar Physic

Data from: Multi-modal signal evolution in birds: re-examining a standard proxy for sexual selection

Sexual selection is proposed to be an important driver of speciation and phenotypic diversification in animal systems. However, previous phylogenetic tests have produced conflicting results, perhaps because they have focused on a single signalling modality (visual ornaments), whereas sexual selection may act on alternative signalling modalities (e.g. acoustic ornaments). Here we compile phenotypic data from 259 avian sister species pairs to assess the relationship between visible plumage dichromatism—a standard index of sexual selection in birds—and macroevolutionary divergence in the other major avian signalling modality: song. We find evidence for a strong negative relationship between the degree of plumage dichromatism and divergence in song traits, which remains significant even when accounting for other key factors, including habitat type, ecological divergence and interspecific interactions. This negative relationship is opposite to the pattern expected by a straightforward interpretation of the sexual selection-diversification hypothesis, whereby higher levels of dichromatism indicating strong sexual selection should be related to greater levels of mating signal divergence regardless of signalling modality. Our findings imply a ‘trade-off’ between the elaboration of visual ornaments and the diversification of acoustic mating signals, and suggest that the effects of sexual selection on diversification can only be determined by considering multiple alternative signalling modalities

Data from: Multi-modal signal evolution in birds: re-examining a standard proxy for sexual selection

Sexual selection is proposed to be an important driver of speciation and phenotypic diversification in animal systems. However, previous phylogenetic tests have produced conflicting results, perhaps because they have focused on a single signalling modality (visual ornaments), whereas sexual selection may act on alternative signalling modalities (e.g. acoustic ornaments). Here we compile phenotypic data from 259 avian sister species pairs to assess the relationship between visible plumage dichromatism—a standard index of sexual selection in birds—and macroevolutionary divergence in the other major avian signalling modality: song. We find evidence for a strong negative relationship between the degree of plumage dichromatism and divergence in song traits, which remains significant even when accounting for other key factors, including habitat type, ecological divergence and interspecific interactions. This negative relationship is opposite to the pattern expected by a straightforward interpretation of the sexual selection-diversification hypothesis, whereby higher levels of dichromatism indicating strong sexual selection should be related to greater levels of mating signal divergence regardless of signalling modality. Our findings imply a ‘trade-off’ between the elaboration of visual ornaments and the diversification of acoustic mating signals, and suggest that the effects of sexual selection on diversification can only be determined by considering multiple alternative signalling modalities