Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor development in aging mice.

Alterations of specific genes can modulate aging. Myc, a transcription factor that regulates the expression of many genes involved in critical cellular functions was shown to have a role in controlling longevity. Decreased expression of Myc inhibited many of the deleterious effects of aging and increased lifespan in mice. Without altering Myc expression, reduced levels of Mtbp, a recently identified regulator of Myc, limit Myc transcriptional activity and proliferation, while increased levels promote Myc-mediated effects. To determine the contribution of Mtbp to the effects of Myc on aging, we studied a large cohort of Mtbp heterozygous mice and littermate matched wild-type controls. Mtbp haploinsufficiency significantly increased longevity and maximal survival in mice. Reduced levels of Mtbp did not alter locomotor activity, litter size, or body size, but Mtbp heterozygous mice did exhibit elevated markers of metabolism, particularly in the liver. Mtbp(+/-) mice also had a significant delay in spontaneous cancer development, which was most prominent in the hematopoietic system, and an altered tumor spectrum compared to Mtbp(+/+) mice. Therefore, the data suggest Mtbp is a regulator of longevity in mice that mimics some, but not all, of the properties of Myc in aging

Light Concentrators for Borexino and CTF

Light concentrators for the solar neutrino experiment Borexino and the Counting Test Facility (CTF) have been developed and constructed. They increase the light yield of these detectors by a factor of 2.5 and 8.8, respectively. Technical challenges like long term stability in various media, high reflectivity and radiopurity have been addressed and the concepts to overcome these difficulties will be described. Gamma spectroscopy measurements of the concentrators show an upper limit of 12e-6 Bq/g for uranium and a value of 120e-6 Bq/g for thorium. Upper limits on other possible contaminations like 26Al are presented. The impact of these results on the performance of Borexino and the CTF are discussed and it is shown that the design goals of both experiments are fulfilled.Comment: submitted to Nuclear Instruments and Methods in Physics Researc

A Rare Case of Toxic Epidermal Necrolysis with Unexpected Fever Resulting from Dengue Virus

Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a life-threatening disease with common development of large wounds. Thus, affected patients are usually treated in specialized centers. Herein, we present a case of TEN in a patient infected with human immunodeficiency virus with the additional, unexpected diagnosis of dengue fever. In this context, we discuss cause, diagnosis, pathology, and treatment of TEN and highlight the role of rare and unexpected findings, as in this case an additional tropical virus infection. We underpin the importance of an interdisciplinary approach involving dermatologists, ophthalmologists, intensive care physicians, burn specialists and various other departments and emphasize the challenge of TEN treatment, especially if rare pathological findings occur

MiniBooNE Results and Neutrino Schemes with 2 sterile Neutrinos: Possible Mass Orderings and Observables related to Neutrino Masses

The MiniBooNE and LSND experiments are compatible with each other when two sterile neutrinos are added to the three active ones. In this case there are eight possible mass orderings. In two of them both sterile neutrinos are heavier than the three active ones. In the next two scenarios both sterile neutrinos are lighter than the three active ones. The remaining four scenarios have one sterile neutrino heavier and another lighter than the three active ones. We analyze all scenarios with respect to their predictions for mass-related observables. These are the sum of neutrino masses as constrained by cosmological observations, the kinematic mass parameter as measurable in the KATRIN experiment, and the effective mass governing neutrinoless double beta decay. It is investigated how these non-oscillation probes can distinguish between the eight scenarios. Six of the eight possible mass orderings predict positive signals in the KATRIN and future neutrinoless double beta decay experiments. We also remark on scenarios with three sterile neutrinos. In addition we make some comments on the possibility of using decays of high energy astrophysical neutrinos to discriminate between the mass orderings in presence of two sterile neutrinos.Comment: 33 pages, 8 figures. Comments added, to appear in JHE

Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema

Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256;SD 0.303;p = 0.0485) and CD74 (mean 1.514;SD 0.397;p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004;SD 0.358;p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: RSD measurement from the LOS-dependent power spectrum of DR12 BOSS galaxies

Citation: Gil-Marin, H., Percival, W. J., Brownstein, J. R., Chuang, C. H., Grieb, J. N., Ho, S., . . . Zhao, G. B. (2016). The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: RSD measurement from the LOS-dependent power spectrum of DR12 BOSS galaxies. Monthly Notices of the Royal Astronomical Society, 460(4), 4188-4209. doi:10.1093/mnras/stw1096We measure and analyse the clustering of the Baryon Oscillation Spectroscopic Survey (BOSS) relative to the line of sight (LOS), for LOWZ and CMASS galaxy samples drawn from the final Data Release 12. The LOWZ sample contains 361 762 galaxies with an effective redshift of z(lowz) = 0.32, and the CMASS sample 777 202 galaxies with an effective redshift of z(cmass) = 0.57. From the power spectrum monopole and quadrupole moments around the LOS, we measure the growth of structure parameter f times the amplitude of dark matter density fluctuations sigma 8 by modelling the redshift-space distortion signal. When the geometrical Alcock-Paczynski effect is also constrained from the same data, we find joint constraints on f sigma(8), the product of the Hubble constant and the comoving sound horizon at the baryondrag epoch H(z) r(s)(z(d)), and the angular distance parameter divided by the sound horizon DA(z)/r(s)(zd). We find f(z(lowz)) sigma(8)(z(lowz)) = 0.394 +/- 0.062, D-A(zlowz)/r(s)(z(d)) = 6.35 +/- 0.19, H(z(lowz)) r(s)(z(d)) = (11.41 +/- 0.56) 103 km s(-1) for the LOWZ sample, and f( z(cmass)) sigma 8(z(cmass)) = 0.444 +/- 0.038, D-A(z(cmass))/r(s)(z(d)) = 9.42 +/- 0.15, H(z(cmass)) r(s)(z(d)) = (13.92 +/- 0.44) 103 km s-1 for the CMASS sample. We find general agreement with previous BOSS DR11 measurements. Assuming the Hubble parameter and angular distance parameter are fixed at fiducial +/- cold dark matter values, we find f( zlowz) sigma(8)( z(lowz))= 0.485 +/- 0.044 and f(z(cmass)) sigma(8)(z(cmass))= 0.436 +/- 0.022 for the LOWZ and CMASS samples, respectively

Effect Threshold for Selenium Toxicity in Juvenile Splittail, Pogonichthys macrolepidotus A

In fish, selenium can bioaccumulate and cause adverse impacts. One of the fish species potentially at risk from selenium in the San Francisco Bay (California, USA) is the splittail (Pogonichthys macrolepidotus). Previous studies have derived a whole body NOAEL and LOAEL of 9.0 and 12.9 mg/kg-dw, respectively, for selenium in juveniles. However, the NOAEL/LOAEL approach leaves some uncertainty regarding the threshold of toxicity. Therefore, the raw data from the original experiment was re-analyzed using a logistic regression to derive EC10 values of 0.9 mg/kg-dw in feed, 7.9 mg/kg-dw in muscle, 18.6 mg/kg-dw in liver for juvenile splittail. Selenium concentrations in the dietary items of wild splittail exceed the EC10 values derived here. Thus, deformities previously reported in wild splittail may have resulted from selenium exposures via the food chain

Elevated vitreous body glial fibrillary acidic protein in retinal diseases

Purpose: Increased expression of glial fibrillary acidic protein (GFAP) is a characteristic of gliotic activation (Müller cells and astrocytes) in the retina. This study assessed vitreous body GFAP levels in various forms of retinal pathology. Methods: This prospective study included 82 patients who underwent vitrectomy (46 retinal detachments (RDs), 13 macular hole (MHs), 15 epiretinal glioses (EGs), 8 organ donors). An established enzyme–linked immunosorbent assay (ELISA, SMI26) was used for quantification of GFAP. Results: The highest concentration of vitreous body GFAP in organ donors was 20 pg/mL and it was used as the cutoff. A significant proportion of patients suffering from RD (65 %) to EG (53 %) had vitreous body GFAP levels above this cutoff when compared to organ donors (0 %, p < 0.0001, p = 0.0194, respectively, Fisher’s exact test) and MH (8 %, p < 0.0001, p = 0.0157, respectively). In RD and EG, vitreous body GFAP levels were correlated with axial length (R = 0.69, R = 0.52, p < 0.05 for both). Conclusions: The data suggest that human vitreous body GFAP is a protein biomarker for glial activation in response to retinal pathologies. Vitreous body GFAP levels may be of interest as a surrogate outcome for experimental treatment strategies in translational studies