Mitochondrial absorption of short wavelength light drives primate blue retinal cones into glycolysis which may increase their pace of aging

Photoreceptors have high energy demands and densely packed mitochondria through which light passes before phototransduction. Old world primates including humans have three cone photoreceptor types mediating color vision with short (S blue), medium (M green), and long (L red) wavelength sensitivities. However, S-cones are enigmatic. They comprise <10% of the total cone population, their responses saturate early, and they are susceptible in aging and disease. Here, we show that primate S-cones actually have few mitochondria and are fueled by glycolysis, not by mitochondrial respiration. Glycolysis has a limited ability to sustain activity, potentially explaining early S-cone saturation. Mitochondria act as optical filters showing reduced light transmission at 400–450 nm where S-cones are most sensitive (420 nm). This absorbance is likely to arise in a mitochondrial porphyrin that absorbs strongly in the Soret band. Hence, reducing mitochondria will improve S-cone sensitivity but result in increased glycolysis as an alternative energy source, potentially increasing diabetic vulnerability due to restricted glucose access. Further, glycolysis carries a price resulting in premature functional decline as seen in aged S-cones. Soret band absorption may also impact on mitochondrial rich M and L cones by reducing sensitivity at the lower end of their spectral sensitivity range resulting in increased differentiation from S-cone responses. These data add to the list of unique characteristic of S-cones and may also explain aspects of their vulnerability

Realtime calibration of the A4 electromagnetic lead fluoride calorimeter

Sufficient energy resolution is the key issue for the calorimetry in particle and nuclear physics. The calorimeter of the A4 parity violation experiment at MAMI is a segmented calorimeter where the energy of an event is determined by summing the signals of neighbouring channels. In this case the precise matching of the individual modules is crucial to obtain a good energy resolution. We have developped a calibration procedure for our total absorbing electromagnetic calorimeter which consists of 1022 lead fluoride (PbF_2) crystals. This procedure reconstructs the the single-module contributions to the events by solving a linear system of equations, involving the inversion of a 1022 x 1022-matrix. The system has shown its functionality at beam energies between 300 and 1500 MeV and represents a new and fast method to keep the calorimeter permanently in a well-calibrated state

Psychosocial Stress and Prostate Cancer: A Theoretical Model

African-American men are more likely to develop and die from prostate cancer than are European-American men; yet, factors responsible for the racial disparity in incidence and mortality have not been elucidated. Socioeconomic disadvantage can lead to psychosocial stress and may be linked to negative lifestyle behaviors. Regardless of socioeconomic position, African-American men routinely experience racism-induced stress. We propose a theoretical framework for an association between psychosocial stress and prostate cancer. With the context of history and culture, we further propose that psychosocial stress may partially explain the variable incidence of prostate cancer between these diverse groups. Psychosocial stress may negatively impact teh immune system leaving the individual susceptible to malingnancies. Behavioral responses to psychosocial stress are amenable to change. If psychosocial stress is found to negatively impact prostate cancer risk, interventions may be designed to modify reactions to environmental demands

Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England

Background: Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years. Methods: Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test. Results: 72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups. Conclusions: Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes

Measurement of the Transverse Beam Spin Asymmetry in Elastic Electron Proton Scattering and the Inelastic Contribution to the Imaginary Part of the Two-Photon Exchange Amplitude

We report on a measurement of the asymmetry in the scattering of transversely polarized electrons off unpolarized protons, A$_\perp$, at two Q$^2$ values of \qsquaredaveragedlow (GeV/c)$^2$ and \qsquaredaveragedhighII (GeV/c)$^2$ and a scattering angle of $30^\circ < \theta_e < 40^\circ$. The measured transverse asymmetries are A$_{\perp}$(Q$^2$ = \qsquaredaveragedlow (GeV/c)$^2$) = (\experimentalasymmetry alulowcorr $\pm$ \statisticalerrorlow$_{\rm stat}$ $\pm$ \combinedsyspolerrorlowalucor$_{\rm sys}$) $\times$ 10$^{-6}$ and A$_{\perp}$(Q$^2$ = \qsquaredaveragedhighII (GeV/c)$^2$) = (\experimentalasymme tryaluhighcorr $\pm$ \statisticalerrorhigh$_{\rm stat}$ $\pm$ \combinedsyspolerrorhighalucor$_{\rm sys}$) $\times$ 10$^{-6}$. The first errors denotes the statistical error and the second the systematic uncertainties. A$_\perp$ arises from the imaginary part of the two-photon exchange amplitude and is zero in the one-photon exchange approximation. From comparison with theoretical estimates of A$_\perp$ we conclude that $\pi$N-intermediate states give a substantial contribution to the imaginary part of the two-photon amplitude. The contribution from the ground state proton to the imaginary part of the two-photon exchange can be neglected. There is no obvious reason why this should be different for the real part of the two-photon amplitude, which enters into the radiative corrections for the Rosenbluth separation measurements of the electric form factor of the proton.Comment: 4 figures, submitted to PRL on Oct.

Development and Validation of a Low-Cost Gas Density Method for Measuring Biochemical Methane Potential (BMP)

Accurate determination of biochemical methane potential (BMP) is important for both biogas research and practice. However, access to laboratory equipment limits the capacity of small laboratories or biogas plants to conduct reliable BMP assays, especially in low- and middle-income countries. This paper describes the development and validation of a new gas density-based method for measuring BMP (GD-BMP). In the GD-BMP method, biogas composition is determined from biogas density. Biogas density is based on bottle mass loss and biogas volume, and these can be accurately measured using only a standard laboratory scale, inexpensive syringes, and a simple manometer. Results from four experiments carried out in three different laboratories showed that the GD-BMP method is both accurate (no significant bias compared to gravimetric or volumetric methods with biogas analysis by gas chromatography) and precise (<3% relative standard deviation is possible). BMP values from the GD-BMP method were also comparable to those measured for the same substrates with an industry standard automated system (AMPTS II) in two independent laboratories (maximum difference 10%). Additionally, the GD-BMP method was shown to be accurate even in the presence of leakage by excluding leakage from mass loss measurements. The proposed GD-BMP method represents a significant breakthrough for both biogas research and the industry. With it, accurate BMP measurement is possible with only a minimal investment in supplies and equipment

A luminosity monitor for the A4 parity violation experiment at MAMI

A water Cherenkov luminosity monitor system with associated electronics has been developed for the A4 parity violation experiment at MAMI. The detector system measures the luminosity of the hydrogen target hit by the MAMI electron beam and monitors the stability of the liquid hydrogen target. Both is required for the precise study of the count rate asymmetries in the scattering of longitudinally polarized electrons on unpolarized protons. Any helicity correlated fluctuation of the target density leads to false asymmetries. The performance of the luminosity monitor, investigated in about 2000 hours with electron beam, and the results of its application in the A4 experiment are presented.Comment: 22 pages, 12 figures, submitted to NIM

An In Vivo Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer

Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen. Among the top positive hits, we conducted an in-depth functional analysis on Pygopus family PHD finger 2 (PYGO2), located in the amplicon at 1q21.3. PYGO2 overexpression enhances primary tumor growth and local invasion to draining lymph nodes. Conversely, PYGO2 depletion inhibits prostate cancer cell invasion in vitro and progression of primary tumor and metastasis in vivo In clinical samples, PYGO2 upregulation associated with higher Gleason score and metastasis to lymph nodes and bone. Silencing PYGO2 expression in patient-derived xenograft models impairs tumor progression. Finally, PYGO2 is necessary to enhance the transcriptional activation in response to ligand-induced Wnt/β-catenin signaling. Together, our results indicate that PYGO2 functions as a driver oncogene in the 1q21.3 amplicon and may serve as a potential prognostic biomarker and therapeutic target for metastatic prostate cancer.Significance: Amplification/overexpression of PYGO2 may serve as a biomarker for prostate cancer progression and metastasis. Cancer Res; 78(14); 3823-33. ©2018 AACR