Observation of dissipative chlorophyll-to-carotenoid energy transfer in light-harvesting complex II in membrane nanodiscs

Abstract Plants prevent photodamage under high light by dissipating excess energy as heat. Conformational changes of the photosynthetic antenna complexes activate dissipation by leveraging the sensitivity of the photophysics to the protein structure. The mechanisms of dissipation remain debated, largely due to two challenges. First, because of the ultrafast timescales and large energy gaps involved, measurements lacked the temporal or spectral requirements. Second, experiments have been performed in detergent, which can induce non-native conformations, or in vivo, where contributions from homologous antenna complexes cannot be disentangled. Here, we overcome both challenges by applying ultrabroadband two-dimensional electronic spectroscopy to the principal antenna complex, LHCII, in a near-native membrane. Our data provide evidence that the membrane enhances two dissipative pathways, one of which is a previously uncharacterized chlorophyll-to-carotenoid energy transfer. Our results highlight the sensitivity of the photophysics to local environment, which may control the balance between light harvesting and dissipation in vivo

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

<b>Background</b><p></p> To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.<p></p> <b>Methods</b><p></p> An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.<p></p> <b>Results</b><p></p> The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.<p></p> <b>Conclusions</b><p></p> It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability

Numerical studies of the Lagrangian approach for reconstruction of the conductivity in a waveguide

We consider an inverse problem of reconstructing the conductivity function in a hyperbolic equation using single space-time domain noisy observations of the solution on the backscattering boundary of the computational domain. We formulate our inverse problem as an optimization problem and use Lagrangian approach to minimize the corresponding Tikhonov functional. We present a theorem of a local strong convexity of our functional and derive error estimates between computed and regularized as well as exact solutions of this functional, correspondingly. In numerical simulations we apply domain decomposition finite element-finite difference method for minimization of the Lagrangian. Our computational study shows efficiency of the proposed method in the reconstruction of the conductivity function in three dimensions

Point-of-care screening for a current Hepatitis C virus infection: influence on uptake of a concomitant offer of HIV screening

Eliminating hepatitis C as a public health threat requires an improved understanding of how to increase testing uptake. We piloted point-of-care testing (POCT) for a current HCV infection in an inner-city Emergency Department (ED) and assessed the influence on uptake of offering concomitant screening for HIV. Over four months, all adults attending ED with minor injuries were first invited to complete an anonymous questionnaire then invited to test in alternating cycles offering HCV POCT or HCV+HIV POCT. Viral RNA was detected in finger-prick blood by GeneXpert. 814/859 (94.8%) questionnaires were returned and 324/814 (39.8%) tests were accepted, comprising 211 HCV tests and 113 HCV+HIV tests. Offering concomitant HIV screening reduced uptake after adjusting for age and previous HCV testing (odds ratio 0.51; 95% confidence interval [CI] 0.38–0.68; p < 0.001). HCV prevalence was 1/324 (0.31%; 95% CI 0.05–1.73); no participant tested positive for HIV. 167/297 (56.2%) POCT participants lived in the most deprived neighbourhoods in England. HCV RNA testing using finger-prick blood was technically feasible. Uptake was moderate and the offer of concomitant HIV screening showed a detrimental impact on acceptability in this low prevalence population. The findings should be confirmed in a variety of other community settings

Cell-based therapeutic strategies for multiple sclerosis

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials

The Association of HIV Counseling and Testing with HIV Risk Behaviors in a Random Population-based Survey in Kisumu, Kenya

HIV testing has been promoted as a key HIV prevention strategy in low-resource settings, despite studies showing variable impact on risk behavior. We sought to examine rates of HIV testing and the association between testing and sexual risk behaviors in Kisumu, Kenya. Participants were interviewed about HIV testing and sexual risk behaviors. They then underwent HIV serologic testing. We found that 47% of women and 36% of men reported prior testing. Two-thirds of participants who tested HIV-positive in this study reported no prior HIV test. Women who had undergone recent testing were less likely to report high-risk behaviors than women who had never been tested; this was not seen among men. Although rates of HIV testing were higher than seen in previous studies, the majority of HIV-infected people were unaware of their status. Efforts should be made to increase HIV testing among this population

An evaluation of osteopathic treatment on psychological outcomes with patients suffering from chronic pain: A prospective observational cohort study collected through a health and well-being academy

Co-morbid mental health conditions such as anxiety, depression and fear avoidance are often associated with chronic pain. This novel study aimed to explore the impact of osteopathic treatment on several psychological outcome measures relating to anxiety, depression, mental health and fear avoidance for a chronic pain population receiving osteopathic treatment over a 2-week period. The findings show that there were significant reductions in anxiety, pain, mental health dysfunction and improvements in self-care. These results are promising, and it is suggested that now a full-scale randomised controlled trial should be conducted

Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

Aidnogenesis via Leptogenesis and Dark Sphalerons

We discuss aidnogenesis, the generation of a dark matter asymmetry via new sphaleron processes associated to an extra non-abelian gauge symmetry common to both the visible and the dark sectors. Such a theory can naturally produce an abundance of asymmetric dark matter which is of the same size as the lepton and baryon asymmetries, as suggested by the similar sizes of the observed baryonic and dark matter energy content, and provide a definite prediction for the mass of the dark matter particle. We discuss in detail a minimal realization in which the Standard Model is only extended by dark matter fermions which form "dark baryons" through an SU(3) interaction, and a (broken) horizontal symmetry that induces the new sphalerons. The dark matter mass is predicted to be approximately 6 GeV, close to the region favored by DAMA and CoGeNT. Furthermore, a remnant of the horizontal symmetry should be broken at a lower scale and can also explain the Tevatron dimuon anomaly.Comment: Minor changes, discussion of present constraints expanded. 16 pages, 2 eps figures, REVTeX

MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo

Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD