Controlled levels of protein modification through a chromatography-mediated bioconjugation.

Synthetically modified proteins are increasingly finding applications as well-defined scaffolds for materials. In practice it remains difficult to construct bioconjugates with precise levels of modification because of the limited number of repeated functional groups on proteins. This article describes a method to control the level of protein modification in cases where there exist multiple potential modification sites. A protein is first tagged with a handle using any of a variety of modification chemistries. This handle is used to isolate proteins with a particular number of modifications via affinity chromatography, and then the handle is elaborated with a desired moiety using an oxidative coupling reaction. This method results in a sample of protein with a well-defined number of modifications, and we find it particularly applicable to systems like protein homomultimers in which there is no way to discern between chemically identical subunits. We demonstrate the use of this method in the construction of a protein-templated light-harvesting mimic, a type of system which has historically been difficult to make in a well-defined manner

Update on the role of genetics in the onset of age-related macular degeneration

Age-related macular degeneration (AMD), akin to other common age-related diseases, has a complex pathogenesis and arises from the interplay of genes, environmental factors, and personal characteristics. The past decade has seen very significant strides towards identification of those precise genetic variants associated with disease. That genes encoding proteins of the (alternative) complement pathway (CFH, C2, CFB, C3, CFI) are major players in etiology came as a surprise to many but has already lead to the development of therapies entering human clinical trials. Other genes replicated in many populations ARMS2, APOE, variants near TIMP3, and genes involved in lipid metabolism have also been implicated in disease pathogenesis. The genes discovered to date can be estimated to account for approximately 50% of the genetic variance of AMD and have been discovered by candidate gene approaches, pathway analysis, and latterly genome-wide association studies. Next generation sequencing modalities and meta-analysis techniques are being employed with the aim of identifying the remaining rarer but, perhaps, individually more significant sequence variations, linked to disease status. Complementary studies have also begun to utilize this genetic information to develop clinically useful algorithms to predict AMD risk and evaluate pharmacogenetics. In this article, contemporary commentary is provided on rapidly progressing efforts to elucidate the genetic pathogenesis of AMD as the field stands at the end of the first decade of the 21st century

Exploring the impact, value and limitations of reflective practice groups for clergy in a Church in Wales diocese

This is an Accepted Manuscript of an article published by Taylor & Francis in Mental Health, Religion and Culture on 3rd September 2020, available online: https://doi.org/10.1080/13674676.2020.1789571This research explores the impact, value and limitations of reflective practice groups for Clergy in a Church in Wales diocese. The aims were to explore what participants of reflective practice groups experience as the impact, value and limitations of their groups, and to better understand any implications for delivery of reflective practice groups for Clergy. Two focus groups comprising of the participants from two reflective practice groups from a diocese in the Church in Wales were interviewed, and the data analysed using Interpretative Phenomenological Analysis. Two superordinate themes emerged along with ten subordinate themes. The key findings are that the participants of both groups clearly found them to be a valuable experience and self-defined the impact on their ministries as: creating more reflective clergy; developing greater wisdom; building and gaining affirmed strategies that they could take back into relationships within their parishes; enabling a different perspective to be gained on management expectations; development of self-preservation strategies for coping with those expectations; improvement in practice and relationships within their work; improving their priestly skills; managing boundaries more appropriately; approaching meetings more positively; managing situations in more helpful ways; and discerning what God may be saying in certain situations

Japanese encephalitis virus-specific proliferative responses of human peripheral blood T lymphocytes

The T lymphocytes play an important role in prevention and recovery from viral infections. To characterize T lymphocyte responses to Japanese encephalitis (JE) virus infections, we analyzed JE virus-specific T lymphocytes in peripheral blood mononuclear cells (PBMC) obtained from seven JE patients and 10 vaccinees who had received a formalin-inactivated, purified JE virus vaccine (Biken vaccine). These PBMC were examined for proliferative responses against live JE virus, a glutaraldehyde-fixed lysate of cells infected with JE virus, and extracellular particles (EPs; subviral membrane vesicles released from cells infected with recombinant vaccinia viruses encoding the JE virus premembrane and envelope proteins). Japanese encephalitis virus-specific T cell proliferation was demonstrated with PBMC from both patients and vaccinees after stimulation with infectious JE virus or the lysate of JE virus-infected cells. Proliferating PBMC included CD4+ T lymphocytes and CD8+ T lymphocytes in responses to either form of JE viral antigens. Responses to EPs were observed only with PBMC from some American vaccinees whose PBMC also responded to the virus and lysate. These results indicate that JE virus infection and immunization with an inactivated JE vaccine induce JE virus-specific CD4+ and CD8+ T memory lymphocytes that can be induced to proliferate by infectious JE virus and noninfectious JE antigens

Impact of Drought on the Spatial Pattern of Transmission of Sehistosoma haematobium in Coastal Kenya

We analyzed temporal changes in spatial patterns of active Schistosoma haematobium infection in different age groups and associated them with ponds infested with Bulinus snails. A major drought between 2001 and 2009 resulted in drying of ponds that were known sources of infection, and we detected very few or no snails in ponds that were infested in the past. The household-level spatial pattern of infection for children of various age groups in 2009 was contrasted with historical data from 2000. The significant local clustering of high- and low-infection levels among school-aged children that occurred in 2000 was absent in 2009. We attribute the disappearance of significant clustering around historical transmission hot spots to a decade-long drought in our study area. The implications of extreme weather and climate conditions on risk and transmission of S. haematobium and their relevance to control strategies are discussed. Copyright © 2011 by The American Society of Tropical Medicine and Hygiene

Farmers and nature conservation: What is known about attitudes, context factors and actions affecting conservation?

Farmers’ attitudes towards viability of specific conservation practices or actions strongly impact their decisions on adoption and change. This review of ‘attitude’ information reveals a wide range of perceptions about what conservation means and what the impacts of adoption will mean in economic and environmental terms. Farmers operate in a tight financial situation, and in parts of the world they are highly dependent on government subsidies, and cannot afford to risk losing that support. Use of conservation practices is most effective when these are understood in the context of the individual farm, and decisions are rooted in land and resource stewardship and long-term concerns about health of the farm and the soil. The attitudes of farmers entering agri-environmental schemes decide the quality of the result. A model is developed to show how attitudes of the farmer, the farming context and agri-environmental schemes interact and thus influence how the farming community affects nature and biodiversity. As new agri-environmental schemes are planned, agricultural development specialists need to recognize the complexity of farmer attitudes, the importance of location and individual farmer circumstances, and the multiple factors that influence decisions. We provide these insights and the model to conservation biologists conducting research in farming areas, decision makers who develop future agri-environmental schemes, educators training tomorrow’s extension officers and nature conservationists, and researchers dealing with nature conservation issues through a combination of scientific disciplines

The development of the Meaning in Life Index (MILI) and its relationship with personality and religious behaviours and beliefs among UK undergraduate students

The scales available for assessing meaning in life appear to be confounded with several related constructs, including purpose in life, satisfaction with life, and goal-directed behaviour. The Meaning in Life Index (MILI), a new instrument devised as a specific measure of meaning in life, was developed from responses to a pool of 22 items rated by a sample of 501 undergraduate students in Wales. The nine-item scale demonstrated sufficient face validity, internal consistency, and scale reliability to commend the instrument for future use. With respect to personality, the MILI scores were most strongly predicted by neuroticism (negatively), and less strongly by extraversion (positively) and psychoticism (negatively). With respect to several religious behavioural variables, those who attended church at least weekly returned significantly higher MILI scores than those who attended church less frequently. Intrinsic religiosity was the only orientation to be significantly associated with the MILI scale scores, although the magnitude of the association was smaller than anticipated. These results suggest that meaning in life is associated more strongly with individual differences in personality than with specific religious behaviours and attitudes. The implications of these results are discussed in terms of individual's personal values and attitudes that might underlie their experience of a meaning in life

Control via electron count of the competition between magnetism and superconductivity in cobalt and nickel doped NaFeAs

Using a combination of neutron, muon and synchrotron techniques we show how the magnetic state in NaFeAs can be tuned into superconductivity by replacing Fe by either Co or Ni. Electron count is the dominant factor, since Ni-doping has double the effect of Co-doping for the same doping level. We follow the structural, magnetic and superconducting properties as a function of doping to show how the superconducting state evolves, concluding that the addition of 0.1 electrons per Fe atom is sufficient to traverse the superconducting domain, and that magnetic order coexists with superconductivity at doping levels less than 0.025 electrons per Fe atom.Comment: 4 pages, 6 figure

Cosmic neutrinos from temporarily gamma-suppressed blazars

Despite the uncovered association of a high-energy neutrino with the apparent flaring state of blazar TXS 0506+056 in 2017, the mechanisms leading to astrophysical particle acceleration and neutrino production are still uncertain. Recent studies found that when transparent to $\gamma$-rays, $\gamma$-flaring blazars do not have the opacity for protons to produce neutrinos. Here we present observational evidence for an alternative explanation, in which $\gamma$-ray emission is suppressed during efficient neutrino production. A large proton and target photon density help produce neutrinos while temporarily suppress the observable $\gamma$-emission due to a large $\gamma \gamma$ opacity. We show that the Fermi-LAT $\gamma$-flux of blazar PKS 1502+106 was at a local minimum when IceCube recorded the coincident high-energy neutrino IC-190730A. Using data from the OVRO 40-meter Telescope, we find that radio emission from PKS 1502+106 at the time period of the coincident neutrino IC-190730A was in a high state, in contrast to earlier time periods when radio and $\gamma$ fluxes are correlated for both low and high states. This points to an active outflow that is $\gamma$-suppressed at the time of neutrino production. We find similar local $\gamma$-suppression in other blazars, including in MAGIC's TeV flux of TXS\,0506+056 and Fermi-LAT's flux of blazar PKS B1424-418 at the time of coincident IceCube neutrino detections. Using temporary $\gamma$-suppression, neutrino-blazar coincidence searches could be substantially more sensitive than previously assumed, enabling the identification of the origin of IceCube's diffuse neutrino flux possibly with already existing data.Comment: 8 pages, 3 figures, accepted to ApJ Letter