Water and the Biology of Prions and Plaques

This is an attempt to account for the insolubility and/or aggregation of prions and plaques in terms of a model of water consisting of an equilibrium between high 
density and low density microdomains. Hydrophobic molecules, including proteins, 
accumulate selectively into stable populations, enriched in high density water, at 
charged sites on biopolymers. In enriched high density water, proteins are probably 
partially unfolded and may precipitate out when released. All extracellular matrices 
contain such charged polymers. Prions, which have been shown to accumulate in soils 
and clays containing silicates and aluminates also probably accumulate in 
extracellular matrices. 
 
Release of proteins follows hydrolysis of the charged groups by highly reactive high 
density water. This is normally a slow process but is greatly accelerated by urea. 
Plaques may form with age and disease because of accumulation of urea and, perhaps, 
glucose in the blood. This favours precipitation of proteins emerging from matrices, 
rather than refolding and solution. Dialysis should, therefore, interfere with plaque 
formation and impede the development of some age-related diseases

Enhancement by cytotoxic agents of artificial pulmonary metastasis.

The formation of lung colonies by i.v. injected Lewis lung-tumour cells in syngeneic recipients was greatly enhanced by prior treatment of the mice with cyclophosphamide. The lung-cloning efficiency was linearly related to cyclophosphamide dose and the optimum time of treatment was 2-4 days before the injection of tumour cells. The resulting lung colonies had a similar size distribution to colonies in untreated recipients. Bleomycin, local thoraric irradiation and whole-body irradiation were much less effective in enhancing the lung-cloning efficiency. Cyclophosphamide also enhanced the take probability of i.m. implanted tumour cells

Generation of frequency sidebands on single photons with indistinguishability from quantum dots

Generation and manipulation of the quantum state of a single photon is at the heart of many quantum information protocols. There has been growing interest in using phase modulators as quantum optics devices that preserve coherence. In this Letter, we have used an electro-optic phase modulator to shape the state vector of single photons emitted by a quantum dot to generate new frequency components (modes) and explicitly demonstrate that the phase modulation process agrees with the theoretical prediction at a single photon level. Through two-photon interference measurements we show that for an output consisting of three modes (the original mode and two sidebands), the indistinguishability of the mode engineered photon, measured through the secondorder intensity correlation (g2(0)) is preserved. This work demonstrates a robust means to generate a photonic qubit or more complex state (e.g., a qutrit) for quantum communication applications by encoding information in the sidebands without the loss of coherence

Establishing an international research collaborative for naturopathy: The International Research Consortium of Naturopathic Academic Clinics (IRCNAC)

© 2017 Elsevier Ltd Naturopathy is a system of healthcare through which practitioners apply core philosophies, theories and principles to integrate medical knowledge with natural treatment options. In recent years the naturopathic community has developed a stronger international coherence. Alongside this growing connectivity in the global naturopathic profession, there have been a number of calls for more systematic research attention to be devoted to naturopathy as a substantive research topic, as well as a need for the naturopathic profession to hone a culture of research and evidence-based practices and skillsets. Progress in this area has been made through the development of more pragmatic and whole systems naturopathic research. One aspect which is currently missing in the global naturopathic research landscape despite this growing pattern of practice-based, whole systems research is the application of international multicentre research projects. In response, we have established a research consortium for naturopathic academic clinics in four countries and across multiple world regions. This paper serves to overview the mission, scope and membership of the research consortium and explore some of the research designs and questions which it may support

Experiences, perceptions and expectations of health services amongst marginalized populations in urban Australia: A meta-ethnographic review of the literature.

BACKGROUND: Poor health outcomes amongst marginalized groups result in part from health inequities related to social and structural determinants of health. Marginalized people report higher incidences of comorbidities, chronic disease and adverse health behaviours than their nondisadvantaged peers. The objective of this review is to examine marginalized Australians' experiences of and access to community-based primary health services in urban locations. METHODS: A systematic search incorporating related MeSH terms and synonyms pertaining to marginalized Australian populations and their health-seeking was conducted across seven databases. We included qualitative studies that reported experiences of health-seeking within community-based primary health care in metropolitan Australia. Participant populations experiencing marginalization due to social stigma and isolation, early-life disadvantage, poor health and/or financial hardship were included. A meta-ethnographic framework was used to synthesize themes across selected studies and researcher triangulation was employed to develop higher-order themes. RESULTS: Search results revealed 26 studies included for critical appraisal and synthesis. Seven higher-order themes were developed describing experiences of health service engagement amongst marginalized groups: (1) Understanding the patient within the context of family and community, (2) Health and cultural beliefs influence health-seeking, (3) Lack of information and poor cultural competence limit utilization of services, (4) Motivation for treatment influences health service engagement, (5) Accessing services, a spectrum of experience-from discrimination to validation, (6) Navigating a complex system in a complex society, (7) Preferences for health care and expectations for systemic change. CONCLUSION: Marginalized Australians experience health disadvantage across micro, meso and macro levels of health system navigation and commonalities in health-seeking were identified across each of the distinct marginalized groups in our analysis. This review outlines important areas of consideration for health care provision and policy development essential to helping address health inequities for a diversity of marginalized populations. PATIENT OR PUBLIC CONTRIBUTION: Whilst patient voices were reported across all studies included within this review, no further patient or public contribution applies to this study

Myosin VIIA is required for aminoglycoside accumulation in cochlear hair cells.

Myosin VIIA is expressed by sensory hair cells and has a primary structure predicting a role in membrane trafficking and turnover, processes that may underlie the susceptibility of hair cells to aminoglycoside antibiotics. [3H]Gentamicin accumulation and the effects of aminoglycosides were therefore examined in cochlear cultures of mice with different missense mutations in the myosin VIIA gene, Myo7a, to see whether myosin VIIA plays a role in aminoglycoside ototoxicity. Hair cells from homozygous mutant Myo7a(sh1) mice, with a mutation in a non-conserved region of the myosin VIIA head, respond rapidly to aminoglycoside treatment and accumulate high levels of gentamicin. Hair cells from homozygous mutant Myo7a(6J) mice, with a mutation at a highly conserved residue close to the ATP binding site of the myosin VIIA head, do not accumulate [3H]gentamicin and are protected from aminoglycoside ototoxicity. Hair cells from heterozygotes of both alleles accumulate [3H]gentamicin and respond to aminoglycosides. Although aminoglycoside uptake is thought to be via apical surface-associated endocytosis, coated pit numbers on the apical membrane of heterozygous and homozygous Myo7a(6J) hair cells are similar. Pulse-chase experiments with cationic ferritin confirm that the apical endocytotic pathway is functional in homozygous Myo7a(6J) hair cells. Transduction currents can be recorded from both heterozygous and homozygous Myo7a(6J) hair cells, suggesting it is unlikely that the drug enters via diffusion through the mechanotransducer channel. The results show that myosin VIIA is required for aminoglycoside accumulation in hair cells. Myosin VIIA may transport a putative aminoglycoside receptor to the hair cell surface, indirectly translocate it to sites of membrane retrieval, or retain it in the endocytotic pathway

Reconstructing pedigrees: some identifiability questions for a recombination-mutation model

Pedigrees are directed acyclic graphs that represent ancestral relationships between individuals in a population. Based on a schematic recombination process, we describe two simple Markov models for sequences evolving on pedigrees - Model R (recombinations without mutations) and Model RM (recombinations with mutations). For these models, we ask an identifiability question: is it possible to construct a pedigree from the joint probability distribution of extant sequences? We present partial identifiability results for general pedigrees: we show that when the crossover probabilities are sufficiently small, certain spanning subgraph sequences can be counted from the joint distribution of extant sequences. We demonstrate how pedigrees that earlier seemed difficult to distinguish are distinguished by counting their spanning subgraph sequences.Comment: 40 pages, 9 figure

catena-Poly[[silver(I)-μ-4-aminopyridine] perchlorate]: a 1-D staircase coordination polymer

Reaction of 4-amino­pyridine with silver(I) perchlorate leads to a one-dimensional coordination polymer, {[Ag(C5H6N2)]ClO4}n, in which the amino­pyridine binds through both N atoms. The perchlorate anion is hydrogen bonded to the amino H atoms and inter­acts weakly with the silver(I) atoms (Ag—O > 2.70 Å), both located on inversion centres, and some aromatic H atoms (O—H > 2.55 ÅA), thereby extending the dimensionality of the assembly. This is the first silver complex in which this ligand acts in a bridging mode