BackgroundWhile genomic data sharing can facilitate important health research and discovery benefits, these must be balanced against potential privacy risks and harms to individuals. Understanding public attitudes and perspectives on data sharing is important given these potential risks and to inform genomic research and policy that aligns with public preferences and needs.MethodsA cross sectional online survey measured attitudes towards genomic data sharing among members of the general public in an Eastern Canadian province.ResultsResults showed a moderate comfort level with sharing genomic (...) data, usually into restricted scientific databases with controlled access. Much lower comfort levels were observed for sharing data into open or publicly accessible databases. While respondents largely approved of sharing genomic data for health research permitted by a research ethics board, many general public members were concerned with who would have access to their data, with higher rates of approval for access from clinical or academic actors, but much more limited approval of access from commercial entities or governments. Prior knowledge about sequencing and about research ethics boards were both related to data sharing attitudes.ConclusionsWith evolving regulations and guidelines for genomics research and data sharing, it is important to consider the perspectives of participants most impacted by these changes. Participant information materials and informed consent documents must be explicit about the safeguards in place to protect genomic data and the policies governing the sharing of data. Increased public awareness of the role of research ethics boards and of the need for genomic data sharing more broadly is also needed. (shrink)

Chemiosmotic coupling − the harnessing of electrochemical ion gradients across membranes to drive metabolism − is as universally conserved as the genetic code. As argued previously in these pages, such deep conservation suggests that ion gradients arose early in evolution, and might have played a role in the origin of life. Alkaline hydrothermal vents harbour pH gradients of similar polarity and magnitude to those employed by modern cells, one of many properties that make them attractive models for life's origin. Their (...) congruence with the physiology of anaerobic autotrophs that use the acetyl CoA pathway to fix CO2 gives the alkaline vent model broad appeal to biologists. Recently, however, a paper by Baz Jackson criticized the hypothesis, concluding that natural pH gradients were unlikely to have played any role in the origin of life. Unfortunately, Jackson mainly criticized his own interpretations of the theory, not what the literature says. This counterpoint is intended to set the record straight. (shrink)

Every year our sun should be losing about 10 20 protons (about a milligram's worth) in this way. This is not much of a loss, but it is irreversible, and it adds up. In 10..

The initial relationships between organisms leading to endosymbiosis and the first eukaryote are currently a topic of hot debate. Here, I present a theory that offers a gradual scenario in which the origins of phagocytosis and mitochondria are intertwined in such a way that the evolution of one would not be possible without the other. In this scenario, the premitochondrial bacterial symbiont became initially associated with a protophagocytic host on the basis of cooperation to kill prey with symbiont‐produced toxins and (...) reactive oxygen species (ROS). Subsequently, the cooperation was focused on the digestion stage, through the acidification of the protophagocytic cavities via exportation of protons produced by the aerobic respiration of the symbiont. The host gained an improved phagocytic capacity and the symbiont received organic compounds from prey. As the host gradually lost its membrane energetics to develop lysosomal digestion, respiration was centralized in the premitochondrial symbiont for energy production for the consortium. (shrink)

It is proposed in this paper that enzymes, by virtue of a number of correctly positioned sites of interaction with substrates, can force the compression of hydrogen bonds, increasing the probability of proton transfer by quantum mechanical tunneling. By such a catalytic mechanism a rate enhancement of many orders of magnitude may be obtained with a very low energy input requirement. The mechanism would, however, require a highly structured catalyst.Pertinent aspects of hydrogen bond theory and of tunneling theory are (...) briefly reviewed. (shrink)

Accumulation of neurotransmitters in the lumen of synaptic vesicles (SVs) relies on the activity of the vacuolar‐type H+‐ATPase. This pump drives protons into the lumen, generating a proton electrochemical gradient (ΔμH+) across the membrane. Recent work has demonstrated that the balance between the chemical (ΔpH) and electrical (ΔΨ) components of ΔμH+ is regulated differently by some distinct vesicle types. As different neurotransmitter transporters use ΔpH and ΔΨ with different relative efficiencies, regulation of this gradient balance has the potential to (...) influence neurotransmitter uptake. Nevertheless, the underlying mechanisms responsible for this regulation remain poorly understood. In this review, we provide an overview of current neurotransmitter uptake models, with a particular emphasis on the distinct roles of the electrical and chemical gradients and current hypotheses for regulatory mechanisms. -/- . (shrink)

A novel photon-based proton model is developed. A proton’s ground state is assumed to be coherent to the degree that all of its mass-energy precipitates into a single uncharged spherical structure. A quantum vortex, initiated by the strong force, but sustained in the proton’s ground state by the circular Unruh effect and a spherical Rindler horizon, is proposed to confine the proton’s mass-energy in its ground state. A direct connection between the circular Unruh effect, the zitterbewegung (...) effect, spin, and general relativity is proposed. Such a structure acts as an uncharged zitterbewegung fermion, and may explain neutrino mass. A ground-state proton’s central zitterbewegung fermion is assumed to be surrounded by a halo of charge shells of both signs. Virtual photon standing waves are assumed to synchronize the inner shell with the central zitterbewegung fermion. The charge shells are proposed to be associated with isospin and proton g-factor. There are only two model inputs—proton mass and quantized electronic charge—and just one adjustable parameter. The adjustable parameter, reduced only by about 0.4% from an initial estimate, provides the proton’s experimentally determined magnetic moment to arbitrary precision. The resulting modeled proton charge radius agrees very well with the 2018 CODATA value. Magnetic moment and charge radius are calculated algebraically in a manner easily understood by undergraduate physics students. This proposed ground-state proton model could be considered a low-energy approximation to a full quantum chromodynamical proton model. (shrink)

Ductin is the highest conserved membrane protein yet found in eukaryotes. It is multifunctional, being the subunit c or proteolipid component of the vacuolar H+‐ATPase and at the same time the protein component of a form of gap junction in metazoan animals. Analysis of its structure shows it to be a tandem repeat of two 8‐kDa domains derived from the subunit c of the F0 proton pore from the F1F0 ATPase. Each domain contains two transmembrane α‐helices, which together may (...) form a four‐helix bundle. In both the V‐ATPase and gap junction channel, ductin is probably arranged as a hexamer of subunits forming a central channel of gap junction‐like proportions. The two functions appear to be seggregated by ductin having two orientations in the bilayer. Ductin is also the major component of the mediatophore, a protein complex which may aid in the release of neurotransmitters across the pre‐synaptic membrane. It is also a target for a class of poorly understood viral polypeptides. These polypeptides are small and highly hydrophobic and some have oncogenic activity. Ductin thus appears to be at the crossroads of a number of biological processes. (shrink)

A novel class of proton‐ATPase has been identified in the vacuolar system of eukaryotic cells. The properties of these enzymes and their relation to other proton‐ATPases is discussed.

Gluten ataxia is a rare immune-mediated neurological disorder caused by the ingestion of gluten. The diagnosis is not straightforward as antibodies are present in only up to 38% of patients, but often at lower titers. The symptoms of ataxia may be mild at the onset but lead to permanent damage if remain untreated. It is characterized by damage to the cerebellum however, the pathophysiology of the disease is not clearly understood. The present study investigated the neurochemical profile of vermis and (...) right cerebellum and structural changes in various brain regions of patients with gluten ataxia and compared it with healthy controls. Volumetric 3-D T1 and T1-weighted magnetic resonance imaging in the three planes of the whole brain and single-voxel 1H- magnetic resonance spectroscopy of the vermis and right cerebellum were acquired on 3 T human MR scanner. The metabolite concentrations were estimated using LC Model while brain volumes were estimated using the online tool volBrain pipeline and CERES and corrected for partial volumes. The levels of neuro-metabolites were found to be significantly lower in vermis, while N-acetyl aspartate + N-acetyl aspartate glutamate and glycerophosphocholine + phosphocholine was lower in cerebellum regions in the patients with gluten ataxia compared to healthy controls. A significant reduction in the white matter of ; reduction in the volumes of cerebellum lobe and thalamus while lateral ventricles were increased in the patients with gluten ataxia compared to healthy controls. The reduced neuronal metabolites along with structural changes in the brain suggested neuronal degeneration in the patients with gluten ataxia. Our preliminary findings may be useful in understanding the gluten-induced cerebral damage and indicated that MRI and MRS may serve as a non-invasive useful tool in the early diagnosis, thereby enabling better management of these patients. (shrink)

Rationale In Belgium, several policies regulating reimbursement of acid suppressant drugs and evidence-based recommendations for clinical practice were issued in a short period of time, creating a unique opportunity to observe their effect on prescribing. Aims and objectives To describe the evolution of prescriptions for acid suppressants and explore the interaction of policies and practice recommendations with prescribing patterns. Method Monthly claims-based data for proton pump inhibitors (PPIs) and H-2-antihistamines by general practitioners, internists and "astroenterologists were obtained from the (...) Belgian national health insurance database (1997-2005). The evolution of reimbursed defined daily doses and expenses after introduction of reimbursement regulations and dissemination of practice recommendations was explored. Results Recommendations had no impact on prescribing. All changes can be related to concomitant policies. Lifting reimbursement restrictions for cheaper products did not control growth or save costs in the Iona term. Only restricting reimbursement of all PPIs managed to curb the growth. We observed an unintended increase of non-omeprazole PPIs by gastroenterologists. Conclusions Reimbursement policies influence prescribing, but their effect can be unintended. A dialogue between policymakers and guideline developers, and evidence-based policies that are linked to clinical guidelines, could be an effective way to pursue both cost-containment and quality of care. (shrink)

Recent studies have provided evidence of associations between neurochemistry and reading (dis)ability (Pugh et al., 2014). Based on a long history of studies indicating that fluent reading entails the automatic convergence of the written and spoken forms of language and our recently proposed Neural Noise Hypothesis (Hancock et al., 2017), we hypothesized that individual differences in cross-modal integration would mediate, at least partially, the relationship between neurochemical concentrations and reading. Cross-modal integration was measured in 231 children using a two-alternative forced (...) choice cross-modal matching task with three language conditions (letters, words, and pseudowords) and two levels of difficulty within each language condition. Neurometabolite concentrations of Choline (Cho), Glutamate (Glu), gamma-Aminobutyric (GABA), and N- acetyl-aspartate (NAA) were then measured in a subset of this sample (n = 70) with Magnetic Resonance Spectroscopy (MRS). A structural equation mediation model revealed that the effect of cross-modal word matching mediated the relationship between increased Glu (which has been proposed to be an index of neural noise) and poorer reading ability. In addition, the effect of cross-modal word matching fully mediated a relationship between increased Cho and poorer reading ability. Multilevel mixed effects models confirmed that lower Cho predicted faster cross-modal matching reaction time, specifically in the hard word condition. These Cho... (shrink)

In a seminal article in the Journal of Medical Ethics, Søren Holm and Tuja Takala analysed two protechnology arguments in bioethics: the hopeful principle and the automatic escalator. They showed how these arguments relate to problematic arguments such as the precautionary principle and the empirical slippery slope argument, and argued that they should be used with great caution. The present article investigates the recent debate on proton beam therapy, where the hopeful principle and the automatic escalator are identified. However, (...) the debate reveals a series of other arguments that deserve similar caution. An analysis of these arguments indicates that the roots of their fallacies are to be found in the ignorance of the uncertainties about risks and benefits and an overly optimistic attitude towards technology and progress. The point is not to argue against proton therapy, but rather to point out that flawed arguments for new technologies, such as proton therapy, can actually hamper their implementation instead of promoting it. Patients deserve the best technology available, not only on the basis of the best available evidence, but also on the basis of the best arguments. (shrink)