Assembly and force measurement with SPM-like probes in holographic optical tweezers

We report a high fidelity tomographic reconstruction of the quantum state of photon pairs generated by parametric down-conversion with orbital angular momentum (OAM) entanglement. Our tomography method allows us to estimate an upper and lower bound for the entanglement between the down-converted photons. We investigate the two-dimensional state subspace defined by the OAM states ±ℓ and superpositions thereof, with ℓ=1, 2, ..., 30. We find that the reconstructed density matrix, even for OAMs up to around ℓ=20, is close to that of a maximally entangled Bell state with a fidelity in the range between F=0.979 and F=0.814. This demonstrates that, although the single count-rate diminishes with increasing ℓ, entanglement persists in a large dimensional state space

Comparing physiological responses to hot and cold stress in a cnidarian–algal holobiont, \u3ci\u3eExaiptasia diaphana\u3c/i\u3e

Coral bleaching—the breakdown of the cnidarian–algal symbiosis—is a major cause of reef decline. The sea anemone Exaiptasia diaphana, commonly known as Aiptasia, is used as a model to study cnidarian-algal symbiosis in laboratory settings. Aiptasia can live with or without symbionts, which allows scientists to study the host combined and separate from the influence of the symbionts. Scientists are able to trigger the breakdown of the symbiosis using heat or cold stress. Cold stress is more commonly used to render aposymbiotic Aiptasia because it seems to be less harmful to the host than bleaching under heat stress. Is cold really less harmful than heat stress? We compared hot and cold stress responses to different stress regiments: a gradual temperature change, a gradual temperature change followed by a sudden temperature change, and a sudden temperature change from ambient conditions. We explored multiple physiological responses of the anemones to determine their level of stress response. We measured mortality and algal density in the host, as well as carbohydrate in the host and symbiont fractions. We also measured peroxide production in algal cultures exposed to the same treatment regimes. After repeating the experiment twice, we found that anemones had different responses, which emphasizes the necessity for repeated experiments in research conducted with live subjects

La communication des neurosciences au tribunal : un courant de recherche à développer = Communicating neurosciences in court: a line of research to develop

Neuroscientists, clinicians, and researchers alike are increasingly called upon to act as expert witnesses in court, including in Canada. Indeed, the court asks to be enlightened to rule on, for instance, the criminal responsibility of an individual or the sentence to give based on a nervous system-related cause. Even if neurosciences are a burgeoning field, communication processes involved in neurosciences expert testimonies have not been the object of the same empirical scrutiny. This article presents pitfalls in knowledge transfer, notably those of the Canadian context, and aims at encouraging the development of a line of research pertaining to the communication of neurosciences by expert witnesses in court. Several arguments are presented. Eventually, scientific discoveries unearthed by this line of research will help to develop specific guidelines, to refine experts’ practices, to maintain their credibility in court, and to optimize knowledge transfer. Some qualitative and quantitative research designs are suggested

Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.Comment: 40 pages, 13 PostScript figure

Superoxide Production by a Manganese-Oxidizing Bacterium Facilitates Iodide Oxidation

The release of radioactive iodine (i.e., iodine-129 and iodine-131) from nuclear reprocessing facilities is a potential threat to human health. The fate and transport of iodine are determined primarily by its redox status, but processes that affect iodine oxidation states in the environment are poorly characterized. Given the difficulty in removing electrons from iodide (I(−)), naturally occurring iodide oxidation processes require strong oxidants, such as Mn oxides or microbial enzymes. In this study, we examine iodide oxidation by a marine bacterium, Roseobacter sp. AzwK-3b, which promotes Mn(II) oxidation by catalyzing the production of extracellular superoxide (O(2)(−)). In the absence of Mn(2+), Roseobacter sp. AzwK-3b cultures oxidized ∼90% of the provided iodide (10 μM) within 6 days, whereas in the presence of Mn(II), iodide oxidation occurred only after Mn(IV) formation ceased. Iodide oxidation was not observed during incubations in spent medium or with whole cells under anaerobic conditions or following heat treatment (boiling). Furthermore, iodide oxidation was significantly inhibited in the presence of superoxide dismutase and diphenylene iodonium (a general inhibitor of NADH oxidoreductases). In contrast, the addition of exogenous NADH enhanced iodide oxidation. Taken together, the results indicate that iodide oxidation was mediated primarily by extracellular superoxide generated by Roseobacter sp. AzwK-3b and not by the Mn oxides formed by this organism. Considering that extracellular superoxide formation is a widespread phenomenon among marine and terrestrial bacteria, this could represent an important pathway for iodide oxidation in some environments

Risk of Parkinson's disease after tamoxifen treatment

<p>Abstract</p> <p>Background</p> <p>Women have a reduced risk of developing Parkinson's disease (PD) compared with age-matched men. Neuro-protective effects of estrogen potentially explain this difference. Tamoxifen, commonly used in breast cancer treatment, may interfere with the protective effects of estrogen and increase risk of PD. We compared the rate of PD in Danish breast cancer patients treated with tamoxifen to the rate among those not treated with tamoxifen.</p> <p>Methods</p> <p>A cohort of 15,419 breast cancer patients identified from the Danish Breast Cancer Collaborative Group database was linked to the National Registry of Patients to identify PD diagnoses. Overall risk and rate of PD following identification into the study was compared between patients treated with tamoxifen as adjuvant hormonal therapy and patients not receiving tamoxifen. Time-dependent effects of tamoxifen treatment on PD rate were examined to estimate the likely induction period for tamoxifen.</p> <p>Results</p> <p>In total, 35 cases of PD were identified among the 15,419 breast cancer patients. No overall effect of tamoxifen on rate of PD was observed (HR = 1.3, 95% CI: 0.64-2.5), but a PD hazard ratio of 5.1 (95% CI: 1.0-25) was seen four to six years following initiation of tamoxifen treatment.</p> <p>Conclusions</p> <p>These results provide evidence that the neuro-protective properties of estrogen against PD occurrence may be disrupted by tamoxifen therapy. Tamoxifen treatments may be associated with an increased rate of PD; however these effects act after four years, are of limited duration, and the adverse effect is overwhelmed by the protection against breast recurrence conferred by tamoxifen therapy.</p

Conformational rearrangements in the transmembrane domain of CNGA1 channels revealed by single-molecule force spectroscopy

Cyclic nucleotide-gated (CNG) channels are activated by binding of cyclic nucleotides. Although structural studies have identified the channel pore and selectivity filter, conformation changes associated with gating remain poorly understood. Here we combine single-molecule force spectroscopy (SMFS) with mutagenesis, bioinformatics and electrophysiology to study conformational changes associated with gating. By expressing functional channels with SMFS fingerprints in Xenopus laevis oocytes, we were able to investigate gating of CNGA1 in a physiological-like membrane. Force spectra determined that the S4 transmembrane domain is mechanically coupled to S5 in the closed state, but S3 in the open state. We also show there are multiple pathways for the unfolding of the transmembrane domains, probably caused by a different degree of \u3b1-helix folding. This approach demonstrates that CNG transmembrane domains have dynamic structure and establishes SMFS as a tool for probing conformational change in ion channels

Common Features at the Start of the Neurodegeneration Cascade

A single-molecule study reveals that neurotoxic proteins share common structural features that may trigger neurodegeneration, thus identifying new targets for therapy and diagnosis

Reducing the health disparities of Indigenous Australians: time to change focus

Background: Indigenous peoples have worse health than non-Indigenous, are over-represented amongst the poor and disadvantaged, have lower life expectancies, and success in improving disparities is limited. To address this, research usually focuses on disadvantaged and marginalised groups, offering only partial understanding of influences underpinning slow progress. Critical analysis is also required of those with the power to perpetuate or improve health inequities. In this paper, using Australia as a case example, we explore the effects of ‘White’, Anglo-Australian cultural dominance in health service delivery to Indigenous Australians. We address the issue using race as an organising principle, underpinned by relations of power.Methods: Interviews with non-Indigenous medical practitioners in Western Australia with extensive experience in Indigenous health encouraged reflection and articulation of their insights into factors promoting or impeding quality health care to Indigenous Australians. Interviews were audio-taped and transcribed. An inductive, exploratory analysis identified key themes that were reviewed and interrogated in light of existing literature on health care to Indigenous people, race and disadvantage. The researchers’ past experience, knowledge and understanding of health care and Indigenous health assisted with data interpretation. Informal discussions were also held with colleagues working professionally in Indigenous policy, practice and community settings.Results: Racism emerged as a key issue, leading us to more deeply interrogate the role ‘Whiteness’ plays in Indigenous health care. While Whiteness can refer to skin colour, it also represents a racialized social structure where Indigenous knowledge, beliefs and values are subjugated to the dominant western biomedical model in policy and practice. Racism towards Indigenous patients in health services was institutional and interpersonal. Internalised racism was manifest when Indigenous patients incorporated racist attitudes and beliefs into their lived experience, lowering expectations and their sense of self-worth.Conclusions: Current health policies and practices favour standardised care where the voice of those who are marginalised is often absent. Examining the effectiveness of such models in reducing health disparities requires health providers to critically reflect on whether policies and practices promote or compromise Indigenous health and wellbeing - an important step in changing the discourse that places Indigenous people at the centre of the problem

Tuning hardness in calcite by incorporation of amino acids

Structural biominerals are inorganic/organic composites that exhibit remarkable mechanical properties. However, the structure–property relationships of even the simplest building unit—mineral single crystals containing embedded macromolecules—remain poorly understood. Here, by means of a model biomineral made from calcite single crystals containing glycine (0–7 mol%) or aspartic acid (0–4 mol%), we elucidate the origin of the superior hardness of biogenic calcite. We analysed lattice distortions in these model crystals by using X-ray diffraction and molecular dynamics simulations, and by means of solid-state nuclear magnetic resonance show that the amino acids are incorporated as individual molecules. We also demonstrate that nanoindentation hardness increased with amino acid content, reaching values equivalent to their biogenic counterparts. A dislocation pinning model reveals that the enhanced hardness is determined by the force required to cut covalent bonds in the molecules