Copper trafficking in eukaryotic systems: current knowledge from experimental and computational efforts

Copper plays a vital role in fundamental cellular functions, and its concentration in the cell must be tightly regulated, as dysfunction of copper homeostasis is linked to severe neurological diseases and cancer. This review provides a compendium of current knowledge regarding the mechanism of copper transfer from the blood system to the Golgi apparatus; this mechanism involves the copper transporter hCtr1, the metallochaperone Atox1, and the ATPases ATP7A/B. We discuss key insights regarding the structural and functional properties of the hCtr1-Atox1-ATP7B cycle, obtained from diverse studies relying on distinct yet complementary biophysical, biochemical, and computational methods. We further address the mechanistic aspects of the cycle that continue to remain elusive. These knowledge gaps must be filled in order to be able to harness our understanding of copper transfer to develop therapeutic approaches with the capacity to modulate copper metabolism

Interstitial gas and density-segregation in vertically-vibrated granular media

We report experimental studies of the effect of interstitial gas on mass-density-segregation in a vertically-vibrated mixture of equal-sized bronze and glass spheres. Sufficiently strong vibration in the presence of interstitial gas induces vertical segregation into sharply separated bronze and glass layers. We find that the segregated steady state (i.e., bronze or glass layer on top) is a sensitive function of gas pressure and viscosity, as well as vibration frequency and amplitude. In particular, we identify distinct regimes of behavior that characterize the change from bronze-on-top to glass-on-top steady-state.Comment: 4 pages, 5 figures, submitted to PRL; accepted in PRE as rapid communication, with revised text and reference

Q^2 Evolution of the Generalized Gerasimov-Drell-Hearn Integral for the Neutron using a ^3He Target

We present data on the inclusive scattering of polarized electrons from a polarized ^3He target at energies from 0.862 to 5.06 GeV, obtained at a scattering angle of 15.5°. Our data include measurements from the quasielastic peak, through the nucleon resonance region, and beyond, and were used to determine the virtual photon cross-section difference σ_(1/2)-σ_(3/2). We extract the extended Gerasimov-Drell-Hearn integral for the neutron in the range of four-momentum transfer squared Q^2 of 0.1–0.9   GeV^2

Comment on "First-principles study of the influence of (110)-oriented strain on the ferroelectric properties of rutile TiO2"

In a recent article, Gr\"{u}nebohm et al. [Phys. Rev. B 84 132105 (2011), arXiv:1106.2820] report that they fail to reproduce the A2u ferroelectric instability of TiO2 in the rutile structure calculated with density functional theory within the PBE-GGA approximation by Montanari et al. [Chem. Phys. Lett 364, 528 (2002)]. We demonstrate that this disagreement arises from an erroneous treatment of Ti 3s and 3p semi-core electrons as core in their calculations. Fortuitously the effect of the frozen semi-core pseudopotential cancels the phonon instability of the PBE exchange-correlation, and the combination yields phonon frequencies similar to the LDA harmonic values. Gr\"{u}nebohm et al. also attempted and failed to reproduce the soft acoustic phonon mode instability under (110) strain reported by Mitev et al. [Phys. Rev. B 81 134303 (2010)]. For this mode the combination of PBE-GGA and frozen semi-core yields a small imaginary frequency of 9.8i. The failure of Gr\"{u}nebohm et al. to find this mode probably arose from numerical limitations of the geometry optimization approach in the presence of a shallow double well potential; the optimization method is not suitable for locating such instabilities.Comment: 5 page

Take the sex out of STI screening! Views of young women on implementing chlamydia screening in General Practice

<p>Abstract</p> <p>Background</p> <p>Australia is developing a chlamydia screening program. This study aimed to determine the attitudes of young women to the introduction of chlamydia screening in Australian General Practice.</p> <p>Methods</p> <p>In-depth face-to-face interviews with 24 young women from across Victoria, Australia, attending a randomly selected sample of general practices.</p> <p>Results</p> <p>Young women reported that they would accept age-based screening for chlamydia in general practice, during both sexual-health and non-sexual-health related consultations. Trust in their general practitioner (GP) was reported to be a major factor in the acceptability of chlamydia screening. The women felt chlamydia screening should be offered to <it>all </it>young women rather than targeted at "high risk" women based on sexual history and they particularly emphasised the importance of normalising chlamydia screening. The women reported that they did not want to be asked to provide a sexual history as part of being asked to have a chlamydia test. Some reported that they would lie if asked how many partners they had had</p> <p>Conclusion</p> <p>Women do not want a sexual history taken when being asked to have a chlamydia test while attending a general practitioner. They prefer the offer of chlamydia screening to be based on age rather than assessment of sexual risk. Chlamydia screening needs to be normalised and destigmatised.</p

Telling partners about chlamydia: how acceptable are the new technologies?

BACKGROUND Partner notification is accepted as a vital component in the control of chlamydia. However, in reality, many sexual partners of individuals diagnosed with chlamydia are never informed of their risk. The newer technologies of email and SMS have been used as a means of improving partner notification rates. This study explored the use and acceptability of different partner notification methods to help inform the development of strategies and resources to increase the number of partners notified. METHODS Semi-structured telephone interviews were conducted with 40 people who were recently diagnosed with chlamydia from three sexual health centres and two general practices across three Australian jurisdictions. RESULTS Most participants chose to contact their partners either in person (56%) or by phone (44%). Only 17% chose email or SMS. Participants viewed face-to-face as the "gold standard" in partner notification because it demonstrated caring, respect and courage. Telephone contact, while considered insensitive by some, was often valued because it was quick, convenient and less confronting. Email was often seen as less personal while SMS was generally considered the least acceptable method for telling partners. There was also concern that emails and SMS could be misunderstood, not taken seriously or shown to others. Despite these, email and SMS were seen to be appropriate and useful in some circumstances. Letters, both from the patients or from their doctor, were viewed more favourably but were seldom used. CONCLUSION These findings suggest that many people diagnosed with chlamydia are reluctant to use the new technologies for partner notification, except in specific circumstances, and our efforts in developing partner notification resources may best be focused on giving patients the skills and confidence for personal interaction.The study was funded by the Australian Federal Government Department of Health and Ageing Chlamydia Pilot Program of Targeted Grants

Better than nothing? Patient-delivered partner therapy and partner notification for chlamydia: the views of Australian general practitioners

BACKGROUND Genital chlamydia is the most commonly notified sexually transmissible infection (STI) in Australia and worldwide and can have serious reproductive health outcomes. Partner notification, testing and treatment are important facets of chlamydia control. Traditional methods of partner notification are not reaching enough partners to effectively control transmission of chlamydia. Patient-delivered partner therapy (PDPT) has been shown to improve the treatment of sexual partners. In Australia, General Practitioners (GPs) are responsible for the bulk of chlamydia testing, diagnosis, treatment and follow up. This study aimed to determine the views and practices of Australian general practitioners (GPs) in relation to partner notification and PDPT for chlamydia and explored GPs' perceptions of their patients' barriers to notifying partners of a chlamydia diagnosis. METHODS In-depth, semi-structured telephone interviews were conducted with 40 general practitioners (GPs) from rural, regional and urban Australia from November 2006 to March 2007. Topics covered: GPs' current practice and views about partner notification, perceived barriers and useful supports, previous use of and views regarding PDPT.Transcripts were imported into NVivo7 and subjected to thematic analysis. Data saturation was reached after 32 interviews had been completed. RESULTS Perceived barriers to patients telling partners (patient referral) included: stigma; age and cultural background; casual or long-term relationship, ongoing relationship or not. Barriers to GPs undertaking partner notification (provider referral) included: lack of time and staff; lack of contact details; uncertainty about the legality of contacting partners and whether this constitutes breach of patient confidentiality; and feeling both personally uncomfortable and inadequately trained to contact someone who is not their patient. GPs were divided on the use of PDPT--many felt concerned that it is not best clinical practice but many also felt that it is better than nothing.GPs identified the following factors which they considered would facilitate partner notification: clear clinical guidelines; a legal framework around partner notification; a formal chlamydia screening program; financial incentives; education and practical support for health professionals, and raising awareness of chlamydia in the community, in particular amongst young people. CONCLUSIONS GPs reported some partners do not seek medical treatment even after they are notified of being a sexual contact of a patient with chlamydia. More routine use of PDPT may help address this issue however GPs in this study had negative attitudes to the use of PDPT. Appropriate guidelines and legislation may make the use of PDPT more acceptable to Australian GPs.The Australian Federal Government Department of Health and Ageing Chlamydia Pilot Program of Targeted Grants funded the study