419 research outputs found
PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond
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Synchronisation and commonalities in metropolitan housing market cycles
This paper examines the degree of commonalities present in the cyclical behavior of the eight largest metropolitan housing markets in Australia. Using two techniques originally in the business cycle literature we consider the degree of synchronization present and secondly decompose the series’ into their permanent and cyclical components. Both empirical approaches reveal similar results. Sydney and Melbourne are closely related to each other and are relatively segmented from the smaller metropolitan areas. In contrast, there is substantial evidence of commonalities in the cyclical behavior of the remaining cities, especially those on the Eastern and Southern coasts of Australia
First report of the presence of hepatitis E virus in Scottish harvested shellfish purchased at retail level
Predictors of podiatry utilisation in Australia: the North West Adelaide Health Study
Background Foot problems are highly prevalent in the community; however no large population-based studies have examined the characteristics of those who do and do not access podiatry services in Australia. The aim of this study was to explore patterns of podiatry utilisation in a population-based sample of people aged 18 years and over living in the northwest region of Adelaide, South Australia.Methods The North West Adelaide Health Study is a representative longitudinal cohort study of 4,060 people randomly selected and recruited by telephone interview. The interview included questions regarding healthcare service utilisation in the past year. Data were also collected on education, income and major medical conditions.Results Overall, 9.5% of the total sample and 17.7% of those who reported foot pain had attended a podiatrist in the past year. Participants who had accessed podiatry treatment were more likely to be female, be aged over 45 years, be obese, and have major chronic medical conditions (osteoporosis, osteoarthritis, diabetes, cardiovascular disease and high blood pressure). Those who reported foot pain but had not accessed a podiatrist were more likely to be male and be aged 20 to 34 years.Conclusion Only a small proportion of people who report foot pain have accessed podiatry services in the past year. There is a need to further promote podiatry services to the general community, particularly to men and younger people.Hylton B Menz, Tiffany K Gill, Anne W Taylor and Catherine L Hil
A survey of foot problems in community-dwelling older Greek Australians
<p>Abstract</p> <p>Background</p> <p>Foot problems are common in older people and are associated with impaired mobility and quality of life. However, the characteristics of foot problems in older Australians for whom English is a second language have not been evaluated.</p> <p>Methods</p> <p>One hundred and four community-dwelling people aged 64 to 90 years with disabling foot pain (according to the case definition of the Manchester Foot Pain and Disability Index, or MFPDI) were recruited from four Greek elderly citizens clubs in Melbourne, Australia. All participants completed a Greek language questionnaire consisting of general medical history, the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire, the MFPDI, and specific questions relating to foot problems and podiatry service utilisation. In addition, all participants underwent a brief clinical foot assessment.</p> <p>Results</p> <p>The MFPDI score ranged from 1 to 30 (median 14), out of a total possible score of 34. Women had significantly higher total MFPDI scores and MFPDI subscale scores. The MFPDI total score and subscale scores were significantly associated with most of the SF-36 subscale scores. The most commonly reported foot problem was difficulty finding comfortable shoes (38%), and the most commonly observed foot problem was the presence of hyperkeratotic lesions (29%). Only 13% of participants were currently receiving podiatry treatment, and 40% stated that they required more help looking after their feet. Those who reported difficulty finding comfortable shoes were more likely to be female, and those who required more help looking after their feet were more likely to be living alone and have osteoarthritis in their knees or back.</p> <p>Conclusions</p> <p>Foot problems appear to be common in older Greek Australians, have a greater impact on women, and are associated with reduced health-related quality of life. These findings are broadly similar to previous studies in English-speaking older people in Australia. However, only a small proportion of this sample was currently receiving podiatry treatment, and a substantial number stated that they required more help looking after their feet. To address this issue, steps need to be taken to increase awareness of podiatry services among older Greek Australians.</p
Biochemical Comparison of Anopheles gambiae and Human NADPH P450 Reductases Reveals Different 2′-5′-ADP and FMN Binding Traits
NADPH-cytochrome P450 oxidoreductase (CPR) plays a central role in chemical
detoxification and insecticide resistance in Anopheles gambiae,
the major vector for malaria. Anopheles gambiae CPR (AgCPR) was
initially expressed in Eschericia coli but failed to bind
2′, 5′-ADP Sepharose. To investigate this unusual trait, we
expressed and purified a truncated histidine-tagged version for side-by-side
comparisons with human CPR. Close functional similarities were found with
respect to the steady state kinetics of cytochrome c reduction,
with rates (kcat) of 105
s−1 and 88 s−1, respectively, for mosquito
and human CPR. However, the inhibitory effects of 2′,5′-ADP on
activity were different; the IC50 value of AgCPR for 2′,
5′ –ADP was significantly higher (6–10 fold) than human CPR
(hCPR) in both phosphate and phosphate-free buffer, indicative of a decrease in
affinity for 2′, 5′- ADP. This was confirmed by isothermal titration
calorimetry where binding of 2′,5′-ADP to AgCPR
(Kd = 410±18 nM) was
∼10 fold weaker than human CPR
(Kd = 38 nM). Characterisation
of the individual AgFMN binding domain revealed much weaker binding of FMN
(Kd = 83±2.0 nM) than the equivalent
human domain (Kd = 23±0.9 nM).
Furthermore, AgCPR was an order of magnitude more sensitive than hCPR to the
reductase inhibitor diphenyliodonium chloride
(IC50 = 28 µM±2 and 361±31
µM respectively). Taken together, these results reveal unusual biochemical
differences between mosquito CPR and the human form in the binding of small
molecules that may aid the development of ‘smart’ insecticides and
synergists that selectively target mosquito CPR
A-Site Residues Move Independently from P-Site Residues in all-Atom Molecular Dynamics Simulations of the 70S Bacterial Ribosome
The ribosome is a large macromolecular machine, and correlated motion between residues is necessary for coordinating function across multiple protein and RNA chains. We ran two all-atom, explicit solvent molecular dynamics simulations of the bacterial ribosome and calculated correlated motion between residue pairs by using mutual information. Because of the short timescales of our simulation (ns), we expect that dynamics are largely local fluctuations around the crystal structure. We hypothesize that residues that show coupled dynamics are functionally related, even on longer timescales. We validate our model by showing that crystallographic B-factors correlate well with the entropy calculated as part of our mutual information calculations. We reveal that A-site residues move relatively independently from P-site residues, effectively insulating A-site functions from P-site functions during translation
The Homeodomain Derived Peptide Penetratin Induces Curvature of Fluid Membrane Domains
BACKGROUND:Protein membrane transduction domains that are able to cross the plasma membrane are present in several transcription factors, such as the homeodomain proteins and the viral proteins such as Tat of HIV-1. Their discovery resulted in both new concepts on the cell communication during development, and the conception of cell penetrating peptide vectors for internalisation of active molecules into cells. A promising cell penetrating peptide is Penetratin, which crosses the cell membranes by a receptor and metabolic energy-independent mechanism. Recent works have claimed that Penetratin and similar peptides are internalized by endocytosis, but other endocytosis-independent mechanisms have been proposed. Endosomes or plasma membranes crossing mechanisms are not well understood. Previously, we have shown that basic peptides induce membrane invaginations suggesting a new mechanism for uptake, "physical endocytosis". METHODOLOGY/PRINCIPAL FINDINGS:Herein, we investigate the role of membrane lipid phases on Penetratin induced membrane deformations (liquid ordered such as in "raft" microdomains versus disordered fluid "non-raft" domains) in membrane models. Experimental data show that zwitterionic lipid headgroups take part in the interaction with Penetratin suggesting that the external leaflet lipids of cells plasma membrane are competent for peptide interaction in the absence of net negative charges. NMR and X-ray diffraction data show that the membrane perturbations (tubulation and vesiculation) are associated with an increase in membrane negative curvature. These effects on curvature were observed in the liquid disordered but not in the liquid ordered (raft-like) membrane domains. CONCLUSIONS/SIGNIFICANCE:The better understanding of the internalisation mechanisms of protein transduction domains will help both the understanding of the mechanisms of cell communication and the development of potential therapeutic molecular vectors. Here we showed that the membrane targets for these molecules are preferentially the fluid membrane domains and that the mechanism involves the induction of membrane negative curvature. Consequences on cellular uptake are discussed
Dietary treatment of Crohn’s disease: perceptions of families with children treated by exclusive enteral nutrition, a questionnaire survey
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