Let me Google that for you:a time series analysis of seasonality in internet search trends for terms related to foot and ankle pain

BACKGROUND: The analysis of internet search traffic may present the opportunity to gain insights into general trends and patterns in information seeking behaviour related to medical conditions at a population level. For prevalent and widespread problems such as foot and ankle pain, this information has the potential to improve our understanding of seasonality and trends within these conditions and their treatments, and may act as a useful proxy for their true incidence/prevalence characteristics. This study aimed to explore seasonal effects, general trends and relative popularity of internet search terms related to foot and ankle pain over the past decade. METHODS: We used the Google Trends tool to obtain relative search engine traffic for terms relating to foot and ankle pain and common treatments from Google search and affiliated pages for major northern and southern hemisphere English speaking nations. Analysis of overall trends and seasonality including summer/winter differences was carried out on these terms. RESULTS: Searches relating to general foot pain were on average 3.4 times more common than those relating to ankle pain, and twice as common as searches relating to heel pain. Distinct seasonal effects were seen in the northern hemisphere, with large increases in search volumes in the summer months compared to winter for foot (p = 0.004, 95 % CI [22.2–32.1]), ankle (p = 0.0078, 95 % CI [20.9–35.5]), and heel pain (p = 0.004, 95 % CI [29.1–45.6]). These seasonal effects were reflected by data from Australia, with the exception of ankle pain. Annual seasonal effects for treatment options were limited to terms related to foot surgery and ankle orthoses (p = 0.031, 95 % CI [3.5–20.9]; p = 0.004, 95 % CI [7.6–25.2] respectively), again increasing in the summer months. CONCLUSIONS: A number of general trends and annual seasonal effects were found in time series internet search data for terms relating to foot and ankle pain. This data may provide insights into these conditions at population levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13047-015-0074-9) contains supplementary material, which is available to authorized users

Governors and directors: Competing models of corporate governance

Why do we use the term ‘corporate governance’ rather than ‘corporate direction’? Early British joint stock companies were normally managed by a single ‘governor’. The ‘court of governors’ or ‘board of directors’ emerged slowly as the ruling body for companies. By the nineteenth century, however, companies were typically run by directors while not-for-profit entities such as hospitals, schools and charitable bodies had governors. The nineteenth century saw steady refinement of the roles of company directors, often in response to corporate scandals, with a gradual change from the notion of the director as a ‘representative shareholder’ to the directors being seen collectively as ‘representatives of the shareholders’. Governors in not-for-profit entities, however, were regarded as having broader responsibilities. The term ‘governance’ itself suggests that corporate boards should be studied as ‘political’ entities rather than merely through economic lenses such as agency theory

Nanomechanical Detection of Itinerant Electron Spin Flip

Spin is an intrinsically quantum property, characterized by angular momentum. A change in the spin state is equivalent to a change in the angular momentum or mechanical torque. This spin-induced torque has been invoked as the intrinsic mechanism in experiments ranging from the measurements of angular momentum of photons g-factor of metals and magnetic resonance to the magnetization reversal in magnetic multi-layers A spin-polarized current introduced into a nonmagnetic nanowire produces a torque associated with the itinerant electron spin flip. Here, we report direct measurement of this mechanical torque and itinerant electron spin polarization in an integrated nanoscale torsion oscillator, which could yield new information on the itinerancy of the d-band electrons. The unprecedented torque sensitivity of 10^{-22} N m/ \sqrt{Hz} may enable applications for spintronics, precision measurements of CP-violating forces, untwisting of DNA and torque generating molecules.Comment: 14 pages, 4 figures. visit http://nano.bu.edu/ for related paper

The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.

Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids1,2. The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols3,4. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions2, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death5. However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines6, which suggests that additional factors govern resistance to ferroptosis. Here, using a synthetic lethal CRISPR-Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2)) as a potent ferroptosis-resistance factor. Our data indicate that myristoylation recruits FSP1 to the plasma membrane where it functions as an oxidoreductase that reduces coenzyme Q10 (CoQ) (also known as ubiquinone-10), which acts as a lipophilic radical-trapping antioxidant that halts the propagation of lipid peroxides. We further find that FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse tumour xenografts. Thus, our data identify FSP1 as a key component of a non-mitochondrial CoQ antioxidant system that acts in parallel to the canonical glutathione-based GPX4 pathway. These findings define a ferroptosis suppression pathway and indicate that pharmacological inhibition of FSP1 may provide an effective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutic agents

Australian Sphingidae – DNA Barcodes Challenge Current Species Boundaries and Distributions

© 2014 Rougerie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al