Wiring Switches to Light Bulbs

Given n buttons and n bulbs so that the ith button toggles the ith bulb and at most two other bulbs, we compute the sharp lower bound on the number of bulbs that can be lit regardless of the action of the buttons.Comment: 19 pages, 14 figure

Toxoplasma gondii-Induced Activation of EGFR Prevents Autophagy Protein-Mediated Killing of the Parasite

Toxoplasma gondii resides in an intracellular compartment (parasitophorous vacuole) that excludes transmembrane molecules required for endosome-lysosome recruitment. Thus, the parasite survives by avoiding lysosomal degradation. However, autophagy can re-route the parasitophorous vacuole to the lysosomes and cause parasite killing. This raises the possibility that T. gondii may deploy a strategy to prevent autophagic targeting to maintain the non-fusogenic nature of the vacuole. We report that T. gondii activated EGFR in endothelial cells, retinal pigment epithelial cells and microglia. Blockade of EGFR or its downstream molecule, Akt, caused targeting of the parasite by LC3(+) structures, vacuole-lysosomal fusion, lysosomal degradation and killing of the parasite that were dependent on the autophagy proteins Atg7 and Beclin 1. Disassembly of GPCR or inhibition of metalloproteinases did not prevent EGFR-Akt activation. T. gondii micronemal proteins (MICs) containing EGF domains (EGF-MICs; MIC3 and MIC6) appeared to promote EGFR activation. Parasites defective in EGF-MICs (MIC1 ko, deficient in MIC1 and secretion of MIC6; MIC3 ko, deficient in MIC3; and MIC1-3 ko, deficient in MIC1, MIC3 and secretion of MIC6) caused impaired EGFR-Akt activation and recombinant EGF-MICs (MIC3 and MIC6) caused EGFR-Akt activation. In cells treated with autophagy stimulators (CD154, rapamycin) EGFR signaling inhibited LC3 accumulation around the parasite. Moreover, increased LC3 accumulation and parasite killing were noted in CD154-activated cells infected with MIC1-3 ko parasites. Finally, recombinant MIC3 and MIC6 inhibited parasite killing triggered by CD154 particularly against MIC1-3 ko parasites. Thus, our findings identified EGFR activation as a strategy used by T. gondii to maintain the non-fusogenic nature of the parasitophorous vacuole and suggest that EGF-MICs have a novel role in affecting signaling in host cells to promote parasite survival

In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.

BACKGROUND: The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape. METHODOLOGY/PRINCIPAL FINDINGS: Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages. CONCLUSIONS: We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies

Determinants of echolocation call frequency variation in the Formosan lesser horseshoe bat (Rhinolophus monoceros)

The origin and maintenance of intraspecific variation in vocal signals is important for population divergence and speciation. Where vocalizations are transmitted by vertical cultural inheritance, similarity will reflect co-ancestry, and thus vocal divergence should reflect genetic structure. Horseshoe bats are characterized by echolocation calls dominated by a constant frequency component that is partly determined by maternal imprinting. Although previous studies showed that constant frequency calls are also influenced by some non-genetic factors, it is not known how frequency relates to genetic structure. To test this, we related constant frequency variation to genetic and non-genetic variables in the Formosan lesser horseshoe bat (Rhinolophus monoceros). Recordings of bats from across Taiwan revealed that females called at higher frequencies than males; however, we found no effect of environmental or morphological factors on call frequency. By comparison, variation showed clear population structure, with frequencies lower in the centre and east, and higher in the north and south. Within these regions, frequency divergence was directional and correlated with geographical distance, suggesting that call frequencies are subject to cultural drift. However, microsatellite clustering analysis showed that broad differences in constant frequency among populations corresponded to discontinuities in allele frequencies resulting from vicariant events. Our results provide evidence that the processes shaping genetic subdivision have concomitant consequences for divergence in echolocation call frequency

Smoking and mental illness: results from population surveys in Australia and the United States

<p>Abstract</p> <p>Background</p> <p>Smoking has been associated with a range of mental disorders including schizophrenia, anxiety disorders and depression. People with mental illness have high rates of morbidity and mortality from smoking related illnesses such as cardiovascular disease, respiratory diseases and cancer. As many people who meet diagnostic criteria for mental disorders do not seek treatment for these conditions, we sought to investigate the relationship between mental illness and smoking in recent population-wide surveys.</p> <p>Methods</p> <p>Survey data from the US National Comorbidity Survey-Replication conducted in 2001–2003, the 2007 Australian Survey of Mental Health and Wellbeing, and the 2007 US National Health Interview Survey were used to investigate the relationship between current smoking, ICD-10 mental disorders and non-specific psychological distress. Population weighted estimates of smoking rates by disorder, and mental disorder rates by smoking status were calculated.</p> <p>Results</p> <p>In both the US and Australia, adults who met ICD-10 criteria for mental disorders in the 12 months prior to the survey smoked at almost twice the rate of adults without mental disorders. While approximately 20% of the adult population had 12-month mental disorders, among adult smokers approximately one-third had a 12-month mental disorder – 31.7% in the US (95% CI: 29.5%–33.8%) and 32.4% in Australia (95% CI: 29.5%–35.3%). Female smokers had higher rates of mental disorders than male smokers, and younger smokers had considerably higher rates than older smokers. The majority of mentally ill smokers were not in contact with mental health services, but their rate of smoking was not different from that of mentally ill smokers who had accessed services for their mental health problem. Smokers with high levels of psychological distress smoked a higher average number of cigarettes per day.</p> <p>Conclusion</p> <p>Mental illness is associated with both higher rates of smoking and higher levels of smoking among smokers. Further, a significant proportion of smokers have mental illness. Strategies that address smoking in mental illness, and mental illness among smokers would seem to be important directions for tobacco control. As the majority of smokers with mental illness are not in contact with mental health services for their condition, strategies to address mental illness should be included as part of population health-based mental health and tobacco control efforts.</p

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

© 2016 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd. The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity

An investigation into the changes relating to duties and image of small to medium sized accountancy firms, with an emphasis on firms in the Midlands, over the past ten years.

The accountancy profession has been continuously evolving over time, particularly in the past ten years. The financial crisis played a big role in changing the method in which accountants interact with their clients; and also the range of duties accountants perform for their clients. Additionally, the image of the profession underwent scrutiny following the revelations of the part accountancy firms played in the collapse of certain banks. This research project aims to provide an in-depth examination of the various changes to the accountancy profession that have arisen in the recent past, with particular focus the fallout from the banks. Finally, the author explores potential routes forward for the accountancy profession. The literature used was mainly from articles found in ‘Accountancy Ireland’ magazines. The author deemed these to be the most relevant to his research project. The author also found online sources extremely helpful. The study was restricted to Chartered Accountancy firms in the counties of Westmeath, Offaly, Roscommon, and Longford. The research methodology consisted of an online questionnaire and a semi-structured interview. In total, the author received twelve responses from the questionnaire. The research findings show that a change has occurred in the profession in the past ten years. New areas of expertise have been introduced. The emergence of IT in the workplace has given practitioners fresh ways in which to interact with their clients. In addition, the image of the profession has certainly suffered a hit due to the recession; however, the author believes the subject of recovery to be high on the agenda of the Institute of Chartered Accounts Ireland