Immunity to K1 killer toxin: internal TOK1 blockade.

K1 killer strains of Saccharomyces cerevisiae harbor RNA viruses that mediate secretion of K1, a protein toxin that kills virus-free cells. Recently, external K1 toxin was shown to directly activate TOK1 channels in the plasma membranes of sensitive yeast cells, leading to excess potassium flux and cell death. Here, a mechanism by which killer cells resist their own toxin is shown: internal toxin inhibits TOK1 channels and suppresses activation by external toxin

Sub-Optimal Allocation of Time in Sequential Movements

The allocation of limited resources such as time or energy is a core problem that organisms face when planning complex actions. Most previous research concerning planning of movement has focused on the planning of single, isolated movements. Here we investigated the allocation of time in a pointing task where human subjects attempted to touch two targets in a specified order to earn monetary rewards. Subjects were required to complete both movements within a limited time but could freely allocate the available time between the movements. The time constraint presents an allocation problem to the subjects: the more time spent on one movement, the less time is available for the other. In different conditions we assigned different rewards to the two tokens. How the subject allocated time between movements affected their expected gain on each trial. We also varied the angle between the first and second movements and the length of the second movement. Based on our results, we developed and tested a model of speed-accuracy tradeoff for sequential movements. Using this model we could predict the time allocation that would maximize the expected gain of each subject in each experimental condition. We compared human performance with predicted optimal performance. We found that all subjects allocated time sub-optimally, spending more time than they should on the first movement even when the reward of the second target was five times larger than the first. We conclude that the movement planning system fails to maximize expected reward in planning sequences of as few as two movements and discuss possible interpretations drawn from economic theory

Dyon Spectrum in CHL Models

We propose a formula for the degeneracy of quarter BPS dyons in a class of CHL models. The formula uses a modular form of a subgroup of the genus two modular group Sp(2,Z). Our proposal is S-duality invariant and reproduces correctly the entropy of a dyonic black hole to first non-leading order for large values of the charges.Comment: LaTeX file, 38 pages, minor changes in section 3.3(v2), minor changes in introduction, appendix A and C(v3

ATM deficiency results in accumulation of DNA-Topoisomerase I covalent intermediates in neural cells

Accumulation of peptide-linked DNA breaks contributes to neurodegeration in humans. This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1) and human hereditary ataxia. TDP1 primarily operates at single-strand breaks (SSBs) created by oxidative stress or by collision of transcription machinery with topoisomerase I intermediates (Top1-CCs). Cellular and cell-free studies have shown that Top1 at stalled Top1-CCs is first degraded to a small peptide resulting in Top1-SSBs, which are the primary substrates for TDP1. Here we established an assay to directly compare Top1-SSBs and Top1-CCs. We subsequently employed this assay to reveal an increased steady state level of Top1-CCs in neural cells lacking Atm; the protein mutated in ataxia telangiectasia. Our data suggest that the accumulation of endogenous Top1-CCs in Atm-/- neural cells is primarily due to elevated levels of reactive oxygen species. Biochemical purification of Top1-CCs from neural cell extract and the use of Top1 poisons further confirmed a role for Atm during the formation/resolution of Top1-CCs. Finally, we report that global transcription is reduced in Atm-/- neural cells and fails to recover to normal levels following Top1-mediated DNA damage. Together, these data identify a distinct role for ATM during the formation/resolution of neural Top1-CCs and suggest that their accumulation contributes to the neuropathology of ataxia telangiectasia

Importance Of Communication In Medicine: Views On Bedside Rounding And Readmissions

Objectives: To study communication in medicine within the context of readmission rates and patient satisfaction, by assessing 1) the perspectives of primary care physicians (PCPs) and home care nurses (HCNs) on why older adults are readmitted to the hospital within 30 days of discharge, and 2) patient perceptions regarding the implementation and value of bedside rounding. Design: Two studies were performed independently. 1) A qualitative study consisting of PCPs and HCNs of patients readmitted to the hospital within 30 days of discharge home. 2) A concurrent mixed methods study consisting of patients admitted to the inpatient medicine service who participated in bedside rounds. Materials and Methods: 1) Semi-structured open-ended qualitative phone interviews, and 2) qualitative in-person interviews followed by surveys including 5-item Likert scales and open-ended written responses. For qualitative analyses, interviews were repeated until thematic saturation was achieved. Results: 1) While PCPs and nurses both mentioned disease progression and multi-morbidity as contributors to readmissions, nurses further described other psychosocial factors like home environment and patient motivation. PCPs often ascribed responsibility for the readmissions to specialists, hospitalists, and emergency physicians. Nurses expressed frustration about the lack of both communication and working relationships between them and PCPs. 2) Patients described positive attributes of bedside rounds: meeting the medical team and understanding more about their illness. Although patients enjoyed undivided attention from physicians, distractions included too many participants in rounds, confusion about roles, and unclear expectations about the goal of rounds. Physicians sought to use patient-centered language, but 53% of patients stated that medical jargon was still used. Male patients reported a statistically significant improvement in their understanding about the plan for the day and borderline significance regarding knowing who was responsible for their care compared to female patients. Conclusion: Communication between HCNs and PCPs, and between patients and hospital teams can be improved. There should be an explicit agreement on roles, responsibilities, and coordination among all providers caring for a patient. Moreover, well-conducted, patient-centered bedside rounds greatly enhance patient-physician rapport and foster patient understanding and satisfaction

A molecular target for viral killer toxin: TOK1 potassium channels.

Killer strains of S. cerevisiae harbor double-stranded RNA viruses and secrete protein toxins that kill virus-free cells. The K1 killer toxin acts on sensitive yeast cells to perturb potassium homeostasis and cause cell death. Here, the toxin is shown to activate the plasma membrane potassium channel of S. cerevisiae, TOK1. Genetic deletion of TOK1 confers toxin resistance; overexpression increases susceptibility. Cells expressing TOK1 exhibit toxin-induced potassium flux; those without the gene do not. K1 toxin acts in the absence of other viral or yeast products: toxin synthesized from a cDNA increases open probability of single TOK1 channels (via reversible destabilization of closed states) whether channels are studied in yeast cells or X. laevis oocytes

Influence of Solution Chemistry on Adsorption of Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) on Boehmite

The persistent nature of perfluorochemicals (PFCs) has attracted global concern in recent years. Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are the most commonly found PFC compounds, and thus their fate and transport play key roles in PFC distribution in the natural environment. The kinetic behavior of PFOS or PFOA on boehmite consists of a fast adsorption process followed by a slow adsorption process which may be attributed to the slow transport of PFOS or PFOA into the boehmite pore surface. The adsorption isotherms estimated the maximum adsorption capacities of PFOS and PFOA on boehmite as 0.877 μg/m2 and 0.633 μg/m2, with the difference primarily due to their different functional groups. The increase of solution pH led to a moderate decrease of PFOS and PFOA adsorption, owing to the increase of ligand exchange reactions and the decrease of electrostatic interactions. The presence of NaCl in solution demonstrated negative effects for PFOS and PFOA adsorption on boehmite surfaces, with potential mechanisms being electrical double layer compression, competitive adsorption of chloride.published_or_final_versio

CHL Dyons and Statistical Entropy Function from D1-D5 System

We give a proof of the recently proposed formula for the dyon spectrum in CHL string theories by mapping it to a configuration of D1 and D5-branes and Kaluza-Klein monopole. We also give a prescription for computing the degeneracy as a systematic expansion in inverse powers of charges. The computation can be formulated as a problem of extremizing a duality invariant statistical entropy function whose value at the extremum gives the logarithm of the degeneracy. During this analysis we also determine the locations of the zeroes and poles of the Siegel modular forms whose inverse give the dyon partition function in the CHL models.Comment: LaTeX file, 48 pages; v2: typos correcte