Electrode measurements of the net charge on muscle proteins

Electrode techniques for measuring Donnan potentials in protein solutions were studied and applied to elucidate the effect of methylation on the net charge of heavy meromyosin (HMM) and the effect of Ca2+ on the net charge of the thin filament proteins. Drifts in potentials, observed for macroelectrodes, were examined and their cause established to be KC1 leakage out of electrodes. The microelectrode technique was applied to protein solutions and microelectrodes with resistance less than 1 MΩ were used: the conditions for manufacturing and maintaining electrodes functional were established. HMM was isolated (from rabbit muscle) and methylated; the modification was verified by amino acid analysis. ATPase activity of methylated HMM was found to be significantly elevated in the presence of Ca2+ and decreased in the presence of EDTA with respect to the activity of the native protein. Values of the net charge of both proteins were determined at pH 6.7 and no significant difference was found between them. Calculations of the theoretical charge of lysine and Nͼ-dimethyllysine were performed which indicated only 0.5% difference at pH 6.7. F-actin, tropomyosin-troponin (Tm-tn) and reconstituted thin filaments (RTFs) were isolated from rabbit muscle. Conditions for preserving the binding between F-actin and Tm-tn were established. Net charges of F-actin, Tm-tn, RTFs and BSA (control) were measured in solutions of pCa 3.2-8.7 at ionic strength 0.02 M and pH 7.0. Significant decrease in the negative charge of the RTFs, Tm-tn and F-actin was observed with increasing concentrations of free Ca2+, between pCa 6.5 and 3 approximately. Values of the molecular and specific charge at pH 7.0 and the isoelectric point were calculated from the amino acid sequences of the main muscle proteins

Convergent reductive evolution and host adaptation in Mycoavidus bacterial endosymbionts of Mortierellaceae fungi

Intimate associations between fungi and intracellular bacterial endosymbionts are becoming increasingly well understood. Phylogenetic analyses demonstrate that bacterial endosymbionts of Mucoromycota fungi are related either to free-living Burkholderia or Mollicutes species. The so-called Burkholderia-related endosymbionts or BRE comprise Mycoavidus, Mycetohabitans and Candidatus Glomeribacter gigasporarum. These endosymbionts are marked by genome contraction thought to be associated with intracellular selection. However, the conclusions drawn thus far are based on a very small subset of endosymbiont genomes, and the mechanisms leading to genome streamlining are not well understood. The purpose of this study was to better understand how intracellular existence shapes Mycoavidus and BRE functionally at the genome level. To this end we generated and analyzed 14 novel draft genomes for Mycoavidus living within the hyphae of Mortierellomycotina fungi. We found that our novel Mycoavidus genomes were significantly reduced compared to free-living Burkholderiales relatives. Using a genome-scale phylogenetic approach including the novel and available existing genomes of Mycoavidus, we show that the genus is an assemblage composed of two independently derived lineages including three well supported clades of Mycoavidus. Using a comparative genomic approach, we shed light on the functional implications of genome reduction, documenting shared and unique gene loss patterns between the three Mycoavidus clades. We found that many endosymbiont isolates demonstrate patterns of vertical transmission and host-specificity, but others are present in phylogenetically disparate hosts. We discuss how reductive evolution and host specificity reflect convergent adaptation to the intrahyphal selective landscape, and commonalities of eukaryotic endosymbiont genome evolution

Economic evaluation of an Australian nurse home visiting programme : a randomised trial at 3 years

Objectives To investigate the additional programme cost and cost-effectiveness of ‘right@home’ Nurse Home Visiting (NHV) programme in relation to improving maternal and child outcomes at child age 3 years compared with usual care. Design A cost–utility analysis from a government-as-payer perspective alongside a randomised trial of NHV over 3-year period. Costs and quality-adjusted lifeyears (QALYs) were discounted at 5%. Analysis used an intention-to-treat approach with multiple imputation. Setting The right@home was implemented from 2013 in Victoria and Tasmania states of Australia, as a primary care service for pregnant women, delivered until child age 2 years. Participants 722 pregnant Australian women experiencing adversity received NHV (n=363) or usual care (clinic visits) (n=359). Primary and secondary outcome measures First, a cost–consequences analysis to compare the additional costs of NHV over usual care, accounting for any reduced costs of service use, and impacts on all maternal and child outcomes assessed at 3 years. Second, cost–utility analysis from a government-as-payer perspective compared additional costs to maternal QALYs to express cost-effectiveness in terms of additional cost per additional QALY gained. Results When compared with usual care at child age 3 years, the right@home intervention cost $A7685 extra per woman (95$A7006 to $A8364) and generated 0.01 more QALYs (95$A50 000 per QALY. Conclusions Benefits of NHV to parenting at 2 years and maternal health and well-being at 3 years translate into marginal maternal QALY gains. Like previous cost-effectiveness results for NHV programmes, right@home is not cost-effective at 3 years. Given the relatively high up-front costs of NHV, long-term follow-up is needed to assess the accrual of health and economic benefits over time

Visual attention and autistic behavior in infants with fragile X syndrome

Fragile X syndrome (FXS) is the leading known inherited cause of intellectual disability and the most common known biological cause of autism. Approximately 25% to 50% of males with FXS meet full diagnostic criteria for autism. Despite the high comorbidity between FXS and autism and the ability to diagnose FXS prenatally or at birth, no studies have examined indicators of autism in infants with FXS. The current study focused on indices of visual attention, one of the earliest and most robust behavioral indicators of autism in idiopathic (non-FXS) autism. Analyses revealed lower HR variability, shallower HR decelerations, and prolonged look durations in 12-month old infants with FXS that were correlated with severity of autistic behavior but not mental age

Climate predicts geographic and temporal variation in mosquito-borne disease dynamics on two continents

Funding: J.M.C., A.D.L., E.F.L., and E.A.M. were supported by a Stanford Woods Institute for the Environment—Environmental Ventures Program grant (PIs: E.A.M., A.D.L., and E.F.L.). E.A.M. was also supported by a Hellman Faculty Fellowship and a Terman Award. A.D.L., B.A.N., F.M.M., E.N.G.S., M.S.S., A.R.K., R.D., A.A., and H.N.N. were supported by a National Institutes of Health R01 grant (AI102918; PI: A.D.L.). E.A.M., A.M.S.I., and S.J.R. were supported by a National Science Foundation (NSF) Ecology and Evolution of Infectious Diseases (EEID) grant (DEB-1518681), and A.M.S.I. and S.J.R. were also supported by an NSF DEB RAPID grant (1641145). E.A.M. was also supported by a National Institute of General Medical Sciences Maximizing Investigators’ Research Award grant (R35GM133439) and an NSF and Fogarty International Center EEID grant (DEB-2011147).Climate drives population dynamics through multiple mechanisms, which can lead to seemingly context-dependent effects of climate on natural populations. For climate-sensitive diseases, such as dengue, chikungunya, and Zika, climate appears to have opposing effects in different contexts. Here we show that a model, parameterized with laboratory measured climate-driven mosquito physiology, captures three key epidemic characteristics across ecologically and culturally distinct settings in Ecuador and Kenya: the number, timing, and duration of outbreaks. The model generates a range of disease dynamics consistent with observed Aedes aegypti abundances and laboratory-confirmed arboviral incidence with variable accuracy (28-85% for vectors, 44-88% for incidence). The model predicted vector dynamics better in sites with a smaller proportion of young children in the population, lower mean temperature, and homes with piped water and made of cement. Models with limited calibration that robustly capture climate-virus relationships can help guide intervention efforts and climate change disease projections.Publisher PDFPeer reviewe