Group additivity calculation of the standard molal thermodynamic properties of aqueous amino acids, polypeptides and unfolded proteins as a function of temperature, pressure and ionization state

International audienceThermodynamic calculation of the chemical speciation of proteins and the limits of protein metastability affords a quantitative understanding of the biogeochemical constraints on the distribution of proteins within and among different organisms and chemical environments. These calculations depend on accurate determination of the ionization states and standard molal Gibbs free energies of proteins as a function of temperature and pressure, which are not generally available. Hence, to aid predictions of the standard molal thermodynamic properties of ionized proteins as a function of temperature and pressure, calculated values are given below of the standard molal thermodynamic properties at 25°C and 1 bar and the revised Helgeson-Kirkham-Flowers equations of state parameters of the structural groups comprising amino acids, polypeptides and unfolded proteins. Group additivity and correlation algorithms were used to calculate contributions by ionized and neutral sidechain and backbone groups to the standard molal Gibbs free energy (? G°), enthalpy (? H°), entropy (S°), isobaric heat capacity (C°P), volume (V°) and isothermal compressibility (?°T) of multiple reference model compounds. Experimental values of C°P, V° and ?°T at high temperature were taken from the recent literature, which ensures an internally consistent revision of the thermodynamic properties and equations of state parameters of the sidechain and backbone groups of proteins, as well as organic groups. As a result, ? G°, ? H°, S° C°P, V° and ?°T of unfolded proteins in any ionization state can be calculated up to T~-300°C and P~-5000 bars. In addition, the ionization states of unfolded proteins as a function of not only pH, but also temperature and pressure can be calculated by taking account of the degree of ionization of the sidechain and backbone groups present in the sequence. Calculations of this kind represent a first step in the prediction of chemical affinities of many biogeochemical reactions, as well as of the relative stabilities of proteins as a function of temperature, pressure, composition and intra- and extracellular chemical potentials of O2 and H2, NH3, H2PO4 and CO2

A microfluidic model of human brain (μHuB) for assessment of blood brain barrier

Microfluidic cellular models, commonly referred to as “organs‐on‐chips,” continue to advance the field of bioengineering via the development of accurate and higher throughput models, captivating the essence of living human organs. This class of models can mimic key in vivo features, including shear stresses and cellular architectures, in ways that cannot be realized by traditional two‐dimensional in vitro models. Despite such progress, current organ‐on‐a‐chip models are often overly complex, require highly specialized setups and equipment, and lack the ability to easily ascertain temporal and spatial differences in the transport kinetics of compounds translocating across cellular barriers. To address this challenge, we report the development of a three‐dimensional human blood brain barrier (BBB) microfluidic model (μHuB) using human cerebral microvascular endothelial cells (hCMEC/D3) and primary human astrocytes within a commercially available microfluidic platform. Within μHuB, hCMEC/D3 monolayers withstood physiologically relevant shear stresses (2.73 dyn/cm2) over a period of 24 hr and formed a complete inner lumen, resembling in vivo blood capillaries. Monolayers within μHuB expressed phenotypical tight junction markers (Claudin‐5 and ZO‐1), which increased expression after the presence of hemodynamic‐like shear stress. Negligible cell injury was observed when the monolayers were cultured statically, conditioned to shear stress, and subjected to nonfluorescent dextran (70 kDa) transport studies. μHuB experienced size‐selective permeability of 10 and 70 kDa dextrans similar to other BBB models. However, with the ability to probe temporal and spatial evolution of solute distribution, μHuBs possess the ability to capture the true variability in permeability across a cellular monolayer over time and allow for evaluation of the full breadth of permeabilities that would otherwise be lost using traditional end‐point sampling techniques. Overall, the μHuB platform provides a simplified, easy‐to‐use model to further investigate the complexities of the human BBB in real‐time and can be readily adapted to incorporate additional cell types of the neurovascular unit and beyond.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149762/1/btm210126_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149762/2/btm210126.pd

Calculation of the relative metastabilities of proteins using the CHNOSZ software package

<p>Abstract</p> <p>Background</p> <p>Proteins of various compositions are required by organisms inhabiting different environments. The energetic demands for protein formation are a function of the compositions of proteins as well as geochemical variables including temperature, pressure, oxygen fugacity and pH. The purpose of this study was to explore the dependence of metastable equilibrium states of protein systems on changes in the geochemical variables.</p> <p>Results</p> <p>A software package called CHNOSZ implementing the revised Helgeson-Kirkham-Flowers (HKF) equations of state and group additivity for ionized unfolded aqueous proteins was developed. The program can be used to calculate standard molal Gibbs energies and other thermodynamic properties of reactions and to make chemical speciation and predominance diagrams that represent the metastable equilibrium distributions of proteins. The approach takes account of the chemical affinities of reactions in open systems characterized by the chemical potentials of basis species. The thermodynamic database included with the package permits application of the software to mineral and other inorganic systems as well as systems of proteins or other biomolecules.</p> <p>Conclusion</p> <p>Metastable equilibrium activity diagrams were generated for model cell-surface proteins from archaea and bacteria adapted to growth in environments that differ in temperature and chemical conditions. The predicted metastable equilibrium distributions of the proteins can be compared with the optimal growth temperatures of the organisms and with geochemical variables. The results suggest that a thermodynamic assessment of protein metastability may be useful for integrating bio- and geochemical observations.</p

A compact, short-pulse laser for near-field, range-gated imaging

This paper describes a compact laser, which produces high power, wide-angle emission for a near-field, range-gated, imaging system. The optical pulses are produced by a 100 element laser diode array (LDA) which is pulsed with a GaAs, photoconductive semiconductor switch (PCSS). The LDA generates 100 ps long, gain-switched, optical pulses at 904 nm when it is driven with 3 ns, 400 A, electrical pulses from a high gain PCSS. Gain switching is facilitated with this many lasers by using a low impedance circuit to drive an array of lasers, which are connected electrically in series. The total optical energy produced per pulse is 10 microjoules corresponding to a total peak power of 100 kW. The entire laser system, including prime power (a nine volt battery), pulse charging, PCSS, and LDA, is the size of a small, hand-held flashlight. System lifetime, which is presently limited by the high gain PCSS, is an active area of research and development. Present limitations and potential improvements will be discussed. The complete range-gated imaging system is based on complementary technologies: high speed optical gating with intensified charge coupled devices (ICCD) developed at Los Alamos National Laboratory (LANL) and high gain, PCSS-driven LDAs developed at Sandia National Laboratories (SNL). The system is designed for use in highly scattering media such as turbid water or extremely dense fog or smoke. The short optical pulses from the laser and high speed gating of the ICCD are synchronized to eliminate the back-scattered light from outside the depth of the field of view (FOV) which may be as short as a few centimeters. A high speed photodiode can be used to trigger the intensifier gate and set the range-gated FOV precisely on the target. The ICCD and other aspects of the imaging system are discussed in a separate paper

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Responsiveness of the EQ-5D in breast cancer patients in their first year after treatment

<p>Abstract</p> <p>Background/aim</p> <p>The EQ-5D is a generic health-related quality of life (HRQoL) measure that is used for the purpose of economic evaluations of health interventions. Therefore, it has to be responsive to meaningful changes in health in the patient population under investigation. The aim of this study was to investigate the responsiveness of the EQ-5D in breast cancer patients in their first year after treatment.</p> <p>Methods</p> <p>The subscale global health of the disease-specific HRQoL measure EORTC QLQ-C30 was used as a reference instrument to determine meaningful changes in health and identify subgroups of patients: patients reporting a moderate-large deterioration, small deterioration, a small improvement, moderate-large improvement, or no change in health status. Responsiveness was evaluated by calculating standardized response means (SRMs) in the five subgroups of patients and performing analysis of variance procedures. The two HRQoL measures were filled out two weeks and one year after finalizing curative treatment for breast cancer (n = 192).</p> <p>Results</p> <p>The EQ-5D was able to capture both improvements and deteriorations in HRQoL. SRMs of the EQ VAS and EQ-5D Index were close to zero in the subgroup reporting no change and increased and decreased adequately in the subgroups reporting small and moderate changes. Additional analysis of variance procedures showed that the EQ-5D was able to differentiate between subgroups of patients with no change and moderate-large deterioration or improvement in health.</p> <p>Conclusion</p> <p>The EQ-5D seems an appropriate measure for the purpose of economic evaluations of health intervention in breast cancer patients after treatment.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN74071417.</p

Life Satisfaction and Sense of Coherence of Breast Cancer Survivors Compared to Women with Mental Depression, Arterial Hypertension and Healthy Controls

The purpose of the study was to compare the life satisfaction (LS) and sense of coherence (SOC) of women recovering from breast cancer (BC) to LS and SOC of women with depression or hypertension and of healthy controls. Finnish Health and Social Support (HeSSup) follow-up survey data in 2003 was linked with national health registries. BC patients were followed up for mortality until the end of 2012. The statistical computations were carried out with SAS (R). There were no significant differences in LS and SOC between the groups with BC, arterial hypertension or healthy controls. Women recovering from BC are as satisfied with their life as healthy controls, and their perceived LS is better and SOC is stronger compared to women with depression. SOC correlated positively (r(2) = 0.36, p <0.001) with LS. However, more studies on determinants of the LS are needed for designing and organizing health care services for BC survivors.Peer reviewe

Psychosocial family factors and glycemic control among children aged 1-15 years with type 1 diabetes: a population-based survey

Background: Being the parents of children with diabetes is demanding. Jay Belsky’s determinants of parenting model emphasizes both the personal psychological resources, the characteristics of the child and contextual sources such as parents’ work, marital relations and social network support as important determinants for parenting. To better understand the factors influencing parental functioning among parents of children with type 1 diabetes, we aimed to investigate associations between the children’s glycated hemoglobin (HbA1c) and 1) variables related to the parents’ psychological and contextual resources, and 2) frequency of blood glucose measurement as a marker for diabetes-related parenting behavior. Methods: Mothers (n = 103) and fathers (n = 97) of 115 children younger than 16 years old participated in a population-based survey. The questionnaire comprised the Life Orientation Test, the Oslo 3-item Social Support Scale, a single question regarding perceived social limitation because of the child’s diabetes, the Relationship Satisfaction Scale and demographic and clinical variables. We investigated associations by using regression analysis. Related to the second aim hypoglycemic events, child age, diabetes duration, insulin regimen and comorbid diseases were included as covariates. Results: The mean HbA1c was 8.1%, and 29% had HbA1c ≤ 7.5%. In multiple regression analysis, lower HbA1c was associated with higher education and stronger perceptions of social limitation among the mothers. A higher frequency of blood glucose measurement was significantly associated with lower HbA1c in bivariate analysis. Higher child age was significantly associated with higher HbA1c both in bivariate and multivariate analysis. A scatterplot indicated this association to be linear. Conclusions: Most families do not reach recommended treatment goals for their child with type 1 diabetes. Concerning contextual sources of stress and support, the families who successfully reached the treatment goals had mothers with higher education and experienced a higher degree of social limitations because of the child’s diabetes. The continuous increasing HbA1c by age, also during the years before puberty, may indicate a need for further exploring the associations between child characteristics, context-related variables and parenting behavior such as factors facilitating the transfer of parents’ responsibility and motivation for continued frequent treatment tasks to their growing children

Standard versus prosocial online support groups for distressed breast cancer survivors: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The Internet can increase access to psychosocial care for breast cancer survivors through online support groups. This study will test a novel prosocial online group that emphasizes both opportunities for getting and giving help. Based on the helper therapy principle, it is hypothesized that the addition of structured helping opportunities and coaching on how to help others online will increase the psychological benefits of a standard online group.</p> <p>Methods/Design</p> <p>A two-armed randomized controlled trial with pretest and posttest. Non-metastatic breast cancer survivors with elevated psychological distress will be randomized to either a standard facilitated online group or to a prosocial facilitated online group, which combines online exchanges of support with structured helping opportunities (blogging, breast cancer outreach) and coaching on how best to give support to others. Validated and reliable measures will be administered to women approximately one month before and after the interventions. Self-esteem, positive affect, and sense of belonging will be tested as potential mediators of the primary outcomes of depressive/anxious symptoms and sense of purpose in life.</p> <p>Discussion</p> <p>This study will test an innovative approach to maximizing the psychological benefits of cancer online support groups. The theory-based prosocial online support group intervention model is sustainable, because it can be implemented by private non-profit or other organizations, such as cancer centers, which mostly offer face-to-face support groups with limited patient reach.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01396174">NCT01396174</a></p