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

Self-Construal and Concerns Elicited by Imagined and Real Health Problems 1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74826/1/j.1559-1816.2007.00283.x.pd

A Prospective Study of the Association of Metacognitive Beliefs and Processes with Persistent Emotional Distress After Diagnosis of Cancer

Two hundred and six patients, diagnosed with primary breast or prostate cancer completed self-report questionnaires on two occasions: before treatment (T1) and 12 months later (T2). The questionnaires included: the Hospital Anxiety and Depression Scale; Impact of Events Scale; the Metacognitions Questionnaire-30 (MCQ-30) and the Illness Perceptions Questionnaire-revised. A series of regression analyses indicated that metacognitive beliefs at T1 predicted between 14 and 19 % of the variance in symptoms of anxiety, depression and trauma at T2 after controlling for age and gender. For all three outcomes, the MCQ-30 subscale ‘negative beliefs about worry’ made the largest individual contribution with ‘cognitive confidence’ also contributing in each case. For anxiety, a third metacognitive variable, ‘positive beliefs about worry’ also predicted variance in T2 symptoms. In addition, hierarchical analyses indicated that metacognitive beliefs explained a small but significant amount of variance in T2 anxiety (2 %) and T2 depression (4 %) over and above that explained by demographic variables, T1 symptoms and T1 illness perceptions. The findings suggest that modifying metacognitive beliefs and processes has the potential to alleviate distress associated with cancer

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

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

Cardiovascular reactivity in a simulated job interview: the role of gender role self-concept

This study investigated the relation of gender role self-concept (G-SC) to cardiovascular and emotional reactions to an ecologically relevant stressor in a sample of graduating male and female university students. Thirty-seven men and 37 women completed the Personal Attribute Questionnaire and worked on four tasks designed to reflect common features of a job interview. Blood pressure and heart rate were measured at baseline, during, and after each task; subjective stress was measured at baseline and after each task. Subjective and objective stress scores were averaged across tasks and analyzed by sex and G-SC (i.e., instrumentality, expressiveness). Results indicated that women as a group demonstrated greater emotional reactivity, but did not differ in their physiological reactions when compared to men. Regardless of sex, participants’ instrumentality scores contributed significantly to the variation in subjective stress response: those scoring high on instrumentality reported less stress, but evidenced greater blood pressure reactivity than those scoring low on instrumentality. These results suggest that gender roles, particularly an instrumental self-concept, may play an important role in both subjective and objective reactions to an ecologically relevant stressor

The validity of the EQ-5D-3L items: An investigation with type 2 diabetes patients from six European countries

Background: Most previous studies concerning the validity of the EQ-5D-3L items refer to applications of only a single language version of the EQ-5D-3L in only one country. Therefore, there is little information concerning the extent to which the results can be generalised across different language versions and

Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, −2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy

Elastically driven, intermittent microscopic dynamics in soft solids

Soft solids with tunable mechanical response are at the core of new material technologies, but a crucial limit for applications is their progressive aging over time, which dramatically affects their functionalities. The generally accepted paradigm is that such aging is gradual and its origin is in slower than exponential microscopic dynamics, akin to the ones in supercooled liquids or glasses. Nevertheless, time- and space-resolved measurements have provided contrasting evidence: dynamics faster than exponential, intermittency, and abrupt structural changes. Here we use 3D computer simulations of a microscopic model to reveal that the timescales governing stress relaxation respectively through thermal fluctuations and elastic recovery are key for the aging dynamics. When thermal fluctuations are too weak, stress heterogeneities frozen-in upon solidification can still partially relax through elastically driven fluctuations. Such fluctuations are intermittent, because of strong correlations that persist over the timescale of experiments or simulations, leading to faster than exponential dynamics.Comment: 7 pages, Supplementary Information include