Partial cooperative unfolding in proteins as observed by hydrogen exchange mass spectrometry

This is an Accepted Manuscript of an article published by Taylor & Francis in International Reviews in Physical Chemistry on 2013-1-1, available online: http://www.tandfonline.com/10.1080/0144235X.2012.751175.Many proteins do not exist in a single rigid conformation. Protein motions, or dynamics, exist and in many cases are important for protein function. The analysis of protein dynamics relies on biophysical techniques that can distinguish simultaneously existing populations of molecules and their rates of interconversion. Hydrogen exchange (HX) detected by mass spectrometry (MS) is contributing to our understanding of protein motions by revealing unfolding and dynamics on a wide timescale, ranging from seconds to hours to days. In this review we discuss HX MS-based analyses of protein dynamics, using our studies of multi-domain kinases as examples. Using HX MS, we have successfully probed protein dynamics and unfolding in the isolated SH3, SH2 and kinase domains of the c-Src and Abl kinase families, as well as the role of inter- and intra-molecular interactions in the global control of kinase function. Coupled with high-resolution structural information, HX MS has proved to be a powerful and versatile tool for the analysis of the conformational dynamics in these kinase systems, and has provided fresh insight regarding the regulatory control of these important signaling proteins. HX MS studies of dynamics are applicable not only to the proteins we illustrate here, but to a very wide range of proteins and protein systems, and should play a role in both classification of and greater understanding of the prevalence of protein motion

Childhood Sexual Abuse and the Development of Recurrent Major Depression in Chinese Women

Background Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set? Method Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. Results We confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19–5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58–3.15), genital (OR 5.24, 95% CI 3.52–8.15) and intercourse (OR 10.65, 95% CI 5.56–23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11–2.27) and phobia (OR 1.41, 95%CI 1.09–1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20–1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02–2.02). Intercourse (OR 3.47, 95%CI 1.66–8.22), use of force and threats (OR 1.95, 95%CI 1.05–3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20–1.64) were significantly associated with recurrent MD

Associations of Educational Attainment, Occupation, Social Class and Major Depressive Disorder among Han Chinese Women

Background The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years. Principal findings We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25–0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77–0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86–0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders. Conclusions In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype

Existence and uniqueness results to positive solutions of integral boundary value problem for fractional q-derivatives

Abstract In this paper,we are interested in the existence and uniqueness of positive solutions for integral boundary value problem with fractional q-derivative: Dqαu(t)+f(t,u(t),u(t))+g(t,u(t))=0,0<t<1,u(0)=Dqu(0)=0,u(1)=μ∫01u(s)dqs, $$\begin{aligned} &D_{q}^{\alpha}u(t)+f\bigl(t,u(t),u(t)\bigr)+g\bigl(t,u(t) \bigr)=0, \quad 0< t< 1, \\ & u(0)=D_{q}u(0)=0, \qquad u(1)=\mu \int_{0}^{1}u(s)\,d_{q}s, \end{aligned}$$ where Dqα $D_{q}^{\alpha}$ is the fractional q-derivative of Riemann–Liouville type, 0<q<1 $0< q<1$, 2<α≤3 $2<\alpha\leq3$, and μ is a parameter with 0<μ<[α]q $0<\mu<[\alpha]_{q}$. By virtue of fixed point theorems for mixed monotone operators, we obtain some results on the existence and uniqueness of positive solutions

Monotonicity of Eventually Positive Solutions for a Second Order Nonlinear Difference Equation

We derive several sufficient conditions for monotonicity of eventually positive solutions on a class of second order perturbed nonlinear difference equation. Furthermore, we obtain a few nonexistence criteria for eventually positive monotone solutions of this equation. Examples are provided to illustrate our main results

Positive Solutions for a Class of Integral Boundary Value Problem of Fractional <i>q</i>-Difference Equations

This paper studies a class of integral boundary value problem of fractional q-difference equations. We first give an explicit expression for the associated Green’s function and obtain an important property of the function. The new property allows us to prove sufficient conditions for the existence of positive solutions based on the associated parameter. The results are derived from the application of a fixed point theorem on order intervals

Minimal Wave Speed in a Competitive Integrodifference System without Comparison Principle

We investigate the traveling wave solutions of a competitive integrodifference system without comparison principle. In the earlier conclusions, a threshold of wave speed is defined while the existence or nonexistence of traveling wave solutions remains open when the wave speed is the threshold. By constructing generalized upper and lower solutions, we confirm the existence of traveling wave solutions when the wave speed is the threshold. Our conclusion completes the known results and shows the different decay behavior of traveling wave solutions compared with the case of large wave speeds

Five-year follow-up of stenting for a symptomatic posterior cerebral artery stenosis

Angioplasty and stenting in symptomatic intracranial stenosis is technically possible and may reduce the risk of stroke in patients with symptomatic arterial stenosis. We report a patient with P1 segment stenosis of posterior cerebral artery treated successfully with angioplasty and stenting with a favorable outcome. He had 5 years of clinical and imaging follow-up and no in-stent stenosis or new ischemic event was observed