Conformational effects on the Circular Dichroism of Human Carbonic Anhydrase II: a multilevel computational study

Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions

Playing with networks : How economists explain

Peer reviewe

On becoming (un)committed: A taxonomy and test of newcomer on-boarding scenarios

How does the bond between the newcomer and the organization develop over time? Process research on temporal patterns of newcomer's early commitment formation has been very scarce because theory and appropriate longitudinal research designs in this area are lacking. From extant research we extract three process-theoretical accounts regarding how the newcomer adjustment process evolves over time: (1) Learning to Love; (2) Honeymoon Hangover; and (3) High Match, Moderate Match, or Low Match. From these scenarios we develop a taxonomy of newcomer adjustment scenarios. Further, we empirically verify these different scenarios by examining naturally occurring "trajectory classes," which are found to display strengthening, weakening, or stabilizing of the employee-organization linkage. For this, we use a sample of 72 Ph. D. graduates whose organizational commitment history was recorded in their first 25 consecutive weeks of new employment. In closing, we discuss the theoretical and practical implications of the scenario-based approach

Overview of diagnosis and management of paediatric headache. Part I: diagnosis

Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life

The Exciton Origin of the Visible Circular Dichroism Spectrum of Bacteriorhodopsin

The visible CD spectrum of bacteriorhodpsin (bR) in purple membrane has a negative CD band at ∼600 nm and a positive band at ∼530 nm and has been variously interpreted as resulting from exciton coupling within the bR trimer, heterogeneity in protein conformation, or the presence of two distinct low-energy electronic transitions in bR. We have performed time-dependent density functional theory (TDDFT) calculations on the protonated Schiff base of retinal (retPSB) in bR to predict the intrinsic CD. The resulting spectroscopic parameters have been used to predict the long-wavelength CD spectrum of retPSB trimers. TDDFT, exciton theory, and classical polarizability (DeVoe) predict a strong negative couplet centered near 570 nm, with a magnitude in good agreement with experiment. Coupling of the retPSB chromophore with aromatic and peptide chromophores has been considered by means of perturbation theory and is responsible for the net positive CD of the 570 nm band. The visible CD spectrum of bR is dominated by exciton interactions