Cognitive Distortions and Antisocial Behavior among Adults with Traumatic Brain Injury

Every year over 1.7 million people sustain a Traumatic Brain Injury (TBI), making it a leading cause of death and disability in the United States. Research has found that TBI is a risk factor for antisocial behavior and criminal acts. The current research seeks to understand the relationship between TBI and antisocial/criminal behavior. The present study specifically looked at the role of self-serving cognitive distortions (rationalizing or inaccurate thinking patterns) in accounting for antisocial behavior among TBI patients. The methods included administering a cognitive distortion measure (i.e., the How I Think Questionnaire), antisocial behavior self- report questions, and demographic measures to adults with a TBI. This exploratory study of a small (n = 25; 1 participant removed for not filling out the antisocial behavior self-report) sample of male and female TBI patients found a trend linking self-serving cognitive distortions to antisocial behavior. Understanding the use of cognitive distortions among TBI patients may contribute to more effective cognitive behavioral therapies and reductions in judicial and health care costs caused by brain-injured individuals.No embargoAcademic Major: NeuroscienceAcademic Major: Psycholog

Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells.

cAMP-dependent protein kinase (PKAc) is a pivotal signaling protein in eukaryotic cells. PKAc has two well-characterized regulatory subunit proteins, RI and RII (each having α and β isoforms), which keep the PKAc catalytic subunit in a catalytically inactive state until activation by cAMP. Previous reports showed that the RIα regulatory subunit is phosphorylated by cGMP-dependent protein kinase (PKG) in vitro, whereupon phosphorylated RIα no longer inhibits PKAc at normal (1:1) stoichiometric ratios. However, the significance of this phosphorylation as a mechanism for activating type I PKA holoenzymes has not been fully explored, especially in cellular systems. In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells. Analysis of a phosphomimetic substitution in RIα (S101E) showed that modification of this site increases PKAc activity in vitro and in cells, even without cAMP stimulation. Numerous techniques were used to show that although Ser101 variants of RIα can bind PKAc, the modified linker region of the S101E mutant has a significantly reduced affinity for the PKAc active site. These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. We have thus proposed a model to explain how PKG phosphorylation of RIα creates a "sensitized intermediate" state that is in effect primed to trigger PKAc activity

An NMR Investigation of the Effect of Hydrogen Bonding on the Rates of Rotation about the C-N Bonds in Urea and Thiourea

The interaction between urea and tetrabutylammonium acetate was investigated in dimethylformamide/ dimethyl sulfoxide solutions using ¹H and 15^N NMR. The chemical-shift behavior of the urea protons is consistent with a urea-acetate hydrogen-bonded complex involving both carboxylate oxygens and the urea hydrogens trans to the carbonyl oxygen with K_assoc = 120 ± 10. Line shape analysis of the temperature-dependent ¹H NMR spectra show that ∆G^‡ for rotation about the C-N bond of urea changes only slightly from 11.0 ± 0.1 to 11.2 ± 0.1 kcal/mol on 1:1 molar addition of tetrabutylammonium acetate to a dilute solution of urea. A parallel investigation of the interaction of thiourea with tetrabutylammonium acetate gave a binding constant, K_assoc = 90 ± 10. The ∆G^‡ for rotation about the C-N bond of thiourea was found to increase from 13.5 ± 0.1 to 14.0 ± 0.1 kcal/mol on 1:1 addition of tetrabutylammonium acetate to a dilute solution of thiourea in dimethylformamide/dimethyl sulfoxide. Measurements were also made of the self-association of several ureas and of ∆G^‡ for rotation about both C(O)-N bonds of 1,1-dimethylurea

Characterization of the flavin–protein interaction in L ‐Lactate oxidase and old yellow enzyme by resonance inverse Raman spectroscopy

Resonance inverse Raman spectroscopy was used to examine the interactions between the flavin and surounding protein in L ‐lactate oxidase (from Mycobacterium smegmatis ) and Old Yellow Enzyme (from brewer's bottom yeast). Spectra were taken of the enzymes both free and bound to various ligands. For L ‐lactate oxidase, the ligands consisted of substrate analogs (acetate, propionate) and inorganic anions (phosphate, sulfate and nitrate). For the inorganic anions, the expected attenuation with detuning was not observed for several bands which are associated with flavin rings II and III. This effect appears to be due to a disruption of ring stacking between the uracil–pyrazine end of the flavin moiety and an aromatic amino acid. A shift in the 1232 cm −1 band and changes in the bandwidths of bands in the 1450–1600 cm −1 region indicate minor reorganization of the hydrogen bonding structure around the isoalloxazine on ligand binding. For Old Yellow Enzyme, the ligand was chloride. Chloride caused a slight change to the Raman spectrum, indicative of decreased hydrogen bonding to the flavin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91123/1/1250180403_ftp.pd

Architecturally diverse proteins converge on an analogous mechanism to inactivate Uracil-DNA glycosylase

Uracil-DNA glycosylase (UDG) compromises the replication strategies of diverse viruses from unrelated lineages. Virally encoded proteins therefore exist to limit, inhibit or target UDG activity for proteolysis. Viral proteins targeting UDG, such as the bacteriophage proteins ugi, and p56, and the HIV-1 protein Vpr, share no sequence similarity, and are not structurally homologous. Such diversity has hindered identification of known or expected UDG-inhibitory activities in other genomes. The structural basis for UDG inhibition by ugi is well characterized; yet, paradoxically, the structure of the unbound p56 protein is enigmatically unrevealing of its mechanism. To resolve this conundrum, we determined the structure of a p56 dimer bound to UDG. A helix from one of the subunits of p56 occupies the UDG DNA-binding cleft, whereas the dimer interface forms a hydrophobic box to trap a mechanistically important UDG residue. Surprisingly, these p56 inhibitory elements are unexpectedly analogous to features used by ugi despite profound architectural disparity. Contacts from B-DNA to UDG are mimicked by residues of the p56 helix, echoing the role of ugi’s inhibitory beta strand. Using mutagenesis, we propose that DNA mimicry by p56 is a targeting and specificity mechanism supporting tight inhibition via hydrophobic sequestration

Mechanisms of base selection by human single-stranded selective monofunctional uracil-DNA glycosylase

hSMUG1 (human single-stranded selective monofunctional uracil-DNA glyscosylase) is one of three glycosylases encoded within a small region of human chromosome 12. Those three glycosylases, UNG (uracil-DNA glycosylase), TDG (thymine-DNA glyscosylase), and hSMUG1, have in common the capacity to remove uracil from DNA. However, these glycosylases also repair other lesions and have distinct substrate preferences, indicating that they have potentially redundant but not overlapping physiological roles. The mechanisms by which these glycosylases locate and selectively remove target lesions are not well understood. In addition to uracil, hSMUG1 has been shown to remove some oxidized pyrimidines, suggesting a role in the repair of DNA oxidation damage. In this paper, we describe experiments in which a series of oligonucleotides containing purine and pyrimidine analogs have been used to probe mechanisms by which hSMUG1 distinguishes potential substrates. Our results indicate that the preference of hSMUG1 for mispaired uracil over uracil paired with adenine is best explained by the reduced stability of a duplex containing a mispair, consistent with previous reports with Escherichia coli mispaired uracil-DNA glycosylase. We have also extended the substrate range of hSMUG1 to include 5-carboxyuracil, the last in the series of damage products from thymine methyl group oxidation. The properties used by hSMUG1 to select damaged pyrimidines include the size and free energy of solvation of the 5-substituent but not electronic inductive properties. The observed distinct mechanisms of base selection demonstrated for members of the uracil glycosylase family help explain how considerable diversity in chemical lesion repair can be achieved

Megan, Inside

page 11

When does cash matter? : evidence for private firms

Using a database of more than 180,000 private companies from 2000 to 2009, we find that the benefits of holding more cash vary substantially with a firm’s size and the conditions it faces. Cash holdings matter most for small firms: when there are negative shocks to industry or macroeconomic conditions, a small firm’s cash holdings are positively associated with changes in its sales and assets. Cash is less important for other conditions. Differences in the benefits of cash holdings between large and small firms are traced to a firm’s ability – and willingness – to increase leverage when there is a cash shortfallUtilizando una base de datos de más de 180.000 empresas privadas desde el año 2000 hasta el 2009, encontramos que los benefi cios de mantener más efectivo varían sustancialmente dependiendo del tamaño y de la situación de cada compañía. La tenencia de liquidez afecta, fundamentalmente, a las pequeñas empresas. En casos de shocks negativos en la industria o en la situación macroeconómica, la tenencias de efectivo por parte de empresas pequeñas se asocia positivamente a los cambios en sus ventas y activos. La liquidez es menos relevante en otros casos. Las diferencias en los benefi cios por mantener efectivo entre grandes y medianas empresas se relaciona con la capacidad, y voluntad, de cada una de ellas de aumentar el apalancamiento cuando hay un défi cit de capita