Quantification of oxidative DNA lesions in tissues of Long-Evans Cinnamon rats by capillary high-performance liquid chromatography-tandem mass spectrometry coupled with stable isotope-dilution method

The purpose of our study was to develop suitable methods to quantify oxidative DNA lesions in the setting of transition metal-related diseases. Transition metal-driven Fenton reactions constitute an important endogenous source of reactive oxygen species (ROS). In genetic diseases with accumulation of transition metal ions, excessive ROS production causes pathophysiological changes, including DNA damage. Wilson's disease is an autosomal recessive disorder with copper toxicosis due to deficiency of ATP7B protein needed for excreting copper into bile. The Long-Evans Cinnamon (LEC) rat bears a deletion in Atp7b gene and serves as an excellent model for hepatic Wilson's disease. We used a sensitive capillary liquid chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS/MS/MS) method in conjunction with the stable isotope-dilution technique to quantify several types of oxidative DNA lesions in the liver and brain of LEC rats. These lesions included 5-formyl-2'-deoxyuridine, 5-hydroxymethyl-2'-deoxyuridine, and the 5'R and 5'S diastereomers of 8,5'-cyclo-2'-deoxyguanosine and 8,5'-cyclo-2'-deoxyadenosine. Moreover, the levels of these DNA lesions in the liver and brain increased with age and correlated with age-dependent regulation of the expression of DNA repair genes in LEC rats. These results provide significant new knowledge for better understanding the implications of oxidative DNA lesions in transition metal-induced diseases, such as Wilson's disease, as well as in aging and aging-related pathological conditions.     

Clinical evaluation of the Alta hip bolt in peritrochanteric hip fractures

We reviewed the clinical and radiographic results of 58 patients with peritrochanteric fractures treated with the Alta hip bolt (a sliding compression device that inserts a dome plunger in the femoral head instead of a hip screw). This group was compared with a group of 53 patients treated with conventional hip screws. Three patients (5.2%) treated with the Alta hip bolt and three patients (5.7%) treated with conventional hip screw had failure of fixation. Failure of fixation consistently occurred in patients with unstable fracture patterns or significant osteopenia. There were no cases of bolt cut-out in stable intertrochanteric fractures. We conclude that the Alta hip bolt performs as well as sliding hip screws in peritrochanteric fractures, but the additional learning curve and increased cost do not justify its routine use at this point in time.     

Crystal structure of DCoH, a bifunctional, protein-binding transcriptional coactivator

DCoH, the dimerization cofactor of hepatocyte nuclear factor-1, stimulates gene expression by associating with specific DNA binding proteins and also catalyzes the dehydration of the biopterin cofactor of phenylalanine hydroxylase. The x-ray crystal structure determined at 3 angstrom resolution reveals that DCoH forms a tetramer containing two saddle-shaped grooves that comprise likely macromolecule binding sites. Two equivalent enzyme active sites flank each saddle, suggesting that there is a spatial connection between the catalytic and binding activities. Structural similarities between the DCoH fold and nucleic acid-binding proteins argue that the saddle motif has evolved to bind diverse ligands or that DCoH unexpectedly may bind nucleic acids.     

Plan parsing for intended response recognition in discourse1

In a discourse the hearer must recognize the response intended by the speaker. To perform this recognition, the hearer must ascertain what plans the speaker is undertaking and how the utterances in the discourse further that plan. To do so, the hearer can parse the initial intentions (recoverable from the utterance) and recognize the plans the speaker has in mind and intends the hearer to know about. This paper reports on a theory of parsing the intentions in discourse. It also discusses the role of another aspect of discourse, discourse markers, that are valuable to intended response recognition.     

Effect of detergents on in vitro 7α-hydroxycholesterol formation by rat liver microsomes

Formation of 7α-hydroxycholesterol by rat liver microsomes was quantitated using a gas chromatograph-mass spectrometer (GC/MS) operated in selected ion monitoring (SIM) mode. Microsomes from normal rat livers incubated for different periods were found to yield increased 7α-hydroxycholesterol with time. This was also true when incubations contained Tween-80, but in this instance, the rate of 7α-hydroxycholesterol production was lower and dependent on the concentration of Tween used. Similarly, Triton X-100, Renex-30, Kyro EOB, Cutscum, and Emulgen 911 all lowered the formation of 7α-hydroxycholesterol by rat liver microsomes, whereas Triton WR-1339 stimulated its production. Analysis of data obtained from following the enzyme reaction over an extended period using an integrated Michaelis-Menten equation indicated the enzyme possesses a very significant affinity for the product (K_s>K_p). Similar analysis shows that Tween-80 is a noncompetitive inhibitor of the enzyme.     

High-speed gas chromatography-multiplex coherent Raman analysis of BTEX

Gas chromatography-multiplex coherent Raman (GC-MCR) is a new tandem technique that can be used for the high-speed analysis of volatile mixtures. BTEX serves as a useful and challenging test sample because of the similarity in boiling point and spectroscopic properties of its constituents. The ability to spectroscopically resolve isomers (e.g., m-xylene and p-xylene) allows GC-MCR to sacrifice chromatographic resolution for speed. The result is the analysis of BTEX in less than 5 min, which is relatively fast compared with other tandem GC techniques.     

Roles of attribution, affect, and cognitive interference in test anxiety.

Examined the impact of performance outcome, task difficulty, and level of test anxiety on attributional accounts for performance and achievement-related affect. 83 undergraduates who had scored high or low on the Test Anxiety Scale worked on tasks of varying difficulty, evaluated their own performance, and then responded to 2 types of attribution items: the brief version of the Differential Emotions Scale and the Cognitive Interference Questionnaire. Meaningful attributional accounts were uncovered; in particular, performance outcome and task difficulty had independent effects on Ss' attributional judgments. Cognitive interference was implicated as a factor contributing to the attributional predispositions of Ss differing in test anxiety, and it was a major determinant of affective reactions. In addition, Ss' affective responses were predictably associated with their perceived performance outcome, level of test anxiety, difficulty of the task, and attributional accounts of the factors influencing their performance. Results are discussed in terms of the cognitive components and phenomenological experience of test anxiety and the consequent impact anxiety may have on achievement-related behavior. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long‐Term Electrical and Mechanical Function Monitoring of a Human‐on‐a‐Chip System

The goal of human‐on‐a‐chip systems is to capture multiorgan complexity and predict the human response to compounds within physiologically relevant platforms. The generation and characterization of such systems is currently a focal point of research given the long‐standing inadequacies of conventional techniques for predicting human outcome. Functional systems can measure and quantify key cellular mechanisms that correlate with the physiological status of a tissue, and can be used to evaluate therapeutic challenges utilizing many of the same endpoints used in animal experiments or clinical trials. Culturing multiple organ compartments in a platform creates a more physiologic environment (organ–organ communication). Here is reported a human 4‐organ system composed of heart, liver, skeletal muscle, and nervous system modules that maintains cellular viability and function over 28 days in serum‐free conditions using a pumpless system. The integration of noninvasive electrical evaluation of neurons and cardiac cells and mechanical determination of cardiac and skeletal muscle contraction allows the monitoring of cellular function, especially for chronic toxicity studies in vitro. The 28‐day period is the minimum timeframe for animal studies to evaluate repeat dose toxicity. This technology can be a relevant alternative to animal testing by monitoring multiorgan function upon long‐term chemical exposure.     

A Surface Chemistry Approach to Tailoring the Hydrophilicity and Lithiophilicity of Carbon Films for Hosting High‐Performance Lithium Metal Anodes

Porous carbon scaffolds can host lithium (Li) metal anodes to potentially enable stable Li metal batteries. However, the poor Li metal wettability on the carbon surface has inhibited the uniform distribution of metallic Li on most carbon scaffolds. Herein, this work reports a lithiophilic top layer through mild surface ozonolysis and ammoniation methods can universally facilitate the infiltration of liquid Li metal into most carbon matrices. Based on this finding, thin, a lightweight Li@carbon film (CF) composite anode with a high practical capacity of 3222 mAh g^?1 and suppressed volume expansion and dendrite formation is reported. It is observed that the deep stripping/plating pre‐cycling yields dense, trunky Li metal in the Li@CF composite, which allows for favorable long‐term cycling performance. The full cell combining the thin Li@CF composite anode and a high‐mass‐loading, cobalt‐free cathode can deliver high reversible capacity, good cycle stability, and good rate capability in the conventional carbonate electrolyte. The present study further establishes the relationship between lithiophilicity and hydrophilicity for carbon materials as well as provides insights into improving the liquid Li metal infiltration into other carbon scaffolds.