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Results from two studies provided strong evidence for the validity of the HiSET® tests, thereby demonstrating that HiSET is a well-developed battery of tests with passing and college and career readiness (CCR) standards that, when met, provide a pathway to postsecondary education, better employment opportunities and wages, and a better quality of life to those who are unable to experience a traditional high school education. Positive relationships exist between HiSET scores and both high school grades and ACT scores, including high levels of agreement between HiSET CCR indicators and ACT CCR indicators. Therefore, evidence supports the claim that HiSET scores are measures of high school equivalency, preparedness for middle skills jobs, and college readiness. Furthermore, there is evidence that passing the HiSET provides value to stakeholders. Passing the HiSET battery is associated with gaining academic and personal skills, college enrollment, employment gains (e.g., obtaining employment, obtaining more full-time employment, wage increases, and improvement in a job or position), and quality-of-life improvements.

Researchers and practitioners in postsecondary and workplace settings recognize the value of noncognitive constructs in predicting academic and vocational success but also perceive that many students or employees are lacking in these areas. In turn, there is increased interest in interventions designed to enhance these constructs. We provide an empirically informed theory of change (ToC) that describes the inputs, mechanisms, and outputs of noncognitive construct interventions (NCIs). The components that inform this ToC include specific relevant constructs that are amenable to intervention, intervention content and mechanisms of change, methodological considerations, moderators of program efficacy, recommendations for evaluating NCIs, and suggested outcomes. In turn, NCIs should provide benefits to individuals, institutions, and society at large and also advance our scientific understanding of this important phenomenon.

Researchers, theorists, and practitioners have expressed a renewed interest in the longitudinal dynamics of personality characteristics in adulthood, including organic life span trajectories and their amenability to volitional change. However, this research has apparently not yet expanded to include the Dark Triad (psychopathy, narcissism, Machiavellianism), despite approximately 2 decades of research that has thoroughly examined other important issues related to construct validity and interpersonal behavior. We argue that researchers in postsecondary, occupational, and community-based settings are in a unique position to study the important phenomenon of Dark Triad malleability, as they are less hindered by obstacles in clinical and forensic contexts that have generated largely inconclusive results. In this article, we discuss several examples of methods for evaluating, quantifying, and interpreting Dark Triad malleability, examples of relevant extant training programs, possibilities for developing new programs, and factors that may moderate training efficacy, including Dark Triad levels themselves. Beyond addressing a fundamental question regarding the nature of these traits, the Dark Triad's destructive tendencies suggest that efforts to reduce them would provide myriad societal benefits and could propel Dark Triad research in an important new direction.

We reviewed the current state of the literature on the intervention-based development of interpersonal skills (e.g., teamwork, leadership) and intrapersonal skills (e.g., personality, motivation, etc.) relevant to success in workplace contexts. We adopted a multidisciplinary approach to our review, evaluating research from 39 reviews and meta-analyses from several fields such as educational psychology, industrial/organizational (I/O) psychology, medicine, and personality psychology, among others, to examine the extent to which noncognitive constructs change as a result of intervention. We discuss key findings and trends and conclude by identifying gaps in the literature and directions for future research. Overall, findings suggest optimism regarding the malleability of noncognitive constructs.

Purpose: To report a case of rapidly progressing rhino-orbital cerebral mucormycosis that was particularly difficult to diagnose, initially presenting as orbital apex syndrome. Major findings: In this case, a 59-year-old male patient with uncontrolled diabetes presented with a history of facial pain with no ocular involvement. Within 1 day of hospitalization, the patient developed complete ophthalmoplegia and total visual impairment of the right eye. Over the course of 2 hospital stays, several biopsies resulted in no significant histopathological findings, and several cultures resulted in growth of only a single colony of rhizopus mucor from the sinonasal mucosa. Given the high clinical suspicion of an invasive fungal infection, a universal PCR test was performed from a rapidly developing abscess in the frontal lobe and confirmed a diagnosis of mucormycosis. Conclusions: Orbital apex syndrome is a significant diagnosis that can be caused by a variety of factors, including those of fungal, bacterial, neoplastic, or inflammatory origin. Fungal infections, are a particularly concerning cause of orbital apex syndrome, given their ability to penetrate in and through the orbit to the brain, often resulting in an alarmingly high mortality rate. Mucormycosis, specifically rhino-orbital cerebral mucormycosis, is a very severe opportunistic invasive fungal infection, most often afflicting the immunocompromised. A clinician must be very thorough in their workup so as to not miss such a devastating diagnosis. Histopathology and cell cultures are currently the gold standard for diagnosis, with the potential to augment their technical success through the use of molecular techniques, such as universal PCR. [ABSTRACT FROM AUTHOR]

Individuals with a high school education represent the largest subset of the U.S. workforce. However, little is known about the employer expectations of these individuals, particularly in the area of soft skills—also known as 21st‐century skills. Online job advertisements offer useful data for examining these expectations, as they may supplement employer survey data and reflect actual recruitment practices. Our analysis of 68,505 online job advertisements suggests that employers hold generally lower expectations for the soft skills of high school–educated individuals than they do for postsecondary‐educated individuals. However, employer expectations for two soft skills—professionalism and customer service skills—appear to be substantially higher for high school–educated individuals than for postsecondary‐educated individuals. Additional results highlight similarities and differences within the high school–educated workforce across nine workplace industries. We discuss the implications of these results not only for high school–educated individuals and the organizations that employ them but also for practitioners and educators charged with assessing and providing training for these skills. Report Number: RR‐23‐03 [ABSTRACT FROM AUTHOR]

This study examined Italian and U.S. children's performance on the English and Italian versions, respectively, of the Cognitive Assessment System (CAS; Naglieri & Conway, 2009; Naglieri & Das, 1997), a test based on a neurocognitive theory of intelligence entitled PASS (Planning, Attention, Simultaneous, and Successive; Naglieri & Das, 1997; Naglieri & Otero, 2011). CAS subtest, PASS scales, and Full Scale scores for Italian (N = 809) and U.S. (N = 1,174) samples, matched by age and gender, were examined. Multigroup confirmatory factor analysis results supported the configural invariance of the CAS factor structure between Italians and Americans for the 5- to 7-year-old (root-mean-square error of approximation [RMSEA] = 0.038; 90% confidence interval [CI] = 0.033, 0.043; comparative fit index [CFI] = 0.96) and 8- to 18-year-old (RMSEA = 0.036; 90% CI = 0.028, 0.043; CFI = 0.97) age groups. The Full Scale standard scores (using the U.S. norms) for the Italian (100.9) and U.S. (100.5) samples were nearly identical. The scores between the samples for the PASS scales were very similar, except for the Attention Scale (d = 0.26), where the Italian sample's mean score was slightly higher. Negligible mean differences were found for 9 of the 13 subtest scores, 3 showed small d-ratios (2 in favor of the Italian sample), and 1 was large (in favor of the U.S. sample), but some differences in subtest variances were found. These findings suggest that the PASS theory, as measured by CAS, yields similar mean scores and showed factorial invariance for these samples of Italian and American children, who differ on cultural and linguistic characteristics. (Contains 5 tables and 1 figure.)

Despite much research, skepticism remains over the possibility of profiling scholastic cheaters. However, several relevant predictor variables and newer diagnostic tools have been overlooked. We remedy this deficit with a series of three studies. Study 1 was a large-scale survey of a broad range of personality predictors of self-reported cheating. Significant predictors included the Dark Triad (Machiavellianism, narcissism, psychopathy) as well as low agreeableness and low conscientiousness. Only psychopathy remained significant in a multiple regression. Study 2 replicated this pattern using a naturalistic, behavioral indicator of cheating, namely, plagiarism as indexed by the Internet service Turn-It-In. Poor verbal ability was also an independent predictor. Study 3 examined possible motivational mediators of the association between psychopathy and cheating. Unrestrained achievement and moral inhibition were successful mediators whereas fear of punishment was not. Practical implications for researchers and educators are discussed. (Contains 3 footnotes, 4 tables, and 1 figure.)

Although many studies have examined individual difference predictors of cheating, insufficient attention has been given to several important personality variables (the Big Five, perfectionism, and subclinical psychopathy). Moreover, insufficient use has been made of concrete indicators of naturalistic scholastic cheating. Using a computer-based behavioral measure, we examined the correlates of multiple-choice exam cheating in several large undergraduate classes. In Study 1, 291 participants completed a comprehensive battery of personality measures. Their cheating on several subsequent exams was best predicted by their level of subclinical psychopathy. A possible artifact is that those high in subclinical psychopathy are less scholastically competent--a factor known to predispose cheating. To address this possibility in Study 2 (N=150), we included measures of cognitive ability and a pre-course knowledge test. After controlling for both ability and prior knowledge, subclinical psychopathy remained a significant predictor of cheating behavior. Demographic variables such as gender, ethnicity and major did not add significantly to the prediction of cheating. Implications for educators and researchers of cheating are discussed.

Previous research has questioned the educational value of taking introductory courses in psychology. Study 1 confirmed the usual null to negative associations between taking introductory psychology and performance in a subsequent psychology course. Study 2 showed that, after controlling for IQ, there was actually a positive association between taking introductory psychology and performance on a psychology knowledge pretest, which, in turn, was positively associated with course performance. Partial correlation analyses suggested that the apparent disadvantages of introductory psychology are an artifact of self-selection. Specifically, although taking introductory psychology provides beneficial knowledge, the choice to take the course may indicate a maladaptive scholastic style-possibly antiscientific mindedness. We recommend advertising psychology courses more properly as science-oriented to avoid misleading potential students.

Developed an item characteristic curve estimation of signal detection theory based personality data. Results for 266 college students taking the Overclaiming Questionnaire (D. Paulhus and N. Bruce, 1990) suggest that this method is a reasonable approach to describing item functioning and that there are advantages to this method over traditional item response theory models. (SLD)

A study is conducted on (Me2DAP)Pt(G)2 complexes (G = N9-substituted guanine derivative; Me2DAP = 2,4-bis(methylamino)pentane with N, C, C, and N stereochemistries of S,R,S,R, S,R,R,R and R,R,R,R) using NMR and CD spectroscopy and molecular mechanics and dynamics calculations. Results show that the favored Me2DAP chelate ring conformations were chair. Two head-to-tail rotamers and one or two head-to-head rotamers were also observed.

H NMR spectroscopy, X-ray crystallography and molecular mechanics/dynamics (MMD) calculations were used to prepare and study (PtXsub2(Mesub2DAP)) complexes. An understanding of the conformations of the coordinated ligands was gained, and the study provides a useful base for investigating the utility of a molecular mechanics/dynamics method, using a force field suited to nucleic acids.

To study the effects of amine ligand bulk, molecular mechanics calculations and NMR spectroscopy is utilized. According to the results, platinum complexes with bulky amine ligands react with two guanines but only one methionine.

Me2DAPPt(GpG) complexes were characterized by NMR and CD spectroscopies and molecular mechanics and dynamics(MMD) calculations. Steric and hydrogen-bonding interligand interactions result in an interplay between the Me2DAP ligand influencing GpG conformation and vice versa.

Highlights • Schedules with consecutive classes without a break cause student fatigue. • Instructor performance improves throughout the day as they repeat the same material. • Early morning classes hinder achievement. • Heterogeneity suggests certain students are more susceptible to schedule fatigue. • Data set is uniquely suited for causal identification of these phenomena. Abstract This study expands our understanding of how school day schedules affect achievement. We focus on three aspects related to scheduling: student fatigue, time of instruction, and instructor schedules. Data cover five academic years at the United States Air Force Academy, where schedules are randomized, grading is standardized, and there is substantial variance in schedule structure. Analyzing over 180,000 student-course outcomes, we find causal evidence of cognitive fatigue brought on by scheduling multiple courses in a row. The expected performance of two students in the same class may differ by as much as 0.15 standard deviations simply owing to their prior schedules. All else equal, students perform better in the afternoon than in the early morning. We also note that instruction improves with repetition. Heterogeneous effects by ability suggest that overall gains are possible. Prioritizing certain schedules would be equivalent to improving teacher quality by one-third of a standard deviation. A reorganization of students' daily school schedules is a promising and potentially low-cost educational intervention. [ABSTRACT FROM AUTHOR]

Unlike cisplatin, which forms bifunctional DNA adducts, monofunctional platinum(II) complexes bind only one strand of DNA and might target cancer without causing auditory side-effects associated with cisplatin treatment. We synthesized the monofunctional triamine-ligated platinum(II) complexes, Pt(diethylenetriamine)Cl, [Pt(dien)Cl]+, and Pt(N,N-diethyldiethylenetriamine)Cl, [Pt(Et2dien)Cl]+, and the monofunctional heterocyclic-ligated platinum(II) complexes, pyriplatin and phenanthriplatin, and compared their 5’-GMP binding rates, cellular compartmental distribution and cellular viability effects. A zebrafish inner ear model was used to determine if the monofunctional complexes and cisplatin caused hearing threshold shifts and reduced auditory hair cell density. The four monofunctional complexes had varied relative GMP binding rates, but similar cytosolic and nuclear compartmental uptake in three cancer cell lines (A549, Caco2, HTB16) and a control cell line (IMR90). Phenanthriplatin had the strongest effect against cellular viability, comparable to cisplatin, followed by [Pt(Et2dien)Cl]+, pyriplatin and [Pt(dien)Cl]+. Phenanthriplatin also produced the highest hearing threshold shifts followed by [Pt(dien)Cl]+, [Pt(Et2dien)Cl]+, cisplatin and pyriplatin. Hair cell counts taken from four regions of the zebrafish saccule showed that cisplatin significantly reduced hair cell density in three regions and phenanthriplatin in only one region, with the other complexes having no significant effect. Utricular hair cell density was not reduced by any of the compounds. Our results suggest that placing greater steric hindrance cis to one side of the platinum coordinating center in monofunctional complexes promotes efficient targeting of the nuclear compartment and guanosine residues, and may be responsible for reducing cancer cell viability. Also, the monofunctional compounds caused hearing threshold shifts with minimal effect on hair cell density, which suggests that they may affect different pathways than cisplatin. [ABSTRACT FROM AUTHOR]

Criminal justice researchers and agencies often look to empirical reviews and meta-analyses when evaluating offender risk instruments. However, variations in meta-analytical methods can influence the interpretation of statistical findings, resulting in potentially misleading conclusions. Through our re-examination of a meta-analysis by Singh, Grann, and Fazel (2011), we outline common methodological problems that may occur and demonstrate how alternative interpretations might be derived. We conclude by providing recommendations for conducting meta-analyses. Suggestions are made for researchers to consider alternative strategies when examining the validity of risk instruments, and for correctional agencies to consider, but go beyond, predictive validity when selecting offender risk instruments. [ABSTRACT FROM PUBLISHER]

A new study of cross-linkage compares cis-Pt(NH3)2G2 complexes and cis-Pt(NH3)2(d(GpG)) retro models.

We examined the interrelationships among symptoms related to autism spectrum disorders (ASD) using a large representative sample and clinical groups of children aged 6 to 11 and youth aged 12 to 18 years rated by parents ( N = 1,881) or teachers ( N = 2,171). The samples included individuals from the United States and Canada from the standardization and validity studies for the Autism Spectrum Rating Scales. A three-factor solution comprising Social/Communication, Unusual Behaviors, and Self-Regulation provided the best fit to the data and was replicated across parent and teacher ratings. High coefficients of congruence across sexes, raters, ethnic groups, and age groups and for clinical groups were obtained. Implications for understanding the symptoms related to ASD and their use in practice are provided. [ABSTRACT FROM AUTHOR]

There is widespread concern that deviant sexual fantasies promote corresponding behaviors. The authors investigated whether that concern is valid in nonoffender samples. Self-reports of nine deviant sexual fantasies and behaviors were compared in two samples of male undergraduates. In Study 1, 95% of respondents reported experiencing at least one sexually deviant fantasy, and 74% reported engaging in at least one sexually deviant behavior. The correlations were all positive and averaged .44. However, only 38% of the high-fantasy group reported acting out fantasies. The effect of pornography use on deviant behaviors was partially mediated by increases in deviant fantasies. Study 2 investigated possible moderators, including eight personality variables. The fantasy-behavior association held only for those high in self-reported psychopathy. In addition, the association between pornography use and deviant sexual behavior held only for participants high in psychopathy. Overall, theoretically relevant individual difference variables moderated the relation between sexually deviant fantasies and behaviors and between pornography use and deviant behaviors. [ABSTRACT FROM AUTHOR]

Of the offensive yet non-pathological personalities in the literature, three are especially prominent: Machiavellianism, subclinical narcissism, and subclinical psychopathy. We evaluated the recent contention that, in normal samples, this ‘Dark Triad’ of constructs are one and the same. In a sample of 245 students, we measured the three constructs with standard measures and examined a variety of laboratory and self-report correlates. The measures were moderately inter-correlated, but certainly were not equivalent. Their only common Big Five correlate was disagreeableness. Subclinical psychopaths were distinguished by low neuroticism; Machiavellians, and psychopaths were low in conscientiousness; narcissism showed small positive associations with cognitive ability. Narcissists and, to a lesser extent, psychopaths exhibited self-enhancement on two objectively scored indexes. We conclude that the Dark Triad of personalities, as currently measured, are overlapping but distinct constructs. [Copyright &y& Elsevier]

A number of self-report psychopathy scales have been used successfully in both clinical and nonclinical settings. However, their factor structure does not adequately capture the four factors (Interpersonal, Affective, Lifestyle, and Antisocial) recently identified in the Psychopathy Checklist-Revised (PCL-R; Hare, 2003) and related measures. This deficit was addressed by upgrading the Self Report Psychopathy Scale (SRP-II; Hare, Hemphill, & Harpur, 1989). In Study 1 (N = 249), an exploratory factor analysis of this experimental version revealed oblique factors similar to those outlined by Hare (2003). In Study 2 (N = 274), confirmatory factor analysis (CFA) confirmed this structure, that is, four distinct but intercorrelated factors. The factors exhibited appropriate construct validity in a nomological network of related personality measures. Links with self-reports of offensive activities (including entertainment preferences and behavior) also supported the construct validity of the oblique four-factor model.

The production of mutations and the reduction in survival of cells treated with alpha,omega-dihaloalkanes is greatly enhanced by the presence of O6-alkylguanine-DNA alkyltransferase (AGT), a DNA repair protein that removes O6-alkylguanine adducts from DNA [Liu, L., Hachey, D. L., Valadez, G., Williams, K. M., Guengerich, F. P., Loktionova, N. A., Kanugula, S., and Pegg, A. E. (2004) J. Biol. Chem. 279, 4250-4259]. The effects of alterations to key residues in the active site of AGT were studied using AGTs with point mutations. It was found that mutants of AGT at positions Tyr114, Arg128, Pro140, Gly156, Gly160, and Tyr158 did not bring about the increase in genotoxicity of 1,2-dibromoethane seen with wild-type AGT, although these mutants, with the exception of those at Tyr114 and Arg128, are known to have sufficient AGT repair function to be able to protect cells from alkylating agents. The R128A mutant was able to react with 1,2-dibromoethane at the Cys145 acceptor site, but the resulting AGT-Cys145S-(CH2)2Br was much less able to produce a covalent adduct with DNA. This result is explained by the need for AGT to induce a structural change in the DNA "flipping" of a guanine nucleotide into the substrate binding pocket where Cys145 is located since the side chain of residue Arg128 plays a critical role in this reaction. Point mutations in AGT at the other sites (Y114A, P140K, and Y158H) reduced the ability of the protein to react with 1,2-dibromoethane as measured by the loss of activity. These results were confirmed by MS analysis of the tryptic peptide that contains the modified Cys145. There was no change in the stability of the AGT-Cys145S-(CH2)2Br intermediate formed in mutants Y158H and P140K. The reaction was studied in detail with mutant P140K using dihaloalkanes of different length; no effect of the mutations was seen with dibromomethane, but an enhanced difference was observed with 1,3-dibromopropane and 1,5-dibromopentane. These results show that even slight alterations in the active site pocket of AGT that do not prevent its ability to protect cells from alkylating agents can block the paradoxical enhancement of the genotoxicity of the larger alpha,omega-dihaloalkanes by reducing the reaction with Cys145.

O(6)-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that removes O(6)-alkylguanine adducts. The interaction of dibromomethane (CH(2)Br(2)) and bromomethyl acetate (BrCH(2)OAc) with AGT was studied in vitro, and the effect of AGT on their toxicity and mutagenicity was investigated using Escherichia coli strain TRG8 (lacking endogenous AGT) that expressed human AGT or its inactive C145A mutant. Both CH(2)Br(2) and BrCH(2)OAc reacted with AGT at its cysteine acceptor site, abolishing its DNA repair activity with the latter agent being much more potent. The formation of AGT-Cys(145)S-CH(2)OAc by BrCH(2)OAc was confirmed by mass spectral analysis, but the presumed AGT-Cys(145)S-CH(2)Br adduct from CH(2)Br(2) was too unstable for such characterization. In the presence of CH(2)Br(2), AGT was covalently cross-linked to an oligodeoxyribonucleotide, 5'-d(AG)(8)-3', but no cross-link was formed by BrCH(2)OAc. Survival of cells exposed to CH(2)Br(2) was reduced, and the number of mutants was greatly increased when wild-type AGT was present. The cytotoxicity of CH(2)Br(2) was similar to that of BrCH(2)CH(2)Br(2), but the mutagenicity was about four times less. Virtually all of the AGT-mediated mutants induced by CH(2)Br(2) in the rpoB gene were at G:C sites with equal numbers of transitions to A:T and transversions to T:A. In contrast, BrCH(2)OAc was more than 10-fold less genotoxic than CH(2)Br(2) and the survival of cells exposed to BrCH(2)OAc was not affected by AGT. The number of mutations (almost all G:C to A:T transitions) induced by BrCH(2)OAc was slightly reduced by the presence of wild-type AGT and substantially increased by the inactive C145A mutant. These results with CH(2)Br(2) are consistent with a mechanism in which reaction at the active site Cys145 residue followed by attack of AGT-Cys(145)S-CH(2)Br at guanine in DNA forms a covalent adduct, which leads to cytotoxicity and to mutagenicity. The results with BrCH(2)OAc suggest that it reacts directly with DNA to form O(6)-(CH(2)OAc)guanine, which, if unrepaired, causes G:C to A:T transitions. Our experiments reveal two novel pathways (direct inactivation of AGT and formation of AGT-Cys(145)S-CH(2)-DNA adducts) by which CH(2)Br(2) may cause damage to the genome in addition to the well-recognized pathway involving activation by GSTs.

Amine conjugates of activated aflatoxin (AF) B(1) are formed in various systems, e.g., buffer amines and with protein lysine groups. Structures have been published in the literature, but the evidence is indirect in that (i) halogenated AFB(1) was usually used as the precursor and (ii) the assignment of the structure of the five-membered ring formed by cyclization is based on NMR chemical shifts. To better define these adducts and distinguish among several possibilities, we synthesized AFB(1) dialdehyde and reacted this with the surrogate methylamine at neutral pH, to simplify the system. The isolated product had the expected molecular ion (mass spectrometry) and showed pH-dependent UV spectra similar to those published for a lysine conjugate. Nuclear Overhauser enhanced spectroscopy (two-dimensional NMR, 800 MHz) of the sample (2H(2)O) showed proximity of the N-CH(3) protons only with a singlet at delta 4.10, assigned to the methylene of the added five-membered ring, but not to a delta 6.53 singlet assigned as the vinylic proton of that ring. All protons in the coumarin-furanone portion of the system were correlated to each other but not to those in the added five-membered ring. These experiments establish the structure as 2,3-dihydro-2-oxo-4-(1,2,3,4-tetrahydro-7-hydroxy-9-methoxy-3,4-dioxocyclopenta[c][1]benzopyran-6-yl)-1H-pyrrole-1-methane. The similarity of the reaction to that occurring in the reaction of AFB(1) dialdehyde with lysine and the agreement of the UV spectra suggest that this structure is applicable for the lysine analogue. The NMR results support the possible structure B of Sabbioni et al. [Sabbioni, G., Skipper, P. L., Buchi, G., and Tannenbaum, S. R. (1987) Carcinogenesis 8, 819-824] and the proposed structure 8 of Sabbioni [Sabbioni, G. (1990) Chem.-Biol. Interact. 75, 1-15] but not alternative proposals. Kinetic and mechanistic considerations of the reaction of lysine with AFB(1) dialdehyde are presented in the previous article in this issue [Guengerich, F. P., Arneson, K. O., Williams, K. M., Deng, Z., and Harris, T. M. (2002) Chem. Res. Toxicol. 15, 780-793].

Aflatoxin (AF) B(1) exo-8,9-epoxide hydrolysis yields AFB(1) dihydrodiol, which undergoes base-catalyzed rearrangement to, and is in equilibrium with, AFB(1) dialdehyde. We investigated the reaction of AFB(1) dialdehyde with albumin to generate a Lys adduct, previously characterized by others [Sabbioni, G., Skipper, P. L., Büchi, G., and Tannenbaum, S. R. (1987) Carcinogenesis8, 819-824; Sabbioni, G. (1990) Chem.-Biol. Interact. 75, 1-15]. Pronase digestion of bovine albumin serum treated with AFB(1) dialdehyde and HPLC yielded the adduct, identified by its characteristic UV and mass spectra. The structure of the Lys-AFB(1) dialdehyde adduct is concluded to be (S)-alpha-amino-2,3-dihydro-2-oxo-4-(1,2,3,4-tetrahydro-7-hydroxy-9-methoxy-3,4-dioxocyclopenta[c][1]benzopyran-6-yl)-1H-pyrrole-1-hexanoic acid, structure B of the former paper and 8 of the latter, based on work with the methylamine adduct described in the following paper in this issue [Guengerich, F. P., Voehler, M., Williams, K. M., Deng, Z., and Harris, T. M. (2002) Chem. Res. Toxicol. 15, 793-798]. The time course of product formation at varying concentrations of AFB(1) dialdehyde could be described by complexation with albumin with a K(d) of 1.5 mM and a first-order reaction rate with the N6-amino group of Lys of 0.033 min(-)(1). The reaction of AFB(1) dialdehyde with N(2)-acetylLys was monitored by UV spectroscopy and yielded a final spectrum similar to that of the described Lys adduct. Kinetic analysis of the changes at pH 7.2 was best described with a scheme involving equilibrium of the dialdehyde with dihydrodiol and a rate-limiting reaction of AFB(1) dialdehyde with the N6 atom of N(2)-acetylLys, with an apparent second-order rate constant of 2.6 x 10(3) M(-)(1) min(-)(1), followed by putative carbinolamine formation and rearrangement, collectively described by a first-order rate constant of 7.6 min(-)(1). Competition experiments with the hydrolysis of AFB(1) exo-8,9-epoxide indicate that N2-acetylLys also reacts with the epoxide at pH 7.2 (k = 350 M(-)(1) min(-)(1)) and 9.5 (k = 1.8 x 10(3) M(-)(1) min(-)(1)). This reaction might contribute to the formation of protein Lys adducts, depending upon the local concentration of free or protein Lys. Mass spectral analysis of trypsin digests of bovine serum albumin modified with AFB(1) dialdehyde indicated selective modification of Lys455 and Lys548. Collectively, these results provide more insight into the mechanism of formation of AFB(1) dialdehyde-protein adducts and indicate that the formation of Lys adducts is a moderately efficient process. The binding of AFB(1) dialdehyde to albumin or the protonation of the N6-amino group retards the reaction with Lys residues.