Structural and electronic similarity but functional difference in methylmalonyl-CoA mutase between coenzyme B12 and the analog 2',5'-dideoxyadenosylcobalamin.

The cofactor analog 2',5'-dideoxyadenosylcobalamin (ddAdoCbl) differs from the natural cofactor coenzyme B12 [5'-deoxyadenosylcobalamin (dAdoCbl)] by lacking only one oxygen atom. The 1H and 13C NMR spectra of ddAdoCbl have been assigned unambiguously by homonuclear and heteronuclear 2D NMR techniques. The 1H, 13C, and 31P chemical shift values for ddAdoCbl were compared with those of another organocobalamin, namely dAdoCbl. This assessment shows that the analog is very similar both electronically and structurally to the natural cofactor. The effectiveness of ddAdoCbl as a cofactor for both the human and Propionibacterium shermanii methylmalonyl-CoA mutases was compared with that of the natural cofactor. ddAdoCbl was found to be a competitive inhibitor with respect to dAdoCbl. Similar binding affinities to both enzymes were found for both the ddAdoCbl analog and the natural cofactor. However, in the presence of ddAdoCbl, the rate of conversion of methylmalonyl-CoA to succinyl-CoA was only 1-2% of that seen with the natural cofactor. There were no changes with time in the visible absorption spectrum of the bound cofactor analog in the presence of substrate, suggesting that the Co-C bond was not cleaved. The CD (circular dichroism) spectra of dAdoCbl and ddAdoCbl are very similar, consistent with the NMR results. The CD spectral changes upon binding to P. shermanii methylmalonyl-CoA mutase are large compared to those reported on the binding of dAdoCbl to ethanolamine ammonia lyase. Furthermore, the CD spectra of both enzyme-bound cobalamins are very similar, suggesting that similar changes in the conformation or structure in these cobalamins occur on binding to the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimensions of everyday memory in young adulthood.

This paper reports the findings of two studies on everyday memory in young adulthood. In Study 1, 387 male and female college students (18-22 years old) completed the 25-item Cognitive Failures Questionnaire (CFQ; Broadbent, Cooper, Fitzgerald & Parkes, 1982). Principal components analysis yielded five internally consistent factors: distractibility; misdirected actions; spatial/kinaesthetic memory; interpersonal intelligence; and memory for names. Further, each of these dimensions was interpretable within an information-processing framework. Study 2 examined the relation of the five everyday memory dimensions obtained in Study 1 to measures of working memory and traditional intelligence in a separate sample of 32 college students. Findings obtained in Study 2 suggest that attentional processes may be important components of the everyday memory construct.

Purification and properties of nuclease SP.

Single-strand-specific nucleases are a diverse and important group of enzymes that are able to cleave a variety of DNA structures present in duplex molecules. Nuclease SP, an enzyme from spinach, has been purified to apparent homogeneity, allowing for the unambiguous characterization of a number of its physical properties as well as its DNA strand cleavage specificities. The effects of ionic strength, pH, divalent metal cations, and temperature on nuclease SP activity have been examined in detail. Nuclease SP was found to be quite thermostable and could be stimulated by Co2+. In addition, the cleavage of UV-damaged and undamaged supercoiled plasmid substrates under a variety of conditions suggests that at least two types of structures are recognized and processed by nuclease SP: UV photoproduct-induced distortions and unwound "nuclease hypersensitive sites". These studies indicate that nuclease SP is functionally related to other single-strand-specific nucleases and is a potential enzymatic tool for probing and manipulating various types of DNA structures.

A human monoclonal antibody that protects mice against Pseudomonas-induced pneumonia.

X-linked immunodeficient (xid) (CBA/N female x DBA/2 male) F1 male mice, when treated with cyclophosphamide, were much more susceptible to challenge with aerosolized Pseudomonas aeruginosa serotype 11 than were control F1 female littermates. Mortality of F1 males was decreased significantly after intravenous administration of human P. aeruginosa serotype 11 O-specific monoclonal antibody. Antibody treatment reduced bacterial titers in the lungs as well as the severity of Pseudomonas-induced lung histopathology.

Absence of adult age differences in forgetting in the Brown-Peterson Task.

Despite some recent evidence to the contrary, no reliable age differences in proactive interference (PI) or retroactive interference (RI) were found in a cross-sectional study of adults aged 18-29 and 63-75. Individual memory span was used as the list length in the Brown-Peterson Task in order to achieve stimulus equivalence of memory loads across individuals and age groups. Data from rehearsers were excluded from the analyses in order to isolate age differences in passive forgetting processes from those in rehearsal. PI was manipulated by presenting categorized or uncategorized memory lists. RI was manipulated, holding distractor task difficulty constant, by using words or tones in a signal detection distractor task. It is concluded that age differences are minimal to nonexistent in passive RI-related processes such as decay and perturbation and in passive PI-related processes such as set effects in semantic encoding.

Absence of age-related proneness to short-term retroactive interference in the absence of rehearsal.

Age differences in short-term retroactive interference, unconfounded with age differences in rehearsal in the retention interval of the Brown-Peterson Task, were not found in a cross-sectional study of adults 18-32 and 64-78 years of age. Degree of retroactive interference was manipulated conjointly with distractor interval length (0-15 s). Individual memory span was assessed and used as the list length in order to achieve stimulus equivalence of memory loads across individuals and age groups. An attention-demanding matching task that adjusted itself in difficulty to the individual's attentional capacity was used as the distractor activity. Covert rehearsal during the retention interval was inferred using several measures, including a comparison of distractor task performance in the presence and in the absence of a memory load, and rehearsers were excluded from the primary analyses. We conclude that there is no interference proneness with increasing age in the present study.

Human monoclonal antibodies that protect mice against challenge with Pseudomonas aeruginosa.

Lymphocytes from healthy volunteers and from cystic fibrosis patients were transformed with Epstein-Barr virus and cultured at a limiting dilution to generate lymphoblastoid cell lines that secreted human monoclonal antibodies specific for lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Three cell lines (RM5, FDD7, and 11F9) produced immunoglobulin M (IgM) antibody species that reacted specifically with P. aeruginosa Fisher immunotypes 2, 4, and 5, respectively, and with LPS extracted from these immunotypes. A fourth cell line (9H10) produced a single IgM antibody species that recognized P. aeruginosa immunotypes 3, 6, and 7 and LPS extracted from them. Monoclonal antibodies secreted by cell lines RM5, FDD7, and 11F9 protected neutropenic mice prophylactically against challenge with P. aeruginosa immunotypes 2, 4, and 5, and those secreted by 9H10 protected against P. aeruginosa immunotypes 3 and 6 but did not protect against immunotype 7. In vivo experiments indicated that antibodies protected mice against infection by increasing the rate of bacterial clearance.

X-linked immunodeficient mice as a model for testing the protective efficacy of monoclonal antibodies against Pseudomonas aeruginosa.

(DBA/N[female] X CBA/2[male])F1 males have been reported to be deficient in producing antibodies against a number of antigens, including carbohydrates (I. Scher, Adv. Immunol. 35:1-71, 1982). We show that F1 male mice, in contrast to females, made less lipopolysaccharide (LPS)-specific antibodies after immunization with heat-inactivated Pseudomonas aeruginosa and had significantly less naturally occurring LPS-specific antibodies. Furthermore, neutropenic males were 50 to 1,000 times more sensitive to challenge with representative isolates belonging to the seven Fisher immunotypes. Administration to neutropenic F1 males of a human monoclonal antibody specific for the O carbohydrates of P. aeruginosa immunotype 2 LPS or administration of serum from rabbits immunized with heat-inactivated P. aeruginosa immunotype 1 raised the level of resistance to bacterial challenge close to that of females. The results show that the X-linked immunodeficient mouse is an excellent model with which to test the protective efficacy of P. aeruginosa-specific monoclonal antibodies.

The relative impact of age and attractiveness stereotypes on persuasion.

The relative impact of the old-age and attractiveness stereotypes on persuasion was investigated. College students read essays that contained either cogent or specious arguments that were attributed either to young or old, socially attractive or unattractive authors. Evaluations of the essay itself were affected only by the quality of the arguments presented. Argument quality and attractiveness interacted to determine perceptions of the author and opinions on the position advocated in the essay: attractive authors were rated higher and were more persuasive than unattractive authors when the essay was strong, but were derogated and unpersuasive relative to unattractive authors when the essay was weak. Age of the author had an impact only on a few of the author-evaluation scales. A hierarchy of stereotype potency in which social attractiveness is prepotent over age is offered tentatively.

Adult age differences in memory for sex of voice.

Young and older adults (elderly in Experiment 1 and middle-aged in Experiment 2) received successive sentence recall tasks for which one-half of the sentences were read in a male voice and one-half in a female voice. With regard to the sex of voice component, the first task was administered under incidental learning conditions and the second under intentional learning conditions. With regard to sentence content, both tasks were administered under intentional learning conditions. The results indicated that encoding voice information is a cognitively effortful, age sensitive process. For older adults, both elderly and middle-aged, enhanced voice encoding under the intentional condition, relative to the incidental condition, was accompanied by a significant decrement in sentence recall. For young adults, the trade off effect was not large enough to reach statistical significance. The age difference apparently reflects the diminished processing capacity of older adults relative to young adults, with the decrease in capacity having its onset by middle age.

Adult age differences in memory for modality attributes.

Young and elderly subjects performed on two memory tasks. The first task involved recognition of word content and identification of each word's sex of voice in the study list. An additional independent variable consisted of intentional versus incidental learning instructions. An age difference favoring young adults was found for both word recognition and sex of voice recognition, confirming earlier evidence found with a more difficult sentence recall task. Comparable age deficits were found on the second task involving word recognition and identification of each word's case format in the study list. Encoding of modality attributes does appear to be an effortful process and is susceptible to age deficits. However, contrary to the age differentiation hypothesis, the cross-task correlation between modality recognition scores was no greater for elderly adults than for young adults.

Modality memory and frequency of occurrence memory for young and middle-aged adults.

Young and middle-aged subjects, matched for scores on a figural relations test, did not differ in memory for either word content or the case format in which study list words had been presented, suggesting that age deficits for modality memory are restricted to late adulthood. Scores on the figural relations test, as a measure of fluid intelligence, correlated positively with case recognition scores, but significantly so only for the young subjects. In addition case recognition memory was more proficient under intentional conditions than under incidental conditions for both age groups, implying that case encoding is a cognitively effortful activity. In agreement with this position, case recognition scores showed an absence of correlation with scores on a frequency judgment task, a task commonly assumed to involve an automatic encoding process.

Adult age differences in recognition memory for a nonsemantic attribute.

The present study tested the generalizability of the adult age deficit commonly found for recognition of word content to the recognition of a nonsemantic attribute. The nonsemantic attribute consisted of the case format (upper versus lower) of words during their study list presentations. Elderly adults, as well as young adults, performed well above chance expectancy on the case recognition task. However, elderly adults, relative to young adults, were also found to have significantly lower recognition scores for case alone as well as for word content plus case. The age sensitivity found for case encoding emplies that this activity is not an automatic memory process. That is, it appears to be mediated by a cognitively effortful process.

Frequency judgments and correlated cognitive abilities in young and elderly adults.

The present study replicated and extended the results obtained earlier by Attig and Hasher (1980) in finding null effects for adult age variation and instructional variation on a relative frequency judgment task. In addition, nonsignificant covariation was found for both young and elderly adults bet ween frequency judgment proficiency and paired-associate learning proficiency, in agreement with the hypothesis that frequency judgment is mediated fully by automatic memory processes over the entire adult lifespan. Fluid intelligence test scores were also found to correlate positively with frequency judgment proficiency for young adults but not for elderly adults.

Effects of word frequency on adult age differences in word memory span.

The present study tested the hypothesis that the age deficits in memory span commonly found in elderly adults are attributable, at least in part, to elaborative rehearsal processes. The test required an analysis of age differences between young and elderly adult subjects in word span for list types varying in word frequency. Significant age deficits were found for all list types, with the magnitude of the deficit increasing as the frequency of intrastring items increased. The pattern of this interaction indicated the involvement of a decreased proficiency in elaborative rehearsal with increasing age as a contributor to the age deficit in word span.