Structure of the m1 muscarinic acetylcholine receptor gene and its promoter

The m1 receptor is one of five muscarinic receptors that mediate the metabotropic actions of acetylcholine in the nervous system where it is expressed predominantly in the telencephalon and autonomic ganglia. RNase protection, primer extension, and 5'-rapid amplification of cDNA ends analysis of a rat cosmid clone containing the entire m1 gene demonstrated that the rat m1 gene consists of a single 657-base pairs (bp) non-coding exon separated by a 13. 5-kilobase (kb) intron from a 2.54-kb coding exon that contains the entire open reading frame. The splice acceptor for the coding exon starting at -71 bp relative to the adenine of the initiating methionine. This genomic structure is similar to that of the m4 gene (Wood, I. C., Roopra, A., Harrington, C. A., and Buckley, N. J. (1995) J. Biol. Chem. 270, 30933-30940 and Wood, I. C., Roopra, A., and Buckley, N. J. (1996) J. Biol. Chem. 271, 14221-14225). Like the m4 gene, the m1 promoter lacks TATA and CAAT consensus motifs, and the first exon and 5'-flanking region are not gc-rich. The 5'-flanking region also contains the consensus regulatory elements Sp-1, NZF-1, AP-1, AP-2, E-box, NFkappaB, and Oct-1. Unike the m4 promoter, there is no evidence of a RE1/NRSE silencer element in the m1 promoter. Deletional analysis and transient transfection assays demonstrates that reporter constructs containing 0.9 kb of 5'-flanking sequence and the first exon are sufficient to drive cell-specific expression of reporter gene in IMR32 neuroblastoma cells while remaining silent in 3T3 fibrobasts.     

The Darwin is in the details.

Comments on the article by A. H. Eagly and W. Wood (see record 1999-05337-002) which examined the origins of sex differences in human behavior. Eagly and Wood argued that social structural theory can explain the origin of psychological sex differences. The present authors suggest that evolutionary models of sex differences are based on a much broader foundation that Eagly and Wood imply. They note that Eagly and Wood misconstrued previous age preference findings as supporting the "common knowledge" that men prefer younger women. Eagly and Wood also showed that as societies approach gender equality in resource access, some sex differences in mate preferences decrease; however, as the current authors note, evolved mechanisms are not environmentally insensitive. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Once again, the origins of sex differences.

Responds to comments by B. X. Friedman et al (see record 2000-05933-013), D. T. Kenrick and N. Li (see record 2000-05933-014), and E. Kleyman (see record 2000-05933-015) on the article by A. H. Eagly and W. Wood (see record 1999-05337-002) which examined the origins of sex differences in human behavior. Eagly and Wood argued that social structural theory can explain the origin of psychological sex differences. In the present article, Eagly and Wood defend their original article against criticism made by the aforementioned authors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

From allies to adversaries?

Comments on the article by A. H. Eagly and W. Wood (see record 1999-05337-002) which examined the origins of sex differences in human behavior. Eagly and Wood argued that social structural theory can explain the origin of psychological sex differences. In the present article, E. Kleyman praises Eagly and Wood for clarifying her confusion as to the difference between the evolutionary theory and the social structural theory views on the origins of sex differences in behavior. She states that before the article by Eagly and Wood it was difficult to see the significant distinctions between the social structural theory's acceptance of evolutionary origins of the human species and evolutionary theory's acceptance of social input and context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Onion or orrisroot: A comment on Bevan's "Tour inside the onion."

E. S. Wood comments that W. Bevan's (see record 1991-28688-001) complaints about the triviality of many contemporary psychology papers and the science-by-the-numbers attitudes of psychology scholars form an eloquent prophesy. Continuing Bevan's metaphor of psychology as an onion, Wood suggests that psychology's innermost layer is an orrisroot. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opinions or Data?

Replies to comments by W. Wood (1962) to the original article by M. R. Feinberg and J. Lefkowitz (see record 1963-02029-001), which assessed the image of industrial psychology among corporate executives. The author discusses five points made by Wood, including issues regarding opinion vs. research findings and original study's methodology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Precision targeting of protein kinases. An affinity label that inactivates the cGMP- but not the cAMP-dependent protein kinase

Although the cAMP-dependent (PKA) and cGMP-dependent protein kinases (PKG) usually participate in unrelated biological processes, their enzymological properties are decidedly similar. Based upon the multitude of comparative studies conducted to date, it appears that these two enzymes exhibit very similar peptide substrate specificities. Furthermore, most inhibitors that have been reported for PKG serve in a nearly equal capacity for PKA. Consequently, the task of distinguishing between these enzymes, especially under in vivo conditions, has proved to be daunting. However, we have recently found that PKA will only phosphorylate non-amino acid residues whose alpha-configuration corresponds to that found in L-amino acids, whereas PKG will catalyze the phosphorylation of residues corresponding to both L- and D-amino acids (Wood, J., Mendelow, M., Yan, X., Corbin, J.D., Francis, S.H., and Lawrence, D.S. (1996) J. Biol. Chem. 271, 174-179). Based on these results, we have designed a potent affinity label for PKG (KI = 21.1 +/- 4.7 microM), that has no measurable activity toward PKA. This represents the first example of an peptide-based inactivator that fully distinguishes between these two closely related enzymes. These results suggest that a similar strategy may provide highly specific inactivators for other protein kinases as well.     

"Are there shared environmental influences on attention-deficit/hyperactivity disorder? Reply to Wood, Buitelaar, Rijsdijk, Asherson, and Kuntsi (2010)": Correction to Burt (2010).

Reports an error in "Are there shared environmental influences on attention-deficit/hyperactivity disorder? Reply to Wood, Buitelaar, Rijsdijk, Asherson, and Kuntsi (2010)" by S. Alexandra Burt (Psychological Bulletin, 2010[May], Vol 136[3], 341-343). In the article, the surname of Jonna Kuntsi is misspelled throughout. The online versions of this article have been corrected. (The following abstract of the original article appeared in record 2010-07936-002.) A recent large-scale meta-analysis of twin and adoption studies indicated that shared environmental influences make important contributions to most forms of child and adolescent psychopathology (Burt, 2009b). The sole exception to this robust pattern of results was observed for attention-deficit/hyperactivity disorder (ADHD), which appeared to be largely genetic (and particularly nonadditive genetic) in origin, with no observable influence of the shared environment. The central thesis of Wood, Buitelaar, Rijsdijk, Asherson, and Kuntsi (2010) is that, contrary to these findings, shared environmental influences are important for ADHD. As evidence for this thesis, Wood et al. presented a summary of prior twin studies, followed by a discussion of 4 methodological issues that may account for my findings in Burt (2009b). I argue that, although the methodological concerns raised by Wood et al. are very important, they do not undermine my earlier results (Burt, 2009b). I close with a discussion of 2 issues that may allow for some shared environmental influences on ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assessing reliability: Critical corrections for a critical examination of the Rorschach Comprehensive System.

J. M. Wood et al (see records 84-17678 and 84-17679) argued that the Rorschach Comprehensive System (CS) lacked many essential pieces of reliability data and that the available evidence indicated that scoring reliability may be little better than chance. Contrary to their assertions, the author suggests why rater agreement should focus on responses rather than summary scores, how field reliability moves away from testing CS scoring principles, and how no psychometric distinction exists between a percentage correct and a percentage agreement index. Also, after reviewing problematic qualities of kappa, a meta-analysis of published data is presented indicating that the CS has excellent chance-corrected interrater reliability (Estimated κ, M?=?.86, range?=?.72–.96). Finally, the author notes that Wood et al ignored at least 17 CS studies of test-retest reliability that contain many of the important data they said were missing. The author concluded that Wood et al's erroneous assertions about the more elementary topic of reliability make suspect their assertions about the more complex topic of validity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fluorescence with Wood's light. Current applications in dermatologic diagnosis, therapy follow-up and prevention

The invisible long-wave ultraviolet radiation (340-450 nm, max.365 nm) produced by a Wood lamp can help to diagnose dermatoses with a characteristic fluorescence (tinea capitis, erythrasma, tinea versicolor, Pseudomonas infections, porphyrians, and pigmentary alterations). It is also used in the detection of medications that are taken systemically (tetracycline) or that are applied to the skin. Recently, a fluorescence technique with Wood light has been used as a preventive measure to monitor and quantify skin protection at the workplace and to teach workers in high-risk occupations the proper use of protective creams.     

Are there shared environmental influences on attention-deficit/hyperactivity disorder? Reply to Wood, Buitelaar, Rijsdijk, Asherson, and Kunsti (2010).

[Correction Notice: An erratum for this article was reported in Vol 136(5) of Psychological Bulletin (see record 2010-17510-007). In the article, the surname of Jonna Kuntsi is misspelled throughout. The online versions of this article have been corrected.] A recent large-scale meta-analysis of twin and adoption studies indicated that shared environmental influences make important contributions to most forms of child and adolescent psychopathology (Burt, 2009b). The sole exception to this robust pattern of results was observed for attention-deficit/hyperactivity disorder (ADHD), which appeared to be largely genetic (and particularly nonadditive genetic) in origin, with no observable influence of the shared environment. The central thesis of Wood, Buitelaar, Rijsdijk, Asherson, and Kunsti (2010) is that, contrary to these findings, shared environmental influences are important for ADHD. As evidence for this thesis, Wood et al. presented a summary of prior twin studies, followed by a discussion of 4 methodological issues that may account for my findings in Burt (2009b). I argue that, although the methodological concerns raised by Wood et al. are very important, they do not undermine my earlier results (Burt, 2009b). I close with a discussion of 2 issues that may allow for some shared environmental influences on ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Incompatible with evolutionary theorizing.

Comments on the article by A. H. Eagly and W. Wood (see record 1999-05337-002) which examined the origins of sex differences in human behavior. Eagly and Wood argued that social structural theory can explain the origin of psychological sex differences. The present article discusses conceptual problems which render Eagly and Wood's theory implausible. The authors see the social structuralists' dualistic interpretation of the origin of human traits as untenable and note that it results from a misunderstanding of what drives the evolution of adaptations. It is also noted that social structuralists' contention that humans do not have evolved psychological sex differences is implausible, because their implicit assumption that the sexes have not faced different adaptive problems over evolutionary history is not true. The authors point out that social structuralists neglect empirical evidence supporting the hypothesis that behavioral sex differences are mediated by hormonal influences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical Judgment in Science: Reply.

Replies to comments published by M. S. Schulz and R. J. Waldinger (see record 2005-11115-010), J. M. Wood and M. T. Nezworski (see record 2005-11115-011), and H. N. Garb and W. M. Grove (see record 2005-11115-012) on the original article by D. Westen and J. Weinberger (see record 2004-19091-002). Schulz and Waldinger (2005) make the important point that just as researchers can capitalize on the knowledge of experienced clinical observers through aggregation, they can aggregate the judgment of lay observers in assessing phenomena such as emotion. The reason, as they articulate, is that skills such as "reading" emotion from facial expression, tone of voice, posture, and the constellation of cues provided in everyday life are an area of expertise for most people, one that is now often called social or emotional intelligence. As psychometricians have known for years, one can increase reliability in many different ways. The comments by Wood and Nezworski (2005) and Garb and Grove (2005) do not address our central thesis--namely, the importance of distinguishing two meanings of clinical. The point of the sentence around which Wood and Nezworski (2005) build their comment was simply that the same biases widely attributed to clinicians are common in scientists as well--a point for which we would be delighted to take credit, but it is one that was actually made much more elegantly by the historian and philosopher of science Thomas Kuhn (1962). The authors respond to Wood and Nezworski's (2005) specific concerns about misrepresentation. In their comment, Garb and Grove (2005) challenge us to document our view that anticlinician prejudice is widespread among many academic clinical psychologists. As research on implicit prejudice suggests, surveys of academic clinical psychologists might indicate little about their implicit attitudes, as evident in Garb and Grove's apparent lack of recognition of the offensive nature of comparing a clinician's attempt to revise his or her understanding when the patient says "I don't think what you just said is right" to astrology and Barnum effects. We appreciate Garb and Grove's (2005) point about potential differential effects of training and experience on reliability and validity of clinical judgment. The data they cite are important and bear consideration. We would offer two caveats, however. Finally, we cannot help but note that this series of comments and our reply to them provide a prototypical example of "clinical" judgment in science--that is, subjective, informal aggregation of data, often leading to a "gestalt" judgment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microalbuminuria, arterial hypertension and the cardiovascular risk

Both the Entamoeba histolytica lectin, a virulence factor for the causative agent of amebiasis, and the mammalian hepatic lectin bind to N-acetylgalactosamine (GalNAc) and galactose (Gal) nonreducing termini on oligosaccharides, with preference for GalNAc. Polyvalent GalNAc-derivatized neoglycoproteins have >1000-fold enhanced binding affinity for both lectins (Adler,P., Wood,S.J., Lee,Y.C., Lee,R.T., Petri,W.A.,Jr. and Schnaar,R.L.,1995, J. Biol. Chem ., 270, 5164-5171). Substructural specificity studies revealed that the 3-OH and 4-OH groups of GalNAc were required for binding to both lectins, whereas only the E.histolytica lectin required the 6-OH group. Whereas GalNAc binds with 4-fold lower affinity to the E.histolytica lectin than to the mammalian hepatic lectin, galactosamine and N-benzoyl galactosamine bind with higher affinity to the E. histolytica lectin. Therefore, a synthetic scheme for converting polyamine carriers to poly-N-acyl galactosamine derivatives (linked through the galactosamine primary amino group) was developed to test whether such ligands would bind the E.histolytica lectin with high specificity and high affinity. Contrary to expectations, polyvalent derivatives including GalN6lys5, GalN4desmosine, GalN4StarburstTMdendrimer, and GalN8StarburstTMdendrimer demonstrated highly enhanced binding to the mammalian hepatic lectin but little or no enhancement of binding to the E.histolytica lectin. We propose that the mammalian hepatic lectin binds with greatest affinity to GalNAc "miniclusters," which mimic branched termini of N-linked oligosaccharides, whereas the E.histolytica lectin binds most effectively to "maxiclusters," which may mimic more widely spaced GalNAc residues on intestinal mucins.     

Increased pulmonary blood flow produces endothelial cell dysfunction in neonatal swine

BACKGROUND: The mechanisms by which increased pulmonary blood flow results in pulmonary hypertension have not been determined. METHODS: To determine if increased pulmonary blood flow produces endothelial dysfunction that precedes vascular remodeling and smooth muscle proliferation, neonatal swine (n = 12) (age, 6.1+/-0.5 days) underwent ligation of the left pulmonary artery (LPA) to increase blood flow to the right lung. At 12 weeks of age, endothelium-dependent vasodilatation was assessed by acetylcholine infusion and endothelium-independent vasodilatation by inhaled nitric oxide (NO) in the LPA group and age-matched controls (CON) (n = 11). RESULTS: Mean pulmonary artery pressure was 24.1+/-3.0 mm Hg in the LPA group and 20.8+/-1.9 mm Hg in the CON group (p < 0.1). Pulmonary vascular resistance was 13.2+/-2.2 Wood units in the LPA group and 5.8+/-0.8 Wood units in the CON group (p = 0.001). Acute occlusion of the left pulmonary artery in the CON group increased pulmonary vascular resistance to 6.9+/-3.9 Wood units (p = 0.04). Administration of acetylcholine in the CON group after preconstriction with the thromboxane A2 analogue U46619 resulted in a 30.6%+/-5.4% decrease in pulmonary vascular resistance. In the LPA group, acetylcholine produced paradoxical vasoconstriction and a 15.4%+/-4.1% increase in pulmonary vascular resistance (p < 0.001 versus CON) indicating loss of endothelium-dependent vasodilatation. Nitric oxide decreased pulmonary vascular resistance by 41.9%+/-3.3% in the CON group and 30.8%+/-2.7% in the LPA group (p = 0.04 versus CON), indicating preserved endothelium-independent vasodilatation in both groups. Morphometric analysis was performed in 4 animals from each group. Medial wall thickness as percent of external diameter of small arteries (<100 microm) was the same in both groups (6.4%+/-0.4% in the LPA group versus 6.6% +/-0.4% in the CON animals; p > 0.1). CONCLUSIONS: Increased pulmonary blood flow in immature animals produces endothelial cell dysfunction with loss of endothelium-dependent vasodilatation before the onset of pulmonary vascular remodeling. Subsequent smooth muscle proliferation may be mediated by endothelium-derived factors.     

Interactions between DNA polymerase beta and the major covalent adduct of the carcinogen (+)-anti-benzo[a]pyrene diol epoxide with DNA at a primer-template junction

A molecular dynamics simulation has been carried out with DNA polymerase beta (beta pol) complexed with a DNA primer-template. The templating guanine at the polymerase active site was covalently modified by the carcinogenic metabolite of benzo[a]pyrene, (+)-anti-benzo[a]pyrene diol epoxide, to form the major (+)-trans-anti-benzo[a]pyrene diol epoxide covalent adduct. Thus, the benzo[a]pyrenyl moiety (BP) is situated in the single-stranded template at the junction between double- and single-stranded DNA. The starting structure was based on the X-ray crystal structure of the rat beta pol primer-template and ddCTP complex [Pelletier, H., Sawaya, M. R., Kumar, A., Wilson, S. H., and Kraut, J. (1994) Science 264, 1891-1903]. During the simulation, the BP and its attached templating guanine rearrange to form a structure in which the BP is closer to parallel with the adjacent base pair. In addition, the templating attached guanine is displaced toward the major groove side and access to its Watson-Crick edge is partly obstructed. This structure is stabilized, in part, by new hydrogen bonds between the BP and beta pol Asn279 and Arg283. These residues are within hydrogen bonding distance to the incoming ddCTP and templating guanine, respectively, in the crystal structure of the beta pol ternary complex. Site-directed mutagenesis has confirmed their role in dNTP binding, discrimination, and catalytic efficiency [Beard, W. A., Osheroff, W. P., Prasad, R., Sawaya, M. R., Jaju, M., Wood, T. G., Kraut, J., Kunkel, T. A., and Wilson, S. H. (1996) J. Biol. Chem. 271, 12141-12144]. The predominant biological effect of the BP is DNA polymerase blockage. Consistent with this biological effect, the computed structure suggests the possibility that the BP's main deleterious impact on DNA synthesis might result at least in part from its specific interactions with key polymerase side chains. Moreover, relatively modest movement of BP and its attached guanine, with some concomitant enzyme motion, is necessary to relieve the obstruction and permit the observed rare incorporation of a dATP opposite the guanine lesion.     

'The structure of phenotypic personality traits": Author's reactions to the six comments.

L. R. Goldberg replies to the comments by R. O. Kroger and L. A. Wood (see record 1994-17497-001), S. Guastello (see record 1994-17488-001), D. R. Comer (see record 1994-17481-001), H. J. Eysenck (see record 1994-17486-001), W. D. Shadel and D. Cervone (see record 1994-17520-001), and H. E. Cattell (see record 1994-17479-001) on Goldberg's (PA, Vol 80:17546) article on the Big Five personality traits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Effect of Anxiety Reduction on Children's School Performance and Social Adjustment": Correction to Wood (2006).

Reports an error in "Effect of anxiety reduction on children's school performance and social adjustment" by Jeffrey Wood (Developmental Psychology, 2006[Mar], Vol 42[2], 345-349). The byline and author note should have included the author's middle initial, J. Thus, the byline and author note should refer to "Jeffrey J. Wood." The correction is reflected in this record. (The following abstract of the original article appeared in record 2006-03514-012.) This study tested the effect of reductions in children's anxiety over time on improvements in school performance and social functioning in the context of participation in a cognitive-behavioral intervention program. Participants included 40 children with high anxiety (6-13 years of age). Independent evaluators, children, and parents rated child anxiety; parents rated school performance; and children and parents rated social functioning. Measures were completed at preintervention, midintervention, and postintervention. Fixed-effects regression analyses and random-effects regression analyses indicated that decreased anxiety was predictive of improved school performance and social functioning over the course of the intervention. These findings suggest that changes in anxiety influence trajectories of children's scholastic and social functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

N-acyl-homoserine lactone-mediated regulation of phenazine gene expression by Pseudomonas aureofaciens 30-84 in the wheat rhizosphere

Pseudomonas aureofaciens 30-84 is a soilborne bacterium that colonizes the wheat rhizosphere. This strain produces three phenazine antibiotics which suppress take-all disease of wheat by inhibition of the causative agent Gaeumannomyces graminis var. tritici. Phenazines also enhance survival of 30-84 within the wheat rhizosphere in competition with other organisms. Expression of the phenazine biosynthetic operon is controlled by the phzR/phzI N-acyl-homoserine lactone (AHL) response system (L. S. Pierson III et al., J. Bacterial 176:3966-3974, 1994; D. W. Wood and L. S. Pierson III, Gene 168:49-53, 1996). By using high-pressure liquid chromatography coupled with high-resolution mass spectrometry, the AHL produced by PhzI has now been identified as N-hexanoyl-homoserine lactone (HHL). In addition, the ability of HHL to serve as an interpopulation signal molecule in the wheat rhizosphere has been examined by using isogenic reporter strains. Disruption of phzI reduced expression of the phenazine biosynthetic operon 1,000-fold in the wheat rhizosphere. Coinoculation of an isogenic strain which produced the endogenous HHL signal restored phenazine gene expression in the phzI mutant to wild-type levels in situ. These results demonstrate that HHL is required for phenazine expression in situ and is an effective interpopulation signal molecule in the wheat rhizosphere.