Book Reviews

Book reviewed int his article:
Basic Neurochemistry , 3rd Edition edited by George J. Siegel, R. Wayne Albers, and Bernard W. Agranoff.
Neurofilaments edited by Charles A. Marotta.     

Riccardo (Rico) Wittek (1944-2008)

Riccardo (Rico) Wittek died 26 September 2008 in Switzerland. Rico was well known for his work on the molecular biology of poxviruses and for his work with the World Health Organization on biosafety that led to international guidelines for work with dangerous infectious agents. His colleagues Erwin G. Van Meir, Daniel Lavanchy, and Bernard Moss have written Rico''s memorial.Lynn W. EnquistEditor in Chief, Journal of Virology     

Deletion of 24 amino acids from the pro-alpha 1(I) chain of type I procollagen in a patient with the Ehlers-Danlos syndrome type VII

A child with the type VII form of the Ehlers-Danlos syndrome was shown to have a structural defect in the amino terminus of the pro-alpha 1(I) chain of type I procollagen. Normal and mutant amino-terminal cyanogen bromide peptides (pN-alpha 1(I) CB0,1 peptides) were purified from the medium of the patient's cultured fibroblasts. Amino acid sequencing of tryptic peptides derived from the mutant pN-alpha 1(I) CB0,1 peptide showed that an expected sequence of 24 amino acids (positions 136-159 of the normal pN-alpha 1(I) CB0,1 peptide) was deleted. The segment deleted from the mutant pro-alpha 1(I) chain contains the small globular region of the NH2-propeptide, the procollagen N-proteinase cleavage site, the NH2-telopeptide, and first triplet of the helix of the alpha I(I) collagen chain (Chu, M.-L., de Wet, W., Bernard, M., Ding, J.F., Morabito, M., Myers, J., Williams, C., and Ramirez, F. (1984) Nature 310, 337-340). Loss of the procollagen N-proteinase cleavage site from the mutant pro-alpha 1(I) chain accounted for the persistence of its NH2-propeptide despite normal production of the N-proteinase by cultured mutant fibroblasts. Collagen production by mutant fibroblasts was doubled possibly due to reduced feedback inhibition by the NH2-propeptides. The child appeared to be heterozygous for the peptide deletion and, as the parents did not show any evidence of the deletion, it is likely that the child had a new mutation of one allele of the pro-alpha 1(I) gene. The deleted peptide corresponds precisely to the sequence coded by exon 46 of the normal pro-alpha 1(I) gene (Chu, M.-L., de Wet, W., Bernard, M., Ding, J.F., Morabito, M., Myers, J., Williams, C., and Ramirez, F. (1984) Nature 310, 337-340).     

Site-directed mutation of the highly conserved region near the Q-loop of the cytochrome bd quinol oxidase from Escherichia coli specifically perturbs heme b595.

Cytochrome bd is one of the two quinol oxidases in the respiratory chain of Escherichia coli. The enzyme contains three heme prosthetic groups. The dioxygen binding site is heme d, which is thought to be part of the heme-heme binuclear center along with heme b(595), which is a high-spin heme whose function is not known. Protein sequence alignments [Osborne, J. P., and Gennis, R. B. (1999) Biochim. Biophys Acta 1410, 32--50] of cytochrome bd quinol oxidase sequences from different microorganisms have revealed a highly conserved sequence (GWXXXEXGRQPW; bold letters indicate strictly conserved residues) predicted to be on the periplasmic side of the membrane between transmembrane helices 8 and 9 in subunit I. The functional importance of this region is investigated in the current work by site-directed mutagenesis. Several mutations in this region (W441A, E445A/Q, R448A, Q449A, and W451A) resulted in a catalytically inactive enzyme with abnormal UV--vis spectra. E445A was selected for detailed analysis because of the absence of the absorption bands from heme b(595). Detailed spectroscopic and chemical analyses, indeed, show that one of the three heme prosthetic groups in the enzyme, heme b(595), is specifically perturbed and mostly missing from this mutant. Surprisingly, heme d, while known to interact with heme b(595), appears relatively unperturbed, whereas the low-spin heme b(558) shows some modification. This is the first report of a mutation that specifically affects the binding site of heme b(595).     

The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors

Understanding the mechanisms controlling cancer cell invasion and metastasis constitutes a fundamental step in setting new strategies for diagnosis, prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of a novel class of serine-threonine protein kinases. Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration. Previous studies have made opposite conclusions as to the role of LIMK1 in tumor cell motility and metastasis, claiming either an increase or decrease in cell motility and metastasis as a result of LIMK1 over expression (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis. 2000. J. Cell Biol. 151:1119-1128; Davila, M., A.R. Frost, W.E. Grizzle, and R. Chakrabarti. 2003. J. Biol. Chem. 278:36868-36875; Yoshioka, K., V. Foletta, O. Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:7247-7252; Nishita, M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell Biol. 171:349-359). We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway. LIMK1-mediated decreases or increases in the activity of the cofilin pathway are shown to cause proportional decreases or increases in motility, intravasation, and metastasis of tumor cells.     

Reducing the number of microlocations in oligonucleotide microchip matrices by the application of degenerate oligonucleotides

The application of degenerate oligonucleotides to DNA Sequencing by Hybridisation with Oligonucleotide Matrix (SHOM) is proposed. The use of degenerate oligonucleotides is regarded as an example of pooling methods that are suitable for various laboratory procedures requiring numerous samples to be assayed. As each DNA sequence coded by four letters (A, G, C, T) may be defined by two sequences: a sequence coded by W and S (W-weak-A or T, S-strong-G or C) and a sequence coded by R and Y (R-purine-A or G, Y-pirymidine-T or C), n4n -nucleotide sequences may be defined with the help of 2xn2sequences. In the place of the originally described microchip matrix composed of all possible unambiguous octanucleotides (4(8)=65 536) attached to the equal number of 65 536 microlocations a matrix composed of 512 microlocations containing 256 2(8)-degenerate octanucleotides is proposed. The matrix contains all 256 possible octanucleotides coded by W and S variations and all 256 possible octanucleotides coded by R and Y variations. The 512 256-degenerate octanucleotides allows to retrieve the same information as 65 536 unambiguous octanucleotides. A variant of the DNA sequence reconstruction method applicable to this system is presented. The use of degenerate oligonucleotides also gives the possibility to apply matrices composed of longer oligonucleotides without increasing the number of microlocations in matrices, which would enable increasing the length of unambiguously reconstructed sequence, e.g. a matrix comprising 131 072 16-mer oligonucleotides i.e. 65 536 65 536-fold degenerate oligonucleotide coded by W and S variations and 65 536 65 536-fold degenerate oligonucleotide coded by R and Y variations could replace one matrix comprising all possible unambiguous 16-mer oligonucleotides (ca. 4.3x10(9)).     

The use of multiple alphabets in kappa-gene immunoglobulin DNA sequence comparisons.

Comparisons within and between the human, mouse and rabbit immunoglobulin-kappa gene (J-C region) DNA sequences are carried out in terms of three two-letter nucleotide alphabets: (i) S-W alphabet (W = A or T; S = G or C); (ii) P-Q alphabet which distinguishes purines (P = A or G) from pyrimidines (Q = C or T); and (iii) a 'control' E-F alphabet (E = A or C; F = G or T). All statistically significant direct repeats within each of the three sequences and all significant block identities (a set of consecutive matching letters) shared by two or more sequences are determined for each alphabet. By contrast to the S-W and E-F alphabets, the P-Q alphabet comparisons reveal an abundance of statistically significant block identities not seen at the nucleotide level. Various interpretations of these P-Q structures with respect to control and functional roles are considered.     

Transformation of DNA sequence data into geometric symbols

Comparative analysis of related DNA sequences has been simplified by the transformation of data in the standard A, G, C, T format into a set of geometric symbols that promote pattern recognition. Previously, comparing more than 2 or 3 sequences simultaneously has been difficult because of the monotonous patterns established by letters. Here 33 sequences are simultaneously compared to demonstrate the ease with which nucleotide substitutions are accurately identified. This has been accomplished by writing a Word-Perfect macro program to facilitate this transformation. Since this word processing program is widely used, performing this kind of analysis is readily achievable in most laboratories involved in DNA sequence analysis.     

Book Reviews

Book reviewed in this article: Social Anthropology . By Godfrey Lienhardt Rethinking Anthropology . By E. R. Leach Societies: Evolutionary and Comparative Perspectives . By Talcott Parsons Kinship and Family Organization . Bernard Farber The Impact of Urbanization in By G. Breese . Societies Series. Cliffs, N.J., 1965. Paperbound, no price stated. Industry. By W. E. Moore; Newly Developing Countries The Hunters . By Elman R. Service The New Guinea Villager . By C. D. Rowley. F. W. Cheshire Behind the Ranges : Patrolling in New Guinea. By J. P. Sinclair Australian Aboriginal Portraits . By Charles P. Mountford Animal Species and Their Evolution . By A. J. Cain The Concise Encyclopadia of Archaeology . Edited by Leonard Cottrell Archaeology: An Introduction . By Clement W. Meighan Marine Archaeology . Edited by Joan du Plat Taylor The Land of Shinar . By Leonard Cottrell Ancient Europe : A Survey. By Stuart Piggott The North Britons : the Prehistory of a Border People. By Richard Feachem The Hardin Village Site . By Lee H. Hanson Pattern and Process in the Early Intermediate Pottery of the Central Coast of Peru . By Thomas C. Patterson     

Physical dimensions influence the functional property of the semicircular canal

The functional dependence of the semicircular canal upon its physical dimensions was evaluated by measuring the internal radius (r), the radius of curvature (R) and the cupula radius (rC) of the posterior canal in 10 freshly dissected frog labyrinths. These values have been compared to the same parameters of the cat labyrinth. The coefficients I, B, K in the Steinhausen equation were determined for both animals. The A ratio between cupula deflection and endolymph displacement was also calculated by utilizing the Bernard equation. The A ratio is three times larger in the frog than in the cat. It follows that if the same acceleration produces similar endolymph displacements in the posterior canal of both animals, the cupula deflection will be larger in the frog. The solution of the Steinhausen equation in the presence of a constant acceleration, however, reveals that the same stimulus intensity will result in a larger endolymph displacement in the cat posterior canal; similarly, the endolymph displacement directly depends on the duration of the stimulating period in both animals. Contrary to the Bernard assumption, these effects generate a G ratio (psi frog/psi cat) which is less than the Q ratio (A frog/A cat). Moreover, G decreases on increasing the duration of the stimulating period. For stimuli of short duration the semicircular canal of a small animal is expected to exhibit a higher sensitivity than that of a larger one. However, the definitive primary afferent discharge will be largely controlled by the receptor/generator potential properties.     

Molecular cloning and characterization of avian N-methyl-d-aspartate receptor type1 (NMDA-R1) gene

Birds have several advantages in the study of memory formation, as imprinting and passive avoidance behaviors in chick are often used as model systems. However, the primary structure of the bird N-methyl-d-aspartate (NMDA) responsive glutamate receptor, which is assumed to play a critical role in memory formation, has not been determined. In this report we describe the cDNA cloning of a subunit of NMDA receptors (NMDA-R1) from duck and analysis of its structure and distribution in the brain. The N-terminal 898 amino acids of the NMDA-R1 were well conserved between duck and mammals, but the homology was completely lost in the C-terminus. In situ hybridization showed that the duck NMDA-R1 gene was expressed throughout the brain as it is in mammals.Special issue dedicated to Dr. Bernard W. Agranoff.     

Components of Attention in Grapheme-Color Synesthesia: A Modeling Approach

Grapheme-color synesthesia is a condition where the perception of graphemes consistently and automatically evokes an experience of non-physical color. Many have studied how synesthesia affects the processing of achromatic graphemes, but less is known about the synesthetic processing of physically colored graphemes. Here, we investigated how the visual processing of colored letters is affected by the congruence or incongruence of synesthetic grapheme-color associations. We briefly presented graphemes (10–150 ms) to 9 grapheme-color synesthetes and to 9 control observers. Their task was to report as many letters (targets) as possible, while ignoring digit (distractors). Graphemes were either congruently or incongruently colored with the synesthetes’ reported grapheme-color association. A mathematical model, based on Bundesen’s (1990) Theory of Visual Attention (TVA), was fitted to each observer’s data, allowing us to estimate discrete components of visual attention. The models suggested that the synesthetes processed congruent letters faster than incongruent ones, and that they were able to retain more congruent letters in visual short-term memory, while the control group’s model parameters were not significantly affected by congruence. The increase in processing speed, when synesthetes process congruent letters, suggests that synesthesia affects the processing of letters at a perceptual level. To account for the benefit in processing speed, we propose that synesthetic associations become integrated into the categories of graphemes, and that letter colors are considered as evidence for making certain perceptual categorizations in the visual system. We also propose that enhanced visual short-term memory capacity for congruently colored graphemes can be explained by the synesthetes’ expertise regarding their specific grapheme-color associations.     

Letter constraints within words in printed English

Summary Due to the manner in which the English language is used, words exhibit strong internal constraints on letters, but some additional constraint may be imposed by the context in which words appear. In order to estimate the internal constraints of words and the overall effect of context, an experiment was carried out using 225 human subjects who predicted letters in each of the first four positions within words, both with and without context prior to the words. It was found that as more letters at the beginning of words are given, prediction of the following letters increases monotonically, but the increase is not smooth. Prediction of the third letter of words given the first two letters is only a little better than prediction of the second letter given only the first. This effect may be explained by the probable combinations of vowels and consonants at the beginning of words. Letters in the first two positions show no improvement due to long context but prediction of later letters is increased by such context so that prediction rises smoothly from the initial letter to the fourth letter. Also, the type of word in which the letters are to be predicted affects the prediction, function words showing more constraint on letters than content words. The difference between function and content words does not take effect, however, until the first two letters of the word are given. Using the prediction data from words preceded by long context, extrapolations of constraint out to the tenth letter were obtained. From the values of constraint at the first ten letter positions it was possible to estimate the maximum unilateral sequential constraint in English. A value of about 48% was obtained which compares with previous estimates of 50%. A further evaluation of the overall effect of context indicates that about 81% of the constraint in English is contained within the words themselves, and the other 19% is due to any additional context.This paper is based on a dissertation submitted to the Department of Psychology, The Johns Hopkins University, in partial fulfillment of the requirements for the Ph. D. degree. The research was done under Contract Nonr-248(55) between the Office of Naval Research and The Johns Hopkins University. This is Report No. 13 under that contract. Reproduction in whole or in part is permitted for any purpose of the United States Government.During the period of this investigation the author was a National Institutes of Health Fellow. The author wishes to thank Wendell R. Garner for his encouragement and advice.     

Maintenance of membrane sheets by cultured oligodendrocytes requires continuous microtubule turnover and Golgi transport

Oligodendrocytes in murine shakeoff cultures elaborate extensive membrane sheets containing networks of microtubules. Several membrane components, including proteolipid protein (PLP) and sulfatide, are transported through the Golgi en route to the plasma membrane or myelin (1,2). This transport is essential for membrane assembly, but its role in continuing maintenance of the sheets is not known. We examined the stability of the membrane sheets following microtubule stabilization with taxol or block of transport into the Golgi with brefeldin A. Within one to three hours, both agents had marked effects on the membrane sheets. While some oligodendrocytes maintained regions of normal membrane sheets, many showed retraction of the sheets, with the majority now exhibiting multiple processes rather than sheets. The distribution of sulfatide, PLP and tubulin in cell bodies, processes and sheets was altered in treated cells, as analyzed by immunocytochemical staining with antibodies to these components. The Golgi apparatus also showed reorganization in the presence of taxol, as visualized by binding of wheat germ agglutinin, a lectin with high affinity for distal Golgi vesicles. All of these effects were reversible when the agents were removed after 3 hours. Thus, maintenance of membrane sheets by oligodendrocytes in culture is a dynamic process, requiring ongoing microtubule turnover and transport of molecules through the Golgi.Abbreviations PLP proteolipid protein - WGA wheat germ agglutinin Special issue dedicated to Dr. Bernard W. Agranoff.     

Book reviews

Book reviewed in this article: E. Müller -Kögler . Pilzkrankheiten bei Insekten. B. P. Uvarov : Grasshoppers and Locusts M. V. Brian : Social Insect Populations Bernard Smit : Insects in Southern Africa: How to Control Them. W. R. Thompson & F. J. Simmonds     

Referral letters and replies from orthopaedic departments: opportunities missed.

OBJECTIVE--To study delays between sending referral letters and the outpatient appointment and to assess the content of referral and reply letters, their educational value, and the extent to which questions asked are answered by reply letters. DESIGN--Retrospective review of referrals to 16 consultant orthopaedic surgeons at five hospitals, comprising 288 referral letters with corresponding replies, by scoring contents of letters. SETTING--Orthopaedic teaching hospitals in Nottingham, Derby, and Mansfield. MAIN OUTCOME MEASURES--Weighted scores of contents of referral and reply letters, assessment of their educational value, and responses to questions in referral letters. RESULTS--Median outpatient delay was 23.4 weeks. There was no significant decrease in waiting time if the referral letter was marked "urgent" but a significantly greater delay (p less than 0.01) if referrals were directed to an unnamed consultant. The content score was generally unsatisfactory for both referrals and replies, and there was no correlation for the content scores of the referral letter and its reply (r = 0.13). Items of education were rare in the referral letters (8/288; 3%) and significantly more common in replies (75/288; 26%) (p much less than 0.001). Senior registrars were significantly more likely to attempt education than other writers (p less than 0.02). Education in replies was significantly related to increased length of the letter (p less than 0.05) and was more likely to occur if the referral was addressed to a named consultant (p less than 0.03). 48 (17%) Referral letters asked questions, of which 21 (44%) received a reply. No factor was found to influence the asking of or replying to questions. CONCLUSIONS--The potential for useful communication in the referral letter and in the reply from orthopaedic surgeons is being missed at a number of levels. The content is often poor, the level of mutual education is low, and the use of the referral letter to determine urgency is deficient. Most questions asked by general practitioners are not answered.     

Als ‘A’ niet meer als ‘a’ wordt herkend. Een analyse van verworven woordblindheid

A right-handed patient, aged 72, manifested alexia without agraphia, a right homonymous hemianopia and an impaired ability to identify visually presented objects. He was completely unable to read words aloud and severely deficient in naming visually presented letters. He responded to orthographic familiarity in the lexical decision tasks of the Psycholinguistic Assessments of Language Processing in Aphasia (PALPA) rather than to the lexicality of the letter strings. He was impaired at deciding whether two letters of different case (e.g., A, a) are the same, though he could detect real letters from made-up ones or from their mirror image. Consequently, his core deficit in reading was posited at the level of the abstract letter identifiers. When asked to trace a letter with his right index finger, kinesthetic facilitation enabled him to read letters and words aloud. Though he could use intact motor representations of letters in order to facilitate recognition and reading, the slow, sequential and error-prone process of reading letter by letter made him abandon further training.     

Visual Acuity and the Crowding Effect in 8- to 17-Year-Old Schoolchildren

Visual acuity (VA) in 292 schoolchildren aged 8–17 years was measured using Landolt Cs, E letters, and rectangular gratings. With the forced choice procedure, the VA measured with Landolt Cs was 1.4 times higher than with other targets, suggesting analysis of the whole image rather than its gaps by the visual system. In addition, the effect of surrounding images on VA estimates was studied with Landolt Cs, E letters, and gratings surrounded by bars, E letters, and gratings, respectively. A crowding effect, i.e., a worse perception of test objects surrounded by other images, was revealed. However, the perception of Landolt Cs, E letters, and gratings showed age-dependent differences. The separation between the stimulus and surrounding images at which the perception of gratings and other images worsened decreased with age increasing up to 16–17 and 12 years, respectively. The age-related differences were explained by the immaturity of selective-attention mechanisms.     

Eye Exercises Enhance Accuracy and Letter Recognition,but Not Reaction Time,in a Modified Rapid Serial Visual Presentation Task

Eye exercises have been prescribed to resolve a multitude of eye-related problems. However, studies on the efficacy of eye exercises are lacking, mainly due to the absence of simple assessment tools in the clinic. Because similar regions of the brain are responsible for eye movements and visual attention, we used a modified rapid serial visual presentation (RSVP) to assess any measurable effect of short-term eye exercise in improvements within these domains. In the present study, twenty subjects were equally divided into control and experimental groups, each of which performed a pre-training RSVP assessment where target letters, to which subjects were asked to respond to by pressing a spacebar, were serially and rapidly presented. Response time to target letters, accuracy of correctly responding to target letters, and correct identification of target letters in each of 12 sessions was measured. The experimental group then performed active eye exercises, while the control group performed a task that minimized eye movements for 18.5 minutes. A final post-training RSVP assessment was performed by both groups and response time, accuracy, and letter identification were compared between and within subject groups both pre- and post-training. Subjects who performed eye exercises were more accurate in responding to target letters separated by one distractor and in letter identification in the post-training RSVP assessment, while latency of responses were unchanged between and within groups. This suggests that eye exercises may prove useful in enhancing cognitive performance on tasks related to attention and memory over a very brief course of training, and RSVP may be a useful measure of this efficacy. Further research is needed on eye exercises to determine whether they are an effective treatment for patients with cognitive and eye-related disorders.