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Chiral poly(ureidophthalimide) foldamers in water.

Poly(ureidophthalimide)s decorated with hydrophilic side chains, that ensure solubility in aqueous media, have been synthesized and characterized by UV/Vis and circular dichroism (CD) spectroscopy. Temperature and concentration dependent CD measurements in water have revealed an almost temperature and concentration independent Cotton effect, indicative for a strong intramolecular organization. Similar studies in THF demonstrate the dynamic nature of the secondary architecture, a characteristic of foldamers. In addition, the bisignated Cotton effect in water is opposite in sign to that in THF, suggestive for a solvent-dependent preference for one helical handedness. Mixing experiments prove the dominance of water in determining the handedness of the helical architecture. The solvent allows for control over the helical architecture and thus governs the supramolecular synthesis.

Circular Dichroism↗

Protein substrates for cGMP-dependent protein phosphorylation in cilia of wild type and atalanta mutants of Paramecium.

In the ciliated protozoan Paramecium, swimming direction is regulated by voltage-gated Ca2+ channels in the ciliary membrane. In response to depolarizing stimuli, intraciliary Ca2+ rises, triggering reversal of the ciliary power stroke and backward swimming. One class of Ca(2+)-unresponsive behavioral mutants of Paramecium, atalanta mutants, cannot swim backward even though they have functional Ca2+ channels in their ciliary membrane. Several atalanta mutants were characterized with regard to several Ca(2+)-dependent activities, but no significant difference between wild type and the mutants was detected. However, one allelic group, atalanta A (initially characterized by Hinrichsen and Kung [1984: Genet. Res. Camb. 43:11-20]), showed a helical swimming path of opposite handedness from that of wild-type cells when detergent-permeabilized cells ("models") were reactivated with MgATP. When cGMP-dependent protein kinase purified from wild-type cells was added to atalanta A models, the handedness of the swimming path was reversed. Cyclic GMP stimulated in vitro phosphorylation of several proteins in isolated cilia, and the pattern of phosphoproteins was very similar for wild type and atalanta mutants, with one exception: a protein of 59 kDa was phosphorylated much less in the mutant ata A. When ciliary proteins were separated by gel electrophoresis and then phosphorylated "on blot" by purified cGMP-dependent protein kinase, phosphoprotein patterns were similar in wild type and ata mutants except that a 48 kDa protein (p48) from ata A3 was more heavily phosphorylated. This difference in p48 phosphorylation was also observed with cGMP-dependent protein kinase purified from ata A3 mutant cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

fMRI study of language lateralization in children and adults.

Language lateralization in the brain is dependent on family history of handedness, personal handedness, pathology, and other factors. The influence of age on language lateralization is not completely understood. Increasing left lateralization of language with age has been observed in children, while the reverse has been noted in healthy young adults. It is not known whether the trend of decreasing language lateralization with age continues in the late decades of life and at what age the inflection in language lateralization trend as a function of age occurs. In this study, we examined the effect of age on language lateralization in 170 healthy right-handed children and adults ages 5-67 using functional MRI (fMRI) and a verb generation task. Our findings indicate that language lateralization to the dominant hemisphere increases between the ages 5 and 20 years, plateaus between 20 and 25 years, and slowly decreases between 25 and 70 years.

Adolescent↗

An analysis of side chain interactions and pair correlations within antiparallel beta-sheets: the differences between backbone hydrogen-bonded and non-hydrogen-bonded residue pairs.

Cross-strand pair correlations are calculated for residue pairs in anti-parallel beta-sheet for two cases: pairs whose backbone atoms are hydrogen bonded together (H-bonded site) and pairs which are not (non-H-bonded site). The statistics show that this distinction is important. When glycine is located on the edge of a sheet, it shows a 3:1 preference for the H-bonded site. The strongest observed correlations are for pairs of disulfide-bonded cystines, many of which adopt a close-packed conformation with each cystine in a spiral conformation of opposite chirality to its partner. It is likely that these pairs are a signature for the family of small, cystine-rich proteins. Most other strong positive and negative correlations involve charged and polar residues. It appears that electrostatic compatibility is the strongest factor affecting pair correlation. Significant correlations are observed for beta- and gamma-branched residues in the non-H-bonded site. An examination of the structures shows a directionality in side chain packing. There is a correlation between (1) the directionality in the packing interactions of non-H-bonded beta- and gamma-branched residue pairs, (2) the handedness of the observed enantiomers of chiral beta-branched side chains, and (3) the handedness of the twist of beta-sheet. These findings have implications for the formation of beta-sheets during protein folding and the mechanism by which the sheet becomes twisted.

Amino Acids↗

Lateralized agonistic responses and hindlimb use in toads.

The recent discovery of forepaw preferences (handedness) in toad species has provided some insight into the evolution of brain lateralization. We tested the prediction that, as in higher vertebrates, visual lateralization and other motor preferences (footedness) also exists in toad species. During feeding periods, South American cane toads, Bufo marinus, showed a population bias to strike with the tongue at other toads occupying their left visual field. This is the first demonstration of lateralized visual behaviour in an amphibian species. Tongue striking at an individual's eyes or head may sometimes delay its approach to prey already seen by the attacker, or may dislodge prey from its mouth. In addition, we report hindlimb preferences (footedness) for contact righting in three species of toad (B. marinus, the European green toad, B. viridis, and the European common toad, B. bufo). After being fully overturned on to their back on a horizontal surface, toads initiated and completed righting using the hindlimbs and with only perfunctory use of the forepaws. Together, the findings of visual lateralization and footedness demonstrate that in toads, as in higher vertebrates, behavioural lateralization is not restricted to handedness. The hypothesis that lateralized brain functions in birds and mammals might have arisen from a common lateralized ancestor is therefore supported. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Assessing the legacy of the GBG model.

A critique of the article by Bryden, McManus, and Bulman-Fleming ("Evaluating the empirical support for the Geschwind-Behan-Galaburda model of cerebral lateralization") is presented. Bryden et al. expose some of the principal weaknesses of the cerebral lateralization model put forth by Geschwind and colleagues and contribute an important meta-analysis of findings concerning the model's predicted relationship between immune disorders and handedness. Nonetheless, the theory put forth by Geschwind and colleagues retains an important legacy despite a multitude of faulty assumptions and predictive failures. Also offered is a brief synopsis of a new model that explains the many positive relationships found among various neurodevelopmental disorders and medical conditions, as well as why abnormal handedness distributions occur in some but not other neurodevelopmental disorders.

Child↗

Environmental influences in hand preference: an African point of view.

In order to examine further the role of cultural and environmental factors in human manual preference, two surveys were undertaken in students from Ivory Coast and Sudan. In the first study (Abidjan, Ivory Coast) 382 secondary students, ages 12 to 22, answered a 20-item manual preference questionnaire. The observed frequency of left-hand preference was 7.9%, with very low left-hand use among the 18-22 age group (1%) and high among the 12-15 age group (14%). In the second study (Khartoum, Sudan) 759 undergraduates, ages 18 to 33, answered a 25-item questionnaire. The observed frequency of left manual preference was 5%. Subjects were also asked to indicate any pressure to change hand for writing, eating, or other manual activities and, in the second study, any upper limb injury which temporarily rendered the subject unable to use his (her) preferred hand. Report of an upper limb injury in the past was related to mixed (or inconsistent) hand preference. In both studies, the target activity against left-hand use was eating. These results show that cultural and environmental factors could change "natural" hand preference in three ways: (i) by changing the hand used for only one activity (e.g., eating), with no change for other familiar unimanual activities; (ii) by reducing the degree of hand preference; (iii) by changing the overall preferred hand, generally reducing the prevalence of left-handedness. The design of handedness studies should allow these possibilities to be distinguished.

Adolescent↗

A performance measure of the degree of hand preference.

The present paper describes a performance method for determining hand preference. The task requires participants to reach into different regions of hemispace to perform various actions (point, pick up, toss, sweep, and position) with a dowel located at each position. In accordance with the participants' hand preference as measured by the Waterloo Handedness Questionnaire, the preferred hand was used more frequently on the various performance tasks. The distribution of hand use in working space indicates that preferred hand use was almost exclusive for actions carried out in ipsilateral hemispace, while it is used only moderately for actions in contralateral hemispace, revealing that this hand is used throughout a wider range of extrapersonal space than the nonpreferred hand. These trends were observed across all of the performance tasks, suggesting that task complexity did not affect the frequency of preferred hand use either overall or, more specifically, in right hemispace, as was predicted. This finding is inconsistent with empirical work on questionnaires indicating that verbal reports of preferred hand use increase for more complex tasks (e.g., Steenhuis & Bryden, 1988). As well, performance on the preferential reaching task correlated significantly with hand preference as measured on the Waterloo Handedness Questionnaire (Bryden, 1977), unlike the other performance measure examined, indicating that the preferential reaching task is sensitive to differences in the degree of hand preference.

Adult↗

MRI asymmetries of Broca's area: the pars triangularis and pars opercularis.

Broca's area, which includes the pars triangularis (PTR) and pars opercularis (POP), is a neuroanatomic region important in speech-language production. Previous data demonstrated that PTR asymmetries are highly correlated with language dominance determined by selective hemispheric anesthesia or Wada testing, suggesting that asymmetries of the PTR may, in part, predict language dominance. The POP, however, has not been measured on volumetric magnetic resonance imaging (MRI), and therefore, it is unclear whether morphological asymmetries of the POP exist, and whether these asymmetries differ in right- and left-handers. The purpose of this study was to determine if measurable asymmetries of the POP exist on MRI, and whether the direction of the asymmetries differ in right- and left-handers. The PTR and POP were measured on volumetric MRI scans of 16 right-handers and 16 left-handers matched for age and gender. There was a significant leftward asymmetry of the PTR in right- and left-handers, although the asymmetry was reduced in the left-handers. In contrast, there was a leftward asymmetry of the POP in right-handers, and a rightward asymmetry in the left-handers. Handedness, derived from a handedness inventory, was positively correlated with POP asymmetry.

Adult↗

Stories about hands, brains, and minds.

The "extreme" versus "mild" classification of handedness of Natsopoulos et al. (1998) is not comparable to that of Annett (review, 1995) because 50% of the former sample were left-handers while the samples of the latter were unselected for handedness. The 20% of the Natsopoulos sample called "extreme" right-handers represent nearly 40% of the general population. The possibility cannot be ruled out that the advantage for right-handers in this sample was due to a small excess of disabled children among left-handers because there were no controls for hand skill or for reading ability.

Brain↗

Methylation of the Z-DNA decamer d(GC)5 potentiates the formation of A-DNA: crystal structure of d(Gm5CGm5CGCGCGC).

It is well known that methylation of alternating Py x Pu sequences potentiates the formation of Z-DNA. However, we have now observed that methylation of the alternating Z-DNA oligomer d(GCGCGCGCGC), which starts with a 5'-purine, unexpectedly stabilizes the A-DNA conformation. The double methyl derivative d(Gm5CGm5CGCGCGC), which crystallizes as duplex A-DNA in the hexagonal space group P6(1)22, a = b = 39.33 A and c = 77.93 A with one strand per asymmetric unit and six duplexes in the unit cell, refined to an R factor of 19.1 for 204 DNA atoms and 43 solvent molecules. This is the first report of a DNA sequence crystallized in both right and left-handed conformations, allowing structural comparisons not previously possible and, more importantly, this is the first time that methylation has been shown to potentiate the formation of A-DNA from a sequence known to crystallize as Z-DNA. From this study, ten base-pairs appear to be the critical length in determining the handedness of d(GC)n-type sequences in the crystalline state. Because methylation of nuclear DNA is linked to a number of cellular processes, including transcriptional inactivation, this study has important implications for the role of A-DNA in methylated regions of genomic DNA and, thus, in the regulation of gene expression. In this context, the structure of d(Gm5Cm5CGCGCGC) will be compared with that of the alternating A-DNA decamer d(GCACGCGTGC) and the alternating Z-DNA decamer d(GCGCGCGCGC) and discussed in terms of the forces that govern the handedness of duplex DNA oligomers.

Base Composition↗

Localization of language-related cortex with 15O-labeled water PET in patients with gliomas.

Measurement of relative cerebral blood flow (CBF) with 15O-labeled water PET has been widely used for brain mapping experiments on language functions in normal volunteers and patients with epilepsy. We focused on the question of whether PET during speech activation is an appropriate method for noninvasive determination of language-related cortex in patients with brain tumors. Furthermore, the suitability of the method for determination of hemispheric language dominance was examined and compared to the results of the Edinburgh Handedness Inventory. Ten right-handed and six left-handed patients with gliomas were examined prior to surgery while repeatedly performing word repetition and verb generation tasks. A set of volumes of interest (VOIs) was drawn on coregistered MRI in order to account for anatomic variability as well as anatomical alterations due to tumor mass effect. Repetition of nouns did not produce significant hemispheric differences. During stimulation by verb generation, reliable lateralized activations of Broca's area and supplementary motor area were detected in all right-handed patients. Of the left-handed patients, two showed clear right lateralization, two activated Broca's area bilaterally, and two had a pattern similar to that of right-handers. Patients with bilateral activations showed the strongest tendency toward bihandedness according to the handedness inventory. Lateralization of supplementary motor area in left-handers corresponded to lateralized activity in Broca's area. Tumors in the vicinity of language-related regions did not alter activation responses. In conclusion, measurement of CBF changes during verb generation permits identification of language-related areas in patients with gliomas with strong lateralization related to hemispheric dominance. These findings may be of particular clinical interest for left-handed patients.

Adult↗

Functional anatomy of dominance for speech comprehension in left handers vs right handers.

In order to study the functional anatomy of hemispheric dominance for language comprehension we compared the patterns of activations and deactivations with PET and H(2)15O during a story-listening task in two groups of normal volunteers selected on the basis of their handedness. The reference task was a silent rest. The results showed asymmetrical temporal activations favoring the left hemisphere in right handers (RH) together with Broca's area and medial frontal activations. A rightward lateralization of deactivations located in the parietal and inferior temporal gyrus was also observed. In left handers (LH) the temporal activations were more symmetrical as were the parietal and inferior frontal deactivations. Broca's area and medial frontal gyrus activations were present in LH. The direct comparison of RH and LH activations revealed larger activations in the left superior temporal, in particular in the left planum temporale and temporal pole of RH, while LH activated an additional right middle temporal region. Individual analysis of LH differences images superimposed on individual MRI planes demonstrated an important variability of functional dominance, with two LH leftward lateralized, two symmetrical, and one showing a rightward lateralization of temporal activations. There was no relationship between functional dominance and handedness scores. These results are in accordance with data from aphasiology that suggest a greater participation of the right hemisphere in language processing in LH. In addition, the presence of bilateral deactivations of the dorsal route could support the assumption that LH ambilaterality concerns, in addition to language, other cognitive functions such as visuospatial processing.

Attention↗

Hemispheric asymmetry of transcallosal inhibition in man.

The transcallosal connecting fibres linking corresponding projection areas of the same muscles of the right and left primary motor cortex may play an important role in control of unilateral movements. It appears that they have mainly inhibitory effects. This was further evaluated by transcranial magnetic stimulation using two focal coils placed on the optimal positions, i.e. the positions with the lowest thresholds at the motor representation areas of the first dorsal interosseous muscle of the left and right sides. A conditioning stimulus was given to one hemisphere 10 ms prior to the test stimulus at the opposite hemisphere. The inhibition was evaluated as relative amplitude reduction. Eleven normal right-handed subjects and 11 normal left-handed subjects participated in this study. Handedness was evaluated by the Oldfield inventory. It was found that in right-handers the inhibition after stimulation of the "dominant" left hemisphere was more marked than after stimulation of the "non-dominant" right hemisphere. In contrast, the group of left-handed subjects showed inhomogeneous findings with either right- or left-side predominant inhibition. It is concluded that not handedness but hemispheric dominance contributes to the laterality of inhibition. The results point to a superior role of the language-dominant hemisphere in governing inter-hemispheric control of motor cortical connections, supporting the view that the "language-dominant" hemisphere is also "motor dominant".

Adult↗

Cerebral potentials during smooth goal-directed hand movements in right-handed and left-handed subjects.

During smooth goal-directed hand movements a negative potential shift can be recorded from the human scalp. This goal-directed movement potential (GDMP) is preponderant over central areas with a maximum at the vertex and, over the motor cortex, contralaterally larger than ipsilaterally to the moving hand. In 11 right-handed and 6 left-handed subjects, the morphology and distribution of these potential shifts were studied in relation to task differences, moving hand and handedness. The results show a functional differentiation of two components of the GDMP: (1), a lateralized, slow negative wave, restricted to the precentral area and selectively varying with the hand used, and (2), a widespread, bilateral symmetrical component, selectively influenced by task-specific and individual factors. Two effects reflect an influence of the subject's handedness on the GDMP: (A) averaged for both hand conditions, there are larger amplitudes over the hemisphere contralateral to the dominant hand, and (b), averaged for both hemispheres, larger amplitudes result from using the non-dominant hand.

Adolescent↗

On the origin of biological chirality via natural beta-decay.

Experimental evidence that longitudinally polarized electrons having the handedness characteristic of terrestrial beta-decay electrons preferentially remove D-leucine from a racemic mixture, coupled with the probable presence of 14C in pre-biotic molecules, offers a plausible hypothesis for the origin of biomolecular handedness.

Carbon Radioisotopes↗

Birth factors and laterality: effects of birth order, parental age, and birth stress on four indices of lateral preference.

As an alternative to genetic theories of handedness, some theorists have offered an environmental mechanism, associated with birth stress, for the appearance of left-handedness. They suggest that brain damage as a result of birth difficulties can lead to a switch in hand preference from the right side to the left side. Consequently, one should find more left-handers in groups where the probability of the occurrence of birth stress is greater. Three studies are presented which explore the laterality of not only hand but also foot, eye, and ear, in a total of 5161 individuals, in an attempt to assess any relationship to birth stress. Maternal age seems to predict deviations from dextrality, dependent on the sex of the offspring, while paternal age and birth order do not. The use of a direct measure of conditions predisposing toward birth stress suggests that these results depend on prenatal or perinatal environmental trauma rather than chromosomal factors.

Adolescent↗

Maternal influences on infant hand-use during play with toys.

Infant hand-use preferences are related to mother's, but not father's, handedness. Since infants match mother's hand-use during toy play, maternal handedness can affect infant hand-use. Twenty-eight mother-infant pairs (14 left-handed and 14 right-handed infants but all right-handed mothers) were videotaped while playing with six toys on the infant's 7-, 9-, and 11-month birthdays. Play was analyzed for five kinds of hand-use biasing situations, but maternal hand-use was the dominant influence. Infant matching of maternal hand-use increased with age and right-handed infants and female infants matched maternal hand-use more frequently. Concordance of hand-use preference between mother and infant seemed to account for both the matching and the stronger preferences of the right-handed compared to the left-handed infants.

Female↗