Psychomotor retardation is linked to frontal alpha asymmetry in major depression

BACKGROUND Psychomotor disturbances are a main clinical feature of major depressive disorder (MDD) but little is known about their EEG signature. One of the most replicated EEG findings in MDD is resting frontal asymmetry in the alpha band (FAA), which is thought to be a correlate of withdrawal behavior and reduced approach motivation. The purpose of this study was to assess psychomotor alterations, alpha band power, FAA and investigate the association between them. METHODS 20 MDD patients and 19 healthy subjects were enrolled. Alpha power and FAA scores were calculated from a resting state EEG. Wrist actigraphy was recorded from the non-dominant arm for 24 h and activity level scores (AL) were extrapolated from the wakeful periods. RESULTS MDD patients had a left-lateralized frontal alpha activity and lower AL scores when compared to healthy subjects. A significant correlation was found between mean FAA and AL scores. A negative covariance between power in the lower alpha range and AL scores over the motor cortex bilaterally was detected. LIMITATIONS Relatively small sample size. Patients were pharmacologically treated with antidepressants. CONCLUSIONS This study replicates the finding of left-lateralized FAA and lower AL scores in MDD patients, and establishes the first evidence of significant correlations between alpha power, FAA scores and measures of motor activity, which may be interpreted as an expression of impaired motivational drive in MDD.

A Vertical Asymmetry in Saccades

Visual exploration of natural scenes imposes demands that differ between the upper and the lower visual hemifield. Yet little is known about how ocular motor performance is affected by the location of visual stimuli or the direction of a behavioural response. We compared saccadic latencies between upper and lower hemifield in a variety of conditions, including short-latency prosaccades, long-latency prosaccades, antisaccades, memory-guided sac- cades and saccades with increased attentional and selection demand. All saccade types, except memory guided saccades, had shorter latencies when saccades were directed to- wards the upper field as compared to downward saccades (p<0.05). This upper field reaction time advantage probably arises in ocular motor rather than visual processing. It may originate in structures involved in motor preparation rather than execution.

Physical and Biological Controls on the Latitudinal Asymmetry of Surface Nutrients and pCO(2) in the Central and Eastern Equatorial Pacific

Surface nutrients and dissolved inorganic carbon (DIC) in the central (CEP) and eastern equatorial Pacific (EEP) show much higher concentrations to the south than to the north of the equator. In this study, the physical and biological controls on this asymmetry are investigated using a coupled physical-biogeochemical model. Two numerical experiments are conducted to examine the effects of asymmetrical photosynthetic efficiency (a) due to asymmetrical iron supply about the equator. The experiment with asymmetrical photosynthesis produces improved results as compared with historical observations. A nitrate budget analysis suggests that in the EEP the divergence of upwelling waters controls the surface nitrate asymmetry with additional contribution from the South Equatorial Current (SEC) carrying nutrient-rich Peru upwelling water. The changes of a affect the surface nitrate distribution but not the overall asymmetry. The SEC further carries excess nitrate to the west and thus extends the asymmetry in the east to the CEP. In the CEP, however, stronger northward than southward transport tends to reduce the nitrate asymmetry, while the asymmetrical photosynthesis would help to maintain it. Similar processes also control the distributions of surface silicate and DIC in the equatorial Pacific, which is also affected by the air-sea CO(2) exchange. The asymmetrical photosynthesis influences the distribution of surface DIC, pCO(2), and the air-sea CO(2) flux, by redistributing about 20% CO(2) flux from the north to the south of the equator. Owing to the adjustment of air-sea CO(2) flux, however, the net surface DIC change is smaller than the direct change associated with primary production.

Consumption asymmetry and the stock market: New evidence through a threshold adjustment model

This paper investigates whether stock market wealth affects real consumption asymmetrically through a threshold adjustment model. The empirical findings for the US show that wealth produces an asymmetric effect on real consumption, with negative 'news' affecting consumption less than positive 'news.' Thus, policy makers may want to focus more attention on preventing asset 'bubbles' than on responding to negative asset shocks.

Consumption Asymmetry and the Stock Market: Empirical Evidence

This paper examines whether U.S. stock-market wealth asymmetrically affects consumption. After identifying asymmetric behavior for consumption and stock market wealth, the results confirm that stock-market wealth asymmetrically affects real per capita consumption. Negative 'news' affects consumption more than positive 'news'.

Evaluation of a 3-Dimensional Measurement System: A Method for Assessing Facial Asymmetry

Submitted in partial fulfillment of the requirements for a Certificate in Orthodontics, Dept. of Orthodontics, University of Connecticut Health Center, 1992

Consumption Asymmetry and the Stock Market: Further Evidence

This paper investigates the presence of asymmetric effects of stock returns on real consumption in the US. After identifying the asymmetric behavior for consumption as well as the wealth effect, the results confirm that stock returns have an asymmetric effect on real consumption, with negative 'news' affecting consumption more than positive 'news'.

Genetic analysis of Pitx2 in left -right asymmetry and cardiovascular development

Pitx2, a paired-related homeobox gene that is mutated in human Rieger Syndrome, plays a key role in transferring the early asymmetric signals to individual organs. Pitx2 encodes three isoforms, Pitx2a, Pitx2b and Pitx2c. I found that Pitx2c was the Pitx2 isoform for regulating left-right asymmetry in heart, lung and the predominant isoform in guts. Previous studies suggested that the generation of left-right asymmetry within individual organs is an all or none, random event. Phenotypic analysis of various Pitx2 allelic combinations, that encode graded levels of Pitx2c, reveals an organ-intrinsic mechanism for regulating left-right asymmetric morphogenesis based on differential response to Pitx2c levels. The heart needs low Pitx2c levels, while the lungs and duodenum require higher doses of Pitx2c. In addition, the duodenal rotation is under strict control of Pitx2c activity. Left-right asymmetry development for aortic arch arteries involves complex vascular remodeling. Left-sided expression of Pitx2c in these developing vessels implied its potential function in this process. In order to determine if Pitx2c also can regulate the left-right asymmetry of the aortic arch arteries, a Pitx2c-specific loss of function mutation is generated. Although in wild type mice, the direction of the aortic arch is always oriented toward the left side, the directions of the aortic arches in the mutants were randomized, showing that Pitx2c also determined the left-right asymmetry of these vessels. I have further showed that the cardiac neural crest wasn't involved in this vascular remodeling process. In addition, all mutant embryos had Double Outlet Right Ventricle (DORV), a common congenital heart disease. This study provided insight into the mechanism of Pitx2c-mediated late stages of left-right asymmetry development and identified the roles of Pitx2c in regulation of aortic arch remodeling and heart development. ^

Ambulacral length with number of pore pairs/tubercles for both species of sea urchins and for six sampling sites to quantify fluctuating asymmetry

The surroundings of the Cortiou sewage are among the most polluted environments of the French Mediterranean Sea (Marseilles, France). So far, no studies have precisely quantified the impact of pollution on the development of organisms in this area.Methods: We used a fluctuating asymmetry (FA) measure of developmental instability (DI) to assess environmental stress in two species of radially symmetric sea urchins (Arbacia lixula and Paracentrotus lividus). For six sampling sites (Cortiou, Riou, Maire, East Maire, Mejean, and Niolon), levels of FA were calculated from continuous and discrete skeletal measures of ambulacral length, number of pore pairs and primary tubercles.Results: For both species, the most polluted sampling site, Cortiou, displayed the highest level of FA, while the Maire and East Maire sampling sites displayed the lowest levels. A. lixula revealed systematic differences in FA among sampling sites for all characters and P. lividus showed differences in FA for the number of primary tubercles.Conclusions: Statistical analyses of FA show a concordance between the spatial patterns of FA among sampling sites and the spatial distribution of sewage discharge pollutants in the Cortiou area. High developmental stress in these sampling sites is associated with exposure to high concentrations of heavy metals and many harmful organic substances contained in wastewater. FA estimated from structures with complex symmetry appears to be a fast and reliable tool to detect subtle differences in FA. Its use in biomonitoring programs for inferring anthropogenic and natural environmental stress is suggested.

(Table 1) Egg size, clutch asymmetry, hatch date and breeding success in south polar skua, brown skua and mixed pairs on King George Island

We studied how environmental conditions affect reproduction in sympatric skua species that differ in their reliance on marine resources: the exclusively marine foraging south polar skua Catharacta maccormicki, the terrestrially foraging brown skua C. antarctica lonnbergi and mixed species pairs with an intermediate diet. Egg size, clutch asymmetry and hatching dates varied between species and years without consistent patterns. In the south polar skuas, 12 to 38% of the variation in these parameters was explained by sea surface temperature, sea ice cover and local weather. In mixed species pairs and brown skuas, the influence of environmental factors on variation in clutch asymmetry and hatching date decreased to 10-29%, and no effect on egg size was found. Annual variation in offspring growth performance also differed between species with variable growth in chicks of south polar skuas and mixed species pairs, and almost uniform growth in brown skuas. Additionally, the dependency on oceanographic and climatic factors, especially local wind conditions, decreased from south polar skuas to brown skua chicks. Consistent in all species, offspring were more sensitive to environmental conditions during early stages; during the late chick stage (>33 d) chick growth was almost independent of environmental conditions. The net breeding success could not be predicted by any environmental factor in any skua species, suggesting it may not be a sensitive indicator of environmental conditions. Hence, the sensitivity of skuas to environmental conditions varied between species, with south polar skuas being more sensitive than brown skuas, and between breeding periods, with the egg parameters being more susceptible to oceanographic conditions. However, during offspring development, local climatic conditions became more important. We conclude that future climate change in the Maritime Antarctic will affect reproduction of skuas more strongly through changes in sea ice cover and sea surface temperature (and the resulting alterations to the marine food web) than through local weather conditions.

Crystal structure of glutamate-1-semialdehyde aminomutase: An α2-dimeric vitamin B6-dependent enzyme with asymmetry in structure and active site reactivity

The three-dimensional structure of glutamate-1-semialdehyde aminomutase (EC 5.4.3.8), an α2-dimeric enzyme from Synechococcus, has been determined by x-ray crystallography using heavy atom derivative phasing. The structure, refined at 2.4-Å resolution to an R-factor of 18.7% and good stereochemistry, explains many of the enzyme’s unusual specificity and functional properties. The overall fold is that of aspartate aminotransferase and related B6 enzymes, but it also has specific features. The structure of the complex with gabaculine, a substrate analogue, shows unexpectedly that the substrate binding site involves residues from the N-terminal domain of the molecule, notably Arg-32. Glu-406 is suitably positioned to repel α-carboxylic acids, thereby suggesting a basis for the enzyme’s reaction specificity. The subunits show asymmetry in cofactor binding and in the mobilities of the residues 153–181. In the unliganded enzyme, one subunit has the cofactor bound as an aldimine of pyridoxal phosphate with Lys-273 and, in this subunit, residues 153–181 are disordered. In the other subunit in which the cofactor is not covalently bound, residues 153–181 are well defined. Consistent with the crystallographically demonstrated asymmetry, a form of the enzyme in which both subunits have pyridoxal phosphate bound to Lys-273 through a Schiff base showed biphasic reduction by borohydride in solution. Analysis of absorption spectra during reduction provided evidence of communication between the subunits. The crystal structure of the reduced form of the enzyme shows that, despite identical cofactor binding in each monomer, the structural asymmetry at residues 153–181 remains.

Three-dimensional image reconstruction of dephosphorylated smooth muscle heavy meromyosin reveals asymmetry in the interaction between myosin heads and placement of subfragment 2

Regulation of the actin-activated ATPase of smooth muscle myosin II is known to involve an interaction between the two heads that is controlled by phosphorylation of the regulatory light chain. However, the three-dimensional structure of this inactivated form has been unknown. We have used a lipid monolayer to obtain two-dimensional crystalline arrays of the unphosphorylated inactive form of smooth muscle heavy meromyosin suitable for structural studies by electron cryomicroscopy of unstained, frozen-hydrated specimens. The three-dimensional structure reveals an asymmetric interaction between the two myosin heads. The ATPase activity of one head is sterically “blocked” because part of its actin-binding interface is positioned onto the converter domain of the second head. ATPase activity of the second head, which can bind actin, appears to be inhibited through stabilization of converter domain movements needed to release phosphate and achieve strong actin binding. When the subfragment 2 domain of heavy meromyosin is oriented as it would be in an actomyosin filament lattice, the position of the heads is very different from that needed to bind actin, suggesting an additional contribution to ATPase inhibition in situ.

From symmetry to asymmetry: Phylogenetic patterns of asymmetry variation in animals and their evolutionary significance

Phylogenetic analyses of asymmetry variation offer a powerful tool for exploring the interplay between ontogeny and evolution because (i) conspicuous asymmetries exist in many higher metazoans with widely varying modes of development, (ii) patterns of bilateral variation within species may identify genetically and environmentally triggered asymmetries, and (iii) asymmetries arising at different times during development may be more sensitive to internal cytoplasmic inhomogeneities compared to external environmental stimuli. Using four broadly comparable asymmetry states (symmetry, antisymmetry, dextral, and sinistral), and two stages at which asymmetry appears developmentally (larval and postlarval), I evaluated relations between ontogenetic and phylogenetic patterns of asymmetry variation. Among 140 inferred phylogenetic transitions between asymmetry states, recorded from 11 classes in five phyla, directional asymmetry (dextral or sinistral) evolved directly from symmetrical ancestors proportionally more frequently among larval asymmetries. In contrast, antisymmetry, either as an end state or as a transitional stage preceding directional asymmetry, was confined primarily to postlarval asymmetries. The ontogenetic origin of asymmetry thus significantly influences its subsequent evolution. Furthermore, because antisymmetry typically signals an environmentally triggered asymmetry, the phylogenetic transition from antisymmetry to directional asymmetry suggests that many cases of laterally fixed asymmetries evolved via genetic assimilation.

Mutations in the rotated abdomen locus affect muscle development and reveal an intrinsic asymmetry in Drosophila.

In bilateral animals, the left and right sides of the body usually present asymmetric structures, the genetic bases of whose generation are still largely unknown [CIBA Foundation (1991) Biological Asymmetry and Handedness, CIBA Foundation Symposium 162 (Wiley, New York), pp. 1-327]. In Drosophila melanogaster, mutations in the rotated abdomen (rt) locus cause a clockwise helical rotation of the body. Even null alleles are viable but exhibit defects in embryonic muscle development, rotation of the whole larval body, and helical staggering of cuticular patterns in abdominal segments of the adult. rotated abdomen is expressed in the embryonic mesoderm and midgut but not in the ectoderm; it encodes a putative integral membrane glycoprotein (homologous to key yeast mannosyltransferases). Mesodermal cells defective in O-glycosylation lead to an impaired larval muscular system. We propose that the staggering of the adult abdominal segments would be a consequence of the relaxation of intrinsic rotational torque of muscle architecture, preventing the colateral alignment of the segmental histoblast cells during their proliferation at metamorphosis.

Introduction of asymmetry in the naturally symmetric restriction endonuclease EcoRV to investigate intersubunit communication in the homodimeric protein.

Type II restriction endonucleases are dimers of two identical subunits that together form one binding site for the double-stranded DNA substrate. Cleavage within the palindromic recognition site occurs in the two strands of the duplex in a concerted manner, due to the action of two catalytic centers, one per subunit. To investigate how the two identical subunits of the restriction endonuclease EcoRV cooperate in binding and cleaving their substrate, heterodimeric versions of EcoRV with different amino acid substitutions in the two subunits were constructed. For this purpose, the ecorV gene was fused to the coding region for the glutathione-binding domain of the glutathione S-transferase and a His6-tag, respectively. Upon cotransformation of Escherichia coli cells with both gene fusions stable homo- and heterodimers of the EcoRV variants are produced, which can be separated and purified to homogeneity by affinity chromatography over Ni-nitrilotriacetic acid and glutathione columns. A steady-state kinetic analysis shows that the activity of a heterodimeric variant with one inactive catalytic center is decreased by 2-fold, demonstrating that the two catalytic centers operate independently from each other. In contrast, heterodimeric variants with a defect in one DNA-binding site have a 30- to 50-fold lower activity, indicating that the two subunits of EcoRV cooperate in the recognition of the palindromic DNA sequence. By combining a subunit with an inactive catalytic center with a subunit with a defect in the DNA-binding site, EcoRV heterodimers were produced that only nick DNA specifically within the EcoRV recognition sequence.