Source-Reconstruction of Event-Related Fields Reveals Hyperfunction and Hypofunction of Cortical Circuits in Antipsychotic-Naive, First-Episode Schizophrenia Patients during Mooney Face Processing

Schizophrenia is characterized by dysfunctions in neural circuits that can be investigated with electrophysiological methods, such as EEG and MEG. In the present human study, we examined event-related fields (ERFs), in a sample of medication-naive, first-episode schizophrenia (FE-ScZ) patients (n � 14) and healthy control participants (n � 17) during perception of Mooney faces to investigate the integrity of neuromagnetic responses and their experience-dependent modification. ERF responses were analyzed for M100, M170, and M250components at the sensor and source levels. In addition, we analyzed peak latency and adaptation effects due to stimulus repetition. FE-ScZ patients were characterized by significantly impaired sensory processing, as indicated by a reduced discrimination index (A�). At the sensor level, M100 and M170 responses in FE-ScZ were within the normal range, whereas the M250 response was impaired. However, source localization revealed widespread elevated activity for M100 and M170 in FE-ScZ and delayed peak latencies for the M100 and M250 responses. In addition, M170 source activity in FE-ScZ was not modulated by stimulus repetitions. The present findings suggest that neural circuits in FE-ScZ may be characterized by a disturbed balance between excitation and inhibition that could lead to a failure to gate information flow and abnormal spreading of activity, which is compatible with dysfunctional glutamatergic neurotransmission

The role of LINEs and CpG islands in dosage compensation on the chicken Z chromosome

Most avian Z genes are expressed more highly in ZZ males than ZW females, suggesting that chromosome-wide mechanisms of dosage compensation have not evolved. Nevertheless, a small percentage of Z genes are expressed at similar levels in males and females, an indication that a yet unidentified mechanism compensates for the sex difference in copy number. Primary DNA sequences are thought to have a role in determining chromosome gene inactivation status on the mammalian X chromosome. However, it is currently unknown whether primary DNA sequences also mediate chicken Z gene compensation status. Using a combination of chicken DNA sequences and Z gene compensation profiles of 310 genes, we explored the relationship between Z gene compensation status and primary DNA sequence features. Statistical analysis of different Z chromosomal features revealed that long interspersed nuclear elements (LINEs) and CpG islands are enriched on the Z chromosome compared with 329 other DNA features. Linear support vector machine (SVM) classifiers, using primary DNA sequences, correctly predict the Z compensation status for >60% of all Z-linked genes. CpG islands appear to be the most accurate classifier and alone can correctly predict compensation of 63% of Z genes. We also show that LINE CR1 elements are enriched 2.7-fold on the chicken Z chromosome compared with autosomes and that chicken chromosomal length is highly correlated with percentage LINE content. However, the position of LINE elements is not significantly associated with dosage compensation status of Z genes. We also find a trend for a higher proportion of CpG islands in the region of the Z chromosome with the fewest dosage-compensated genes compared with the region containing the greatest concentration of compensated genes. Comparison between chicken and platypus genomes shows that LINE elements are not enriched on sex chromosomes in platypus, indicating that LINE accumulation is not a feature of all sex chromosomes. Our results suggest that CpG islands are not randomly distributed on the Z chromosome and may influence Z gene dosage compensation status

Mechanisms and Evolutionary Patterns of Mammalian and Avian Dosage Compensation

A large-scale comparative gene expression study reveals the different ways in which the chromosome-wide gene dosage reductions resulting from sex chromosome differentiation events were compensated during mammalian and avian evolution

Turnover of Sex Chromosomes in the Stickleback Fishes (Gasterosteidae)

Diverse sex-chromosome systems are found in vertebrates, particularly in teleost fishes, where different systems can be found in closely related species. Several mechanisms have been proposed for the rapid turnover of sex chromosomes, including the transposition of an existing sex-determination gene, the appearance of a new sex-determination gene on an autosome, and fusions between sex chromosomes and autosomes. To better understand these evolutionary transitions, a detailed comparison of sex chromosomes between closely related species is essential. Here, we used genetic mapping and molecular cytogenetics to characterize the sex-chromosome systems of multiple stickleback species (Gasterosteidae). Previously, we demonstrated that male threespine stickleback fish (Gasterosteus aculeatus) have a heteromorphic XY pair corresponding to linkage group (LG) 19. In this study, we found that the ninespine stickleback (Pungitius pungitius) has a heteromorphic XY pair corresponding to LG12. In black-spotted stickleback (G. wheatlandi) males, one copy of LG12 has fused to the LG19-derived Y chromosome, giving rise to an X1X2Y sex-determination system. In contrast, neither LG12 nor LG19 is linked to sex in two other species: the brook stickleback (Culaea inconstans) and the fourspine stickleback (Apeltes quadracus). However, we confirmed the existence of a previously reported heteromorphic ZW sex-chromosome pair in the fourspine stickleback. The sex-chromosome diversity that we have uncovered in sticklebacks provides a rich comparative resource for understanding the mechanisms that underlie the rapid turnover of sex-chromosome systems

Mammalian sex determination—insights from humans and mice

Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models

Sea surface temperature control on the distribution of far-traveled Southern Ocean ice-rafted detritus during the Pliocene

The flux and provenance of ice-rafted detritus (IRD) deposited in the Southern Ocean can reveal information about the past instability of Antarctica's ice sheets during different climatic conditions. Here we present a Pliocene IRD provenance record based on the Ar/Ar ages of ice-rafted hornblende grains from Ocean Drilling Program Site 1165, located near Prydz Bay in the Indian Ocean sector of the Southern Ocean, along with the results of modeled sensitivity tests of iceberg trajectories and their spatial melting patterns under a range of sea surface temperatures (SSTs). Our provenance results reveal that IRD and hence icebergs in the Prydz Bay area were mainly sourced from (i) the local Prydz Bay region and (ii) the remote Wilkes Land margin located at the mouth of the low-lying Aurora Subglacial Basin. A series of IRD pulses, reaching up to 10 times background IRD flux levels, were previously identified at Site 1165 between 3.3 and 3.0Ma. Our new results reveal that the average proportion of IRD sourced from distal Wilkes Land margin doubles after 3.3Ma. Our iceberg trajectory-melting models show that slower iceberg melting under cooling SSTs over this middle Pliocene interval allowed Wilkes Land icebergs to travel farther before melting. Hence, declining SSTs can account for a large part of the observed IRD provenance record at Site 1165. In early Pliocene IRD layers, sampled at suborbital resolution around 4.6Ma, we find evidence for significant increases in icebergs derived from Wilkes Land during very warm interglacials. This is suggestive of large-scale destabilization of the East Antarctic Ice Sheet in the Aurora Subglacial Basin, as far-traveled icebergs would have to overcome enhanced melting in warmer SSTs. Our results highlight the importance of considering SSTs when interpreting IRD flux and provenance records in distal locations

Treatment of critical neonatal edema with hemo-ultrafiltration

Three neonates with extreme edema associated with cardiovascular and renal insufficiency were treated with hemo-ultrafiltration for removal of critical edema fluid. In each patient peritoneal dialysis had not been effective in expedient fluid removal. Ultrafiltration was accomplished by occlusion of the proximal dialysate portal of a Travenol EX12-11, 0.8 m2 dialyzer and the application of vacuum suction to the distal portal. Blood flow ranged from 10-25 ml/min. The rate of ultrafiltration averaged 0.57 ml/kg/min resulting in losses of 4-16% of body weight. Episodes of hypotension were associated with too rapid ultrafiltration rate and not total volume removed. All patients tolerated the procedure. Two of the three patients demonstrated improvement in blood pressure, oxygenation and urine flow following the ultrafiltration. Ultrafiltration in the newborn may be a useful therapeutic procedure when conventional treatment fails

Assignment of SOX1 to platypus chromosome 20q by fluorescence in situ hybridization

M.L. Delbridge M.C. Wallis P.J. Kirby A.E. Alsop F. Grützner and J.A.M. Grave