A Upf3b-mutant mouse model with behavioral and neurogenesis defects.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders.

A prospective study of bipolar disorder vulnerability in relation to behavioural activation, behavioural inhibition and dysregulation of the Behavioural Activation System.

BACKGROUND: The weak regulation, or "dysregulation", of the Behavioural Activation System (BAS) is implicated in the development and recurrence of bipolar disorder. However, there has been a lack of prospective studies investigating the predictive role of BAS dysregulation in relation to bipolar-vulnerability. Furthermore, no studies have tested the prospective predictive utility of the DYS self-report measure of BAS dysregulation in an analogue sample. The goal of the current study was to redress this gap. METHODS: Participants (n=127) completed baseline self-report measures of mood symptoms (Internal States Scale [ISS]), the Hypomanic Personality Scale (HPS), behavioural activation, inhibition and dysregulation of BAS (BIS/BAS and DYS), and at six months, the Mood Disorders Questionnaire (MDQ). RESULTS: Linear regression analysis indicated a significant main effect of BAS Dysregulation, and a significant interaction between BIS and BAS Fun Seeking, on prospective MDQ scores whilst controlling for baseline mood symptoms and HPS scores. The interaction effect indicated that the relationship between high BAS Fun Seeking and follow-up MDQ scores was strongest when BIS scores were high, whilst the lowest MDQ scores were observed for a combination of low BAS Fun Seeking and high BIS. However, DYS scores were the stronger predictor of MDQ scores compared to the BAS Fun Seeking and BIS interaction. CONCLUSIONS: Bipolar-vulnerability is prospectively associated with heightened BAS Dysregulation, as measured by the DYS subscale, similar to prior findings in clinical samples. Further research investigating the longer-term associations between BAS Dysregulation with the development of clinically significant bipolar mood symptoms is required.

Atmospherically relevant core-shell aerosol studied using optical trapping and Mie scattering.

Solid core-liquid shell aerosols have been trapped in a counter-propagating optical trap confirming potential core-shell morphology in the atmosphere. Mie spectroscopy can be used to measure the core radius and film thickness to 0.5 and 1 nm precision respectively and to measure the wavelength dependent refractive indices of silica (core) and oleic acid (shell).

Characterization of Escherichia coli populations from gulls, landfill trash, and wastewater using ribotyping.

Due to their opportunistic and gregarious nature, gulls may be important reservoirs and vectors for anthropogenically derived fecal pathogens in coastal areas. We used ribotyping, a genotypic bacterial source tracking method, to compare populations of Escherichia coli among herring gulls Larus argentatus, great black-backed gulls L. marinus, wastewater, and landfill trash in New Hampshire and Maine, USA. Concentrations of E. coli in gull feces varied widely among individuals, but were generally high (6.0 x 10(1) to 2.5 x 10(9) g(-1) wet weight). Of 39 E. coli isolates from L. argentatus, 67% had banding patterns that were > or = 90% similar to those from wastewater and trash, whereas only 39% of 36 L. marinus isolates exhibited > or = 90% similarity to these sources. Strains of E. coli from gulls matched (> or = 90% similarity) more strains from wastewater (39% matching) than from trash (15% matching). E. coli isolates from L. marinus feces exhibited a greater diversity of banding patterns than did isolates from L. argentatus. There were more unique E. coli banding patterns in trash samples than in wastewater, and higher diversity indices in the former compared to the latter. These findings suggest that both species of gulls, especially L. argentatus, obtain fecal bacteria from wastewater and landfill trash, which they may transport to recreational beaches and waters. Our results also indicate that E. coli populations may vary widely between gull species, and between the anthropogenic habitats that they frequent, i.e. landfills and wastewater treatment facilities.

Circadian rhythms, multilevel models of emotion and bipolar disorder--an initial step towards integration?

This paper sets out possible links between disruption of circadian rhythms in bipolar disorder and the affective symptom, which are experienced in this disorder. Evidence is drawn from Healy and Williams' [Psychiatr. Dev. 1 (1989) 49.] review of circadian function in manic depression, along with later reports, which indicate a role for disrupted circadian rhythms in both depressed and manic phases of manic depression (bipolar disorder). This is integrated within a version of the multilevel model of emotion proposed by Power and Dalgleish [Cognition and emotion: from order to disorder. Hove: Psychology Press (1997); Behav. Cognit. Psychother. 27 (1999) 129.]. The aim of this process is to propose a possible psychological mechanism by which the disruption of circadian rhythms might result in the observed clinical symptoms of bipolar disorder. The integration of these approaches leads to a number of specific testable hypotheses that are relevant to future research into the psychological treatment and understanding of bipolar disorder.

Gulfwatch: monitoring spatial and temporal patterns of trace metal and organic contaminants in the Gulf of Maine (1991-1997) with the blue mussel, Mytilus edulis L.

Gulfwatch, established in 1991, is an international contaminant monitoring program in which the blue mussel, Mytilus edulis, is used as an indicator of the level and extent of contamination in the Gulf of Maine. Since 1991, trace metals, PAHs, PCBs, and OC pesticides have been measured in mussel tissues at 56 sites. The distribution of most metals was relatively uniform throughout the Gulf with the exception of Ag, Pb and Cr. However, the concentration of organic contaminants increased in a north-to-south direction. High concentrations of contaminants were correlated with large human population density and proximity to large rivers. Temporal analysis of five sites revealed that the majority of contaminant concentrations were either unchanged or decreasing. The concentrations of most contaminants were lower than the median of the National Status and Trends (NS & T) Mussel Watch with the exceptions of Cr, Hg, Pb and sigma PCB24. Hg concentrations at > 80% of the Gulfwatch sites exceeded the NS & T median +1 SD. Gulfwatch continues as a primary contaminant monitoring program in the Gulf of Maine.

Impaired associative learning in chronic schizophrenics and their first-degree relatives: a study of latent inhibition and the Kamin blocking effect.

The performance of chronic schizophrenic probands (n=21), their first-degree schizotypal (22) and non-schizotypal (19) relatives, and normal controls (24), was measured in two associative learning paradigms, latent inhibition and the Kamin blocking effect. These paradigms assess the effects on learning of initial exposure to other learning contingencies. The normal subjects showed latent inhibition (retarded learning of an association between a burst of white noise and a visually displayed counter increment, if the subject had first been pre-exposed to the white noise without any other consequence) and Kamin blocking (retarded learning of an association between two visual stimuli, if the conditioned stimulus was presented simultaneously with a second, already conditioned stimulus). The schizophrenic probands and both the schizotypal and non-schizotypal relatives were severely impaired in basic associative learning, performing much worse than the normal subjects in the control conditions (i.e. those lacking stimulus pre-exposure of any kind) of both the latent inhibition and the Kamin paradigms and also showed a loss of the normal latent inhibition and Kamin blocking effects. The performance of the three clinically defined groups was statistically indistinguishable. These findings contrast with previous reports of the performance of normal subjects classified as schizotypal by questionnaire, who are not impaired in basic associative learning, and are particularly fast to learn after stimulus pre-exposure. The results question the assumption that high schizotypy, as assessed by questionnaire, is like schizotypy in schizophrenic kin. The severe impairment in basic associative learning in schizophrenic patients and their kin warrants further investigation.

A program design to promote clinical judgment.

This article describes a unique continuing education program designed to enhance critical thinking, clinical judgment, and communication skills of practicing nurses in an acute care setting. The program design and implementation strategies are described in detail. The authors include specific examples for those who want to develop a similar program to improve the practice of registered nurses in the acute care setting.

Is Bradburn's measure of psychological well-being fair to introverts? A study among 16- to 18-yr.-old students.

A sample of 242 students between the ages of 16 and 18 years, attending schools in the North East of England, completed the Bradburn Balanced Affect Scale together with the abbreviated form of the Revised Eysenck Personality Questionnaire. The findings show that scores on the Bradburn scale (indicating psychological well-being as assessed by balanced affect) are correlated significantly and positively with scores for Extraversion (.25), negatively with Neuroticism (.52) and nonsignificantly with Psychoticism. The implications of these findings are discussed for the assessment of psychological well-being among introverts.

Interesting times on Krakatau: stand dynamics in the 1990s.

The Krakatau Islands, Indonesia, have provided an opportunity for ecologists to track primary succession from the 'clean slate' of 1883, through forest closure in the 1920s, to the contemporary period, in which successional changes take the form of alterations in composition and stature of forest stands rather than gross changes in ecosystem type. This paper reports on permanent forest plots established on the islands in 1989, and fully surveyed again in both 1992 and 1997. Since 1989, the plots have been subject to natural disturbance phenomena in the form of varying combinations of, for example, deposition of volcanic ejecta, landslides, lightning strikes, storm damage and drought. These effects have been concentrated between 1992 and 1997, during which the volcano Anak Krakatau has deposited ash on the islands of Sertung and Panjang, but not on Rakata. Data on stand responses are presented for growth rates (dbh (diameter at breast height, 1.3 m) increment), stem recruitment and mortality, biomass changes partitioned into mortality, ingrowth and growth of established trees), and compositional shifts. The discussion focuses on evaluation of questions and successional models framed earlier in the programme. One general finding is that the stand dominants as of 1989 have tended to decline in number within the plots, generally through low levels of recruitment failing to balance rates of mortality. The effects of disturbance to the plots appear to be evident in terms of mortality and recruitment, dbh increment, and changes in biomass. The patterns of change in the eight plots are quite varied, such that relatively few generalizations are possible. The difficulties of establishing meaningful baseline rates for tree growth and stand biomass are discussed.

Cognitive functioning and GABAA/benzodiazepine receptor binding in schizophrenia: a 123I-iomazenil SPET study.

BACKGROUND: The role of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in schizophrenia has previously been investigated using postmortem material. Recently, using single photon emission tomography (SPET) with the selective benzodiazepine antagonist 123I-Iomazenil as the radioligand, we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia. The present study aimed to build on this using the same in vivo scanning techniques, and relating findings to cognitive functioning. METHODS: Ten nonpsychiatric control subjects and 15 schizophrenic patients, matched for age and handedness, were scanned. A battery of neuropsychologic tests was also administered. RESULTS: Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance, in the schizophrenic group compared to the control group. CONCLUSIONS: Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning, involving memory and visual attention processes, in the schizophrenic group but not in the control group. A role for GABA in the pathophysiology of schizophrenia is suggested. Limitations of the present study and suggestions for future research are discussed.

Disruption of the Kamin blocking effect in schizophrenia and in normal subjects following amphetamine.

The Kamin blocking effect (KBE) is an established animal learning paradigm measuring selective processing, in which reduced blocking reflects allocation of greater processing resources to non-relevant information. Two KBE tasks are described below. Results from studies using the first (between-subjects) task indicate that KBE is abolished in acute schizophrenics with positive psychotic symptoms. It is also abolished in the relatives of schizophrenic subjects, although interpretation of this finding is hampered by poor performance of subjects in the control condition. The second (within-subjects) task indicated abolition of KBE in schizophrenic patients with positive psychotic symptoms. Administration of acute amphetamine to normal human subjects did not significantly disrupt performance on the first task. Whilst for the second task, although blocking was limited to placebo subjects, overall pre-exposure effects are not sufficiently strong to indicate specific drug effects.

Kamin blocking is not disrupted by amphetamine in human subjects.

The effect of oral amphetamine administration on the Kamin-blocking effect in healthy volunteer subjects was investigated. Against predictions, Kamin blocking was not disrupted by either a high or low oral dose of D-amphetamine under conditions which have, in previous studies, led to disruption of a related learning phenomenon (latent inhibition). This lack of effect of amphetamine administration upon Kamin blocking weakens hypotheses that this cognitive process is mediated by the same changes in dopaminergic activity which affect latent inhibition. Currently, the only data which show strong comparative associations between Kamin blocking and latent inhibition are when they are applied to schizophrenic populations. These results may suggest that Kamin blocking and latent inhibition may be measuring different aspects of schizophrenic cognitive dysfunction.

Babesia bovis: genome size, number of chromosomes and telomeric probe hybridisation.

Pulsed field gel electrophoresis of intact chromosomes of Babesia bovis revealed four chromosomes in the haploid genome. A telomere probe, derived from Plasmodium berghei, hybridised to eight SfiI restriction fragments of genomic B. bovis DNA digests indicating the presence of four chromosomes. A small subunit (18S) ribosomal RNA gene probe hybridised to the third chromosome only. The genome size of B. bovis is estimated to be 9.4 million base pairs. The sizes of chromosomes 1, 2, 3 and 4 are estimated to be 1.4, 2.0, 2.8 and 3.2 million base pairs, respectively.

A brief mental health outcome scale: relationships between scale scores and diagnostic/sociodemographic variables in the long-term mentally ill.

The Global Assessment of Functioning (GAF) scale is a quick and simple measure of overall psychological disturbance. A recent study by our group reported the reliability and validity of the scale in a population of severely mentally ill people. The current study extends the analysis of this population to consider a number of questions, i.e. what are the associations for this group between variations in GAF scores and sociodemographic variables? Are lower scores associated with particular diagnoses for the group assessed? What are the characteristics of those patients whose scores were most variable? What were the completion rates for use of the scale? No associations were observed between GAF score and the sociodemographic variables used in this study. Lower GAF scores were associated with psychotic diagnoses. Those with most varying scores were, in the main, white European non-immigrant males with a diagnosis of schizophrenia. Completion rates for the study were reasonable at 73.8%. This study involved the repeated assessment of a large number of clients by a changing multidisciplinary team. Inspite of the extended nature of the study, completion rates remained reasonable, suggesting that the scale was acceptable for routine clinical use. The GAF in itself, however, appears to be unsuitable for making individual treatment decision but could be used as a first step before using more sophisticated scales.

A brief mental health outcome scale-reliability and validity of the Global Assessment of Functioning (GAF).

BACKGROUND: The Global Assessment of Functioning (GAF) is a quick and simple measure of overall psychological disturbance. However, there is little research on the reliability and validity of this measure in severely mentally ill populations. METHOD: Multidisciplinary keyworkers assessed 103 patients at monthly intervals over a 6-month period. Overall GAF scores were obtained, with additional separate ratings for symptoms and disability. These were compared with changes in antipsychotic medication and support needs over the same period. RESULTS: Satisfactory reliability was obtained for total GAF score and for symptom and disability measures, in spite of raters having only one brief training session. All GAF scores were associated with current support needs of patients. Symptom and disability scores were associated with changes in antipsychotic medication in the previous month. Only symptom score was associated with increases in antipsychotic medication at time of rating. CONCLUSION: GAF proved to be a reliable and, within the limits of the indicators used, a valid measure of psychiatric disturbance in our sample of the severely mentally ill. Differences in relationships between the three GAF scores and medication/support needs indicate the usefulness of obtaining all three scores for monitoring levels and type of psychiatric disturbance in this population.

Analysis of the functional potential of mouse CD4+ T cells using a high-efficiency cloning system.

In order to examine the functional potential of individual mouse CD4+ T cells selected, as far as possible, in a random manner, a high-efficiency cloning system driven by Con A was utilized. Under optimal conditions, cloning efficiencies of CD4+ cells of about 50% were regularly attained. Although the relative proportion of different TH subsets varied depending on the cloning conditions, the high cloning efficiency, coupled with the analysis of over 100 clones, allowed important conclusions to be drawn regarding the general construction of the mouse CD4+ T cell repertoire. (1) At least 50% of all mouse splenic CD4+ T cells have the potential to produce IL4, supporting the view that TH subsets arise by an instructional or regulatory mechanism, rather than by selection. (2) TH0 clones produce amounts of IL2 and IL4 similar to those produced by TH1 and TH2 clones, respectively, but secrete much lower quantities of IFN than TH1 clones. (3) A large proportion of TH2 clones secrete measurable amounts of IFN. (4) Lymphokine secretion patterns among CD4+ T cells are clearly not determined at random, since IL2 production is always accompanied by IFN production. (5) At least 50% of all mouse splenic CD4+ T cells have cytolytic capacity as shown by killing in a 20-hr assay, but only a proportion can also kill in 4-hr assays. Killing in 4-hr assays was strongly correlated with the ability to secrete IL2, regardless of whether IL4 was also secreted.

Loss of the Kamin blocking effect in acute but not chronic schizophrenics.

Differences between research diagnostic criteria (RDC)-diagnosed acute and chronic schizophrenics and normal controls were studied using a Kamin blocking procedure. Blocking is an established animal learning procedure, thought by some researchers to reflect selective attention; decreased blocking indicates increased processing of irrelevant stimuli. It was predicted that this pattern would be obtained in acute schizophrenics, tested soon after admission, for two reasons: (1) evidence from previous clinical studies indicates that acute schizophrenics are more aware of nonsalient aspects of their environment than controls; and (2) blocking is disrupted in animals in a hyperdopaminergic state and restored by neuroleptic medication. This was the case: acute, but not chronic, schizophrenics showed disrupted blocking. This disruption was especially clear in those acute schizophrenics tested within 2 weeks of hospital admission. By the second test session (in a cross-over design), there was some evidence of normalization in performance in the acute schizophrenics. These findings are considered with regard to the dopamine hypothesis of schizophrenia.