Hunger increases negative and decreases positive emotions in women with a healthy weight.

The term 'hangry' is colloquially used to describe being "bad tempered or irritable as a result of hunger," but remarkably few studies have examined the effect of hunger on emotions. Yet, women attempting to restrict their food intake may be at risk of becoming entangled in a vicious cycle of hunger and negative emotions. That is, hunger may lead to negative emotions, which can lead to overeating and overeating can, in turn, provoke subsequent restriction leading to more hunger. Therefore the aim of this study was to examine the effect of hunger on positive and negative emotions in women with a healthy BMI, and the role of subclinical eating disorder symptoms in this effect. We randomly assigned women to a hunger condition (fasting for 14 h, n = 53) or satiated condition (eat breakfast before the study, n = 55), and they completed the Eating Disorder Examination Questionnaire and the Profile of Mood States in the lab. Hungry women reported overall higher negative emotions (higher tension, anger, fatigue, and confusion) and lower positive emotions (lower vigour and marginally lower esteem-related affect) than satiated women. Moreover, for satiated but not for hungry women, higher eating disorder symptoms were associated with lower esteem-related affect. These findings show that food restriction leads to negative emotions, and practitioners and individuals should be aware of these implications of food restriction on mental health. Second, clinicians and individuals should be wary of relatively low esteem-related affect when satiated in individuals with eating disorder symptoms, as it could serve as a maintaining factor in eating pathology.

Anger Responses in Adolescents: Relationship with Punishment and Reward Sensitivity.

A substantial proportion of youth with anxiety disorders shows comorbid behavioral (anger) problems. Such comorbid profile is associated with low treatment effectiveness and negative (longterm) outcomes. This study was therefore designed to examine trait factors that may promote anger responding in adolescents. By presenting participants (N = 158, mean age = 15.7, 56% female) with a series of common anger-eliciting situations, we tested whether high reward sensitivity would be associated with anger via perceived non-reward, and high punishment sensitivity via perceived threat. In line with the hypotheses, an indirect effect of reward sensitivity on anger was found via perceived non-reward, and an indirect effect of punishment sensitivity on anger via perceived threat. The latter association also had an indirect effect via perceived non-reward. High punishment and reward sensitivity may thus set adolescents at risk for developing (comorbid) anger problems via heightened threat and non-reward perceptions.

Genome Wide Conditional Mouse Knockout Resources.

The International Knockout Mouse Consortium (IKMC) developed high throughput gene trapping and gene targeting pipelines that produced mostly conditional mutations of more than 18,500 genes in C57BL/6N mouse embryonic stem (ES) cells which have been archived and are freely available to the research community as a frozen resource. From this unprecedented resource more than 6,000 mutant mouse strains have been produced by the IKMC and mostly the International Mouse Phenotyping Consortium (IMPC). In addition, a cre-driver resource was established including 250 inducible cre-driver mouse strains in a C57BL/6 background. Complementing the cre-driver resource, a collection of comprising 27 cre-driver rAAVs has also been produced. The resources can be easily accessed at the IKMC/IMPC web portal (www.mousephenotype.org). The IKMC/IMPC resource is a standardized reference library of mouse models with defined genetic backgrounds that enables the analysis of gene-disease associations in mice of different genetic makeup and should therefore have a major impact on biomedical research.

A new bacteriophage P1-derived vector for the propagation of large human DNA fragments.

We have designed a P1 vector (pCYPAC-1) for the introduction of recombinant DNA into E. coli using electroporation procedures. The new cloning system, P1-derived artificial chromosomes (PACs), was used to establish an initial 15,000 clone library with an average insert size of 130-150 kilobase pairs (kb). No chimaerism has been observed in 34 clones, by fluorescence in situ hybridization. Similarly, no insert instability has been observed after extended culturing, for 20 clones. We conclude that the PAC cloning system will be useful in the mapping and detailed analysis of complex genomes.

Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy.

Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new polymorphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein 'dysferlin'. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset).

Co-occurrence of social anxiety and depression symptoms in adolescence: differential links with implicit and explicit self-esteem?

BACKGROUND: Social anxiety and depression often co-occur. As low self-esteem has been identified as a risk factor for both types of symptoms, it may help to explain their co-morbidity. Current dual process models of psychopathology differentiate between explicit and implicit self-esteem. Explicit self-esteem would reflect deliberate self-evaluative processes whereas implicit self-esteem would reflect simple associations in memory. Previous research suggests that low explicit self-esteem is involved in both social anxiety and depression whereas low implicit self-esteem is only involved in social anxiety. We tested whether the association between symptoms of social phobia and depression can indeed be explained by low explicit self-esteem, whereas low implicit self-esteem is only involved in social anxiety. METHOD: Adolescents during the first stage of secondary education (n=1806) completed the Revised Child Anxiety and Depression Scale (RCADS) to measure symptoms of social anxiety and depression, the Rosenberg Self-Esteem Scale (RSES) to index explicit self-esteem and the Implicit Association Test (IAT) to measure implicit self-esteem. RESULTS: There was a strong association between symptoms of depression and social anxiety that could be largely explained by participants' explicit self-esteem. Only for girls did implicit self-esteem and the interaction between implicit and explicit self-esteem show small cumulative predictive validity for social anxiety, indicating that the association between low implicit self-esteem and social anxiety was most evident for girls with relatively low explicit self-esteem. Implicit self-esteem showed no significant predictive validity for depressive symptoms. CONCLUSIONS: The findings support the view that both shared and differential self-evaluative processes are involved in depression and social anxiety.

Personal characteristics of World War Two survivor offspring related to the presence of indirect intrusions.

Background: A substantial proportion of clinical World War Two survivor offspring reports intrusions about war events they did not experience themselves. Objective: To help identify factors that contribute to the development of such indirect intrusions (i.e. intrusions about non-self-experienced traumatic events), we examined the personal characteristics of survivor offspring that were related to the presence of indirect intrusions. To explore the specificity of these relationships, we compared characteristics related to the presence of indirect and direct intrusions (i.e. intrusions about self-experienced traumatic events). Methods: Participants (N = 98) were post-war offspring of World War Two survivors in treatment in one of two clinics specialized in mental health services for war victims. We assessed the presence of indirect and direct intrusions as well as the following personal characteristics: gender, education level, trait dissociation, affect intensity, attentional control, mental imagery, fantasy proneness, and current psychopathology. Results: Reports of indirect intrusions were more frequent in individuals high in fantasy proneness, trait dissociation, and current psychopathology. Reports of direct intrusions were more frequent in women, individuals scoring high on trait dissociation, affect intensity, and current psychopathology. Fantasy proneness was a unique correlate of indirect intrusions. Conclusions: These findings are consistent with the idea that intrusions are the result of (re)constructive processes affected by several factors including personal characteristics. HIGHLIGHTS: Offspring of World War Two survivors often experience indirect intrusions.We examined personal characteristics related to indirect and direct intrusions.Fantasy proneness was the best predictor of indirect intrusions.Gender was the best predictor of direct intrusions.

Antecedentes: Una proporción sustancial de los descendientes sobrevivientes clínicos de la Segunda Guerra Mundial reportan intrusiones sobre eventos de guerra que no experimentaron ellos mismos.Objetivo: Para ayudar a identificar los factores que contribuyen al desarrollo de tales intrusiones indirectas (es decir, intrusiones sobre eventos traumáticos no-auto-experimentados) examinamos las características personales de los hijos sobrevivientes que estaban relacionadas con la presencia de intrusiones indirectas. Para explorar la especificidad de estas relaciones, comparamos las características relacionadas con la presencia de intrusiones indirectas y directas (es decir, intrusiones sobre eventos traumáticos auto-experimentados).Métodos: Los participantes (N = 98) fueron hijos de sobrevivientes de la Segunda Guerra Mundial que estaban en tratamiento en alguna de las dos clínicas especializadas en servicios de salud mental para víctimas de guerra. Se evaluó la presencia de intrusiones indirectas y directas, así como las siguientes características personales: sexo, nivel educativo, disociación de rasgos, intensidad afectiva, control atencional, imaginería mental, propensión a la fantasía y psicopatología actual.Resultados: Los informes de intrusiones indirectas fueron más frecuentes en individuos con alta propensión a la fantasía, disociación de rasgos y psicopatología actual. Los informes de intrusiones directas fueron más frecuentes en mujeres, individuos con puntajes altos en disociación de rasgos, intensidad afectiva y psicopatología actual. La propensión a la fantasía fue un correlato único de las intrusiones indirectas.Conclusiones: Estos hallazgos son consistentes con la idea de que las intrusiones son el resultado de procesos (re)constructivos afectados por varios factores, incluidas las características personales.

Disorder-specific automatic self-associations in depression and anxiety: results of The Netherlands Study of Depression and Anxiety.

BACKGROUND: Cognitive theory points to the importance of negative self-schemas in the onset and maintenance of depression and anxiety disorders. Hereby, it is important to distinguish between automatic and explicit self-schemas, reflecting different cognitive-motivational systems. This study tested whether patients with a current major depression and/or anxiety disorder are characterized by automatic self-anxious and self-depressive associations and whether these associations are disorder specific. METHOD: Patients (n=2329) and non-clinical controls (n=652) were tested as part of The Netherlands Study of Depression and Anxiety, a multi-center, longitudinal, cohort study with patients from different health care settings. Patient groups and non-clinical controls (18-65 years of age) were compared with regard to automatic self-anxious and self-depressive associations measured with the Implicit Association Test. RESULTS: Individuals with an anxiety disorder showed enhanced self-anxious associations, whereas individuals with a depression showed enhanced self-depressive associations. Individuals with co-morbid disorders scored high on both automatic self-associations. Although remitted individuals showed weaker automatic self-associations than people with a current disorder, their automatic self-anxious/depressed associations were still significantly stronger than those of the control group. Importantly, automatic self-associations showed predictive validity for the severity of anxious and depressive symptoms over and above explicit self-beliefs. CONCLUSIONS: This study represents the first evidence that automatic self-anxious and self-depressive associations are differentially involved in anxiety disorders and depression. This may help to explain the refractoriness of these disorders and points to the potential importance of automatic self-associations in the development of psychopathological symptoms.

Attentional Bias for Cues Signaling Punishment and Reward in Adolescents: Cross-Sectional and Prognostic Associations with Symptoms of Anxiety and Behavioral Disorders.

Heightened reward sensitivity has been proposed as a risk factor for developing behavioral disorders whereas heightened punishment sensitivity has been related to the development of anxiety disorders in youth. Combining a cross-sectional (n = 696, mean age = 16.14) and prospective (n = 598, mean age = 20.20) approach, this study tested the hypotheses that an attentional bias for punishing cues is involved in the development of anxiety disorders and an attentional bias for rewarding cues in the development of behavioral disorders. A spatial orientation task was used to examine the relation between an attentional bias for punishing cues and an attentional bias for rewarding cues with anxiety and behavioral problems in a subsample of a large prospective population cohort study. Our study indicates that attentional biases to general cues of punishment and reward do not seem to be important risk factors for the development of anxiety or behavioral problems respectively. It might be that attentional biases play a role in the maintenance of psychological problems. This remains open for future research.

A BAC-based physical map of the major autosomes of Drosophila melanogaster.

We constructed a bacterial artificial chromosome (BAC)-based physical map of chromosomes 2 and 3 of Drosophila melanogaster, which constitute 81% of the genome. Sequence tagged site (STS) content, restriction fingerprinting, and polytene chromosome in situ hybridization approaches were integrated to produce a map spanning the euchromatin. Three of five remaining gaps are in repeat-rich regions near the centromeres. A tiling path of clones spanning this map and STS maps of chromosomes X and 4 was sequenced to low coverage; the maps and tiling path sequence were used to support and verify the whole-genome sequence assembly, and tiling path BACs were used as templates in sequence finishing.

Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation.

AIM AND METHOD: We analysed DNA samples isolated from individuals born with cleft lip and cleft palate to identify deletions and duplications of candidate gene loci using array comparative genomic hybridisation (array-CGH). RESULTS: Of 83 syndromic cases analysed we identified one subject with a previously unknown 2.7 Mb deletion at 22q11.21 coinciding with the DiGeorge syndrome region. Eighteen of the syndromic cases had clinical features of Van der Woude syndrome and deletions were identified in five of these, all of which encompassed the interferon regulatory factor 6 (IRF6) gene. In a series of 104 non-syndromic cases we found one subject with a 3.2 Mb deletion at chromosome 6q25.1-25.2 and another with a 2.2 Mb deletion at 10q26.11-26.13. Analyses of parental DNA demonstrated that the two deletion cases at 22q11.21 and 6q25.1-25.2 were de novo, while the deletion of 10q26.11-26.13 was inherited from the mother, who also has a cleft lip. These deletions appear likely to be causally associated with the phenotypes of the subjects. Estrogen receptor 1 (ESR1) and fibroblast growth factor receptor 2 (FGFR2) genes from the 6q25.1-25.2 and 10q26.11-26.13, respectively, were identified as likely causative genes using a gene prioritization software. CONCLUSION: We have shown that array-CGH analysis of DNA samples derived from cleft lip and palate subjects is an efficient and productive method for identifying candidate chromosomal loci and genes, complementing traditional genetic mapping strategies.

Rainbow smelt (Osmerus mordax) genomic library and EST resources.

Genomic resources in rainbow smelt (Osmerus mordax) enable us to examine the genome duplication process in salmonids and test hypotheses relating to the fate of duplicated genes. They further enable us to pursue physiological and ecological studies in smelt. A bacterial artificial chromosome library containing 52,410 clones with an average insert size of 146 kb was constructed. This library represents an 11-fold average coverage of the rainbow smelt (O. mordax) genome. In addition, several complementary deoxyribonucleic acid libraries were constructed, and 36,758 sequences were obtained and combined into 12,159 transcripts. Over half of these transcripts have been identified, several of which have been associated with cold adaptation. These basic resources show high levels of similarity (86%) to salmonid genes and provide initial support for genome duplication in the salmonid ancestor. They also facilitate identification of genes important to fish and direct us toward new technologies for other studies in fish biology.

Approach-avoidance of facial affect is moderated by the presence of an observer-irrelevant trigger.

This study examined whether approach-avoidance related behaviour elicited by facial affect is moderated by the presence of an observer-irrelevant trigger that may influence the observer's attributions of the actor's emotion. Participants were shown happy, disgusted, and neutral facial expressions. Half of these were presented with a plausible trigger of the expression (a drink). Approach-avoidance related behaviour was indexed explicitly through a questionnaire (measuring intentions) and implicitly through a manikin version of the affective Simon task (measuring automatic behavioural tendencies). In the absence of an observer-irrelevant trigger, participants expressed the intention to avoid disgusted and approach happy facial expressions. Participants also showed a stronger approach tendency towards happy than towards disgusted facial expressions. The presence of the observer-irrelevant trigger had a moderating effect, decreasing the intention to approach happy and to avoid disgusted expressions. The trigger had no moderating effect on the approach-avoidance tendencies. Thus the influence of an observer-irrelevant trigger appears to reflect more of a controlled than automatic process.

An integrated high-resolution physical map of the DPC/BRCA2 region at chromosome 13q12.

We identified a homozygous deletion in a pancreatic carcinoma (DPC) that localized to a 1-cM region at chromosome 13q12.3, which lay within the 6-cM locus of familial breast cancer susceptibility (BRCA-2). Here we present a physical map of the region, consisting of YAC, PAC, and cosmid contigs. The YAC contig comprises 16 clones that together span the entire BRCA2 region. The PAC contig comprises 22 clones that together span the DPC region. Seventy cosmid clones were localized within and near the DPC region. Thirty-five sequence-tagged sites were defined and localized within the map. The map indicates the size of the DPC region to be near 250 kb, and provides mapped and cloned resources for the search for the putative tumor suppressor gene(s) in the region.

Online attentional bias modification training targeting anxiety and depression in unselected adolescents: Short- and long-term effects of a randomized controlled trial.

Based on information processing models of anxiety and depression, we investigated the efficacy of multiple sessions of online attentional bias modification training to reduce attentional bias and symptoms of anxiety and depression, and to increase emotional resilience in youth. Unselected adolescents (N = 340, age: 11-18 years) were randomly allocated to eight sessions of a dot-probe, or a visual search-based attentional training, or one of two corresponding placebo control conditions. Cognitive and emotional measures were assessed pre- and post-training; emotional outcome measures also at three, six and twelve months follow-up. Only visual search training enhanced attention for positive information, and this effect was stronger for participants who completed more training sessions. Symptoms of anxiety and depression reduced, whereas emotional resilience improved. However, these effects were not especially pronounced in the active conditions. Thus, this large-scale randomized controlled study provided no support for the efficacy of the current online attentional bias modification training as a preventive intervention to reduce symptoms of anxiety or depression or to increase emotional resilience in unselected adolescents. However, the absence of biased attention related to symptomatology at baseline, and the large drop-out rates at follow-up preclude strong conclusions.

Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma.

We have isolated a gene, called MN1, which resides on chromosome 22 and which was found to be disrupted by a balanced translocation (4;22) in meningioma 32. The MN1 gene spans about 70 kb and consists of at least two large exons of approximately 4.7 kb and 2.8 kb. The MN1 cDNA codes for a protein of 1319 amino acids when the first methionine in the open reading frame is used. The MN1 cDNA contains two CAG repeats, one of which codes for a string of 28 glutamines. The t(4;22) disrupts the 5'-exon within the open reading frame. In meningioma 32 no expression of the MN1 mRNA is observed. These results suggest that inactivation of the MN1 gene in this tumour may contribute to its pathogenesis.

Do health care providers' attitudes towards back pain predict their treatment recommendations? Differential predictive validity of implicit and explicit attitude measures.

The current study aimed to measure the differential predictive value of implicit and explicit attitude measures on treatment behaviour of health care providers. Thirty-six physiotherapy students completed a measure of explicit treatment attitude (Pain Attitudes And Beliefs Scale For Physiotherapists-PABS-PT) and a measure of implicit treatment attitude (Extrinsic Affective Simon Task-EAST). Furthermore, they gave treatment recommendations for a patient simulating back pain on three video scenes. The implicit and explicit measures of attitudes were only weakly related to each other. However, both were differentially related to treatment recommendations. The implications of the differential predictive value of implicit and explicit attitude measures for treatment behaviour are discussed.

A comparative map of bovine chromosome 19 based on a combination of mapping on a bacterial artificial chromosome scaffold map, a whole genome radiation hybrid panel and the human draft sequence.

We have constructed a medium density physical map of bovine chromosome 19 using a combination of mapping loci on both a bovine bacterial artificial chromosome (BAC) scaffold map and a whole genome radiation hybrid (WGRH) panel. The resulting map contains 70 loci spanning the length of bovine chromosome 19. Three contiguous groups of BACs were identified on the basis of multiple loci mapping to individual BAC clones. Bovine chromosome 19 was found in this study to be comprised almost entirely from regions of human chromosome 17, with a small region putatively assigned to human chromosome 10. Fourteen breakpoints between the bovine and human chromosomes were detected, with a possibility of five more based on ordering of the WGRH map.

Semiautomated clone verification by real-time PCR using molecular beacons.

Conventional, high-throughput PCR analysis of common elements utilizing numerous primer sets and template DNA requires multiple rounds of PCR to ensure optimal conditions. Laborious gel electrophoresis and staining is then necessary to visualize amplification products. We propose novel multicolor molecular beacons, to establish a high-throughput, PCR-based sequence tagged site (STS) detection system that swiftly and accurately confirms marker content in template containing common repeat elements. A simple, one-tube, real-time PCR assay system was developed to specifically detect regions containing CA and GATA repeats. Ninety-six samples can be confirmed for marker content in a closed-tube format in 3 h, eliminating product confirmation on agarose gels and avoiding crossover contamination. Multiple STSs can be detected simultaneously in the same reaction tube by utilizing molecular beacons labeled with multicolor fluorophores. Template DNA from 260 RPCI-11 bacterial artificial chromosome (BAC) clones was examined for the presence of CA and/or GATA repeats using molecular beacon PCR and compared with conventional PCR results of the same clones. Of the 205 clones containing CA and GATA repeats, we were able to identify 129 clones (CA, n = 99; GATA, n = 30) by using molecular beacons and only 121 clones (CA, n = 92; GATA, n = 29) by conventional PCR amplification. As anticipated, 55 clones that contained sequences other than CA or GATA failed molecular beacon detection. Molecular beacon PCR, employing beacons specific for tandem repeat elements, provides a fast, accurate, and sensitive multiplex detection assay that will expedite verification of marker content in a multitude of template containing these repeats.

Dual Alu polymerase chain reaction primers and conditions for isolation of human chromosome painting probes from hybrid cells.

A method for rapid and efficient production of chromosome- and chromosome-region specific probes for fluorescent in situ hybridization (FISH) detectable by simple fluorescent microscopy is described. The procedure is based on simultaneous use of two inter-Alu-polymerase chain reaction (PCR) primers for extraction of highly heterogeneous human DNA from interspecific somatic cell hybrids containing the chromosome regions of interest. Probes so produced do not hybridize to centromeric sequences and simultaneously band the target chromosomes, making them useful for unambiguous identification of chromosomal elements and breakpoints associated with cancer.