Polycomb group (PcG) proteins prevent the assembly of abnormal synaptonemal complex structures during meiosis.

The synaptonemal complex (SC) is a proteinaceous scaffold that is assembled between paired homologous chromosomes during the onset of meiosis. Timely expression of SC coding genes is essential for SC assembly and successful meiosis. However, SC components have an intrinsic tendency to self-organize into abnormal repetitive structures, which are not assembled between the paired homologs and whose formation is potentially deleterious for meiosis and gametogenesis. This creates an interesting conundrum, where SC genes need to be robustly expressed during meiosis, but their expression must be carefully regulated to prevent the formation of anomalous SC structures. In this manuscript, we show that the Polycomb group protein Sfmbt, the Drosophila ortholog of human MBTD1 and L3MBTL2, is required to avoid excessive expression of SC genes during prophase I. Although SC assembly is normal after Sfmbt depletion, SC disassembly is abnormal with the formation of multiple synaptonemal complexes (polycomplexes) within the oocyte. Overexpression of the SC gene corona and depletion of other Polycomb group proteins are similarly associated with polycomplex formation during SC disassembly. These polycomplexes are highly dynamic and have a well-defined periodic structure. Further confirming the importance of Sfmbt, germ line depletion of this protein is associated with significant metaphase I defects and a reduction in female fertility. Since transcription of SC genes mostly occurs during early prophase I, our results suggest a role of Sfmbt and other Polycomb group proteins in downregulating the expression of these and other early prophase I genes during later stages of meiosis.

The Enhancing Role of Emotion Regulation in the Links between Early Positive Memories and Self-harm and Suicidal Ideation in Adolescence.

Adolescence is a critical developmental period associated with an increased variety of interrelated risks and vulnerabilities. Previous studies have found associations between early memories of warmth and safeness, as well as emotion regulation, and self-harm and suicidal ideation in adolescence. Additionally, these early emotional memories have been found to be positively linked with some indicators of emotion regulation during this period. The present cross-sectional study extends prior research by exploring the moderating role of emotion regulation in the relationships between early memories of warmth and safeness, as well as each of the following risk-related outcomes in adolescence, in younger (i.e., 13-15) and older (i.e., 16-19) adolescents: suicidal ideation and self-harm and its associated functions (i.e., automatic and social reinforcement. Three self-report measures of these early emotional memories, emotion regulation, and risk-related outcomes, and a sample of 7918 Portuguese adolescents (53.3% females), with ages ranging from 13 to 19 (Mage = 15.5), were used. In both age groups, at high levels of emotion regulation, early memories of warmth and safeness had a greater (negative) effect on suicidal ideation and the automatic reinforcement function of self-harm, compared to at average and low levels of emotion regulation. These findings highlight the enhancing role of emotion regulation on the associations between early memories of warmth and safeness and some risk-related outcomes in adolescents, both younger and older, which reveals the relevance of targeting emotion regulation when preventing or tackling these outcomes, regardless of adolescents' levels of early memories of warmth and safeness.

"Help Me Control My Impulses!": Adolescent Impulsivity and Its Negative Individual, Family, Peer, and Community Explanatory Factors.

The literature shows that impulsivity, prevalent in adolescence, is negatively linked with a variety of psychosocial factors (e.g., positive interpersonal relationships, emotion regulation); however, there is limited research examining the relative contribution of multiple factors for this trait nor exploring how these factors influence the associations between impulsivity and risk-related outcomes. Drawing on multiple components of the unified theory of development (i.e., psychological variables, peers subsystem, community subsystem, family processes subsystem), this cross-sectional study aims to identify explanatory psychosocial variables (i.e., early memories of warmth and safeness, rational decision-making style, resilience, emotion regulation, coping, parental attachment, social group attachment, satisfaction with school and family-related variables) that are negatively related with impulsivity, in younger (13-15) and older (16-19 years) adolescents, and explore their moderating role in the associations between this trait and some risk-related outcomes (i.e., verbal aggression, anger, self-harm, other high-risk behaviors). A representative sample of 6894 adolescents (52.9% female) living in the Azores (Portugal), with ages ranging from 13 to 19 (M = 15.4), was used. Two stepwise multiple regressions, one for each age group, revealed that only emotion regulation, parental attachment, and social group attachment had a negative effect on impulsivity in both age groups; additionally, satisfaction with teachers also had this effect in younger adolescents. The first three variables weakened the positive associations between impulsivity and the risk-related outcomes. These results suggest that the psychological system and all subsystems of the social context measured play a relevant role in explaining adolescent impulsivity and that it may be reduced by promoting emotion regulation, positive parenting practices, healthier relationships with peers, and healthier relationships with teachers.

NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning.

The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During Drosophila midblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, the Drosophila ortholog of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron of gurken Germline depletion of Salsa and splice site mutations within gurken first intron impair both adult female fertility and oocyte dorsal-ventral patterning, due to an abnormal expression of Gurken. Supporting causality, the fertility and dorsal-ventral patterning defects observed after Salsa depletion could be suppressed by the expression of a gurken construct without its first intron. Altogether, our results suggest that one of the key rate-limiting functions of Salsa during oogenesis is to ensure the correct expression and efficient splicing of the first intron of gurken mRNA. Retention of gurken first intron compromises the function of this gene most likely because it undermines the correct structure and function of the transcript 5'UTR.

General Practice/Family Medicine Portuguese doctors: "technicists" or "systemics"?

To study if the consultation's problems classification of a fictitious case by General and Family Medicine doctors, showed the characteristics of being a mechanistic or a systemic approach. Exploratory cross-sectional observational study in a convenience sample of the General Practice/Family Medicine population, internees included, in April 2020, applying a modified real world clinical case. Central Portugal and the Autonomous Region of Azores. General Practice/Family Medicine specialists and internees. Electronic Doctors invitation to participate, anonymously, in specific doctor's social networks. A self-fulfilling questionnaire was used to verify the classification of a clinical case in Subjective, Assessment and Plan (from the SOAP methodology) with the response options of the International Classification of Primary Health Care (ICPC2) in chapters P (Psychological) and Z (Social) possible for this case. "Technicists" doctors, only classifying "P" codes and "Systemics" classifying "P+Z" or only "Z" ICPC2 codes were defined. Differences between genders, work place, being an internee or specialist and being a tutor in specialized formation were studied. A sample of 227 30% (n=68) males, specialists represented 66% (n=149), of whom 49% (n=73) were internee's tutors and 34% (n=78) were internees, was studied. In the Subjective chapter of the SOAP methodology, 44.1% (n=100) were "technicists", for Assessment n=93 (40.8%) were "technicists" and for P chapter classification 56.8% were "technicists". For S, A and P chapters classification there was no significant difference between the considered variables. In this sample General Practice/Family Medicine Portuguese doctors were more "systemic" for the S and A chapters of the SOAP model, And "technicists" in the P chapter.

Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P < 10-52), Latino (Nagelkerke's R2 = 0.089; liability R2 = 0.021; P < 10-58), and European individuals (Nagelkerke's R2 = 0.089; liability R2 = 0.037; P < 10-113), further highlighting the advantages of incorporating data from diverse human populations.

Construct validity, sensitivity and specificity of the USCD Performance-based Skill Assessment 2 in a mixed Portuguese sample.

Assessment batteries of functional capacity provide robust indicators of real-world functioning in major psychiatric illnesses and important information on an individual's ability to live autonomously and pursue relevant psychosocial goals. OBJECTIVES: This study explores the psychometric properties of the Portuguese USCD Performance-based Skill Assessment 2 (UPSA-2-PT) in a mixed sample of Portuguese participants. METHOD: A sample of 110 participants, 37 patients diagnosed with schizophrenia, 27 first-degree relatives of patients and 46 controls were administered the UPSA-2-PT and self-report questionnaires. The UPSA-2-PT reliability was assessed through inter-rater reliability and internal consistency, convergent validity with community integration and a receiver operating curve analysis was conducted to establish scores' sensitivity and specificity. Youden's Index was used to determine an optimal UPSA-2-PT cutoff score. RESULTS: Findings show an excellent inter-rater reliability, good internal consistency and construct validity, consistent with previous studies in Western countries. The UPSA-2-PT also showed a good discriminant ability between patients and controls, and an overall percentage of correct classification of 86.7% based on the 81.59 cutoff. DISCUSSION: Findings are congruous with previous versions, strengthening the body of evidence supporting the construct validity and providing a useful tool for research and clinical purposes to practitioners.

Are shame and self-criticism the path to the pervasive effect of social stress reactivity on social functioning in psychosis?

It is widely known that stress reactivity and social functioning impairment are important difficulties in people with psychosis. However, the specific impact of stress reactivity on social functioning and its underlying mechanisms are still less explored. Social rank variables, such as shame and self-criticism, have been pointed out as relevant in the development, maintenance of several types of psychosocial suffering and, specifically, in psychotic disorders. This study's aim was to explore the associations between external shame, self-criticism, social stress reactivity, and social functioning difficulties and understand the mediator role of shame and self-criticism in the relationship between social stress reactivity and social functioning. Seventy-seven participants with a psychotic disorder filled in self-reported measures of stress reactivity, shame, and self-criticism and were clinically evaluated for social functioning. To study the associations between variables in the study, Spearman correlation coefficients were used. The PROCESS macro was used to test the sequential mediation analyses. All variables under study were associated with each other, and social stress reactivity predicted social functioning difficulties through external shame, whereas self-criticism was not a significant mediator. The present study highlights the role of external shame in the pathway from stress reactivity to social impairment. These results inform recovery-oriented interventions and reinforce the relevance of considering social competitive mentality when working with people with psychosis. Further research is needed to clarify the role of self-to-self relationship in social impairment and to identify other mechanisms aimed at dealing with shame used by people with psychosis.

Correction to: Validation of the Community Integration Scale for Adults with Psychiatric Disorders (CIS-APP-34).

The original version of the article unfortunately contained a typo in the author name.

Validation of the Community Integration Scale for Adults with Psychiatric Disorders (CIS-APP-34).

The current focus on community integration of individuals with psychiatric problems is attracting an increasing interest in the psychological literature, as it is regarded as a favorable factor in the recovery and for the well-being of these individuals. The Community Integration Scale of Adults with Psychiatric Disorders (CIS-APP-34) is a self-report scale developed to assess community integration in several dimensions. The main goal of the current study is to explore the psychometric properties of CIS-APP-34 in a sample of 411 participants with and without a psychiatric illness, with ages between 19 and 91 years old, living in the Azores Islands, Portugal. A confirmatory factor analysis was carried out to confirm the latent structure of the scale, and a five-factor model has presented good fit indices. Further analysis showed that the CIS-APP-34 is a measure with good reliability, validity and discriminant ability.

Psychosocial roots of paranoid ideation: The role of childhood experiences, social comparison, submission, and shame.

BACKGROUND: Social experiences have a significant impact on cognitive functioning and appraisals of social interactions. Specifically, recalls of antipathy from parents, submissiveness, and bullying during childhood can have a significant influence on paranoid ideation later in life. METHOD: Multiple hierarchical regression analysis was performed on a sample of 91 patients diagnosed with paranoid schizophrenia in remission and active phase, their first-degree relatives (n = 32) and unaffected controls (n = 64). OBJECTIVES: Exploring the impact of distal (events from childhood) and proximal factors (current cognitive, emotional, and behavioural aspects of social functioning) in the frequency, degree of conviction, and distress resulting from paranoid ideation in the participants from 4 samples. RESULTS: Proximal and distal factors (shame, submissive behaviour, negative social comparison, antipathy from father) predicted several aspects of paranoid ideation. Those variables had a differential impact in affected patients and healthy controls. DISCUSSION: Finding suggests different variables being involved in paranoid ideation, and the specificities of patients with paranoid schizophrenia should be considered in the development of more effective psychotherapeutic interventions.

Influence of Family and Childhood Memories in the Development and Manifestation of Paranoid Ideation.

Several studies point out to the influence of social experiences on perceptions of the environment and others in cognitive functioning and different aspects of psychopathology. The current study aimed at studying the influence of the psychosocial risk factors in a mixed sample of participants from the general population and affected by paranoid schizophrenia. The extent to which the existence of negative life events and events that are threatening to the inner models of the self (i.e., history of maltreatment, physical, social or psychological abuse) or the memories of these traumatic events occurring during childhood are related to the existence of paranoid beliefs in adulthood was explored. Results suggested that memories of parental behaviours characterized by antipathy from both parental figures, submissiveness and bullying victimization were important predictors of paranoid ideation in adult life. This further emphasizes the need for understanding the family and social dynamics of people presenting paranoid ideations to the development of therapeutic interventions that can effectively reduce the invalidation caused by severe psychopathology, as is the case of schizophrenia. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Memories of family dynamics characterized by behaviours of antipathy from both parental figures, submissiveness and bullying victimization are important predictors of paranoid ideation in adult life. The study highlights the importance of exploring subjective recalls of feelings and behaviours associated with early rearing experiences, peer relationships and themes related to social rank theory in the roots of internal models of relationship with the self and others in the general sample, patients diagnosed with schizophrenia and their first-degree relatives. Our findings indicate that schizophrenic patients in active phase differ regarding memories of threat and submission and are more likely to remember childhood experiences perceived as threatening during an active phase than when in remission. It is possible that by changing these internal models and social interaction styles, patients may be able to get involved in more cooperating and affiliative interactions, disconfirming these early beliefs about others being rejecting, critical or hostile towards the self, and more effectively reducing the invalidation caused by positive and negative symptomatology of schizophrenia on social functioning.

Association study of 83 candidate genes for bipolar disorder in chromosome 6q selected using an evidence-based prioritization algorithm.

BACKGROUND: Prior genome-scans of bipolar disorder have revealed chromosome 6q22 as a promising candidate region. However, linkage disequilibrium (LD) mapping studies have yet to identify replicated susceptibility loci. METHODS: We analyzed 1,422 LD-tagging single nucleotide polymorphisms (SNPs) in 83 genes to test single-marker and locus-wide evidence of association with bipolar disorder in the NIMH Genetics Initiative bipolar pedigrees and the Portuguese Island Collection (PIC) (N = 1,093 in 528 informative pairs). Both studies previously demonstrated significant evidence of linkage to 6q. SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Evidence of single-marker association was assessed using the generalized disequilibrium test (GDT). Empirical estimates of gene-wide significance were obtained by permutation (via 100,000 gene-dropping simulations) of Fisher's combined test of P-values for each locus. RESULTS: No single variant yielded significant experiment-wide evidence of association, for either the combined sample or in each subsample. Our gene-dropping simulations identified nominally significant gene-wide associations with multiple loci, of which NT5DC1 in the NIMH subsample and CCNC in the PIC were the strongest candidates. However, no one gene consistently exceeded empirical significance criteria in both independent samples or survived Bonferroni correction for the number of genes tested. CONCLUSIONS: Using a gene-based approach to family-based association, we identified gene-wide associations with several genes, though no single locus was significantly associated with bipolar disorder in both cohorts. This suggests that chromosome 6q may harbor multiple susceptibility loci or that complex patterns of LD in this region may confound approaches based on common SNPs. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Genetic overlap of schizophrenia and bipolar disorder in a high-density linkage survey in the Portuguese Island population.

Recent family and genome-wide association studies strongly suggest shared genetic risk factors for schizophrenia (SZ) and bipolar disorder (BP). However, linkage studies have not been used to test for statistically significant genome-wide overlap between them. Forty-seven Portuguese families with sibpairs concordant for SZ, BP, or psychosis (PSY, which includes either SZ or psychotic BP) were genotyped for over 57,000 markers using the Affymetrix 50K Xba SNP array. NPL and Kong and Cox LOD scores were calculated in Merlin for all three phenotypes. Empirical significance was determined using 1,000 gene-dropping simulations. Significance of genome-wide genetic overlap between SZ and BP was determined by the number of simulated BP scans having the same number of loci jointly linked with the real SZ scan, and vice versa. For all three phenotypes, a number of regions previously linked in this sample remained so. For BP, chromosome 1p36 achieved significance (11.54-15.71 MB, LOD = 3.51), whereas it was not even suggestively linked at lower marker densities, as did chromosome 11q14.1 (89.32-90.15 MB, NPL = 4.15). Four chromosomes had loci at which both SZ and BP had NPL ≥ 1.98, which was more than would be expected by chance (empirical P = 0.01 using simulated SZ scans; 0.07 using simulated BP scans), although they did not necessarily meet criteria for suggestive linkage individually. These results suggest that high-density marker maps may provide greater power and precision in linkage studies than lower density maps. They also further support the hypothesis that SZ and BP share at least some risk alleles.

Iodine Intake and Related Cognitive Function Impairments in Elementary Schoolchildren.

Iodine deficiency, the most common cause of preventable mental impairment worldwide, has been linked to poorer intellectual function in several studies. However, to our knowledge, no studies have been performed in moderate iodine-deficient schoolchildren using the complete form of Wechsler Intelligence Scale for Children (WISC-III; Portuguese version). The main purpose of this study was to ascertain whether moderate iodine deficiency would affect the cognitive function of schoolchildren (7-11 years old; 3rd and 4th grades). Raven's Colored Progressive Matrices (CPM; Portuguese version) were used for measuring the intelligence quotient (IQ) of the total population (n = 256; median UIC = 66.2 µg/L), and the WISC-III was used to study two selected subgroups: one moderately iodine-deficient (n = 30) and the other with adequate iodine intake (n = 30). WISC-III was shown to be the prime instrument for cognitive function assessment among moderate iodine-deficient schoolchildren; this subgroup had a Full-Scale IQ 15.13 points lower than the adequate iodine intake subgroup, with a magnitude effect of d = 0.7 (p = 0.013). Significant differences were also registered in 6 of the 13 Verbal-Performance IQ subtests. Moderate iodine deficiency has a substantial impact on mental development and cognitive functioning of schoolchildren, with significant impairment in both Performance IQ and Verbal IQ spectrum, adversely impacting their educational performance.

Expression Profiling in Ovarian Cancer Reveals Coordinated Regulation of BRCA1/2 and Homologous Recombination Genes.

Predictive biomarkers are crucial in clarifying the best strategy to use poly(ADP-ribose) polymerase inhibitors (PARPi) for the greatest benefit to ovarian cancer patients. PARPi are specifically lethal to cancer cells that cannot repair DNA damage by homologous recombination (HR), and HR deficiency is frequently associated with BRCA1/2 mutations. Genetic tests for BRCA1/2 mutations are currently used in the clinic, but results can be inconclusive due to the high prevalence of rare DNA sequence variants of unknown significance. Most tests also fail to detect epigenetic modifications and mutations located deep within introns that may alter the mRNA. The aim of this study was to investigate whether quantitation of BRCA1/2 mRNAs in ovarian cancer can provide information beyond the DNA tests. Using the nCounter assay from NanoString Technologies, we analyzed RNA isolated from 38 ovarian cancer specimens and 11 normal fallopian tube samples. We found that BRCA1/2 expression was highly variable among tumors. We further observed that tumors with lower levels of BRCA1/2 mRNA showed downregulated expression of 12 additional HR genes. Analysis of 299 ovarian cancer samples from The Cancer Genome Atlas (TCGA) confirmed the coordinated expression of BRCA1/2 and HR genes. To facilitate the routine analysis of BRCA1/2 mRNA in the clinical setting, we developed a targeted droplet digital PCR approach that can be used with FFPE samples. In conclusion, this study underscores the potential clinical benefit of measuring mRNA levels in tumors when BRCA1/2 DNA tests are negative or inconclusive.

The neurocognitive and functional profile of schizophrenia in a genetically homogenous European sample.

Schizophrenia is a complex heritable brain disorder that entails significant social, neurocognitive, and functional deficits, and significant psychosocial challenges to affected and unaffected family members. In this cross-sectional study, we explore impairments in specific neurocognitive and social cognition processes in patients affected with schizophrenia, unaffected relatives, and in controls to provide a characterization of a genetically homogenous European sample from an endophenotypic and functional standpoint. A sample of 38 affected patients, 28 first-degree relatives, and 97 controls performed a series of computerized and skills-based assessments. Samples were compared across several neurocognitive, social, and functional domains. Significant impairments in episodic memory, executive function, social cognition, complex cognition, sensorimotor domains were found in patients and first-degree relatives. Findings also showed increased processing speed in memory and other complex cognitive processes relevant to autonomous living. A discriminant function analysis yielded 2 functions allowing 79% of correct group classifications based on social cognition and functional skills, neurocognition, and age. The study highlights the importance of resourcing to wide-ranging assessment methodologies, of developing research efforts to further understand the decline of social and neurocognitive processes, and the need for designing more targeted intervention strategies to be implemented both with affected patients and families.

The mediating role of unmet needs in the relationship between displacement and psychological adjustment: A study of cancer survivors from a Portuguese island region.

PURPOSE: The present study aims to explore whether the association between previous displacement to mainland Portugal to perform cancer therapy and current psychological adaptation is mediated by cancer survivors' unmet needs in terms of their emotional experience, financial concerns, access and continuity of care, and relations with others. METHOD: This cross-sectional study included a sample of 173 cancer survivors from the Azores archipelago (Portugal) recruited from a local oncological health unit. Participants completed a sociodemographic and clinical questionnaire and self-report measures assessing their unmet needs and psychological adaptation. Two parallel multiple mediation models were tested. RESULTS: Azorean cancer survivors live with unmet needs, especially emotional needs (M = 16.68, SD = 10.78). Displacement was indirectly associated with both anxious (indirect effect = 0.58, SE = 0.27, 95% Bias Corrected and accelerated Confidence Interval = [0.05, 1.15]) and depressive symptomatology (indirect effect = 0.36, SE = 0.17, 95% Bias Corrected and accelerated Confidence Interval = [0.03, 0.84]) through unmet emotional needs. CONCLUSION: Previous displacements seem to play an important role in the way cancer survivors adapt to survivorship by contributing to higher levels of unmet emotional needs. These findings can provide a scientific and clinical contribution to other isolated or island regions in the world where survivors face similar constraints.

Depletion of the yeast nuclear exosome subunit Rrp6 results in accumulation of polyadenylated RNAs in a discrete domain within the nucleolus.

Recent data reveal that a substantial fraction of transcripts generated by RNA polymerases I, II, and III are rapidly degraded in the nucleus by the combined action of the exosome and a noncanonical poly(A) polymerase activity. This work identifies a domain within the yeast nucleolus that is enriched in polyadenylated RNAs in the absence of the nuclear exosome RNase Rrp6 or the exosome cofactor Mtr4. In normal yeast cells, poly(A)(+) RNA was undetectable in the nucleolus but the depletion of either Rrp6 or Mtr4 led to the accumulation of polyadenylated RNAs in a discrete subnucleolar region. This nucleolar poly(A) domain is enriched for the U14 snoRNA and the snoRNP protein Nop1 but is distinct from the nucleolar body that functions in snoRNA maturation. In strains lacking both Rrp6 and the poly(A) polymerase Trf4, the accumulation of poly(A)(+) RNA was suppressed, suggesting the involvement of the Trf4-Air1/2-Mtr4 polyadenylation (TRAMP) complex. The accumulation of polyadenylated snoRNAs in a discrete nucleolar domain may promote their recognition as substrates for the exosome.