Identification of depression and anxiety during pregnancy: A systematic review and meta-analysis of test accuracy.

INTRODUCTION: Depression and anxiety are significant contributors to maternal perinatal morbidity and a range of negative child outcomes. This systematic review and meta-analysis aimed to review and assess the diagnostic test accuracy of selected screening tools (Edinburgh Postnatal Depression Scale [EPDS], EPDS-3A, Patient Health Questionnaire [PHQ-9]-, PHQ-2, Matthey Generic Mood Question [MGMQ], Generalized Anxiety Disorder scale [GAD-7], GAD-2, and the Whooley questions) used to identify women with antenatal depression or anxiety in Western countries. MATERIAL AND METHODS: On January 16, 2023, we searched 10 databases (CINAHL, Cochrane Library, CRD Database, Embase, Epistemonikos, International HTA Database, KSR Evidence, Ovid MEDLINE, PROSPERO and PsycINFO); the references of included studies were also screened. We included studies of any design that compared case-identification with a relevant screening tool to the outcome of a diagnostic interview based on the Diagnostic and Statistical Manual of Mental Disorders, fourth or fifth edition (DSM-IV or DSM-5), or the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10). Diagnoses of interest were major depressive disorder and anxiety disorders. Two authors independently screened abstracts and full-texts for relevance and evaluated the risk of bias using QUADAS-2. Data extraction was performed by one person and checked by another team member for accuracy. For synthesis, a bivariate model was used. The certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). REGISTRATION: PROSPERO CRD42021236333. RESULTS: We screened 8276 records for eligibility and included 16 original articles reporting on diagnostic test accuracy: 12 for the EPDS, one article each for the GAD-2, MGMQ, PHQ-9, PHQ-2, and Whooley questions, and no articles for the EPDS-3A or GAD-7. Most of the studies had moderate to high risk of bias. Ten of the EPDS articles provided data for synthesis at cutoffs ≥10 to ≥14 for diagnosing major depressive disorder. Cutoff ≥10 gave the optimal combined sensitivity (0.84, 95% confidence interval [CI]: 0.75-0.90) and specificity (0.87, 95% CI: 0.79-0.92). CONCLUSIONS: Findings from the meta-analysis suggest that the EPDS alone is not perfectly suitable for detection of major depressive disorder during pregnancy. Few studies have evaluated the other instruments, therefore, their usefulness for identification of women with depression and anxiety during pregnancy remains very uncertain. At present, case-identification with any tool may best serve as a complement to a broader dialogue between healthcare professionals and their patients.

Immune globulin subcutaneous, human 20% solution (Xembify®), a new high concentration immunoglobulin product for subcutaneous administration.

Immune globulin subcutaneous, human 20% solution (IGSC-C 20%, Xembify®)-a new 20% immunoglobulin (IgG) liquid product for subcutaneous (SC) administration-has been developed by Grifols. The IGSC-C 20% formulation is based on knowledge acquired from the formulation of Immune Globulin Injection (Human),10% Caprylate/Chromatography Purified (IGIV-C 10%, Gamunex®-C). The protein concentration was increased from 10% to 20% to provide a smaller volume for SC administration. The IGSC-C 20% manufacturing process employs the same caprylate/chromatography purification steps as IGIV-C 10%, with the addition of an ultrafiltration step so that the product can be formulated at a higher protein concentration. IGSC-C 20% has been produced at full industrial scale to support clinical studies and licensure. These batches were characterized using a comprehensive panel of analytical testing. The new IGSC-C 20% product maintains the same composition, neutralizing activity, purity, and quality characteristics found in IGIV-C 10%.

Immunoglobulin G from single plasma donor in immune globulin intravenous causes false positive pyrogen test.

A sudden, unprecedented failure of USP rabbit pyrogen tests for multiple 10% IGIV-C lots prompted a thorough investigation of the root cause for this phenomenon. All microbe-related testing, including Limulus amebocyte lysate test for endotoxin, proved negative, and no deficiencies were discovered in manufacturing. Plasma pool composition analysis revealed that a single plasma donor ("Donor X″) was common to all pyrogenic IGIV-C lots and that as little as one unit of "Donor X″ plasma (in a pool of ∼4500 units) was sufficient to cause IGIV-C lot failure in the USP rabbit pyrogen test. Whole plasma and Protein A-purified IgG from "Donor X″ caused a temperature increase in rabbits; however, all IgG samples tested pyrogen-negative in two in vitro cell-based pyrogen tests. Flow cytometry showed that "Donor X″ IgG bound strongly to rabbit white blood cells (WBC) but minimally to human WBC. Exclusion of "Donor X″ plasma from manufacturing marked the end of IGIV-C lots registering positive in the USP rabbit pyrogen test. This failure of multiple 10% IGIV-C lots to pass the USP rabbit pyrogen test was demonstrated to be due to the highly unusual anti-rabbit-leukocyte specificity of IgG from a single donor.

An Interaction between RRP6 and SU(VAR)3-9 Targets RRP6 to Heterochromatin and Contributes to Heterochromatin Maintenance in Drosophila melanogaster.

RNA surveillance factors are involved in heterochromatin regulation in yeast and plants, but less is known about the possible roles of ribonucleases in the heterochromatin of animal cells. Here we show that RRP6, one of the catalytic subunits of the exosome, is necessary for silencing heterochromatic repeats in the genome of Drosophila melanogaster. We show that a fraction of RRP6 is associated with heterochromatin, and the analysis of the RRP6 interaction network revealed physical links between RRP6 and the heterochromatin factors HP1a, SU(VAR)3-9 and RPD3. Moreover, genome-wide studies of RRP6 occupancy in cells depleted of SU(VAR)3-9 demonstrated that SU(VAR)3-9 contributes to the tethering of RRP6 to a subset of heterochromatic loci. Depletion of the exosome ribonucleases RRP6 and DIS3 stabilizes heterochromatic transcripts derived from transposons and repetitive sequences, and renders the heterochromatin less compact, as shown by micrococcal nuclease and proximity-ligation assays. Such depletion also increases the amount of HP1a bound to heterochromatic transcripts. Taken together, our results suggest that SU(VAR)3-9 targets RRP6 to a subset of heterochromatic loci where RRP6 degrades chromatin-associated non-coding RNAs in a process that is necessary to maintain the packaging of the heterochromatin.

Support interventions to reduce psychological distress in families experiencing stillbirth in high income countries: A systematic review.

BACKGROUND: Previous research indicates disparities in the care of bereaved parents and siblings following a stillbirth in the family. The aim of this systematic review was to assess the effects of interventions aimed at reducing psychological distress among parents or siblings in high-income countries after experiencing a stillbirth. METHODS: The databases CINAHL, Medline, PsycInfo, Cochrane Library, and EMBASE were searched in August 2022. RESULTS: Four intervention studies from the United States (US), the United Kingdom (UK), Finland, and Australia, met the inclusion criteria. The interventions comprised a perinatal grief support team; a perinatal counselling service; a grief support program; and a support package including contacts with peer supporters and health care staff. No studies of interventions for siblings were found. The results could not be synthesised due to disparities in interventions and outcome measures. The risk of bias was assessed as high in all four studies and the certainty for all outcomes was rated as very low. CONCLUSION: More controlled trials with rigorous methods are needed to evaluate the effect of bereavement support interventions in parents and siblings after stillbirth. Future studies should include a core outcome set to make them more comparable. Most of the studies in this review were assessed to have an overall high risk of bias, mainly due to problems with missing outcome data; thus, future studies could specifically target this problem.

Production and purification of TAL6003: a novel version of the protease plasmin.

TAL6003 is an engineered form of human plasmin under development for thrombolytic therapy. TAL6003 (38.2kDa) contains nine disulfide bonds distributed within and between its two functional domains, a 25.2 kDa serine protease domain linked to a 13.0 kDa kringle I domain; kringles 2-5 present in native human plasmin have been deleted from this plasmin molecule. TAL6003 is expressed as its zymogen in Escherichia coli and is harvested in inclusion bodies. Following solubilization of inclusion bodies with urea as the chaotrope and glutathione as the reducing agent, this zymogen is refolded by dilution to a final concentration of 0.5mg/ml, with a yield of 48% (relative to total zymogen). Refolded TAL6003 zymogen is filtered, diafiltered, and filtered again prior to capture and purification on SP Sepharose, which is highly effective in removing host-cell protein. Subsequent affinity purification on ECH-Lysine Sepharose serves to capture polypeptide chains containing correctly refolded kringle 1 domain, which is the locus of the molecule's lysine-binding site, and to further eliminate host-cell protein. TAL6003 zymogen eluted from the ECH-Lysine Sepharose column is activated to TAL6003 with streptokinase, with an activity yield of approximately 80%. Proteolytically active TAL6003 is stripped of streptokinase by passage through an anion-exchange (Q) membrane and is then affinity purified on Benzamidine Sepharose, which serves to remove unreacted TAL6003 zymogen and proteolytically degraded TAL6003. An ultrafiltration/diafiltration step, to concentrate and to formulate TAL6003, completes the purification process. The final product exhibited a specific activity of close to unity and high purity by several relevant criteria.

Approaches to neuroprotection in pediatric neurocritical care.

Acute neurologic injuries represent a common cause of morbidity and mortality in children presenting to the pediatric intensive care unit. After primary neurologic insults, there may be cerebral brain tissue that remains at risk of secondary insults, which can lead to worsening neurologic injury and unfavorable outcomes. A fundamental goal of pediatric neurocritical care is to mitigate the impact of secondary neurologic injury and improve neurologic outcomes for critically ill children. This review describes the physiologic framework by which strategies in pediatric neurocritical care are designed to reduce the impact of secondary brain injury and improve functional outcomes. Here, we present current and emerging strategies for optimizing neuroprotective strategies in critically ill children.

Care and support when a baby is stillborn: A systematic review and an interpretive meta-synthesis of qualitative studies in high-income countries.

INTRODUCTION: Approximately 2 million babies are stillborn annually worldwide, most in low- and middle-income countries. Present review studies of the parental and healthcare providers' experiences of stillbirth often include a variety of settings, which may skew the findings as the available resources can vary considerably. In high-income countries, the prevalence of stillbirth is low, and support programs are often initiated immediately when a baby with no signs of life is detected. There is limited knowledge about what matters to parents, siblings, and healthcare providers when a baby is stillborn in high-income countries. OBJECTIVES: This systematic review and interpretive meta-synthesis aim to identify important aspects of care and support for parents, siblings, and healthcare professionals in high-income countries from the diagnosis of stillbirth throughout the birth and postpartum period. METHODS: A systematic review and qualitative meta-synthesis were conducted to gain a deeper and broader understanding of the available knowledge about treatment and support when stillbirth occurred. Relevant papers were identified by systematically searching international electronic databases and citation tracking. The quality of the included studies was assessed, and the data was interpreted and synthesised using Gadamer's hermeneutics. The review protocol, including qualitative and quantitative study approaches, was registered on PROSPERO (CRD42022306655). RESULTS: Sixteen studies were identified and included in the qualitative meta-synthesis. Experiences of care and support were interpreted and identified as four fusions. First, Personification is of central importance and stresses the need to acknowledge the baby as a unique person. The parents became parents even though their baby was born dead: The staff should also be recognised as the individuals they are with their personal histories. Second, the personification is reinforced by a respectful attitude where the parents are confirmed in their grief; the baby is treated the same way a live baby would be. Healthcare professionals need enough time to process their experiences before caring for other families giving birth. Third, Existential issues about life and death become intensely tangible for everyone involved, and they often feel lonely and vulnerable. Healthcare professionals also reflect on the thin line between life and death and often question their performance, especially when lacking collegial and organisational support. Finally, the fusion Stigmatisation focused on how parents, siblings, and healthcare professionals experienced stigma expressed as a sense of loneliness, vulnerability, and being deviant and marginalised when a baby died before or during birth. GRADE CERQual ratings for the four fusions ranged from moderate to high confidence. CONCLUSIONS: The profound experiences synthesised in the fusions of this meta-synthesis showed the complex impacts the birth of a baby with no signs of life had on everyone involved. These fusions can be addressed and supported by applying person-centred care to all individuals involved. Hence, grief may be facilitated for parents and siblings, and healthcare professionals may be provided with good conditions in their professional practice. Furthermore, continuing education and support to healthcare professionals may facilitate them to provide compassionate care and support to affected parents and siblings. The fusions should also be considered when implementing national recommendations, guidelines, and clinical practice.

Synthesis of stoichiometric FeS2 through plasma-assisted sulfurization of Fe2O3 nanorods.

Pyrite (FeS(2)) thin films were synthesized using a H(2)S plasma to sulfurize hematite (Fe(2)O(3)) nanorods deposited by chemical bath deposition. The high S activity within the plasma enabled a direct solid-state transformation between the two materials, bypassing S-deficient contaminant phases (Fe(1-x)S). The application of plasma dramatically enhanced both the rate of conversion and the quality of the resulting material; stoichiometric FeS(2) was obtained at a moderate temperature of 400 °C using a chalcogen partial pressure <6 × 10(-5) atm. As the S:Fe atomic ratio increased from 0 to 2.0, the apparent optical band gap dropped from 2.2 (hematite) to ~1 eV (pyrite), with completely converted layers exhibiting absorption coefficients >10(5) cm(-1) in the visible range. Room-temperature conductivity of FeS(2) films was on the order of 10(-4) S cm(-1) and approximately doubled under calibrated solar illumination.

Neonatal Aneurysm Rupture in a Child with a De Novo Variant to ANKRD17.

Ankyrin repeat domain 17 (ANKRD17) is postulated to play a role in the integrity of blood vessels and has been reported to be associated with developmental delays, epilepsy, and growth restriction. Whereas ANKRD17-deficient mice have been demonstrated to experience catastrophic hemorrhages, vascular malformations have not been reported in human patients with pathogenic variants to ANKRD17. We report a term male neonate with a heterozygous de novo variant to ANKRD17 (ANKRD17; c6988 C > G, P.[P2330a]) who experienced subarachnoid hemorrhage from a ruptured aneurysm involving the left middle cerebral artery. He experienced acute symptomatic seizures and required clipping of his aneurysm at 35 days of life, later progressing to developing multifocal drug-resistant epilepsy. To our knowledge, this case represents the first report of a cerebrovascular malformation from a patient with ANKRD17. Further work is needed to investigate whether pathogenic variants to ANKRD17 can lead to cerebral aneurysms or other cerebrovascular malformations in children.

A new role for the transcriptional corepressor SIN3; regulation of centromeres.

Centromeres play a vital role in maintaining the genomic stability of eukaryotes by coordinating the equal distribution of chromosomes to daughter cells during mitosis and meiosis. Fission yeast (S. pombe) centromeres consist of a 4-9 kb central core region and 30-100 kb of flanking inner (imr/B) and outer (otr/K) repeats. These sequences direct a laminar kinetochore structure similar to that of human centromeres. Centromeric heterochromatin is generally underacetylated. We have previously shown that inhibition of histone deacetylases (HDACs) caused hyperacetylation of centromeres and defective chromosome segregation. SIN3 is a HDAC corepressor that has the ability to mediate HDAC targeting in the repression of promoters. In this study, we have characterized S. pombe sin three corepressors (Pst1p and Pst2p) to investigate whether SIN3-HDAC is required in the regulation of centromeres. We show that only pst1-1 and not pst2Delta cells displayed anaphase defects and thiabendazole sensitivity. pst1-1 cells showed reduced centromeric silencing, increased histone acetylation in centromeric chromatin, and defective centromeric sister chromatid cohesion. The HDAC Clr6p and Pst1p coimmunoprecipitated, and Pst1p colocalized with centromeres, particularly in binucleate cells. These data are consistent with a model in which Pst1p-Clr6p temporally associate with centromeres to carry out the initial deacetylation necessary for subsequent steps in heterochromatin formation.

Functional divergence between histone deacetylases in fission yeast by distinct cellular localization and in vivo specificity.

Histone deacetylases (HDACs) are important for gene regulation and the maintenance of heterochromatin in eukaryotes. Schizosaccharomyces pombe was used as a model system to investigate the functional divergence within this conserved enzyme family. S. pombe has three HDACs encoded by the hda1(+), clr3(+), and clr6(+) genes. Strains mutated in these genes have previously been shown to display strikingly different phenotypes when assayed for viability, chromosome loss, and silencing. Here, conserved differences in the substrate binding pocket identify Clr6 and Hda1 as class I HDACs, while Clr3 belongs in the class II family. Furthermore, these HDACs were shown to have strikingly different subcellular localization patterns. Hda1 was localized to the cytoplasm, while most of Clr3 resided throughout the nucleus. Finally, Clr6 was localized exclusively on the chromosomes in a spotted pattern. Interestingly, Clr3, the only HDAC present in the nucleolus, was required for ribosomal DNA (rDNA) silencing. Clr3 presumably acts directly on heterochromatin, since it colocalized with the centromere, mating-type region, and rDNA as visualized by in situ hybridization. In addition, Clr3 could be cross-linked to mat3 in chromatin immunoprecipitation experiments. Western analysis of bulk histone preparations indicated that Hda1 (class I) had a generally low level of activity in vivo and Clr6 (class I) had a high level of activity and broad in vivo substrate specificity, whereas Clr3 (class II) displayed its main activity on acetylated lysine 14 of histone H3. Thus, the distinct functions of the S. pombe HDACs are likely explained by their distinct cellular localization and their different in vivo specificities.

A comparison of chemical pretreatment methods for improving saccharification of cotton stalks.

The effectiveness of sulfuric acid (H(2)SO(4)), sodium hydroxide (NaOH), hydrogen peroxide (H(2)O(2)), and ozone pretreatments for conversion of cotton stalks to ethanol was investigated. Ground cotton stalks at a solid loading of 10% (w/v) were pretreated with H(2)SO(4), NaOH, and H(2)O(2) at concentrations of 0.5%, 1%, and 2% (w/v). Treatment temperatures of 90 degrees C and 121 degrees C at 15 psi were investigated for residence times of 30, 60, and 90 min. Ozone pretreatment was performed at 4 degrees C with constant sparging of stalks in water. Solids from H(2)SO(4), NaOH, and H(2)O(2) pretreatments (at 2%, 60 min, 121 degrees C/15 psi) showed significant lignin degradation and/or high sugar availability and hence were hydrolyzed by Celluclast 1.5L and Novozym 188 at 50 degrees C. Sulfuric acid pretreatment resulted in the highest xylan reduction (95.23% for 2% acid, 90 min, 121 degrees C/15 psi) but the lowest cellulose to glucose conversion during hydrolysis (23.85%). Sodium hydroxide pretreatment resulted in the highest level of delignification (65.63% for 2% NaOH, 90 min, 121 degrees C/15 psi) and cellulose conversion (60.8%). Hydrogen peroxide pretreatment resulted in significantly lower (p

Can abstract screening workload be reduced using text mining? User experiences of the tool Rayyan.

BACKGROUND: One time-consuming aspect of conducting systematic reviews is the task of sifting through abstracts to identify relevant studies. One promising approach for reducing this burden uses text mining technology to identify those abstracts that are potentially most relevant for a project, allowing those abstracts to be screened first. OBJECTIVES: To examine the effectiveness of the text mining functionality of the abstract screening tool Rayyan. User experiences were collected. METHODS: Rayyan was used to screen abstracts for 6 reviews in 2015. After screening 25%, 50%, and 75% of the abstracts, the screeners logged the relevant references identified. A survey was sent to users. RESULTS: After screening half of the search result with Rayyan, 86% to 99% of the references deemed relevant to the study were identified. Of those studies included in the final reports, 96% to 100% were already identified in the first half of the screening process. Users rated Rayyan 4.5 out of 5. DISCUSSION: The text mining function in Rayyan successfully helped reviewers identify relevant studies early in the screening process.

The incorporation of 5-fluorouracil into RNA affects the ribonucleolytic activity of the exosome subunit Rrp6.

5-Fluorouracil (5FU) is a fluoropyrimidine used for the treatment of solid tumors. 5FU is a precursor of dTTP and UTP during biogenesis, and it interferes with both DNA and RNA metabolism. The RNA exosome, a multisubunit complex with ribonucleolytic activity, has been identified as one of the targets of 5FU in yeast. Studies in human cells have shown that the catalytic subunit of the nuclear exosome, Rrp6, is specifically targeted. Here, we have investigated the direct effect of 5FU on the activity of Rrp6 in Drosophila S2 cells, and we have identified two aspects of Rrp6 function that are altered by 5FU. First, gel filtration analysis revealed that the repertoire of multimolecular complexes that contain Rrp6 is modified by exposure to 5FU, which is consistent with the proposal that incorporation of 5FU into RNA leads to the sequestration of Rrp6 in ribonucleoprotein complexes. Second, the incorporation of 5FU into RNA renders the RNA less susceptible to degradation by Rrp6, as shown by Rrp6 activity assays in vitro. Our results imply that aberrant transcripts synthesized in 5FU-treated cells cannot be turned over efficiently by the surveillance machinery. Together with previous results on the mechanisms of action of 5FU, our findings suggest that the cytotoxicity of 5FU at the RNA level is the result of at least three different effects: the increased levels of retroviral transcripts with mutagenic potential, the reduced synthesis of ribosomes, and the inhibition of the nuclear RNA surveillance pathways. Drugs that reinforce any of these effects may boost the cytotoxicity of 5FU.

The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins.

Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the exosome is recruited to the transcribed genes. Here we study the core exosome subunit Rrp4 in two insect model systems, Chironomus and Drosophila. We show that a significant fraction of Rrp4 is associated with the nascent pre-mRNPs and that a specific mRNA-binding protein, Hrp59/hnRNP M, interacts in vivo with multiple exosome subunits. Depletion of Hrp59 by RNA interference reduces the levels of Rrp4 at transcription sites, which suggests that Hrp59 is needed for the exosome to stably interact with nascent pre-mRNPs. Our results lead to a revised mechanistic model for cotranscriptional quality control in which the exosome is constantly recruited to newly synthesized RNAs through direct interactions with specific hnRNP proteins.

Sin3: a flexible regulator of global gene expression and genome stability.

SIN3 was first identified genetically as a global regulator of transcription. Sin3 is a large protein composed mainly of protein-interaction domains, whose function is to provide structural support for a heterogeneous Sin3/histone deacetylase (HDAC) complex. The core Sin3/HDAC complex is conserved from yeast to man and consists of eight proteins. In addition to HDACs, Sin3 can sequester other enzymatic functions, including nucleosome remodeling, DNA methylation, N-acetylglucoseamine transferase activity, and histone methylation. Since the Sin3/HDAC complex lacks any DNA-binding activity, it must be targeted to gene promoters by interacting with DNA-binding proteins. Although most research on Sin3 has focused on its role as a corepressor, mounting evidence suggests that Sin3 can also positively regulate transcription. Furthermore, Sin3 is key to the propagation of epigenetically silenced domains and is required for centromere function. Thus, Sin3 provides a platform to deliver multiple combinations modifications to the chromatin, using both sequence-specific and sequence-independent mechanisms.

Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast.

We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast (Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 (class III) and Hos2 (class I) have a role in preventing histone loss; Clr6 (class I) is the principal enzyme in promoter-localized repression. Hos2 has an unexpected role in promoting high expression of growth-related genes by deacetylating H4K16Ac in their open reading frames. Clr3 (class II) acts cooperatively with Sir2 throughout the genome, including the silent regions: rDNA, centromeres, mat2/3 and telomeres. The most significant acetylation sites are H3K14Ac for Clr3 and H3K9Ac for Sir2 at their genomic targets. Clr3 also affects subtelomeric regions which contain clustered stress- and meiosis-induced genes. Thus, this combined genomic approach has uncovered different roles for fission yeast HDACs at the silent regions in repression and activation of gene expression.

Dicer is required for chromosome segregation and gene silencing in fission yeast cells.

RNA interference is a form of gene silencing in which the nuclease Dicer cleaves double-stranded RNA into small interfering RNAs. Here we report a role for Dicer in chromosome segregation of fission yeast. Deletion of the Dicer (dcr1+) gene caused slow growth, sensitivity to thiabendazole, lagging chromosomes during anaphase, and abrogated silencing of centromeric repeats. As Dicer in other species, Dcr1p degraded double-stranded RNA into approximately 23 nucleotide fragments in vitro, and dcr1Delta cells were partially rescued by expression of human Dicer, indicating evolutionarily conserved functions. Expression profiling demonstrated that dcr1+ was required for silencing of two genes containing a conserved motif.