Exploring the highly reduced spliceosome of Pseudoloma neurophilia.

Spliceosomal introns evolved early in eukaryogenesis, originating from self-splicing group II introns that invaded the proto-eukaryotic genome1. Elements of these ribozymes, now called snRNAs (U1, U2, U4, U5, U6), were co-opted to excise these invasive elements. Prior to eukaryotic diversification, the spliceosome is predicted to have accumulated hundreds of proteins2. This early complexification has obscured our understanding of spliceosomal evolution. Reduced systems with few introns and tiny spliceosomes give insights into the plasticity of the splicing reaction and provide an opportunity to study the evolution of the spliceosome3,4. Microsporidia are intracellular parasites possessing extremely reduced genomes that have lost many, and in some instances all, introns5. In the purportedly intron-lacking genome of the microsporidian Pseudoloma neurophilia6, we identified two introns that are spliced at high levels. Furthermore, with only 14 predicted proteins, the P. neurophilia spliceosome could be the smallest known. Intriguingly, the few proteins retained are divergent compared to canonical orthologs. Even the central spliceosomal protein Prp8, which originated from the proteinaceous component of group II introns, is extremely divergent. This is unusual given that Prp8 is highly conserved across eukaryotes, including other microsporidia. All five P. neurophilia snRNAs are present, and all but U2 have diverged extensively, likely resulting from the loss of interacting proteins. Despite this divergence, U1 and U2 are predicted to pair with intron sequences more extensively than previously described. The P. neurophilia spliceosome is retained to splice a mere two introns and, with few proteins and reliance on RNA-RNA interactions, could function in a manner more reminiscent of presumed ancestral splicing.

Microsporidia.

In this Quick guide, Thomas Whelan and Naomi Fast introduce the microsporidia: obligate intracellular parasites with the most extremely reduced genomes known in eukaryotes.

Contrasting outcomes of genome reduction in mikrocytids and microsporidians.

BACKGROUND: Intracellular symbionts often undergo genome reduction, losing both coding and non-coding DNA in a process that ultimately produces small, gene-dense genomes with few genes. Among eukaryotes, an extreme example is found in microsporidians, which are anaerobic, obligate intracellular parasites related to fungi that have the smallest nuclear genomes known (except for the relic nucleomorphs of some secondary plastids). Mikrocytids are superficially similar to microsporidians: they are also small, reduced, obligate parasites; however, as they belong to a very different branch of the tree of eukaryotes, the rhizarians, such similarities must have evolved in parallel. Since little genomic data are available from mikrocytids, we assembled a draft genome of the type species, Mikrocytos mackini, and compared the genomic architecture and content of microsporidians and mikrocytids to identify common characteristics of reduction and possible convergent evolution. RESULTS: At the coarsest level, the genome of M. mackini does not exhibit signs of extreme genome reduction; at 49.7 Mbp with 14,372 genes, the assembly is much larger and gene-rich than those of microsporidians. However, much of the genomic sequence and most (8075) of the protein-coding genes code for transposons, and may not contribute much of functional relevance to the parasite. Indeed, the energy and carbon metabolism of M. mackini share several similarities with those of microsporidians. Overall, the predicted proteome involved in cellular functions is quite reduced and gene sequences are extremely divergent. Microsporidians and mikrocytids also share highly reduced spliceosomes that have retained a strikingly similar subset of proteins despite having reduced independently. In contrast, the spliceosomal introns in mikrocytids are very different from those of microsporidians in that they are numerous, conserved in sequence, and constrained to an exceptionally narrow size range (all 16 or 17 nucleotides long) at the shortest extreme of known intron lengths. CONCLUSIONS: Nuclear genome reduction has taken place many times and has proceeded along different routes in different lineages. Mikrocytids show a mix of similarities and differences with other extreme cases, including uncoupling the actual size of a genome with its functional reduction.

Spliceosome assembly and regulation: insights from analysis of highly reduced spliceosomes.

Premessenger RNA splicing is catalyzed by the spliceosome, a multimegadalton RNA-protein complex that assembles in a highly regulated process on each intronic substrate. Most studies of splicing and spliceosomes have been carried out in human or S. cerevisiae model systems. There exists, however, a large diversity of spliceosomes, particularly in organisms with reduced genomes, that suggests a means of analyzing the essential elements of spliceosome assembly and regulation. In this review, we characterize changes in spliceosome composition across phyla, describing those that are most frequently observed and highlighting an analysis of the reduced spliceosome of the red alga Cyanidioschyzon merolae We used homology modeling to predict what effect splicing protein loss would have on the spliceosome, based on currently available cryo-EM structures. We observe strongly correlated loss of proteins that function in the same process, for example, in interacting with the U1 snRNP (which is absent in C. merolae), regulation of Brr2, or coupling transcription and splicing. Based on our observations, we predict splicing in C. merolae to be inefficient, inaccurate, and post-transcriptional, consistent with the apparent trend toward its elimination in this lineage. This work highlights the striking flexibility of the splicing pathway and the spliceosome when viewed in the context of eukaryotic diversity.

Microsporidian Introns Retained against a Background of Genome Reduction: Characterization of an Unusual Set of Introns.

Spliceosomal introns are ubiquitous features of eukaryotic genomes, but the mechanisms responsible for their loss and gain are difficult to identify. Microsporidia are obligate intracellular parasites that have significantly reduced genomes and, as a result, have lost many if not all of their introns. In the microsporidian Encephalitozoon cuniculi, a relatively long intron was identified and was spliced at higher levels than the remaining introns. This long intron is part of a set of unique introns in two unrelated genes that show high levels of sequence conservation across diverse microsporidia. The introns possess a unique internal conserved region, which overlaps with a shared, predicted stem-loop structure. The unusual similarity and retention of these long introns in reduced microsporidian genomes could indicate that these introns function similarly, are homologous, or both. Regardless, the significant genome reduction in microsporidia provides a rare opportunity to understand intron evolution.

Midwives' perceptions and experiences of engaging fathers in perinatal services.

BACKGROUND: The active engagement of fathers in maternity care is associated with long-term benefits for the father, their partner, and their child. Midwives are ideally placed to engage fathers, but few studies have explored midwives' experiences of working with men. Therefore, the aim of this study was to describe midwives' perceptions and experiences of engaging fathers in perinatal services. METHOD: A multi-method approach was utilised. Registered midwives (N=106) providing perinatal services to families in Australia participated in an online survey. Of these, 13 also participated in semi-structured telephone interviews. Descriptive analyses summarised the online survey data. The interview data were coded using semantic thematic analysis. RESULTS: Survey results indicated that midwives unanimously agreed that engaging fathers is part of their role and acknowledged the importance of receiving education to develop knowledge and skills about fathers. Analysis of the telephone interviews led to the identification of a range of strategies, facilitators and barriers to engaging fathers in midwifery services. Some of these were related to characteristics of midwives, factors related specifically to fathers, and several external factors relating to organisational policies. CONCLUSIONS: Findings from this study could inform maternity health care policies, as well the development of resources, education and ongoing professional training for midwives to promote father-inclusive practice.

Fathers' postnatal distress, parenting self-efficacy, later parenting behavior, and children's emotional-behavioral functioning: A longitudinal study.

Fathers' postnatal distress has been associated with subsequent emotional and behavioral problems for children; however, the mechanisms by which this occurs have received less attention. One potential pathway could be via the negative effects that father mental health problems and parenting self-efficacy (PSE) in the postnatal period have on later parenting behaviors. Using a nationally representative cohort of Australian father-child dyads (N = 3,741), the long-term relationships between fathers' psychological distress and PSE in the postnatal period, parenting behavior when children were aged 4-5 years, and emotional-behavioral outcomes for children aged 8-9 years were explored. Path analysis indicated that high distress and low PSE in the postnatal period was associated with higher levels of hostile parenting and lower parenting consistency when children were aged 4-5 years; in turn, these were associated with poorer child outcomes at 8-9 years. These results remained significant after controlling for socioeconomic position, couple relationship quality, mothers' and fathers' mental health, and fathers' concurrent parenting behavior. The pathways among PSE, parenting hostility, parenting consistency, and children's outcomes at age 8-9 years differed for fathers of boys compared with fathers of girls. Results highlight the importance of father-inclusive assessments of postnatal mental health. Support programs targeting new fathers' perceptions of parenting competence may be particularly important for fathers experiencing postnatal distress. For fathers, building a stronger sense of parenting competence in the postnatal period is important for later parenting behavior, which relates to children's emotional and behavioral outcomes during middle childhood. (PsycINFO Database Record

A SYSTEMATIC REVIEW OF INTERVENTIONS TARGETING PATERNAL MENTAL HEALTH IN THE PERINATAL PERIOD.

Interventions targeting parents' mental health in the perinatal period are critical due to potential consequences of perinatal mental illness for the parent, the infant, and their family. To date, most programs have targeted mothers. This systematic review explores the current status and evidence for intervention programs aiming to prevent or treat paternal mental illness in the perinatal period. Electronic databases were systematically searched to identify peer-reviewed studies that described an intervention targeting fathers' mental health in the perinatal period. Mental health outcomes included depression, anxiety, and stress as well as more general measures of psychological functioning. Eleven studies were identified. Three of five psychosocial interventions and three massage-technique interventions reported significant effects. None of the couple-based interventions reported significant effects. A number of methodological limitations were identified, including inadequate reporting of study designs, and issues with the timing of interventions. The variability in outcomes measures across the studies made it difficult to evaluate the overall effectiveness of the interventions. Father-focused interventions aimed at preventing perinatal mood problems will be improved if future studies utilize more rigorous research strategies.

Modifiable partner factors associated with perinatal depression and anxiety: a systematic review and meta-analysis.

BACKGROUND: Perinatal distress is a significant public health problem that adversely impacts the individual and their family. The primary objective of this systematic review and meta-analysis was to identify factors that partners can modify to protect each other from developing perinatal depression and anxiety. METHOD: In accordance with the PRISMA statement, we reviewed the risk and protective factors associated with perinatal depression and anxiety symptoms that partners can potentially modify without professional assistance (PROSPERO reference CRD42014007524). Participants were new or expectant parents aged 16 years or older. The partner factors were sub-grouped into themes (e.g., instrumental support) based on a content analysis of the scale items and measure descriptions. A series of meta-analyses were conducted to estimate the pooled effect sizes of associations. RESULTS: We included 120 publications, reporting 245 associations with depression and 44 with anxiety. Partner factors with sound evidence that they protect against both perinatal depression and anxiety are: emotional closeness and global support. Partner factors with a sound evidence base for depression only are communication, conflict, emotional and instrumental support, and relationship satisfaction. LIMITATIONS: This review is limited by the lack of generalizability to single parents and the inability to systematically review moderators and mediators, or control for baseline symptoms. CONCLUSION: The findings suggest that future prevention programs targeting perinatal depression and anxiety should aim to enhance relationship satisfaction, communication, and emotional closeness, facilitate instrumental and emotional support, and minimize conflict between partners.

The relationship between grandparent satisfaction, meaning, and generativity.

This study investigated predictors of grandparent satisfaction. Participants were 149 non-custodial grandparents (100 grandmothers, 49 grandfathers) aged up to 80 years. They completed grandparent satisfaction, meaning, and generativity scales, and indicated levels of weekly childcare contact with grandchildren. As expected, increasing levels of generativity predicted greater satisfaction, as did valued elder and centrality meanings. Unexpectedly, reinvolvement, immortality, and indulgence meanings were not predictors, nor was childcare contact. There was only partial support for grandparent gender as a predictor: being a grandmother predicted greater satisfaction, but this effect disappeared when the meaning and generativity variables were included in the analysis. In conclusion, the findings highlight the significance the role can have for many grandparents. Grandparenting can be satisfying because it provides a sense of purpose, and feeling of being valued during middle and later life when generative developmental needs are greatest.