Diverse values of nature for sustainability.

Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature's diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature's values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a 'values crisis' underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature's diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.

Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila.

Acquisition of chromatin modifications during embryogenesis distinguishes different regions of an initially naïve genome. In many organisms, repetitive DNA is packaged into constitutive heterochromatin that is marked by di/trimethylation of histone H3K9 and the associated protein HP1a. These modifications enforce the unique epigenetic properties of heterochromatin. However, in the early Drosophila melanogaster embryo, the heterochromatin lacks these modifications, which appear only later, when rapid embryonic cell cycles slow down at the midblastula transition (MBT). Here we focus on the initial steps restoring heterochromatic modifications in the embryo. We describe the JabbaTrap, a technique for inactivating maternally provided proteins in embryos. Using the JabbaTrap, we reveal a major requirement for the methyltransferase Eggless/SetDB1 in the establishment of heterochromatin. In contrast, other methyltransferases contribute minimally. Live imaging reveals that endogenous Eggless gradually accumulates on chromatin in interphase but then dissociates in mitosis, and its accumulation must restart in the next cell cycle. Cell cycle slowing as the embryo approaches the MBT permits increasing accumulation and action of Eggless at its targets. Experimental manipulation of interphase duration shows that cell cycle speed regulates Eggless. We propose that developmental slowing of the cell cycle times embryonic heterochromatin formation.

Mitigation of age-dependent accumulation of defective mitochondrial genomes.

Unknown processes promote the accumulation of mitochondrial DNA (mtDNA) mutations during aging. Accumulation of defective mitochondrial genomes is thought to promote the progression of heteroplasmic mitochondrial diseases and degenerative changes with natural aging. We used a heteroplasmic Drosophila model to test 1) whether purifying selection acts to limit the abundance of deleterious mutations during development and aging, 2) whether quality control pathways contribute to purifying selection, 3) whether activation of quality control can mitigate accumulation of deleterious mutations, and 4) whether improved quality control improves health span. We show that purifying selection operates during development and growth but is ineffective during aging. Genetic manipulations suggest that a quality control process known to enforce purifying selection during oogenesis also suppresses accumulation of a deleterious mutation during growth and development. Flies with nuclear genotypes that enhance purifying selection sustained higher genome quality, retained more vigorous climbing activity, and lost fewer dopaminergic neurons. A pharmacological agent thought to enhance quality control produced similar benefits. Importantly, similar pharmacological treatment of aged mice reversed age-associated accumulation of a deleterious mtDNA mutation. Our findings reveal dynamic maintenance of mitochondrial genome fitness and reduction in the effectiveness of purifying selection during life. Importantly, we describe interventions that mitigate and even reverse age-associated genome degeneration in flies and in mice. Furthermore, mitigation of genome degeneration improved well-being in a Drosophila model of heteroplasmic mitochondrial disease.

Temporal control of late replication and coordination of origin firing by self-stabilizing Rif1-PP1 hubs in Drosophila.

In the metazoan S phase, coordinated firing of clusters of origins replicates different parts of the genome in a temporal program. Despite advances, neither the mechanism controlling timing nor that coordinating firing of multiple origins is fully understood. Rif1, an evolutionarily conserved inhibitor of DNA replication, recruits protein phosphatase 1 (PP1) and counteracts firing of origins by S-phase kinases. During the midblastula transition (MBT) in Drosophila embryos, Rif1 forms subnuclear hubs at each of the large blocks of satellite sequences and delays their replication. Each Rif1 hub disperses abruptly just prior to the replication of the associated satellite sequences. Here, we show that the level of activity of the S-phase kinase, DDK, accelerated this dispersal program, and that the level of Rif1-recruited PP1 retarded it. Further, Rif1-recruited PP1 supported chromatin association of nearby Rif1. This influence of nearby Rif1 can create a "community effect" counteracting kinase-induced dissociation such that an entire hub of Rif1 undergoes switch-like dispersal at characteristic times that shift in response to the balance of Rif1-PP1 and DDK activities. We propose a model in which the spatiotemporal program of late replication in the MBT embryo is controlled by self-stabilizing Rif1-PP1 hubs, whose abrupt dispersal synchronizes firing of associated late origins.

TALE-light imaging reveals maternally guided, H3K9me2/3-independent emergence of functional heterochromatin in Drosophila embryos.

Metazoans start embryogenesis with a relatively naïve genome. The transcriptionally inert, late-replicating heterochromatic regions, including the constitutive heterochromatin on repetitive sequences near centromeres and telomeres, need to be re-established during development. To explore the events initiating heterochromatin formation and examine their temporal control, sequence specificity, and immediate regulatory consequence, we established a live imaging approach that enabled visualization of steps in heterochromatin emergence on specific satellite sequences during the mid-blastula transition (MBT) in Drosophila. Unexpectedly, only a subset of satellite sequences, including the 359-base-pair (bp) repeat sequence, recruited HP1a at the MBT. The recruitment of HP1a to the 359-bp repeat was dependent on HP1a's chromoshadow domain but not its chromodomain and was guided by maternally provided signals. HP1a recruitment to the 359-bp repeat was required for its programmed shift to later replication, and ectopic recruitment of HP1a was sufficient to delay replication timing of a different repeat. Our results reveal that emergence of constitutive heterochromatin follows a stereotyped developmental program in which different repetitive sequences use distinct interactions and independent pathways to arrive at a heterochromatic state. This differential emergence of heterochromatin on various repetitive sequences changes their replication order and remodels the DNA replication schedule during embryonic development.

Interphase-arrested Drosophila embryos activate zygotic gene expression and initiate mid-blastula transition events at a low nuclear-cytoplasmic ratio.

Externally deposited eggs begin development with an immense cytoplasm and a single overwhelmed nucleus. Rapid mitotic cycles restore normality as the ratio of nuclei to cytoplasm (N/C) increases. A threshold N/C has been widely proposed to activate zygotic genome transcription and onset of morphogenesis at the mid-blastula transition (MBT). To test whether a threshold N/C is required for these events, we blocked N/C increase by down-regulating cyclin/Cdk1 to arrest early cell cycles in Drosophila. Embryos that were arrested two cell cycles prior to the normal MBT activated widespread transcription of the zygotic genome including genes previously described as N/C dependent. Zygotic transcription of these genes largely retained features of their regulation in space and time. Furthermore, zygotically regulated post-MBT events such as cellularization and gastrulation movements occurred in these cell cycle-arrested embryos. These results are not compatible with models suggesting that these MBT events are directly coupled to N/C. Cyclin/Cdk1 activity normally declines in tight association with increasing N/C and is regulated by N/C. By experimentally promoting the decrease in cyclin/Cdk1, we uncoupled MBT from N/C increase, arguing that N/C-guided down-regulation of cyclin/Cdk1 is sufficient for genome activation and MBT.

From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition.

Many, if not most, embryos begin development with extremely short cell cycles that exhibit unusually rapid DNA replication and no gap phases. The commitment to the cell cycle in the early embryo appears to preclude many other cellular processes that only emerge as the cell cycle slows just prior to gastrulation at a major embryonic transition known as the mid-blastula transition (MBT). As reviewed here, genetic and molecular studies in Drosophila have identified changes that extend S phase and introduce a post-replicative gap phase, G2, to slow the cell cycle. Although many mysteries remain about the upstream regulators of these changes, we review the core mechanisms of the change in cell cycle regulation and discuss advances in our understanding of how these might be timed and triggered. Finally, we consider how the elements of this program may be conserved or changed in other organisms.

Rif1 prolongs the embryonic S phase at the Drosophila mid-blastula transition.

In preparation for dramatic morphogenetic events of gastrulation, rapid embryonic cell cycles slow at the mid-blastula transition (MBT). In Drosophila melanogaster embryos, down-regulation of cyclin-dependent kinase 1 (Cdk1) activity initiates this slowing by delaying replication of heterochromatic satellite sequences and extending S phase. We found that Cdk1 activity inhibited the chromatin association of Rap1 interacting factor 1 (Rif1), a candidate repressor of replication. Furthermore, Rif1 bound selectively to satellite sequences following Cdk1 down-regulation at the MBT. In the next S phase, Rif1 dissociated from different satellites in an orderly schedule that anticipated their replication. Rif1 lacking potential phosphorylation sites failed to dissociate and dominantly prevented completion of replication. Loss of Rif1 in mutant embryos shortened the post-MBT S phase and rescued embryonic cell cycles disrupted by depletion of the S phase-promoting kinase, cell division cycle 7 (Cdc7). Our work shows that Rif1 and S phase kinases compose a replication timer controlling first the developmental onset of late replication and then the precise schedule of replication within S phase. In addition, we describe how onset of late replication fits into the progressive maturation of heterochromatin during development.

Obstetrical and Newborn Outcomes Among Patients With SARS-CoV-2 During Pregnancy.

We report on the perinatal outcomes of pregnant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 2 hospitals in Montréal, Québec. Outcomes of 45 patients with SARS-CoV-2 during pregnancy were compared with those of 225 patients without infection. Sixteen percent of patients with SARS-CoV-2 delivered preterm, compared with 9% of patients without (P = 0.28). Median gestational age at delivery (39.3 (interquartile range [IQR] 37.7-40.4) wk vs. 39.1 [IQR 38.3-40.1] wk) and median birth weight (3250 [IQR 2780-3530] g vs. 3340 [IQR 3025-3665] g) were similar between groups. The rate of cesarean delivery was 29% for patients with SARS-CoV-2. Therefore, we did not find important differences in outcomes associated with SARS-CoV-2. Our findings may be limited to women with mild COVID-19 diagnosed in the third trimester.

Embryonic onset of late replication requires Cdc25 down-regulation.

The Drosophila midblastula transition (MBT), a major event in embryogenesis, remodels and slows the cell cycle. In the pre-MBT cycles, all genomic regions replicate simultaneously in rapid S phases that alternate with mitosis, skipping gap phases. At the MBT, down-regulation of Cdc25 phosphatase and the resulting inhibitory phosphorylation of the mitotic kinase Cdk1 create a G2 pause in interphase 14. However, an earlier change in interphase 14 is the prolongation of S phase. While the signals modifying S phase are unknown, the onset of late replication-where replication of constitutively heterochromatic satellite sequences is delayed-extends S-phase 14. We injected Cdc25 mRNA to bypass the developmentally programmed down-regulation of Cdc25 at the MBT. Introduction of either Cdc25 isoform (String or Twine) or enhanced Cdk1 activity triggered premature replication of late-replicating sequences, even after their specification, and thereby shortened S phase. Reciprocally, reduction of Cdk1 activity by knockdown of mitotic cyclins extended pre-MBT S phase. These findings suggest that high Cdc25 and Cdk1 contribute to the speed of the rapid, pre-MBT S phases and that down-regulation of these activities plays a broader role in MBT-associated changes than was previously suspected.

Timing the Drosophila Mid-Blastula Transition: A Cell Cycle-Centered View.

At the mid-blastula transition (MBT), externally developing embryos refocus from increasing cell number to elaboration of the body plan. Studies in Drosophila reveal a sequence of changes in regulators of Cyclin:Cdk1 that increasingly restricts the activity of this cell cycle kinase to slow cell cycles during early embryogenesis. By reviewing these events, we provide an outline of the mechanisms slowing the cell cycle at and around the time of MBT. The perspectives developed should provide a guiding paradigm for the study of other MBT changes as the embryo transits from maternal control to a regulatory program centered on the expression of zygotic genes.

Perceptions of impact: Invasive alien plants in the urban environment.

Many alien plant species are introduced to urban areas to create, augment or restore ecosystem services (ES). However, many of these species spread beyond original plantings, sometimes causing negative effects on existing ES or creating novel ecosystem disservices (EDS). An understanding of the perceptions of urban residents regarding invasive alien plants (IAPs) and the ES and EDS they provide is needed for the effective prioritisation of IAP management efforts in cities. Using the city of Cape Town, South Africa as a case study, we conducted questionnaire-based surveys (online and face-to-face) to determine the perceptions of urban residents regarding IAPs and their capacity to provide ES and EDS. Most urban residents perceive IAPs negatively (i.e. agreeing that they create EDS), but many recognise their importance in providing ES. Although most residents are not opposed to the management of IAPs, such actions are not perceived as a high priority relative to other environmental problems. Socio-demographic variables such as age, education, environmental awareness, and ethnicity shape urban residents' perceptions of IAPs. Older, more educated respondents were more likely to perceive IAPs negatively, while respondents with greater environmental awareness were aware of the benefits provided by IAPs. This study highlights the need to integrate public perceptions into the planning and management of IAPs and emphasises the importance of including ES assessments into the decision-making process, particularly in urban areas.

Navigating complexity through knowledge coproduction: Mainstreaming ecosystem services into disaster risk reduction.

Achieving the policy and practice shifts needed to secure ecosystem services is hampered by the inherent complexities of ecosystem services and their management. Methods for the participatory production and exchange of knowledge offer an avenue to navigate this complexity together with the beneficiaries and managers of ecosystem services. We develop and apply a knowledge coproduction approach based on social-ecological systems research and assess its utility in generating shared knowledge and action for ecosystem services. The approach was piloted in South Africa across four case studies aimed at reducing the risk of disasters associated with floods, wildfires, storm waves, and droughts. Different configurations of stakeholders (knowledge brokers, assessment teams, implementers, and bridging agents) were involved in collaboratively designing each study, generating and exchanging knowledge, and planning for implementation. The approach proved useful in the development of shared knowledge on the sizable contribution of ecosystem services to disaster risk reduction. This knowledge was used by stakeholders to design and implement several actions to enhance ecosystem services, including new investments in ecosystem restoration, institutional changes in the private and public sector, and innovative partnerships of science, practice, and policy. By bringing together multiple disciplines, sectors, and stakeholders to jointly produce the knowledge needed to understand and manage a complex system, knowledge coproduction approaches offer an effective avenue for the improved integration of ecosystem services into decision making.

A multi-criterion approach for prioritizing areas in urban ecosystems for active restoration following invasive plant control.

Resources for biodiversity conservation and invasive plant management are limited, and restoring invaded vegetation is labour-intensive and expensive. Managers must prioritize their actions to achieve their goals efficiently and effectively. They must distinguish between areas that require only the removal of invasive alien plants ("passive restoration") from those that require additional restoration measures ("active restoration"). This study used a multi-criterion approach (Analytical Hierarchical Process) to develop a framework for identifying areas that require active restoration, and then to prioritize these areas for active restoration. The South African city of Cape Town is used as a test case to illustrate the utility of the framework. Framework criteria selected in determining the need for active restoration included: dominant alien species invading the area, density of invasion, duration of invasion, indigenous vegetation cover, adjacent land use, level of disturbance, size of the area, aspect, soil texture, soil depth and erodibility, slope and vegetation type. In deciding which areas to prioritize for active restoration, factors such as vegetation conservation status, selection in a regional conservation plan and connectivity function were assessed. Importance in ecosystem functioning (by providing a diversity of habitats and soil conservation) and the delivery of ecosystem service benefits were also considered. The resulting framework provides an objective tool for prioritizing sites for active restoration.

Correction to: Managing Urban Plant Invasions: a Multi-Criteria Prioritization Approach.

The original version of the article unfortunately contained an error with the figure captions. The appropriate captions for Fig. 3-6 are published accordingly. The original article has been corrected.

Managing Urban Plant Invasions: a Multi-Criteria Prioritization Approach.

Alien plant invasions in urban areas can have considerable impact on biodiversity and ecosystem services (ES). Managing urban plant invasions is particularly challenging given the complex interactions between ecological, economic and social elements that exist in the urban milieu. Strategic landscape-scale insights are crucial for guiding management, as are tactical site-scale perspectives to plan and coordinate control efforts on the ground. Integrating these requirements to enhance management efficiency is a major challenge. Decision-support models have considerable potential for guiding and informing management strategies when problems are complex. This study uses multi-criteria decision tools to develop a prioritization framework for managing invasive alien plants (IAPs) in urban areas at landscape and local scales. We used the Analytic Hierarchy Process (AHP; a multi-criteria decision support model) to develop and rank criteria for prioritising IAP management in the City of Cape Town (CoCT), South Africa. Located within a global biodiversity hotspot, Cape Town has a long history of alien plant introductions and a complex socio-political make-up, creating a useful system to explore the challenges associated with managing urban plant invasions. To guide the prioritization of areas for IAP management across the CoCT, a stakeholder workshop was held to identify a goal and criteria for consideration, and to assess the relative importance given to each criterion in IAP management. Workshop attendees were drawn from multiple disciplines involved with different aspects of IAP research and management: government departments, scientists and researchers, and managers with a diverse set of skills and interests. We selected spatial datasets and applied our multi-criteria decision analysis in a Geographic Information System (GIS) to develop a landscape-scale prioritization map. To address issues relevant in an urban setting, we also modified an existing IAP management framework to develop a tactical (site-level) prioritization scheme for guiding on-the-ground control operations. High-priority sites for IAP management were identified at landscape- and local scales across the study area. Factors related to safety and security emerged as pivotal features for setting spatially-explicit priorities for management. The approach applied in this study can be useful for managers in all urban settings to guide the selection and prioritization of areas for IAP management.

The impact of hospital accreditation on quality measures: an interrupted time series analysis.

BACKGROUND: Developing countries frequently use hospital accreditation to guarantee quality and patient safety. However, implementation of accreditation standards is demanding on organisations. Furthermore, the empirical literature on the benefits of accreditation is sparse and this is the first empirical interrupted time series analysis designed to examine the impact of healthcare accreditation on hospital quality measures. METHODS: The study was conducted in a 150-bed multispecialty hospital in Abu Dhabi, United Arab Emirates. The quality performance outcomes were observed over a 48 month period. The quality performance differences were compared across monthly intervals between two time segments, 1 year pre- accreditation (2009) and 3 years post-accreditation (2010, 2011 and 2012) for the twenty-seven quality measures. The principal data source was a random sample of 12,000 patient records drawn from a population of 50,000 during the study period (January 2009 to December 2012). Each month (during the study period), a simple random sample of 24 percent of patient records was selected and audited, resulting in 324,000 observations. The measures (structure, process and outcome) are related to important dimensions of quality and patient safety. RESULTS: The study findings showed that preparation for the accreditation survey results in significant improvement as 74% of the measures had a significant positive pre-accreditation slope. Accreditation had a larger significant negative effect (48% of measures) than a positive effect (4%) on the post accreditation slope of performance. Similarly, accreditation had a larger significant negative change in level (26%) than a positive change in level (7%) after the accreditation survey. Moreover, accreditation had no significant impact on 11 out of the 27 measures. However, there is residual benefit from accreditation three years later with performance maintained at approximately 90%, which is 20 percentage points higher than the baseline level in 2009. CONCLUSIONS: Although there is a transient drop in performance immediately after the survey, this study shows that the improvement achieved from accreditation is maintained during the three year accreditation cycle.

Mapping ecological processes and ecosystem services for prioritizing restoration efforts in a semi-arid Mediterranean river basin.

Semi-arid Mediterranean regions are highly susceptible to desertification processes which can reduce the benefits that people obtain from healthy ecosystems and thus threaten human wellbeing. The European Union Biodiversity Strategy to 2020 recognizes the need to incorporate ecosystem services into land-use management, conservation, and restoration actions. The inclusion of ecosystem services into restoration actions and plans is an emerging area of research, and there are few documented approaches and guidelines on how to undertake such an exercise. This paper responds to this need, and we demonstrate an approach for identifying both key ecosystem services provisioning areas and the spatial relationship between ecological processes and services. A degraded semi-arid Mediterranean river basin in north east Spain was used as a case study area. We show that the quantification and mapping of services are the first step required for both optimizing and targeting of specific local areas for restoration. Additionally, we provide guidelines for restoration planning at a watershed scale; establishing priorities for improving the delivery of ecosystem services at this scale; and prioritizing the sub-watersheds for restoration based on their potential for delivering a combination of key ecosystem services for the entire basin.

The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing.

Many metazoan cells can take up exogenous double-stranded (ds) RNA and use it to initiate an RNA silencing response, however, the mechanism for this uptake is ill-defined. Here, we identify the pathway for dsRNA uptake in Drosophila melanogaster S2 cells. Biochemical and cell biological analyses, and a genome-wide screen for components of the dsRNA-uptake machinery, indicated that dsRNA is taken up by an active process involving receptor-mediated endocytosis. Pharmacological inhibition of endocytic pathways disrupted exogenous dsRNA entry and the induction of gene silencing. This dsRNA uptake mechanism seems to be evolutionarily conserved, as knockdown of orthologues in Caenorhabditis elegans inactivated the RNA interference response in worms. Thus, this entry pathway is required for systemic RNA silencing in whole organisms. In Drosophila cells, pharmacological evidence suggests that dsRNA entry is mediated by pattern-recognition receptors. The possible role of these receptors in dsRNA entry may link RNA interference (RNAi) silencing to other innate immune responses.

Stepwise modifications of transcriptional hubs link pioneer factor activity to a burst of transcription.

Binding of transcription factors (TFs) promotes the subsequent recruitment of coactivators and preinitiation complexes to initiate eukaryotic transcription, but this time course is usually not visualized. It is commonly assumed that recruited factors eventually co-reside in a higher-order structure, allowing distantly bound TFs to activate transcription at core promoters. We use live imaging of endogenously tagged proteins, including the pioneer TF Zelda, the coactivator dBrd4, and RNA polymerase II (RNAPII), to define a cascade of events upstream of transcriptional initiation in early Drosophila embryos. These factors are sequentially and transiently recruited to discrete clusters during activation of non-histone genes. Zelda and the acetyltransferase dCBP nucleate dBrd4 clusters, which then trigger pre-transcriptional clustering of RNAPII. Subsequent transcriptional elongation disperses clusters of dBrd4 and RNAPII. Our results suggest that activation of transcription by eukaryotic TFs involves a succession of distinct biomolecular condensates that culminates in a self-limiting burst of transcription.