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Identification of regulators of Toxoplasma gondii bradyzoite development and cyst formation is the most direct way to address the importance of parasite development in long-term persistence and reactivation of this parasite. Here we show that a T. gondii gene (named Regulator of Cystogenesis 1; ROCY1) is sufficient for T. gondii bradyzoite formation in vitro and in vivo. ROCY1 encodes an RNA binding protein that has a preference for 3 regulatory regions of hundreds of T. gondii transcripts, and its RNA-binding domains are required to mediate bradyzoite development. Female mice infected with ΔROCY1 parasites have reduced (>90%) cyst burden. While viable parasites can be cultivated from brain tissue for up to 6 months post-infection, chronic brain-resident ΔROCY1 parasites have reduced oral infectivity compared to wild type. Despite clear defects in bradyzoite formation and oral infectivity, ΔROCY1 parasites were able to reactivate with similar timing and magnitude as wild type parasites for up to 5 months post-infection. Therefore while ROCY1 is a critical regulator of the bradyzoite developmental pathway, it is not required for parasite reactivation, raising new questions about the persisting life stage responsible for causing recrudescent disease.

Substance abuse disorders are linked to alteration of circadian rhythms, although the molecular and neuronal pathways implicated have not been fully elucidated. Addictive drugs, such as cocaine, induce a rapid increase of dopamine levels in the brain. Here, we show that acute administration of cocaine triggers reprogramming in circadian gene expression in the striatum, an area involved in psychomotor and rewarding effects of drugs. This process involves the activation of peroxisome protein activator receptor gamma (PPARγ), a nuclear receptor involved in inflammatory responses. PPARγ reprogramming is altered in mice with cell-specific ablation of the dopamine D2 receptor (D2R) in the striatal medium spiny neurons (MSNs) (iMSN-D2RKO). Administration of a specific PPARγ agonist in iMSN-D2RKO mice elicits substantial rescue of cocaine-dependent control of circadian genes. These findings have potential implications for development of strategies to treat substance abuse disorders.

In the original version of this Article, references in the Methods section incorrectly referred to references in the Supplementary References section. The relevant references (now numbered 20, 27, 42, 47, 69-80) have been removed from the Supplementary References section of the Supplementary Information file and added to the References section of the main manuscript, in both the PDF and HTML versions of the Article.

Antipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive. Here, we report a pharmacogenetic interaction related to a core cognitive dysfunction in patients with schizophrenia. We show that genetic variations reducing dysbindin-1 expression can identify individuals whose executive functions respond better to antipsychotic drugs, both in humans and in mice. Multilevel ex vivo and in vivo analyses in postmortem human brains and genetically modified mice demonstrate that such interaction between antipsychotics and dysbindin-1 is mediated by an imbalance between the short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function within the prefrontal cortex. These findings reveal one of the pharmacodynamic mechanisms underlying individual cognitive response to treatment in patients with schizophrenia, suggesting a potential approach for improving the use of antipsychotic drugs.

Human activity and related land use change are the primary cause of accelerated soil erosion, which has substantial implications for nutrient and carbon cycling, land productivity and in turn, worldwide socio-economic conditions. Here we present an unprecedentedly high resolution (250 × 250 m) global potential soil erosion model, using a combination of remote sensing, GIS modelling and census data. We challenge the previous annual soil erosion reference values as our estimate, of 35.9 Pg yr -1 of soil eroded in 2012, is at least two times lower. Moreover, we estimate the spatial and temporal effects of land use change between 2001 and 2012 and the potential offset of the global application of conservation practices. Our findings indicate a potential overall increase in global soil erosion driven by cropland expansion. The greatest increases are predicted to occur in Sub-Saharan Africa, South America and Southeast Asia. The least developed economies have been found to experience the highest estimates of soil erosion rates.

Melioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei. However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conduct a comprehensive genomic analysis of 1,391 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identifies three dominant lineages, each with unique gene sets potentially enhancing bacterial fitness in the environment. We find that recombination drives lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage reveal increased expression of lineage-specific genes under environmental conditions in two out of three lineages. This underscores the potential importance of environmental persistence for these dominant lineages. The study also highlights the influence of environmental factors such as terrain slope, altitude, and river direction on the geographical dispersal of B. pseudomallei. Collectively, our findings suggest that environmental persistence may play a role in facilitating the spread of B. pseudomallei, and as a prerequisite for exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies. An environmental bacterium, Burkholderia pseudomallei causes melioidosis, a fatal infection. A study from NE Thailand identifies that dominant lineages carry specific gene sets enhancing environmental persistence. [ABSTRACT FROM AUTHOR]

A major feature of the Anthropocene is the drastic increase in global soil erosion. Soil erosion is threatening Earth habitability not only as soils are an essential component of the Earth system but also because societies depend on soils. However, proper quantification of the impact of human activities on erosion over thousands of years is still lacking. This is particularly crucial in mountainous areas, where the highest erosion rates are recorded. Here we use the Lake Bourget catchment, one of the largest in the European Alps, to estimate quantitatively the impact of human activities on erosion. Based on a multi-proxy, source-to-sink approach relying on isotopic geochemistry, we discriminate the effects of climate fluctuations from those of human activities on erosion over the last 10,000 years. We demonstrate that until 3800 years ago, climate is the only driver of erosion. From that time on, climate alone cannot explain the measured rates of erosion. Thanks to an unprecedented regional paleoenvironmental reconstruction, we highlight that the development of pastoralism at high altitudes from the Bronze Age onwards and the extension of agriculture starting in the Middle Ages were key factors in the drastic increase in erosion observed in the Alps. Using a lake sediment core taken from the European Alps and combining a source-sink approach with isotope geochemistry, it has been established that the effects of human activities have outweighed those of climate on erosion for more than 3800 years. [ABSTRACT FROM AUTHOR]

Cortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Here, we show cortical thinning patterns primarily located in the lateral frontal and parietal heteromodal nodes during childhood and adolescence, which are structurally constrained by white matter network architecture and are particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible in another independent dataset. These findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence. Cortical morphology shows maturation during childhood and adolescence. Here the authors show this is structurally constrained by a diffusion network model and that this constraint is linked to gene expression profiles of microstructural development. [ABSTRACT FROM AUTHOR]

Precipitation whiplash, including abrupt shifts between wet and dry extremes, can cause large adverse impacts on human and natural systems. Here we quantify observed and projected changes in characteristics of sub-seasonal precipitation whiplash and investigate the role of individual anthropogenic influences on these changes. Results show that the occurrence frequency of global precipitation whiplash is projected to be 2.56 ± 0.16 times higher than in 1979–2019 by the end of the 21st Century, with increasingly rapid and intense transitions between two extremes. The most dramatic increases of whiplash show in the polar and monsoon regions. Changes in precipitation whiplash show a much higher percentage change than precipitation totals. In historical simulations, anthropogenic greenhouse gas (GHG) and aerosol emissions have increased and decreased precipitation whiplash occurrences, respectively. By 2079, anthropogenic GHGs are projected to increase 55 ± 4% of the occurrences risk of precipitation whiplash, which is driven by shifts in circulation patterns conducive to precipitation extremes. This study shows that the occurrence frequency of global precipitation whiplash is projected to be ~2.6 times higher by the end of the 21st century compared to 1979–2019, with increasingly rapid and intense transitions between the two extremes. [ABSTRACT FROM AUTHOR]

While the ecological significance of hyporheic exchange and fine particle transport in rivers is well established, these processes are generally considered irrelevant to riverbed morphodynamics. We show that coupling between hyporheic exchange, suspended sediment deposition, and sand bedform motion strongly modulates morphodynamics and sorts bed sediments. Hyporheic exchange focuses fine-particle deposition within and below mobile bedforms, which suppresses bed mobility. However, deposited fines are also remobilized by bedform motion, providing a mechanism for segregating coarse and fine particles in the bed. Surprisingly, two distinct end states emerge from the competing interplay of bed stabilization and remobilization: a locked state in which fine particle deposition completely stabilizes the bed, and a dynamic equilibrium in which frequent remobilization sorts the bed and restores mobility. These findings demonstrate the significance of hyporheic exchange to riverbed morphodynamics and clarify how dynamic interactions between coarse and fine particles produce sedimentary patterns commonly found in rivers. Here the authors show that hyporheic flow, bed morphology, and bed stability are intimately related, and that this relationship is expressed as distinct locked and segregated states of bedform dynamics, which carries implications for river system behavior in general and the storage of carbon, nutrients, and contaminants in particular. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that forest disturbances are changing in response to global change, yet local variability in disturbance remains high. We quantified this considerable variability and analyzed whether recent disturbance episodes around the globe were consistently driven by climate, and if human influence modulates patterns of forest disturbance. We combined remote sensing data on recent (2001–2014) disturbances with in-depth local information for 50 protected landscapes and their surroundings across the temperate biome. Disturbance patterns are highly variable, and shaped by variation in disturbance agents and traits of prevailing tree species. However, high disturbance activity is consistently linked to warmer and drier than average conditions across the globe. Disturbances in protected areas are smaller and more complex in shape compared to their surroundings affected by human land use. This signal disappears in areas with high recent natural disturbance activity, underlining the potential of climate-mediated disturbance to transform forest landscapes. [ABSTRACT FROM AUTHOR]

Tropical ecosystems are large carbon stores that are vulnerable to climate change. The sparseness of ground-based measurements has precluded verification of these ecosystems being a net annual source (+ve) or sink (−ve) of atmospheric carbon. We show that two independent satellite data sets of atmospheric carbon dioxide (CO2), interpreted using independent models, are consistent with the land tropics being a net annual carbon emission of ( median minimum maximum ) 1.0 3 - 0.20 + 1.73 and 1.6 0 + 1.39 + 2.11 petagrams (PgC) in 2015 and 2016, respectively. These pan-tropical estimates reflect unexpectedly large net emissions from tropical Africa of 1.4 8 + 0.80 + 1.95 PgC in 2015 and 1.6 5 + 1.14 + 2.42 PgC in 2016. The largest carbon uptake is over the Congo basin, and the two loci of carbon emissions are over western Ethiopia and western tropical Africa, where there are large soil organic carbon stores and where there has been substantial land use change. These signals are present in the space-borne CO2 record from 2009 onwards. Tropical land ecosystems contain vast carbon reservoirs, but their influence on atmospheric CO2 is poorly understood. Here the authors use new carbon-observing satellites to reveal a large emission source over northern tropical Africa, where there are large soil carbon stores and substantial land use changes. [ABSTRACT FROM AUTHOR]