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A CRISPR screening approach shows that endoplasmic reticulum (ER)-associated protein complexes, including the oligosaccharyltransferase (OST) protein complex, are important for infection by dengue virus and other related mosquito-borne flaviviruses, whereas hepatitis C virus is dependent on distinct entry factors, RNA binding proteins and FAD biosynthesis. Host factors required for flavivirus infection Jan Carette and colleagues use a CRISPR screening approach to identify cellular genes with important roles in the lifecycle of two important human flaviviruses: dengue virus and hepatitis C virus. The authors show that endoplasmic-reticulum-associated protein complexes, including the oligosaccharyltransferase (OST) protein complex, are important for infection by dengue virus and other related mosquito-borne flaviviruses, whereas hepatitis C virus is dependent on distinct entry factors, RNA binding proteins and FAD biosynthesis. Also in this issue of Nature , Michael Diamond and colleagues report that the endoplasmic-reticulum-associated signal peptidase complex is required for infection by numerous flaviviruses, including West Nile, dengue and Zika viruses, but not for infection by other types of virus or for host protein synthesis. The Flaviviridae are a family of viruses that cause severe human diseases. For example, dengue virus (DENV) is a rapidly emerging pathogen causing an estimated 100 million symptomatic infections annually worldwide 1 . No approved antivirals are available to date, and clinical trials with a tetravalent dengue vaccine showed disappointingly low protection rates 2 . Hepatitis C virus (HCV) also remains a major medical problem, with 160 million chronically infected patients worldwide and only expensive treatments available 3 . Despite distinct differences in their pathogenesis and modes of transmission, the two viruses share common replication strategies 4 . A detailed understanding of the host functions that determine viral infection is lacking. Here we use a pooled CRISPR genetic screening strategy 5 , 6 to comprehensively dissect host factors required for these two highly important Flaviviridae members. For DENV, we identified endoplasmic-reticulum (ER)-associated multi-protein complexes involved in signal sequence recognition, N -linked glycosylation and ER-associated degradation. DENV replication was nearly completely abrogated in cells deficient in the oligosaccharyltransferase (OST) complex. Mechanistic studies pinpointed viral RNA replication and not entry or translation as the crucial step requiring the OST complex. Moreover, we show that viral non-structural proteins bind to the OST complex. The identified ER-associated protein complexes were also important for infection by other mosquito-borne flaviviruses including Zika virus, an emerging pathogen causing severe birth defects 7 . By contrast, the most significant genes identified in the HCV screen were distinct and included viral receptors, RNA-binding proteins and enzymes involved in metabolism. We found an unexpected link between intracellular flavin adenine dinucleotide (FAD) levels and HCV replication. This study shows notable divergence in host-dependency factors between DENV and HCV, and illuminates new host targets for antiviral therapy.

Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.

Global food demand is rising, and serious questions remain about whether supply can increase sustainably 1 . Land-based expansion is possible but may exacerbate climate change and biodiversity loss, and compromise the delivery of other ecosystem services 2 , 3 , 4 , 5 – 6 . As food from the sea represents only 17% of the current production of edible meat, we ask how much food we can expect the ocean to sustainably produce by 2050. Here we examine the main food-producing sectors in the ocean—wild fisheries, finfish mariculture and bivalve mariculture—to estimate ‘sustainable supply curves’ that account for ecological, economic, regulatory and technological constraints. We overlay these supply curves with demand scenarios to estimate future seafood production. We find that under our estimated demand shifts and supply scenarios (which account for policy reform and technology improvements), edible food from the sea could increase by 21–44 million tonnes by 2050, a 36–74% increase compared to current yields. This represents 12–25% of the estimated increase in all meat needed to feed 9.8 billion people by 2050. Increases in all three sectors are likely, but are most pronounced for mariculture. Whether these production potentials are realized sustainably will depend on factors such as policy reforms, technological innovation and the extent of future shifts in demand. Modelled supply curves show that, with policy reform and technological innovation, the production of food from the sea may increase sustainably, perhaps supplying 25% of the increase in demand for meat products by 2050.

A screen for compounds that alleviate the inhibitory effect of influenza NS1 on host gene expression and suppress viral toxicity found naphthalimides that could upregulate REDD1, an mTORC1 inhibitor, revealing that viruses inhibit REDD1 to activate the mTORC1 pathway. A chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed NS1-mediated inhibition of host gene expression. A counterscreen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular stomatitis virus (VSV). The mechanism of action occurs through activation of REDD1 expression and concomitant inhibition of mammalian target of rapamycin complex 1 (mTORC1) via TSC1–TSC2 complex. The antiviral activity of naphthalimides was abolished in REDD1 −/− cells. Inhibition of REDD1 expression by viruses resulted in activation of the mTORC1 pathway. REDD1 −/− cells prematurely upregulated viral proteins via mTORC1 activation and were permissive to virus replication. In contrast, cells conditionally expressing high concentrations of REDD1 downregulated the amount of viral protein. Thus, REDD1 is a new host defense factor, and chemical activation of REDD1 expression represents a potent antiviral intervention strategy.

Climate change, mismanaged resource extraction, and pollution are reshaping global marine ecosystems with direct consequences on human societies. Sustainable ocean development requires knowledge and data across disciplines, scales and knowledge types. Although several disciplines are generating large amounts of data on marine socio-ecological systems, such information is often underutilized due to fragmentation across institutions or stakeholders, limited standardization across scale, time or disciplines, and the fact that information is often not searchable within existing databases. Compiling metadata, the information which describes existing sets of data, is an effective tool that can address these challenges, particularly when metadata corresponding to multiple datasets can be combined to integrate, organize and classify multidisciplinary data. Here, using Mexico as a case study, we describe the compilation and analysis of a metadatabase of ocean knowledge that aims to improve access to information, facilitate multidisciplinary data sharing and integration, and foster collaboration among stakeholders. We also evaluate the knowledge trends and gaps for informing ocean management. Analysis of the metadatabase highlights that past and current research in Mexico focuses strongly on ecology and fisheries, with biological data more consistent over time and space compared to data on human dimensions. Regional imbalances in available information were also evident, with most available information corresponding to the Gulf of California, Campeche Bank and Caribbean and less available for the central and south Pacific and the western Gulf of Mexico. Despite existing knowledge gaps in Mexico and elsewhere, we argue that systematic efforts such as this can often reveal an abundance of information for decision-makers to develop policies that meet key commitments on ocean sustainability. Surmounting current cross-scale social and ecological challenges for sustainability requires transdisciplinary approaches. Metadatabases are critical tools to make efficient use of existing data, highlight and address strengths and deficiencies, and develop scenarios to inform policies for managing complex marine social-ecological systems.

Jellyfish are economically important organisms in diverse countries, carnivorous organisms that consume various prey (crustaceans, mollusks, bivalves, etc .) and dissolved carbohydrates in marine waters. This study was focused on detecting and quantifying the activity of digestive glycosidases from the cannonball jellyfish ( Stomolophus sp. 2) to understand carbohydrate digestion and its temporal-spatial variation. Twenty-three jellyfish gastric pouches were collected in 2015 and 2016 in the Gulf of California in three localities (Las Guásimas, Hermosillo, and Caborca). Nine samples were in intra-localities from Las Guásimas. Chitinase (Ch), β -glucosidase ( β -glu), and β - N -acetylhexosaminidase ( β -NAHA) were detected in the gastric pouches. However, cellulase, exoglucanase, α -amylase, polygalacturonase, xylanase, and κ -carrageenase were undetected. Detected enzymes showed halotolerant glycolytic activity ( i = 0–4 M NaCl), optimal pH, and temperature at 5.0 and 30–50 °C, respectively. At least five β -glucosidase and two β -N-acetylhexosaminidase were detected using zymograms; however, the number of proteins with chitinase activity is not precise. The annual variation of cannonball jellyfish digestive glycosidases from Las Guásimas between 2015–2016 does not show significant differences despite the difference in phytoplankton measured as chlorophyll α (1.9 and 3.4 mg/m 3 , respectively). In the inter-localities, the glycosidase activity was statistically different in all localities, except for β - N -acetylhexosaminidase activity between Caborca and Hermosillo (3,009.08 ± 87.95 and 3,101.81 ± 281.11 mU/g of the gastric pouch, respectively), with chlorophyll α concentrations of 2.6, 3.4 mg/m 3 , respectively. For intra-localities, the glycosidase activity did not show significant differences, with a mean chlorophyll α of 1.3 ± 0.1 mg/m 3 . These results suggest that digestive glycosidases from Stomolophus sp. 2 can hydrolyze several carbohydrates that may belong to their prey or carbohydrates dissolved in marine waters, with salinity over ≥ 0.6 M NaCl and diverse temperature (4–80 °C) conditions. Also, chlorophyll α is related to glycosidase activity in both seasons and inter-localities, except for chitinase activity in an intra-locality (Las Guásimas).

Despite its importance in fisheries studies, there is insufficient understanding on the effect of sampling error or bias on individual growth and other stock indicators. We show the influence of sample length distributions on parameter estimates, illustrating with an example. For the brown swimming crab, we simulated length samples in five configurations and estimated parameters of von Bertalanffy (k, L∞L∞ , t0), asymptotic weight ( W∞W∞ ), weight-length relationship (a, b), growth performance (ϕ’) and condition factor (Kn). Parameter estimates were compared with baseline values using relative bias, standard error and root mean square error. The results show that the accuracy and bias of parameter estimates depend on the lengths sampled. For example, the bias and accuracy of L∞L∞ and W∞W∞ vary inversely with sampled length, whereas combining length segments yields smaller biases of k and t0 than those of L∞L∞ and W∞W∞ . In general, the accuracy of parameter estimates does not always depend on sampling the entire length range, and errors are not the same for all parameters. These results are useful to guide sampling when resources are scarce. We discuss potential reasons for incomplete length sample structure and offer recommendations to obtain best estimates for parameters of interest.

The Upper Gulf of California (UGC) hosts a rich marine biodiversity. Complex climatic processes generate high biological productivity enabling the use of resources in a complex socio‐ecological processes (SEPs). Through a literature review, evolution and aggravation of the SEP over 50 years are analyzed. The crisis peaked in the last decade related to vaquita, an endangered marine porpoise at the blink of extinction, and the illegal catch of totoaba, an endangered fish species, both endemic. Over the first three decades, stakeholders defined positions, while disorder in fisheries and reduction of vaquita population occurred. Corrective actions were implemented during the last two decades including diversification of markets for local fisheries, development of fishing technologies, and environmental regulations. Most actions failed, consolidating an ill governance aggravated by poaching of totoaba and drug trafficking. The evolution of the conflict includes (1) transition from community passivity to conservation efforts, to resistance and collective violence against them; (2) transition in the design and implementation of conservation actions from civil organizations to the government, facilitated by the disengagement of philanthropic donors for conservation, and reduction of support for civil organizations; (3) interventions by the Mexican Navy coordinated with the Sea Shepherd Conservation Society; and (4) weakening of the International Committee for the Recovery of Vaquita an international scientific moral authority to propose vaquita conservation. The federal government and the local fishing sector currently discuss scenarios that aim to authorize use of driftnets and gillnets, contrasting with the predominant conservation logic.

Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), cause severe human disease. Co-opting cellular factors for viral translation and viral genome replication at the endoplasmic reticulum is a shared replication strategy, despite different clinical outcomes. Although the protein products of these viruses have been studied in depth, how the RNA genomes operate inside human cells is poorly understood. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we took an RNA-centric viewpoint of flaviviral infection and identified several hundred proteins associated with both DENV and ZIKV genomic RNA in human cells. Genome-scale knockout screens assigned putative functional relevance to the RNA–protein interactions observed by ChIRP-MS. The endoplasmic-reticulum-localized RNA-binding proteins vigilin and ribosome-binding protein 1 directly bound viral RNA and each acted at distinct stages in the life cycle of flaviviruses. Thus, this versatile strategy can elucidate features of human biology that control the pathogenesis of clinically relevant viruses. A survey of the cellular RNA-binding proteins (RBPs) that interact with dengue virus and Zika virus genomic RNA identifies ribosome-binding protein 1 and vigilin as bona fide RBPs able to promote viral RNA translation, replication and stability.

Illegal wildlife trade threatens species globally. Conservation farming introduces farmed substitutes to reduce poaching. Predicting if farming will succeed necessitates understanding how supply and demand interact and how markets respond. We focus on illegal trade for totoaba ( Totoaba macdonaldi ), dominated by a Mexican cartel, which has continued unabated despite long-standing prohibitions. We investigate if farmed totoaba can successfully compete with poaching and support a healthy wild totoaba population. We simulate an illegal supply chain describing the current trade: poachers sell to traders who sell to end-markets. If traders reduce the quantity supplied in response to farming, poaching could decrease by 28%, but if traders select a price that undercuts farming, poaching may increase by 6%. Under both responses, a stable wild population is maintained. Our results are sensitive to costs, demand, product substitutability, market structure, and combinations thereof, and we discuss how to quantitatively evaluate and mitigate for these issues.