The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.
Logged and structurally degraded tropical forests are fast becoming one of the most prevalent land-use types throughout the tropics and are routinely assumed to be a net carbon sink because they experience rapid rates of tree regrowth. Yet this assumption is based on forest biomass inventories that record carbon stock recovery but fail to account for the simultaneous losses of carbon from soil and necromass. Here, we used forest plots and an eddy covariance tower to quantify and partition net ecosystem CO2 exchange in Malaysian Borneo, a region that is a hot spot for deforestation and forest degradation. Our data represent the complete carbon budget for tropical forests measured throughout a logging event and subsequent recovery and found that they constitute a substantial and persistent net carbon source. Consistent with existing literature, our study showed a significantly greater woody biomass gain across moderately and heavily logged forests compared with unlogged forests, but this was counteracted by much larger carbon losses from soil organic matter and deadwood in logged forests. We estimate an average carbon source of 1.75 ± 0.94 Mg C ha-1 yr-1 within moderately logged plots and 5.23 ± 1.23 Mg C ha-1 yr-1 in unsustainably logged and severely degraded plots, with emissions continuing at these rates for at least one-decade post-logging. Our data directly contradict the default assumption that recovering logged and degraded tropical forests are net carbon sinks, implying the amount of carbon being sequestered across the world's tropical forests may be considerably lower than currently estimated.
Is there a universal hierarchy of the senses, such that some senses (e.g., vision) are more accessible to consciousness and linguistic description than others (e.g., smell)? The long-standing presumption in Western thought has been that vision and audition are more objective than the other senses, serving as the basis of knowledge and understanding, whereas touch, taste, and smell are crude and of little value. This predicts that humans ought to be better at communicating about sight and hearing than the other senses, and decades of work based on English and related languages certainly suggests this is true. However, how well does this reflect the diversity of languages and communities worldwide? To test whether there is a universal hierarchy of the senses, stimuli from the five basic senses were used to elicit descriptions in 20 diverse languages, including 3 unrelated sign languages. We found that languages differ fundamentally in which sensory domains they linguistically code systematically, and how they do so. The tendency for better coding in some domains can be explained in part by cultural preoccupations. Although languages seem free to elaborate specific sensory domains, some general tendencies emerge: for example, with some exceptions, smell is poorly coded. The surprise is that, despite the gradual phylogenetic accumulation of the senses, and the imbalances in the neural tissue dedicated to them, no single hierarchy of the senses imposes itself upon language.
The Toba volcanic system in Indonesia has produced two of the largest eruptions (>2,000 km3 dense-rock equivalent [DRE] each) on Earth since the Quaternary. U-Pb crystallization ages of zircon span a period of ∼600 ky before each eruptive event, and in the run-up to each eruption, the mean and variance of the zircons' U content decrease. To quantify the process of accumulation of eruptible magma underneath the Toba caldera, we integrated these observations with thermal and geochemical modeling. We show that caldera-forming eruptions at Toba are the result of progressive thermal maturation of the upper crustal magma reservoir, which grows and chemically homogenizes, by sustained magma influx at average volumetric rates between 0.008 and 0.01 km3/y over the past 2.2 My. Protracted thermal pulses related to magma-recharge events prime the system for eruption without necessarily requiring an increased magma-recharge rate before the two supereruptions. If the rate of magma input was maintained since the last supereruption of Toba at 75 ka, eruptible magma is currently accumulating at a minimum rate of ∼4.2 km3 per millennium, and the current estimate of the total volume of potentially eruptible magma available today is a minimum of ∼315 km3 Our approach to evaluate magma flux and the rate of eruptible magma accumulation is applicable to other volcanic systems capable of producing supereruptions and thereby could help in assessing the potential of active volcanic systems to feed supereruptions.
The deformation-coordination ability between ductile metal and brittle dispersive ceramic particles is poor, which means that an improvement in strength will inevitably sacrifice ductility in dispersion-strengthened metallic materials. Here, we present an inspired strategy for developing dual-structure-based titanium matrix composites (TMCs) that achieve 12.0% elongation comparable to the matrix Ti6Al4V alloys and enhanced strength compared to homostructure composites. The proposed dual-structure comprises a primary structure, namely, a TiB whisker-rich region engendered fine grain Ti6Al4V matrix with a three-dimensional micropellet architecture (3D-MPA), and an overall structure consisting of evenly distributed 3D-MPA "reinforcements" and a TiBw-lean titanium matrix. The dual structure presents a spatially heterogeneous grain distribution with 5.8 μm fine grains and 42.3 μm coarse grains, which exhibits excellent hetero-deformation-induced (HDI) hardening and achieves a 5.8% ductility. Interestingly, the 3D-MPA "reinforcements" show 11.1% isotropic deformability and 66% dislocation storage, which endows the TMCs with good strength and loss-free ductility. Our enlightening method uses an interdiffusion and self-organization strategy based on powder metallurgy to enable metal matrix composites with the heterostructure of the matrix and the configuration of reinforcement to address the strength-ductility trade-off dilemma.
Social disturbance in interpersonal relationships is the primary source of stress in humans. Spexin (SPX, SPX1a in cichlid), an evolutionarily conserved neuropeptide with diverse physiological functions, is up-regulated in the brain during chronic social defeat stress in teleost. On the other hand, repeated exposure to social stress can lead to dysregulation of the monoaminergic system and increase the vulnerability of developing depression. Since dysfunction of the serotonin (5-hydroxytryptamine, 5-HT) system is associated with social stress and the pathophysiology of depression, the present study investigated the regulatory relationship between the central 5-HT system and SPX1a in the male teleost, Nile tilapia (Oreochromis niloticus). To identify stress factors that regulate SPX1a gene expression, cortisol, dexamethasone (DEX), and 5-HT were used to treat tilapia brain primary cultures. Our study shows cortisol and DEX treatment had no effect on SPX1a gene expression, but SPX1a gene expression was down-regulated following 5-HT treatment. Anatomical localization showed a close association between 5-HT immunoreactive projections and SPX1a neurons in the semicircular torus. In addition, 5-HT receptors (5-HT2B) were expressed in SPX1a neurons. SPX1a immunoreactive neurons and SPX1a gene expression were significantly increased in socially defeated tilapia. On the other hand, citalopram (antidepressant, 5-HT antagonist) treatment to socially defeated tilapia normalized SPX1a gene expression to control levels. Taken together, the present study shows that 5-HT is an upstream regulator of SPX1a and that the inhibited 5-HT activates SPX1a during social defeat.
Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223 BCP ALL cases using RNA sequencing. Fourteen BCP ALL gene expression subgroups (G1 to G14) were identified. Apart from extending eight previously described subgroups (G1 to G8 associated with MEF2D fusions, TCF3-PBX1 fusions, ETV6-RUNX1-positive/ETV6-RUNX1-like, DUX4 fusions, ZNF384 fusions, BCR-ABL1/Ph-like, high hyperdiploidy, and KMT2A fusions), we defined six additional gene expression subgroups: G9 was associated with both PAX5 and CRLF2 fusions; G10 and G11 with mutations in PAX5 (p.P80R) and IKZF1 (p.N159Y), respectively; G12 with IGH-CEBPE fusion and mutations in ZEB2 (p.H1038R); and G13 and G14 with TCF3/4-HLF and NUTM1 fusions, respectively. In pediatric BCP ALL, subgroups G2 to G5 and G7 (51 to 65/67 chromosomes) were associated with low-risk, G7 (with ≤50 chromosomes) and G9 were intermediate-risk, whereas G1, G6, and G8 were defined as high-risk subgroups. In adult BCP ALL, G1, G2, G6, and G8 were associated with high risk, while G4, G5, and G7 had relatively favorable outcomes. This large-scale transcriptome sequence analysis of BCP ALL revealed distinct molecular subgroups that reflect discrete pathways of BCP ALL, informing disease classification and prognostic stratification. The combined results strongly advocate that RNA sequencing be introduced into the clinical diagnostic workup of BCP ALL.
Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.
Rising global demands for food and biofuels are driving forest clearance in the tropics. Oil-palm expansion contributes to biodiversity declines and carbon emissions in Southeast Asia. However, the magnitudes of these impacts remain largely unquantified until now. We produce a 250-m spatial resolution map of closed canopy oil-palm plantations in the lowlands of Peninsular Malaysia (2 million ha), Borneo (2.4 million ha), and Sumatra (3.9 million ha). We demonstrate that 6% (or ≈880,000 ha) of tropical peatlands in the region had been converted to oil-palm plantations by the early 2000s. Conversion of peatswamp forests to oil palm led to biodiversity declines of 1% in Borneo (equivalent to four species of forest-dwelling birds), 3.4% in Sumatra (16 species), and 12.1% in Peninsular Malaysia (46 species). This land-use change also contributed to the loss of ≈140 million Mg of aboveground biomass carbon, and annual emissions of ≈4.6 million Mg of belowground carbon from peat oxidation. Additionally, the loss of peatswamp forests implies the loss of carbon sequestration service through peat accumulation, which amounts to ≈660,000 Mg of carbon annually. By 2010, 2.3 million ha of peatswamp forests were clear-felled, and currently occur as degraded lands. Reforestation of these clearings could enhance biodiversity by up to ≈20%, whereas oil-palm establishment would exacerbate species losses by up to ≈12%. To safeguard the region's biodiversity and carbon stocks, conservation and reforestation efforts should target Central Kalimantan, Riau, and West Kalimantan, which retain three-quarters (3.9 million ha) of the remaining peatswamp forests in Southeast Asia.
The malaria parasite Plasmodium falciparum has a nonphotosynthetic plastid called the apicoplast, which contains its own genome. Regulatory mechanisms for apicoplast gene expression remain poorly understood, despite this organelle being crucial for the parasite life cycle. Here, we identify a nuclear-encoded apicoplast RNA polymerase σ subunit (sigma factor) which, along with the α subunit, appears to mediate apicoplast transcript accumulation. This has a periodicity reminiscent of parasite circadian or developmental control. Expression of the apicoplast subunit gene, apSig, together with apicoplast transcripts, increased in the presence of the blood circadian signaling hormone melatonin. Our data suggest that the host circadian rhythm is integrated with intrinsic parasite cues to coordinate apicoplast genome transcription. This evolutionarily conserved regulatory system might be a future target for malaria treatment.
Learners of most languages are faced with the task of acquiring words to talk about number and quantity. Much is known about the order of acquisition of number words as well as the cognitive and perceptual systems and cultural practices that shape it. Substantially less is known about the acquisition of quantifiers. Here, we consider the extent to which systems and practices that support number word acquisition can be applied to quantifier acquisition and conclude that the two domains are largely distinct in this respect. Consequently, we hypothesize that the acquisition of quantifiers is constrained by a set of factors related to each quantifier's specific meaning. We investigate competence with the expressions for "all," "none," "some," "some…not," and "most" in 31 languages, representing 11 language types, by testing 768 5-y-old children and 536 adults. We found a cross-linguistically similar order of acquisition of quantifiers, explicable in terms of four factors relating to their meaning and use. In addition, exploratory analyses reveal that language- and learner-specific factors, such as negative concord and gender, are significant predictors of variation.
Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact of resistance on malaria disease burden is limited. A cluster randomized trial was conducted in Sudan with pyrethroid-resistant and carbamate-susceptible malaria vectors. Clusters were randomly allocated to receive either long-lasting insecticidal nets (LLINs) alone or LLINs in combination with indoor residual spraying (IRS) with a pyrethroid (deltamethrin) insecticide in the first year and a carbamate (bendiocarb) insecticide in the two subsequent years. Malaria incidence was monitored for 3 y through active case detection in cohorts of children aged 1 to <10 y. When deltamethrin was used for IRS, incidence rates in the LLIN + IRS arm and the LLIN-only arm were similar, with the IRS providing no additional protection [incidence rate ratio (IRR) = 1.0 (95% confidence interval [CI]: 0.36-3.0; P = 0.96)]. When bendiocarb was used for IRS, there was some evidence of additional protection [interaction IRR = 0.55 (95% CI: 0.40-0.76; P < 0.001)]. In conclusion, pyrethroid resistance may have had an impact on pyrethroid-based IRS. The study was not designed to assess whether resistance had an impact on LLINs. These data alone should not be used as the basis for any policy change in vector control interventions.
Compartmentalization was likely essential for primitive chemical systems during the emergence of life, both for preventing leakage of important components, i.e., genetic materials, and for enhancing chemical reactions. Although life as we know it uses lipid bilayer-based compartments, the diversity of prebiotic chemistry may have enabled primitive living systems to start from other types of boundary systems. Here, we demonstrate membraneless compartmentalization based on prebiotically available organic compounds, α-hydroxy acids (αHAs), which are generally coproduced along with α-amino acids in prebiotic settings. Facile polymerization of αHAs provides a model pathway for the assembly of combinatorially diverse primitive compartments on early Earth. We characterized membraneless microdroplets generated from homo- and heteropolyesters synthesized from drying solutions of αHAs endowed with various side chains. These compartments can preferentially and differentially segregate and compartmentalize fluorescent dyes and fluorescently tagged RNA, providing readily available compartments that could have facilitated chemical evolution by protecting, exchanging, and encapsulating primitive components. Protein function within and RNA function in the presence of certain droplets is also preserved, suggesting the potential relevance of such droplets to various origins of life models. As a lipid amphiphile can also assemble around certain droplets, this further shows the droplets' potential compatibility with and scaffolding ability for nascent biomolecular systems that could have coexisted in complex chemical systems. These model compartments could have been more accessible in a "messy" prebiotic environment, enabling the localization of a variety of protometabolic and replication processes that could be subjected to further chemical evolution before the advent of the Last Universal Common Ancestor.
Southeast Asian ovalocytosis (SAO) is a hereditary condition that is widespread in parts of Southeast Asia. The ovalocytic erythrocytes are rigid and resistant to invasion by various malarial parasites. We have previously found that the underlying defect in SAO involves band 3 protein, the major transmembrane protein, which has abnormal structure and function. We now report two linked mutations in the erythrocyte band 3 gene in SAO: (i) a deletion of codons 400-408 and (ii) a substitution, A----G, in the first base of codon 56 leading to substitution of Lys-56 by Glu-56. The first defect leads to a deletion of nine amino acids in the boundary of cytoplasmic and membrane domains of band 3. This defect has been detected in all 30 ovalocytic subjects from Malaysia, the Philippines, and two unrelated coastal regions of Papua New Guinea, whereas it was absent in all 30 controls from Southeast Asia and 20 subjects of different ethnic origin from the United States. The Lys-56----Glu substitution has likewise been found in all SAO subjects. However, it has also been detected in 5 of the 50 control subjects, suggesting that it represents a linked polymorphism. We conclude that the deletion of codons 400-408 in the band 3 gene constitutes the underlying molecular defect in SAO.
In the billion-dollar global illegal wildlife trade, rosewoods have been the world's most trafficked wild product since 2005. Dalbergia cochinchinensis and Dalbergia oliveri are the most sought-after rosewoods in the Greater Mekong Subregion. They are exposed to significant genetic risks and the lack of knowledge on their adaptability limits the effectiveness of conservation efforts. Here, we present genome assemblies and range-wide genomic scans of adaptive variation, together with predictions of genomic offset to climate change. Adaptive genomic variation was differentially associated with temperature and precipitation-related variables between the species, although their natural ranges overlap. The findings are consistent with differences in pioneering ability and in drought tolerance. We predict their genomic offsets will increase over time and with increasing carbon emission pathway but at a faster pace in D. cochinchinensis than in D. oliveri. These results and the distinct gene-environment association in the eastern coastal edge of Vietnam suggest species-specific conservation actions: germplasm representation across the range in D. cochinchinensis and focused on hotspots of genomic offset in D. oliveri. We translated our genomic models into a seed source matching application, seedeR, to rapidly inform restoration efforts. Our ecological genomic research uncovering contrasting selection forces acting in sympatric rosewoods is of relevance to conserving tropical trees globally and combating risks from climate change.
We have used electron probe microanalysis to examine Southeast Asian nephrite (jade) artifacts, many archeologically excavated, dating from 3000 B.C. through the first millennium A.D. The research has revealed the existence of one of the most extensive sea-based trade networks of a single geological material in the prehistoric world. Green nephrite from a source in eastern Taiwan was used to make two very specific forms of ear pendant that were distributed, between 500 B.C. and 500 A.D., through the Philippines, East Malaysia, southern Vietnam, and peninsular Thailand, forming a 3,000-km-diameter halo around the southern and eastern coastlines of the South China Sea. Other Taiwan nephrite artifacts, especially beads and bracelets, were distributed earlier during Neolithic times throughout Taiwan and from Taiwan into the Philippines.
More than half the world's rainforest has been lost to agriculture since the Industrial Revolution. Among the most widespread tropical crops is oil palm (Elaeis guineensis): global production now exceeds 35 million tonnes per year. In Malaysia, for example, 13% of land area is now oil palm plantation, compared with 1% in 1974. There are enormous pressures to increase palm oil production for food, domestic products, and, especially, biofuels. Greater use of palm oil for biofuel production is predicated on the assumption that palm oil is an "environmentally friendly" fuel feedstock. Here we show, using measurements and models, that oil palm plantations in Malaysia directly emit more oxides of nitrogen and volatile organic compounds than rainforest. These compounds lead to the production of ground-level ozone (O(3)), an air pollutant that damages human health, plants, and materials, reduces crop productivity, and has effects on the Earth's climate. Our measurements show that, at present, O(3) concentrations do not differ significantly over rainforest and adjacent oil palm plantation landscapes. However, our model calculations predict that if concentrations of oxides of nitrogen in Borneo are allowed to reach those currently seen over rural North America and Europe, ground-level O(3) concentrations will reach 100 parts per billion (10(9)) volume (ppbv) and exceed levels known to be harmful to human health. Our study provides an early warning of the urgent need to develop policies that manage nitrogen emissions if the detrimental effects of palm oil production on air quality and climate are to be avoided.
Food production is a major driver of global environmental change and the overshoot of planetary sustainability boundaries. Greater affluence in developing nations and human population growth are also increasing demand for all foods, and for animal proteins in particular. Consequently, a growing body of literature calls for the sustainable intensification of food production, broadly defined as "producing more using less". Most assessments of the potential for sustainable intensification rely on only one or two indicators, meaning that ecological trade-offs among impact categories that occur as production intensifies may remain unaccounted for. The present study addresses this limitation using life cycle assessment (LCA) to quantify six local and global environmental consequences of intensifying aquaculture production in Bangladesh. Production data are from a unique survey of 2,678 farms, and results show multidirectional associations between the intensification of aquaculture production and its environmental impacts. Intensification (measured in material and economic output per unit primary area farmed) is positively correlated with acidification, eutrophication, and ecotoxicological impacts in aquatic ecosystems; negatively correlated with freshwater consumption; and indifferent with regard to global warming and land occupation. As production intensifies, the geographical locations of greenhouse gas (GHG) emissions, acidifying emissions, freshwater consumption, and land occupation shift from the immediate vicinity of the farm to more geographically dispersed telecoupled locations across the globe. Simple changes in fish farming technology and management practices that could help make the global transition to more intensive forms of aquaculture be more sustainable are identified.
This article examines two strands of discourse on wild capture fisheries; one that focuses on resource sustainability and environmental impacts, another related to food and nutrition security and human well-being. Available data and research show that, for countries most dependent on fish to meet the nutritional requirements of their population, wild capture fisheries remain the dominant supplier. Although, contrary to popular narratives, the sustainability of these fisheries is not always and everywhere in crisis, securing their sustainability is essential and requires considerable effort across a broad spectrum of fishery systems. An impediment to achieving this is that the current research and policy discourses on environmental sustainability of fisheries and food security remain only loosely and superficially linked. Overcoming this requires adoption of a broader sustainability science paradigm to help harness synergies and negotiate tradeoffs between food security, resource conservation, and macroeconomic development goals. The way society chooses to govern fisheries is, however, an ethical choice, not just a technical one, and we recommend adding an ethical dimension to sustainability science as applied to fisheries.