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Southern Peru desert shattered by the great 2001 earthquake: Implications for paleoseismic and paleo-El Nino-Southern Oscillation records

In the desert region around the coastal city of Ilo, the great southern Peru earthquake of June 23, 2001 (8.2-8.4 moment magnitude), produced intense and widespread ground-failure effects. These effects included abundant landslides, pervasive ground cracking, microfracturing of surficial hillslope materials, collapse of drainage banks over long stretches, widening of hillside rills, and lengthening of first-order tributary channels. We have coined the term "shattered landscape" to describe the severity of these effects. Long-term consequences of this landscape shattering are inferred to include increased runoff and sediment transport during postearthquake rainstorms. This inference was confirmed during the first minor postearthquake rainstorm there, which occurred in June and July of 2002. Greater amounts of rainfall in this desert region have historically been associated with El Nin??o events. Previous studies of an unusual paleoflood deposit in this region have concluded that it is the product of El Nin??o-generated precipitation falling on seismically disturbed landscapes. The effects of the 2001 earthquake and 2002 rainstorm support that conclusion.

Proceedings of the National Academy of Sciences of

Emissions pathways, climate change, and impacts on California

The magnitude of future climate change depends substantially on the greenhouse gas emission pathways we choose. Here we explore the implications of the highest and lowest Intergovernmental Panel on Climate Change emissions pathways for climate change and associated impacts in California. Based on climate projections from two state-of-the-art climate models with low and medium sensitivity (Parallel Climate Model and Hadley Centre Climate Model, version 3, respectively), we find that annual temperature increases nearly double from the lower B1 to the higher A1fi emissions scenario before 2100. Three of four simulations also show greater increases in summer temperatures as compared with winter. Extreme heat and the associated impacts on a range of temperature-sensitive sectors are substantially greater under the higher emissions scenario, with some interscenario differences apparent before midcentury. By the end of the century under the B1 scenario, heatwaves and extreme heat in Los Angeles quadruple in frequency while heat-related mortality increases two to three times; alpine/subalpine forests are reduced by 50-75%; and Sierra snowpack is reduced 30-70%. Under A1fi, heatwaves in Los Angeles are six to eight times more frequent, with heat-related excess mortality increasing five to seven times; alpine/subalpine forests are reduced by 75-90%; and snowpack declines 73-90%, with cascading impacts on runoff and streamflow that, combined with projected modest declines in winter precipitation, could fundamentally disrupt California's water rights system. Although interscenario differences in climate impacts and costs of adaptation emerge mainly in the second half of the century, they are strongly dependent on emissions from preceding decades.

Proceedings of the National Academy of Sciences of

Host population persistence in the face of introduced vector-borne diseases: Hawaii amakihi and avian malaria

The past quarter century has seen an unprecedented increase in the number of new and emerging infectious diseases throughout the world, with serious implications for human and wildlife populations. We examined host persistence in the face of introduced vector-borne diseases in Hawaii, where introduced avian malaria and introduced vectors have had a negative impact on most populations of Hawaiian forest birds for nearly a century. We studied birds, parasites, and vectors in nine study areas from 0 to 1,800 m on Mauna Loa Volcano, Hawaii from January to October, 2002. Contrary to predictions of prior work, we found that Hawaii amakihi (Hemignathus virens), a native species susceptible to malaria, comprised from 24.5% to 51.9% of the avian community at three low-elevation forests (55-270 m). Amakihi were more abundant at low elevations than at disease-free high elevations, and were resident and breeding there. Infection rates were 24-40% by microscopy and 55-83% by serology, with most infected individuals experiencing low-intensity, chronic infections. Mosquito trapping and diagnostics provided strong evidence for year-round local transmission. Moreover, we present evidence that Hawaii amakihi have increased in low elevation habitats on south-eastern Hawaii Island over the past decade. The recent emergent phenomenon of recovering amakihi populations at low elevations, despite extremely high prevalence of avian malaria, suggests that ecological or evolutionary processes acting on hosts or parasites have allowed this species to recolonize low-elevation habitats. A better understanding of the mechanisms allowing coexistence of hosts and parasites may ultimately lead to tools for mitigating disease impacts on wildlife and human populations.

Proceedings of the National Academy of Sciences of

Paleoclimate and Amerindians: Evidence from stable isotopes and atmospheric circulation

Two Amerindian demographic shifts are attributed to climate change in the northwest plains of North America: at ???11,000 calendar years before present (yr BP), Amerindian culture apparently split into foothills-mountains vs. plains biomes; and from 8,000-5,000 yr BP, scarce archaeological sites on the open plains suggest emigration during xeric "Altithermal" conditions. We reconstructed paleoclimates from stable isotopes in prehistoric bison bone and relations between weather and fractions of C4 plants in forage. Further, we developed a climate-change model that synthesized stable isotope, existing qualitative evidence (e.g., palynological, erosional), and global climate mechanisms affecting this midlatitude region. Our isotope data indicate significant warming from ???12,400 to 11,900 yr BP, supporting climate-driven cultural separation. However, isotope evidence of apparently wet, warm conditions at 7,300 yr BP refutes emigration to avoid xeric conditions. Scarcity of archaeological sites is best explained by rapid climate fluctuations after catastrophic draining of the Laurentide Lakes, which disrupted North Atlantic Deep Water production and subsequently altered monsoonal inputs to the open plains.

Proceedings of the National Academy of Sciences of

Discovery of a unique Ig heavy-chain (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish

During the analysis of Ig superfamily members within the available rainbow trout (Oncorhynchus mykiss) EST gene index, we identified a unique Ig heavy-chain (IgH) isotype. cDNAs encoding this isotype are composed of a typical IgH leader sequence and a VDJ rearranged segment followed by four Ig superfamily C-1 domains represented as either membrane-bound or secretory versions. Because teleost fish were previously thought to encode and express only two IgH isotypes (IgM and IgD) for their humoral immune repertoire, we isolated all three cDNA isotypes from a single homozygous trout (OSU-142) to confirm that all three are indeed independent isotypes. Bioinformatic and phylogenetic analysis indicates that this previously undescribed divergent isotype is restricted to bony fish, thus we have named this isotype "IgT" (??) for teleost fish. Genomic sequence analysis of an OSU-142 bacterial artificial chromosome (BAC) clone positive for all three IgH isotypes revealed that IgT utilizes the standard rainbow trout VH families, but surprisingly, the IgT isotype possesses its own exclusive set of DH and JH elements for the generation of diversity. The IgT D and J segments and ?? constant (C) region genes are located upstream of the D and J elements for IgM, representing a genomic IgH architecture that has not been observed in any other vertebrate class. All three isotypes are primarily expressed in the spleen and pronephros (bone marrow equivalent), and ontogenically, expression of IgT is present 4 d before hatching in developing embryos. ?? 2005 by The National Academy of Sciences of the USA.

Proceedings of the National Academy of Sciences of

Degassing Lakes Nyos and Monoun: Defusing certain disaster

Since the catastrophic releases of CO 2 in the 1980s, Lakes Nyos and Monoun in Cameroon experienced CO 2 recharge at alarming rates of up to 80 mol/m 2 per yr. Total gas pressures reached 8.3 and 15.6 bar in Monoun (2003) and Nyos (2001), respectively, resulting in gas saturation levels up to 97%. These natural hazards are distinguished by the potential for mitigation to prevent future disasters. Controlled degassing was initiated at Nyos (2001) and Monoun (2003) amid speculation it could inadvertently destabilize the lakes and trigger another gas burst. Our measurements indicate that water column structure has not been compromised by the degassing and local stability is increasing in the zones of degassing. Furthermore, gas content has been reduced in the lakes ≈12-14%. However, as gas is removed, the pressure at pipe inlets is reduced, and the removal rate will decrease over time. Based on 12 years of limnological measurements we developed a model of future removal rates and gas inventory, which predicts that in Monoun the current pipe will remove ≈30% of the gas remaining before the natural gas recharge balances the removal rate. In Nyos the single pipe will remove ≈25% of the gas remaining by 2015; this slow removal extends the present risk to local populations. More pipes and continued vigilance are required to reduce the risk of repeat disasters. Our model indicates that 75-99% of the gas remaining would be removed by 2010 with two pipes in Monoun and five pipes in Nyos, substantially reducing the risks.

Lakes Nyos and Monoun

Soil nutrients influence spatial distributions of tropical trees species

The importance of niche vs. neutral assembly mechanisms in structuring tropical tree communities remains an important unsettled question in community ecology [Bell G (2005) Ecology 86:1757-1770]. There is ample evidence that species distributions are determined by soils and habitat factors at landscape (<104 km2) and regional scales. At local scales (<1 km2), however, habitat factors and species distributions show comparable spatial aggregation, making it difficult to disentangle the importance of niche and dispersal processes. In this article, we test soil resource-based niche assembly at a local scale, using species and soil nutrient distributions obtained at high spatial resolution in three diverse neotropical forest plots in Colombia (La Planada), Ecuador (Yasuni), and Panama (Barro Colorado Island). Using spatial distribution maps of >0.5 million individual trees of 1,400 species and 10 essential plant nutrients, we used Monte Carlo simulations of species distributions to test plant-soil associations against null expectations based on dispersal assembly. We found that the spatial distributions of 36-51% of tree species at these sites show strong associations to soil nutrient distributions. Neutral dispersal assembly cannot account for these plant-soil associations or the observed niche breadths of these species. These results indicate that belowground resource availability plays an important role in the assembly of tropical tree communities at local scales and provide the basis for future investigations on the mechanisms of resource competition among tropical tree species. ?? 2007 by The National Academy of Sciences of the USA.

Proceedings of the National Academy of Sciences of

Whole-ecosystem study shows rapid fish-mercury response to changes in mercury deposition

Methylmercury contamination of fisheries from centuries of industrial atmospheric emissions negatively impacts humans and wild-life worldwide. The response of fish methylmercury concentrations to changes in mercury deposition has been difficult to establish because sediments/soils contain large pools of historical contamination, and many factors in addition to deposition affect fish mercury. To test directly the response of fish contamination to changing mercury deposition, we conducted a whole-ecosystem experiment, increasing the mercury load to a lake and its watershed by the addition of enriched stable mercury isotopes. The isotopes allowed us to distinguish between experimentally applied mercury and mercury already present in the ecosystem and to examine bioaccumulation of mercury deposited to different parts of the watershed. Fish methylmercury concentrations responded rapidly to changes in mercury deposition over the first 3 years of study. Essentially all of the increase in fish methylmercury concentrations came from mercury deposited directly to the lake surface. In contrast, <1% of the mercury isotope deposited to the watershed was exported to the lake. Steady state was not reached within 3 years. Lake mercury isotope concentrations were still rising in lake biota, and watershed mercury isotope exports to the lake were increasing slowly. Therefore, we predict that mercury emissions reductions will yield rapid (years) reductions in fish methylmercury concentrations and will yield concomitant reductions in risk. However, a full response will be delayed by the gradual export of mercury stored in watersheds. The rate of response will vary among lakes depending on the relative surface areas of water and watershed.

Proceedings of the National Academy of Sciences of

A cold phase of the East Pacific triggers new phytoplankton blooms in San Francisco Bay

Ecological observations sustained over decades often reveal abrupt changes in biological communities that signal altered ecosystem states. We report a large shift in the biological communities of San Francisco Bay, first detected as increasing phytoplankton biomass and occurrences of new seasonal blooms that began in 1999. This phytoplankton increase is paradoxical because it occurred in an era of decreasing wastewater nutrient inputs and reduced nitrogen and phosphorus concentrations, contrary to the guiding paradigm that algal biomass in estuaries increases in proportion to nutrient inputs from their watersheds. Coincidental changes included sharp declines in the abundance of bivalve mollusks, the key phytoplankton consumers in this estuary, and record high abundances of several bivalve predators: Bay shrimp, English sole, and Dungeness crab. The phytoplankton increase is consistent with a trophic cascade resulting from heightened predation on bivalves and suppression of their filtration control on phytoplankton growth. These community changes in San Francisco Bay across three trophic levels followed a state change in the California Current System characterized by increased upwelling intensity, amplified primary production, and strengthened southerly flows. These diagnostic features of the East Pacific "cold phase" lead to strong recruitment and immigration of juvenile flatfish and crustaceans into estuaries where they feed and develop. This study, built from three decades of observation, reveals a previously unrecognized mechanism of ocean-estuary connectivity. Interdecadal oceanic regime changes can propagate into estuaries, altering their community structure and efficiency of transforming land-derived nutrients into algal biomass.

California

Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model

Malaria infections frequently consist of mixtures of drug-resistant and drug-sensitive parasites. If crowding occurs, where clonal population densities are suppressed by the presence of coinfecting clones, removal of susceptible clones by drug treatment could allow resistant clones to expand into the newly vacated niche space within a host. Theoretical models show that, if such competitive release occurs, it can be a potent contributor to the strength of selection, greatly accelerating the rate at which resistance spreads in a population. A variety of correlational field data suggest that competitive release could occur in human malaria populations, but direct evidence cannot be ethically obtained from human infections. Here we show competitive release after pyrimethamine curative chemotherapy of acute infections of the rodent malaria Plasmodium chabaudi in laboratory mice. The expansion of resistant parasite numbers after treatment resulted in enhanced transmission-stage densities. After the elimination or near-elimination of sensitive parasites, the number of resistant parasites increased beyond that achieved when a competitor had never been present. Thus, a substantial competitive release occurred, markedly elevating the fitness advantages of drug resistance above those arising from survival alone. This finding may explain the rapid spread of drug resistance and the subsequently brief useful lifespans of some antimalarial drugs. In a second experiment, where subcurative chemotherapy was administered, the resistant clone was only partly released from competitive suppression and experienced a restriction in the size of its expansion after treatment. This finding raises the prospect of harnessing in-host ecology to slow the spread of drug resistance. ?? 2007 by The National Academy of Sciences of the USA.

Proceedings of the National Academy of Sciences of

Warming of the Indian Ocean threatens eastern and southern African food security but could be mitigated by agricultural development

Since 1980, the number of undernourished people in eastern and southern Africa has more than doubled. Rural development stalled and rural poverty expanded during the 1990s. Population growth remains very high, and declining per-capita agricultural capacity retards progress toward Millennium Development goals. Analyses of in situ station data and satellite observations of precipitation have identified another problematic trend: main growing-season rainfall receipts have diminished by ???15% in food-insecure countries clustered along the western rim of the Indian Ocean. Occurring during the main growing seasons in poor countries dependent on rain-fed agriculture, these declines are societally dangerous. Will they persist or intensify? Tracing moisture deficits upstream to an anthropogenically warming Indian Ocean leads us to conclude that further rainfall declines are likely. We present analyses suggesting that warming in the central Indian Ocean disrupts onshore moisture transports, reducing continental rainfall. Thus, late 20th-century anthropogenic Indian Ocean warming has probably already produced societally dangerous climate change by creating drought and social disruption in some of the world's most fragile food economies. We quantify the potential impacts of the observed precipitation and agricultural capacity trends by modeling 'millions of undernourished people' as a function of rainfall, population, cultivated area, seed, and fertilizer use. Persistence of current tendencies may result in a 50% increase in undernourished people by 2030. On the other hand, modest increases in per-capita agricultural productivity could more than offset the observed precipitation declines. Investing in agricultural development can help mitigate climate change while decreasing rural poverty and vulnerability. ?? 2008 by The National Academy of Sciences of the USA.

Proceedings of the National Academy of Sciences of

Egg size variation among tropical and temperate songbirds: An embryonic temperature hypothesis

Species with 'slow' life history strategies (long life, low fecundity) are thought to produce high-quality offspring by investing in larger, but fewer, young. Larger eggs are indeed associated with fewer eggs across taxa and can yield higher-quality offspring. Tropical passerines appear to follow theory because they commonly exhibit slow life history strategies and produce larger, but fewer, eggs compared with northern species. Yet, I show here that relative egg mass (corrected for adult mass) varies extensively in the tropics and subtropics for the same clutch size, and this variation is unexplained. I propose a hypothesis to explain egg size variation both within the tropics and between latitudes: Relative egg mass increases in species with cooler egg temperatures and longer embryonic periods to offset associated increases in energetic requirements of embryos. Egg temperatures of birds are determined by parental incubation behavior and are often cooler among tropical passerines because of reduced parental attentiveness of eggs. Here, I show that cooler egg temperatures and longer embryonic periods explained the enigmatic variation in egg mass within and among regions, based on field studies in tropical Venezuela (36 species), subtropical Argentina (16 species), and north temperate Arizona (20 species). Alternative explanations are not supported. Thus, large egg sizes may reflect compensation for increased energetic requirements of cool egg temperatures and long embryonic periods that result from reduced parental attentiveness in tropical birds. ?? 2008 by The National Academy of Sciences of the USA.

Proceedings of the National Academy of Sciences of

Evaluation of the sustainability of deep groundwater as an arsenic-safe resource in the Bengal Basin

Tens of millions of people in the Bengal Basin region of Bangladesh and India drink groundwater containing unsafe concentrations of arsenic. This high-arsenic groundwater is produced from shallow (<100 m) depths by domestic and irrigation wells in the Bengal Basin aquifer system. The government of Bangladesh has begun to install wells to depths of >150 m where groundwater arsenic concentrations are nearly uniformly low, and many more wells are needed, however, the sustainability of deep, arsenic-safe groundwater has not been previously assessed. Deeper pumping could induce downward migration of dissolved arsenic, permanently destroying the deep resource. Here, it is shown, through quantitative, large-scale hydrogeologic analysis and simulation of the entire basin, that the deeper part of the aquifer system may provide a sustainable source of arsenic-safe water if its utilization is limited to domestic supply. Simulations provide two explanations for this result: deep domestic pumping only slightly perturbs the deep groundwater flow system, and substantial shallow pumping for irrigation forms a hydraulic barrier that protects deeper resources from shallow arsenic sources. Additional analysis indicates that this simple management approach could provide arsenic-safe drinking water to >90% of the arsenic-impacted region over a 1,000-year timescale. This insight may assist water-resources managers in alleviating one of the world's largest groundwater contamination problems.

Proceedings of the National Academy of Sciences of

Regulating continent growth and composition by chemical weathering

Continents ride high above the ocean floor because they are underlain by thick, low-density, Si-rich, and Mg-poor crust. However, the parental magmas of continents were basaltic, which means they must have lost Mg relative to Si during their maturation into continents. Igneous differentiation followed by lower crustal delamination and chemical weathering followed by subduction recycling are possible solutions, but the relative magnitudes of each process have never been quantitatively constrained because of the lack of appropriate data. Here, we show that the relative contributions of these processes can be obtained by simultaneous examination of Mg and Li (an analog for Mg) on the regional and global scales in arcs, delaminated lower crust, and river waters. At least 20% of Mg is lost from continents by weathering, which translates into >20% of continental mass lost by weathering (40% by delamination). Chemical weathering leaves behind a more Si-rich and Mg-poor crust, which is less dense and hence decreases the probability of crustal recycling by subduction. Net continental growth is thus modulated by chemical weathering and likely influenced by secular changes in weathering mechanisms. ?? 2008 by The National Academy of Sciences of the USA.

Proceedings of the National Academy of Sciences of

An introduced and a native vertebrate hybridize to form a genetic bridge to a second native species

The genetic impacts of hybridization between native and introduced species are of considerable conservation concern, while the possibility of reticulate evolution affects our basic understanding of how species arise and shapes how we use genetic data to understand evolutionary diversification. By using mitochondrial NADH dehydrogenase subunit 2 (ND2) sequences and 467 amplified fragment-length polymorphism nuclear DNA markers, we show that the introduced white sucker (Catostomus commersoni) has hybridized with two species native to the Colorado River Basin - the flannelmouth sucker (Catostomus latipinnis) and the bluehead sucker (Catostomus discobolus). Hybrids between the flannelmouth sucker and white sucker have facilitated introgression between the two native species, previously isolated by reproductive barriers, such that individuals exist with contributions from all three genomes. Most hybrids had the mitochondrial haplotype of the introduced white sucker, emphasizing its pivotal role in this three-way hybridization. Our findings highlight how introduced species can threaten the genetic integrity of not only one species but also multiple previously reproductively isolated species. Furthermore, this complex three-way reticulate (as opposed to strictly bifurcating) evolution suggests that seeking examples in other vertebrate systems might be productive. Although the present study involved an introduced species, similar patterns of hybridization could result from natural processes, including stream capture or geological formations (e.g., the Bering land bridge). ?? 2008 by The National Academy of Sciences of the USA.

Proceedings of the National Academy of Sciences of

Aquatic insect ecophysiological traits reveal phylogenetically based differences in dissolved cadmium susceptibility

We used a phylogenetically based comparative approach to evaluate the potential for physiological studies to reveal patterns of diversity in traits related to susceptibility to an environmental stressor, the trace metal cadmium (Cd). Physiological traits related to Cd bioaccumulation, compartmentalization, and ultimately susceptibility were measured in 21 aquatic insect species representing the orders Ephemeroptera, Plecoptera, and Trichoptera. We mapped these experimentally derived physiological traits onto a phylogeny and quantified the tendency for related species to be similar (phylogenetic signal). All traits related to Cd bioaccumulation and susceptibility exhibited statistically significant phylogenetic signal, although the signal strength varied among traits. Conventional and phylogenetically based regression models were compared, revealing great variability within orders but consistent, strong differences among insect families. Uptake and elimination rate constants were positively correlated among species, but only when effects of body size and phylogeny were incorporated in the analysis. Together, uptake and elimination rates predicted dramatic Cd bioaccumulation differences among species that agreed with field-based measurements. We discovered a potential tradeoff between the ability to eliminate Cd and the ability to detoxify it across species, particularly mayflies. The best-fit regression models were driven by phylogenetic parameters (especially differences among families) rather than functional traits, suggesting that it may eventually be possible to predict a taxon's physiological performance based on its phylogenetic position, provided adequate physiological information is available for close relatives. There appears to be great potential for evolutionary physiological approaches to augment our understanding of insect responses to environmental stressors in nature. ?? 2008 by The National Academy of Sciences of the USA.

Proceedings of the National Academy of Sciences of

Homage to Linnaeus: How many parasites? How many hosts?

Estimates of the total number of species that inhabit the Earth have increased significantly since Linnaeus's initial catalog of 20,000 species. The best recent estimates suggest that there are ≈6 million species. More emphasis has been placed on counts of free-living species than on parasitic species. We rectify this by quantifying the numbers and proportion of parasitic species. We estimate that there are between 75,000 and 300,000 helminth species parasitizing the vertebrates. We have no credible way of estimating how many parasitic protozoa, fungi, bacteria, and viruses exist. We estimate that between 3% and 5% of parasitic helminths are threatened with extinction in the next 50 to 100 years. Because patterns of parasite diversity do not clearly map onto patterns of host diversity, we can make very little prediction about geographical patterns of threat to parasites. If the threats reflect those experienced by avian hosts, then we expect climate change to be a major threat to the relatively small proportion of parasite diversity that lives in the polar and temperate regions, whereas habitat destruction will be the major threat to tropical parasite diversity. Recent studies of food webs suggest that ≈75% of the links in food webs involve a parasitic species; these links are vital for regulation of host abundance and potentially for reducing the impact of toxic pollutants. This implies that parasite extinctions may have unforeseen costs that impact the health and abundance of a large number of free-living species.

Proceedings of the National Academy of Sciences of

Humid tropical forest clearing from 2000 to 2005 quantified by using multitemporal and multiresolution remotely sensed data

Forest cover is an important input variable for assessing changes to carbon stocks, climate and hydrological systems, biodiversity richness, and other sustainability science disciplines. Despite incremental improvements in our ability to quantify rates of forest clearing, there is still no definitive understanding on global trends. Without timely and accurate forest monitoring methods, policy responses will be uninformed concerning the most basic facts of forest cover change. Results of a feasible and cost-effective monitoring strategy are presented that enable timely, precise, and internally consistent estimates of forest clearing within the humid tropics. A probability-based sampling approach that synergistically employs low and high spatial resolution satellite datasets was used to quantify humid tropical forest clearing from 2000 to 2005. Forest clearing is estimated to be 1.39% (SE 0.084%) of the total biome area. This translates to an estimated forest area cleared of 27.2 million hectares (SE 2.28 million hectares), and represents a 2.36% reduction in area of humid tropical forest. Fifty-five percent of total biome clearing occurs within only 6% of the biome area, emphasizing the presence of forest clearing “hotspots.” Forest loss in Brazil accounts for 47.8% of total biome clearing, nearly four times that of the next highest country, Indonesia, which accounts for 12.8%. Over three-fifths of clearing occurs in Latin America and over one-third in Asia. Africa contributes 5.4% to the estimated loss of humid tropical forest cover, reflecting the absence of current agro-industrial scale clearing in humid tropical Africa.

Proceedings of the National Academy of Sciences of