The deep, hot biosphere.

There are strong indications that microbial life is widespread at depth in the crust of the Earth, just as such life has been identified in numerous ocean vents. This life is not dependent on solar energy and photosynthesis for its primary energy supply, and it is essentially independent of the surface circumstances. Its energy supply comes from chemical sources, due to fluids that migrate upward from deeper levels in the Earth. In mass and volume it may be comparable with all surface life. Such microbial life may account for the presence of biological molecules in all carbonaceous materials in the outer crust, and the inference that these materials must have derived from biological deposits accumulated at the surface is therefore not necessarily valid. Subsurface life may be widespread among the planetary bodies of our solar system, since many of them have equally suitable conditions below, while having totally inhospitable surfaces. One may even speculate that such life may be widely disseminated in the universe, since planetary type bodies with similar subsurface conditions may be common as solitary objects in space, as well as in other solar-type systems.     

Thermochronologic perspectives on the deep-time evolution of the deep biosphere

The Earth’s deep biosphere hosts some of its most ancient chemolithotrophic lineages. The history of habitation in this environment is thus of interest for understanding the origin and evolution of life. The oldest rocks on Earth, formed about 4 billion years ago, are in continental cratons that have experienced complex histories due to burial and exhumation. Isolated fracture-hosted fluids in these cratons may have residence times older than a billion years, but understanding the history of their microbial communities requires assessing the evolution of habitable conditions. Here, we present a thermochronological perspective on the habitability of Precambrian cratons through time. We show that rocks now in the upper few kilometers of cratons have been uninhabitable (>∼122 °C) for most of their lifetime or have experienced high-temperature episodes, such that the longest record of habitability does not stretch much beyond a billion years. In several cratons, habitable conditions date back only 50 to 300 million years, in agreement with dated biosignatures. The thermochronologic approach outlined here provides context for prospecting and interpreting the little-explored geologic record of the deep biosphere of Earth’s cratons, when and where microbial communities may have thrived, and candidate areas for the oldest records of chemolithotrophic microbes.

Research in the last few decades has revealed a vast global rock- and sediment-hosted subsurface biosphere in marine sediments, hydrothermal vents at midocean ridges, porespace and fractures in oceanic crust and continental sedimentary rocks, and fracture systems of continental igneous and metamorphic rock (1–3). Most current estimates show that this deep biosphere hosts the majority of microbial life on Earth (estimated ∼90% of bacteria and archaea) and about 10 to 20% of all terrestrial biomass (4–6). These communities compose a large but variable part of unclassified microbial “dark-matter” metagenome and subsurface phyla with no known closely related surface relatives, and they thrive independently of the surface photosphere (7–10). Metabolic activity at great depth in this vast, dark, and largely anoxic environment relies largely on abiotic, energy-yielding chemolithotrophic reactions, including oxidation of abiotic H₂ (1), methanogenesis, and sulfate reduction (7), and on recycling of metabolic waste products (11). Shallower parts of these ecosystems are dominated by heterotrophic communities that utilize descending dissolved organic carbon (12).The abundance of cells in the subsurface decreases with depth in both marine (13) and continental environments (5) due to decreasing surface-derived carbon and increasing temperatures. Higher metabolic rates and biomass generation are observed (e.g., for methanogens and methanotrophs) at temperatures below ∼85 °C (14, 15). At depths where temperatures approach and exceed 100 °C, hyperthermophiles dominate (14), but these also require temperatures below about 121 to 122 °C (16, 17).Evidence from fluid inclusions and molecular dating suggest that microbial methanogenesis originated early on Earth (18, 19), and methanogens have been proposed as one of the primary life forms, evolving before phototrophs like cyanobacteria (20). Life at earth’s surface proliferated in the Ordovician, and it has been proposed that before the plant colonization of the continents, life in the subsurface composed the majority of biomass (21). Yet, there is very little knowledge of when life colonized the deep subsurface of the fractured crust and for how long the communities and metabolisms of the deep rock–hosted biosphere may have evolved and persisted (22).Of particular interest for these questions and their astrobiological implications (22) are some of the oldest terrestrial rocks, which are exposed on all continents in Precambrian cratons. Recent applications of microscale stable isotope techniques, surveys for preserved organic molecules, and geochronology of mineral precipitates in fluid-filled fractures have revealed evidence for ancient microbial methanogenesis, methane oxidation, and sulfate reduction in one craton, the Fennoscandian Shield (23, 24). This shows the potential for reconstructing the history of deep-time subsurface microbial activity, but we currently lack a useful conceptual framework and geologic context for predicting and prospecting for potentially long-lived and evolutionarily informative deep chemolithotrophic life in these environments.Recent work using radiogenic noble-gas isotopes suggests that brines in isolated pockets of the deep fracture networks within Archaean basement rocks may have residence times of 10⁷ to 10⁹ y (25). Examples include 2.8-km-deep fluids isolated from the photosphere since ∼25 million years (Ma) (26) in a South African gold mine carrying extant chemolithotrophic microbes (27), and 2.5-km-deep saline fluids with 20- to 50-Ma residence times from the Outokumpu deep drill hole in Finland contain active archaeal and bacterial communities (28). In the Canadian Shield, fracture fluids from 2.4- and 2.9-km depths in Ontario’s Kidd Creek Mine have mean residence times of as old as 1.1 to 1.7 billion years (Ga) (25) and 1.0 to 2.2 Ga (29), respectively. Younger residence times (200 to 900 Ma) are interpreted for fracture fluids from mines in Sudbury, Ontario, hosted by rocks formed by meteorite impact at 1.85 Ga (29).However, fluid residence times provide only limited constraints on potential microbial habitation histories, and extant biologic activity in a given setting is not necessarily directly descended from ancient ancestors of the same local environment. Cell counts and culture-based methods indicate active archaeal and bacterial communities in the fracture fluids in Kidd Creek mine (30), and clumped isotope signatures suggest microbial methanotrophy at 2.4-km depth (31). Signatures of mass-independent sulfur isotope fractionation in the deep Kidd Creek fluids suggest a long-standing sulfur cycle but likely reflect oxidation of wall rock sulfides postdating the Archaean ore formation (32). While multiple lines of evidence provide intriguing suggestions that microbial life in this and other settings may be old, there are currently few constraints on the timing of active microbial habitation. For the Kidd Creek location, Li et al. (32) state that the crustal section has been at the same depth over the past 2 Ga, based on estimates of limited denudation of the shield rocks since this time (33). However, as we show here, the thermochronologic record suggests that this and other cratons (34, 35) likely experienced complex burial and exhumation histories, with important implications for their habitation history.Here, we present a previously unexplored thermochronological deep-time perspective to interpreting the temperature-controlled habitability of the Precambrian cratons on earth. This framework builds on the recent advances in intermediate- and low-temperature thermochronology and is coupled to radioisotopic dating constraints on mineral-hosted biosignatures in cratons, where they have been documented thus far. This approach predicts the temporal and regional distribution and history of ancient and currently habitable conditions, as well as high-temperature burial episodes, in the upper continental crust, and points to craton locations most likely to feature the longest record of isolated microbial chemolithotrophic evolution on Earth.     

Microbial diversity in the deep sea and the underexplored "rare biosphere"

The evolution of marine microbes over billions of years predicts that the composition of microbial communities should be much greater than the published estimates of a few thousand distinct kinds of microbes per liter of seawater. By adopting a massively parallel tag sequencing strategy, we show that bacterial communities of deep water masses of the North Atlantic and diffuse flow hydrothermal vents are one to two orders of magnitude more complex than previously reported for any microbial environment. A relatively small number of different populations dominate all samples, but thousands of low-abundance populations account for most of the observed phylogenetic diversity. This "rare biosphere" is very ancient and may represent a nearly inexhaustible source of genomic innovation. Members of the rare biosphere are highly divergent from each other and, at different times in earth's history, may have had a profound impact on shaping planetary processes.     

Fluid mixing and the deep biosphere of a fossil Lost City-type hydrothermal system at the Iberia Margin

Subseafloor mixing of reduced hydrothermal fluids with seawater is believed to provide the energy and substrates needed to support deep chemolithoautotrophic life in the hydrated oceanic mantle (i.e., serpentinite). However, geosphere-biosphere interactions in serpentinite-hosted subseafloor mixing zones remain poorly constrained. Here we examine fossil microbial communities and fluid mixing processes in the subseafloor of a Cretaceous Lost City-type hydrothermal system at the magma-poor passive Iberia Margin (Ocean Drilling Program Leg 149, Hole 897D). Brucite−calcite mineral assemblages precipitated from mixed fluids ca. 65 m below the Cretaceous paleo-seafloor at temperatures of 31.7 ± 4.3 °C within steep chemical gradients between weathered, carbonate-rich serpentinite breccia and serpentinite. Mixing of oxidized seawater and strongly reducing hydrothermal fluid at moderate temperatures created conditions capable of supporting microbial activity. Dense microbial colonies are fossilized in brucite−calcite veins that are strongly enriched in organic carbon (up to 0.5 wt.% of the total carbon) but depleted in ¹³C (δ¹³C_TOC = −19.4‰). We detected a combination of bacterial diether lipid biomarkers, archaeol, and archaeal tetraethers analogous to those found in carbonate chimneys at the active Lost City hydrothermal field. The exposure of mantle rocks to seawater during the breakup of Pangaea fueled chemolithoautotrophic microbial communities at the Iberia Margin, possibly before the onset of seafloor spreading. Lost City-type serpentinization systems have been discovered at midocean ridges, in forearc settings of subduction zones, and at continental margins. It appears that, wherever they occur, they can support microbial life, even in deep subseafloor environments.Serpentinized mantle rocks constitute a major component of oceanic plates, subduction zones, and passive margins. Serpentinization systems have existed throughout most of Earth’s history, and it has been suggested that mixing of serpentinization fluids with Archean seawater produced conditions conducive to abiotic synthesis and the emergence of life on Earth (1). The Lost City hydrothermal field, located ∼15 km off the Mid-Atlantic Ridge axis at 30°N (2–4), represents the archetype of low-temperature seafloor serpentinization systems at slow-spreading midocean ridges and serves as an excellent present-day analog to fossil serpentinite-hosted hydrothermal systems in such environments. Lost City vents warm (≤ 91 °C), high-pH (9–11) fluids enriched in dissolved calcium, H₂, CH₄, formate, and other short-chain hydrocarbons (2, 5, 6). In contrast to high-temperature black smoker-type chimneys consisting of Cu−Fe sulfides, the Lost City chimneys are composed of brucite and calcium carbonate (aragonite, calcite), which form when serpentinization fluids (SF) mix with seawater (SW) (7),Ca2++OH-+HCO3-=CaCO3+H2OSF SF SWMg2++2OH-=Mg(OH)2.SW SFNascent Lost City chimneys are dominated by aragonite and brucite, whereas older structures are dominated by calcite. During aging, brucite undersaturated in seawater dissolves and aragonite recrystallizes to calcite (7).Actively venting chimneys host a microbial community with a relatively high proportion of methanogenic archaea (the Lost City Methanosarcinales), methanotrophic bacteria, and sulfur-oxidizing bacteria, whereas typical sulfate-reducing bacteria are rare (8–10). Geochemical evidence for significant microbial sulfate reduction in basement lithologies and distinct microbial communities in Lost City vent fluids and chimneys suggest that subsurface communities may be different from those in chimney walls (8, 9, 11). The lack of modern seawater bicarbonate and low CO₂/³He in Lost City fluids clearly indicate bicarbonate removal before venting, but it remains unclear if bicarbonate removal occurred by “dark” microbial carbon fixation in a serpentinization-fueled deep biosphere, by carbonate precipitation, or both (12).Other active and fossil seafloor hydrothermal systems similar to Lost City exist in a range of seafloor environments, including the Mid-Atlantic Ridge (13), New Caledonia (14), and the Mariana forearc (15, 16). Bathymodiolus mussels are, in some places, associated with these systems, suggesting that active serpentinization is supporting not only microbial chemosynthetic ecosystems but also macrofaunal communities (16). However, biological processes in the subseafloor of these Lost City-type systems are poorly understood.     

Commonness and rarity in the marine biosphere

Explaining patterns of commonness and rarity is fundamental for understanding and managing biodiversity. Consequently, a key test of biodiversity theory has been how well ecological models reproduce empirical distributions of species abundances. However, ecological models with very different assumptions can predict similar species abundance distributions, whereas models with similar assumptions may generate very different predictions. This complicates inferring processes driving community structure from model fits to data. Here, we use an approximation that captures common features of “neutral” biodiversity models—which assume ecological equivalence of species—to test whether neutrality is consistent with patterns of commonness and rarity in the marine biosphere. We do this by analyzing 1,185 species abundance distributions from 14 marine ecosystems ranging from intertidal habitats to abyssal depths, and from the tropics to polar regions. Neutrality performs substantially worse than a classical nonneutral alternative: empirical data consistently show greater heterogeneity of species abundances than expected under neutrality. Poor performance of neutral theory is driven by its consistent inability to capture the dominance of the communities’ most-abundant species. Previous tests showing poor performance of a neutral model for a particular system often have been followed by controversy about whether an alternative formulation of neutral theory could explain the data after all. However, our approach focuses on common features of neutral models, revealing discrepancies with a broad range of empirical abundance distributions. These findings highlight the need for biodiversity theory in which ecological differences among species, such as niche differences and demographic trade-offs, play a central role.Determining how biodiversity is maintained in ecological communities is a long-standing ecological problem. In species-poor communities, niche and demographic differences between species can often be estimated directly and used to infer the importance of alternative mechanisms of species coexistence (1–3). However, the “curse of dimensionality” prevents the application of such species-by-species approaches to high-diversity assemblages: the number of parameters in community dynamics models increases more rapidly than the amount of data, as species richness increases. Moreover, most species in high-diversity assemblages are very rare, further complicating the estimation of strengths of ecological interactions among species, or covariation in different species’ responses to environmental fluctuations. Consequently, ecologists have focused instead on making assumptions about the overall distribution of demographic rates, niche sizes, or other characteristics of an assemblage, and then deriving the aggregate assemblage properties implied by those assumptions (4–8). One of the most commonly investigated of these assemblage-level properties is the species abundance distribution (SAD)—the pattern of commonness and rarity among species (9–11). Ecologists have long sought to identify mechanisms that can explain common features of, and systematic differences among, the shapes of such distributions, and have used the ability to reproduce empirical SADs as a key test of biodiversity theory in species-rich systems (4, 6, 11–14).Over the last decade, one of the most prevalent and influential approaches to explaining the structure of high-diversity assemblages has been neutral theory of biodiversity (12, 15, 16). Neutral models assume that individuals are demographically and ecologically equivalent, regardless of species. Thus, variation in relative abundance among species arises purely from demographic stochasticity: chance variation in the fates of individuals (i.e., birth, death, immigration, and speciation events). Most studies investigating neutral theory aim to determine whether community structure in nature is consistent with the theory’s core species equivalence assumption. This is typically done by assessing the fit of a neutral model to empirical data, sometimes relative to a putatively nonneutral alternative (17–20). However, although all neutral models share the species equivalence assumption, they differ with respect to auxiliary assumptions, such as the mode of speciation assumed, leading to different predictions for SADs and other ecological patterns. Indeed, attempts to draw conclusions from tests of neutral theory are almost invariably disputed, largely due to arguments about the extent to which alternative auxiliary assumptions can materially alter neutral theory’s ability to explain the data (11, 12, 18, 21).An alternative, potentially more robust approach to evaluating neutral theory was proposed by Pueyo (22), based on approximating neutral and nonneutral dynamics as successively higher-order perturbations of a model for the idealized case of pure random drift in abundances. This approach predicts that a gamma distribution should approximate the distribution of species abundances for small departures for random drift, whereas assemblages exhibiting greater departures from neutrality should be better approximated by a lognormal distribution. This raises the possibility that a comparison of gamma and lognormal SADs could offer a robust test for the signature of nonneutrality in species abundance data, provided that the gamma distribution provides a sufficiently close approximation to SADs produced by neutral models.Here, we evaluate Pueyo’s framework and apply it to patterns of commonness and rarity in 1,185 SADs from 14 marine ecosystems ranging from shallow reef platforms to abyssal depths, and from the tropics to polar regions (Fig. 1 and Tables S1 and S2). First, we test the gamma neutral approximation against several models of community dynamics that share the core neutrality assumption of species equivalence, but make different assumptions about the speciation process, spatial structure of the metacommunity, and the nature of competition between individuals. Then, we analyze the marine species abundance data, to evaluate whether they are consistent with the hypothesis that marine assemblages are neutrally structured. Finally, we ask whether patterns of commonness and rarity deviate from neutral expectation in idiosyncratic ways, or whether there are particular features of real SADs that cannot be captured by neutral models.Open in a separate windowFig. 1.Sampling locations of SADs. Color and symbol combinations correspond to particular ecosystems. These symbols are reproduced in the surrounding panels, which show observed and fitted SADs for the site-level data (averaged across sites) of the corresponding ecosystem. The bars represent the mean proportion of species at each site in different octave classes of abundance, across all sites in the corresponding dataset [the first bar represents species with abundance 1, then abundances 2–3, abundances 4–7, etc. (10)]. The blue and red lines show the mean of fitted values from site-by-site fits of the Poisson-gamma and Poisson-lognormal distributions to the data, respectively.     

Imprint of denitrifying bacteria on the global terrestrial biosphere

Loss of nitrogen (N) from land limits the uptake and storage of atmospheric CO₂ by the biosphere, influencing Earth''s climate system and myriads of the global ecological functions and services on which humans rely. Nitrogen can be lost in both dissolved and gaseous phases; however, the partitioning of these vectors remains controversial. Particularly uncertain is whether the bacterial conversion of plant available N to gaseous forms (denitrification) plays a major role in structuring global N supplies in the nonagrarian centers of Earth. Here, we use the isotope composition of N (¹⁵N/¹⁴N) to constrain the transfer of this nutrient from the land to the water and atmosphere. We report that the integrated ¹⁵N/¹⁴N of the natural terrestrial biosphere is elevated with respect to that of atmospheric N inputs. This cannot be explained by preferential loss of ¹⁴N to waterways; rather, it reflects a history of low ¹⁵N/¹⁴N gaseous N emissions to the atmosphere owing to denitrifying bacteria in the soil. Parameterizing a simple model with global N isotope data, we estimate that soil denitrification (including N₂) accounts for ≈1/3 of the total N lost from the unmanaged terrestrial biosphere. Applying this fraction to estimates of N inputs, N₂O and NO_x fluxes, we calculate that ≈28 Tg of N are lost annually via N₂ efflux from the natural soil. These results place isotopic constraints on the widely held belief that denitrifying bacteria account for a significant fraction of the missing N in the global N cycle.     

Ecology of the rare microbial biosphere of the Arctic Ocean

Understanding the role of microbes in the oceans has focused on taxa that occur in high abundance; yet most of the marine microbial diversity is largely determined by a long tail of low-abundance taxa. This rare biosphere may have a cosmopolitan distribution because of high dispersal and low loss rates, and possibly represents a source of phylotypes that become abundant when environmental conditions change. However, the true ecological role of rare marine microorganisms is still not known. Here, we use pyrosequencing to describe the structure and composition of the rare biosphere and to test whether it represents cosmopolitan taxa or whether, similar to abundant phylotypes, the rare community has a biogeography. Our examination of 740,353 16S rRNA gene sequences from 32 bacterial and archaeal communities from various locations of the Arctic Ocean showed that rare phylotypes did not have a cosmopolitan distribution but, rather, followed patterns similar to those of the most abundant members of the community and of the entire community. The abundance distributions of rare and abundant phylotypes were different, following a log-series and log-normal model, respectively, and the taxonomic composition of the rare biosphere was similar to the composition of the abundant phylotypes. We conclude that the rare biosphere has a biogeography and that its tremendous diversity is most likely subjected to ecological processes such as selection, speciation, and extinction.     

Shrinking the malaria map: progress and prospects

In the past 150 years, roughly half of the countries in the world eliminated malaria. Nowadays, there are 99 endemic countries-67 are controlling malaria and 32 are pursuing an elimination strategy. This four-part Series presents evidence about the technical, operational, and financial dimensions of malaria elimination. The first paper in this Series reviews definitions of elimination and the state that precedes it: controlled low-endemic malaria. Feasibility assessments are described as a crucial step for a country transitioning from controlled low-endemic malaria to elimination. Characteristics of the 32 malaria-eliminating countries are presented, and contrasted with countries that pursued elimination in the past. Challenges and risks of elimination are presented, including Plasmodium vivax, resistance in the parasite and mosquito populations, and potential resurgence if investment and vigilance decrease. The benefits of elimination are outlined, specifically elimination as a regional and global public good. Priorities for the next decade are described.     

Prokaryotes: The unseen majority

The number of prokaryotes and the total amount of their cellular carbon on earth are estimated to be 4–6 × 10³⁰ cells and 350–550 Pg of C (1 Pg = 10¹⁵ g), respectively. Thus, the total amount of prokaryotic carbon is 60–100% of the estimated total carbon in plants, and inclusion of prokaryotic carbon in global models will almost double estimates of the amount of carbon stored in living organisms. In addition, the earth’s prokaryotes contain 85–130 Pg of N and 9–14 Pg of P, or about 10-fold more of these nutrients than do plants, and represent the largest pool of these nutrients in living organisms. Most of the earth’s prokaryotes occur in the open ocean, in soil, and in oceanic and terrestrial subsurfaces, where the numbers of cells are 1.2 × 10²⁹, 2.6 × 10²⁹, 3.5 × 10³⁰, and 0.25–2.5 × 10³⁰, respectively. The numbers of heterotrophic prokaryotes in the upper 200 m of the open ocean, the ocean below 200 m, and soil are consistent with average turnover times of 6–25 days, 0.8 yr, and 2.5 yr, respectively. Although subject to a great deal of uncertainty, the estimate for the average turnover time of prokaryotes in the subsurface is on the order of 1–2 × 10³ yr. The cellular production rate for all prokaryotes on earth is estimated at 1.7 × 10³⁰ cells/yr and is highest in the open ocean. The large population size and rapid growth of prokaryotes provides an enormous capacity for genetic diversity.     

Misconduct accounts for the majority of retracted scientific publications

A detailed review of all 2,047 biomedical and life-science research articles indexed by PubMed as retracted on May 3, 2012 revealed that only 21.3% of retractions were attributable to error. In contrast, 67.4% of retractions were attributable to misconduct, including fraud or suspected fraud (43.4%), duplicate publication (14.2%), and plagiarism (9.8%). Incomplete, uninformative or misleading retraction announcements have led to a previous underestimation of the role of fraud in the ongoing retraction epidemic. The percentage of scientific articles retracted because of fraud has increased ∼10-fold since 1975. Retractions exhibit distinctive temporal and geographic patterns that may reveal underlying causes.     

Patterns of new versus recycled primary production in the terrestrial biosphere

Nitrogen (N) and phosphorus (P) availability regulate plant productivity throughout the terrestrial biosphere, influencing the patterns and magnitude of net primary production (NPP) by land plants both now and into the future. These nutrients enter ecosystems via geologic and atmospheric pathways and are recycled to varying degrees through the plant–soil–microbe system via organic matter decay processes. However, the proportion of global NPP that can be attributed to new nutrient inputs versus recycled nutrients is unresolved, as are the large-scale patterns of variation across terrestrial ecosystems. Here, we combined satellite imagery, biogeochemical modeling, and empirical observations to identify previously unrecognized patterns of new versus recycled nutrient (N and P) productivity on land. Our analysis points to tropical forests as a hotspot of new NPP fueled by new N (accounting for 45% of total new NPP globally), much higher than previous estimates from temperate and high-latitude regions. The large fraction of tropical forest NPP resulting from new N is driven by the high capacity for N fixation, although this varies considerably within this diverse biome; N deposition explains a much smaller proportion of new NPP. By contrast, the contribution of new N to primary productivity is lower outside the tropics, and worldwide, new P inputs are uniformly low relative to plant demands. These results imply that new N inputs have the greatest capacity to fuel additional NPP by terrestrial plants, whereas low P availability may ultimately constrain NPP across much of the terrestrial biosphere.     

Shrinking lung syndrome and systemic auto-immune disease

INTRODUCTION: Shrinking lung syndrome usually manifest in dyspnea, decreased lung volume associated with elevated diaphragm. It reports with systemic autoimmune disease and physiopathological mechanism is controversial. EXEGESIS: We report three shrinking lung syndrome observations in which two cases were diagnosed at the time to onset of autoimmune disease. The three patients were treated with corticosteroid, two of them necessitated theophylline. Review of the literature highlight 60 cases and permit to discuss physiopathological mechanisms which remain uncertain. Diaphragmatic dysfunction (because of myositis or neuropathy) represented by abnormal transdiaphragmatic pressures is actually discussed. CONCLUSION: Shrinking lung syndrome is rare but must be considered in patient with autoimmune disease and dyspnea. The diagnosis can be difficult because of clinical, pathological and functional features which are controversial. The optimum treatment is unknown.     

Progression to AIDS in the majority of asymptomatic HIV-infected people

Sixty-eight asymptomatic HIV-seropositive people with a CD4 lymphocyte count above 400/mm3 at the first examination were followed up every year over a 3-year period, by monitoring the biological markers of AIDS (CD4 lymphocyte decrease, loss of anti-p24 or anti-p17 antibodies, positive p24 antigenemia, increase of erythrocyte sedimentation rate, and of serum levels of immunoglobulin G. immunoglobulin A, neopterin and beta 2-microglobulin). The percentages of subjects positive for at least one marker at the first, second, third and fourth examinations were 66, 88, 94 and 97%, respectively. The increase in the number of markers with time was significant (chi-square test; P less than 0.001). This increase suggests a progression to AIDS in the majority of asymptomatic seropositive subjects, even those without a decreased CD4 lymphocyte count.