Catálogo de publicaciones - revistas

<jats:p>Sulfate reduction is a globally important redox process in marine sediments, yet global rates are poorly quantified. We developed an artificial neural network trained with 199 sulfate profiles, constrained with geomorphological and geochemical maps to estimate global sulfate-reduction rate distributions. Globally, 11.3 teramoles of sulfate are reduced yearly (~15% of previous estimates), accounting for the oxidation of 12 to 29% of the organic carbon flux to the sea floor. Combined with global cell distributions in marine sediments, these results indicate a strong contrast in sub–sea-floor prokaryote habitats: In continental margins, global cell numbers in sulfate-depleted sediment exceed those in the overlying sulfate-bearing sediment by one order of magnitude, whereas in the abyss, most life occurs in oxic and/or sulfate-reducing sediments.</jats:p>

<jats:p> The geological materials in Earth's lowermost mantle control the characteristics and interpretation of seismic ultra–low velocity zones at the base of the core-mantle boundary. Partial melting of the bulk lower mantle is often advocated as the cause, but this does not explain the nonubiquitous character of these regional seismic features. We explored the melting properties of mid-oceanic ridge basalt (MORB), which can reach the lowermost mantle after subduction of oceanic crust. At a pressure representative of the core-mantle boundary (135 gigapascals), the onset of melting occurs at ~3800 kelvin, which is ~350 kelvin below the mantle solidus. The SiO <jats:sub>2</jats:sub> -rich liquid generated either remains trapped in the MORB material or solidifies after reacting with the surrounding MgO-rich mantle, remixing subducted MORB with the lowermost mantle. </jats:p>

<jats:p>Reef corals are highly sensitive to heat, yet populations resistant to climate change have recently been identified. To determine the mechanisms of temperature tolerance, we reciprocally transplanted corals between reef sites experiencing distinct temperature regimes and tested subsequent physiological and gene expression profiles. Local acclimatization and fixed effects, such as adaptation, contributed about equally to heat tolerance and are reflected in patterns of gene expression. In less than 2 years, acclimatization achieves the same heat tolerance that we would expect from strong natural selection over many generations for these long-lived organisms. Our results show both short-term acclimatory and longer-term adaptive acquisition of climate resistance. Adding these adaptive abilities to ecosystem models is likely to slow predictions of demise for coral reef ecosystems.</jats:p>

<jats:p>The evolution of the ratite birds has been widely attributed to vicariant speciation, driven by the Cretaceous breakup of the supercontinent Gondwana. The early isolation of Africa and Madagascar implies that the ostrich and extinct Madagascan elephant birds (Aepyornithidae) should be the oldest ratite lineages. We sequenced the mitochondrial genomes of two elephant birds and performed phylogenetic analyses, which revealed that these birds are the closest relatives of the New Zealand kiwi and are distant from the basal ratite lineage of ostriches. This unexpected result strongly contradicts continental vicariance and instead supports flighted dispersal in all major ratite lineages. We suggest that convergence toward gigantism and flightlessness was facilitated by early Tertiary expansion into the diurnal herbivory niche after the extinction of the dinosaurs.</jats:p>

<jats:p> Decisions take time if information gradually accumulates to a response threshold, but the neural mechanisms of integration and thresholding are unknown. We characterized a decision process in <jats:italic>Drosophila</jats:italic> that bears the behavioral signature of evidence accumulation. As stimulus contrast in trained odor discriminations decreased, reaction times increased and perceptual accuracy declined, in quantitative agreement with a drift-diffusion model. <jats:italic>FoxP</jats:italic> mutants took longer than wild-type flies to form decisions of similar or reduced accuracy, especially in difficult, low-contrast tasks. RNA interference with <jats:italic>FoxP</jats:italic> expression in αβ core Kenyon cells, or the overexpression of a potassium conductance in these neurons, recapitulated the <jats:italic>FoxP</jats:italic> mutant phenotype. A mushroom body subdomain whose development or function require the transcription factor FoxP thus supports the progression of a decision toward commitment. </jats:p>

<jats:p> We examined how correlated firing controls axon remodeling, using in vivo time-lapse imaging and electrophysiological analysis of individual retinal ganglion cell (RGC) axons that were visually stimulated either synchronously or asynchronously relative to neighboring inputs in the <jats:italic>Xenopus laevis</jats:italic> optic tectum. RGCs stimulated out of synchrony rapidly lost the ability to drive tectal postsynaptic partners while their axons grew and added many new branches. In contrast, synchronously activated RGCs produced fewer new branches, but these were more stable. The effects of synchronous activation were prevented by the inhibition of neurotransmitter release and <jats:italic>N</jats:italic> -methyl- <jats:sc>d</jats:sc> -aspartate receptor (NMDAR) blockade, which is consistent with a role for synaptic NMDAR activation in the stabilization of axonal branches and suppression of further exploratory branch addition. </jats:p>

<jats:p> The canonical genetic code is assumed to be deeply conserved across all domains of life with very few exceptions. By scanning 5.6 trillion base pairs of metagenomic data for stop codon reassignment events, we detected recoding in a substantial fraction of the &gt;1700 environmental samples examined. We observed extensive <jats:italic>opal</jats:italic> and <jats:italic>amber</jats:italic> stop codon reassignments in bacteriophages and of <jats:italic>opal</jats:italic> in bacteria. Our data indicate that bacteriophages can infect hosts with a different genetic code and demonstrate phage-host antagonism based on code differences. The abundance and diversity of genetic codes present in environmental organisms should be considered in the design of engineered organisms with altered genetic codes in order to preclude the exchange of genetic information with naturally occurring species. </jats:p>

<jats:p> Adrenal Cushing’s syndrome is caused by excess production of glucocorticoid from adrenocortical tumors and hyperplasias, which leads to metabolic disorders. We performed whole-exome sequencing of 49 blood-tumor pairs and RNA sequencing of 44 tumors from cortisol-producing adrenocortical adenomas (ACAs), adrenocorticotropic hormone–independent macronodular adrenocortical hyperplasias (AIMAHs), and adrenocortical oncocytomas (ADOs). We identified a hotspot in the <jats:italic>PRKACA</jats:italic> gene with a L205R mutation in 69.2% (27 out of 39) of ACAs and validated in 65.5% of a total of 87 ACAs. Our data revealed that the activating L205R mutation, which locates in the P+1 loop of the protein kinase A (PKA) catalytic subunit, promoted PKA substrate phosphorylation and target gene expression. Moreover, we discovered the recurrently mutated gene <jats:italic>DOT1L</jats:italic> in AIMAHs and <jats:italic>CLASP2</jats:italic> in ADOs. Collectively, these data highlight potentially functional mutated genes in adrenal Cushing’s syndrome. </jats:p>

<jats:p> Cushing’s syndrome is caused by excess cortisol production from the adrenocortical gland. In corticotropin-independent Cushing’s syndrome, the excess cortisol production is primarily attributed to an adrenocortical adenoma, in which the underlying molecular pathogenesis has been poorly understood. We report a hotspot mutation (L206R) in <jats:italic>PRKACA</jats:italic> , which encodes the catalytic subunit of cyclic adenosine monophosphate (cAMP)–dependent protein kinase (PKA), in more than 50% of cases with adrenocortical adenomas associated with corticotropin-independent Cushing’s syndrome. The L206R PRKACA mutant abolished its binding to the regulatory subunit of PKA (PRKAR1A) that inhibits catalytic activity of PRKACA, leading to constitutive, cAMP-independent PKA activation. These results highlight the major role of cAMP-independent activation of cAMP/PKA signaling by somatic mutations in corticotropin-independent Cushing’s syndrome, providing insights into the diagnosis and therapeutics of this syndrome. </jats:p>

<jats:p>Long recognized as an evolutionarily ancient cell type involved in tissue homeostasis and immune defense against pathogens, macrophages are being rediscovered as regulators of several diseases, including cancer. Here we show that in mice, mammary tumor growth induces the accumulation of tumor-associated macrophages (TAMs) that are phenotypically and functionally distinct from mammary tissue macrophages (MTMs). TAMs express the adhesion molecule Vcam1 and proliferate upon their differentiation from inflammatory monocytes, but do not exhibit an “alternatively activated” phenotype. TAM terminal differentiation depends on the transcriptional regulator of Notch signaling, RBPJ; and TAM, but not MTM, depletion restores tumor-infiltrating cytotoxic T cell responses and suppresses tumor growth. These findings reveal the ontogeny of TAMs and a discrete tumor-elicited inflammatory response, which may provide new opportunities for cancer immunotherapy.</jats:p>