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The archaeological record shows that large pre-Inca agricultural systems supported settlements for centuries around the ravines and oases of northern Chile’s hyperarid Atacama Desert. This raises questions about how such productivity was achieved and sustained, and its social implications. Using isotopic data of well-preserved ancient plant remains from Atacama sites, we show a dramatic increase in crop nitrogen isotope values (δ15N) from around ad 1000. Maize was most affected, with δ15N values as high as +30‰, and human bone collagen following a similar trend; moreover, their carbon isotope values (δ13C) indicate a considerable increase in the consumption of maize at the same time. We attribute the shift to extremely high δ15N values—the highest in the world for archaeological plants—to the use of seabird guano to fertilize crops. Guano—‘white gold’ as it came to be called—thus sustained agricultural intensification, supporting a substantial population in an otherwise extreme environment. The source of pre-Inca agriculture in the Atacama Desert of Chile has been the subject of multiple theories, but this Article uses preserved maize remains to deduce that coastal guano deposits were utilized in an impressive display of social and ecological sophistication.

The Atacama Desert in Chile—hyperarid and with high–ultraviolet irradiance levels—is one of the harshest environments on Earth. Yet, dozens of species grow there, including Atacama-endemic plants. Herein, we establish the Talabre–Lejia transect (TLT) in the Atacama as an unparalleled natural laboratory to study plant adaptation to extreme environmental conditions. We characterized climate, soil, plant, and soil–microbe diversity at 22 sites (every 100 m of altitude) along the TLT over a 10-y period. We quantified drought, nutrient deficiencies, large diurnal temperature oscillations, and pH gradients that define three distinct vegetational belts along the altitudinal cline. We deep-sequenced transcriptomes of 32 dominant plant species spanning the major plant clades, and assessed soil microbes by metabarcoding sequencing. The top-expressed genes in the 32 Atacama species are enriched in stress responses, metabolism, and energy production. Moreover, their root-associated soils are enriched in growth-promoting bacteria, including nitrogen fixers. To identify genes associated with plant adaptation to harsh environments, we compared 32 Atacama species with the 32 closest sequenced species, comprising 70 taxa and 1,686,950 proteins. To perform phylogenomic reconstruction, we concatenated 15,972 ortholog groups into a supermatrix of 8,599,764 amino acids. Using two codon-based methods, we identified 265 candidate positively selected genes (PSGs) in the Atacama plants, 64% of which are located in Pfam domains, supporting their functional relevance. For 59/184 PSGs with an Arabidopsis ortholog, we uncovered functional evidence linking them to plant resilience. As some Atacama plants are closely related to staple crops, these candidate PSGs are a “genetic goldmine” to engineer crop resilience to face climate change.

Background: For decades, mitochondrial dysfunctions and the generation of reactive oxygen species have been proposed to promote the development and progression of the amyloid pathology in Alzheimer’s disease, but this association is still debated. In particular, it is still unclear if mitochondrial dysfunctions are a trigger or rather a consequence of the formation of amyloid aggregates, and in particular, the role of the different mitochondrial oxidative phosphorylation complexes in Alzheimer’s patients’ brain remains poorly understood. Methods: To study how mitochondrial Complex III defects affect amyloid beta pathology in vivo , we partially knocked out mitochondrial Complex III (CIII KO ) in mature forebrain neurons of an Alzheimer’s mouse model that develops plaque pathology (APP/PS1). Results: We found that Complex III dysfunction in adult neurons induced mild oxidative stress which did not correlate with increased amyloid beta accumulation. In fact, CIII KO -AD mice showed decreased plaque number, decreased Aβ42 toxic fragment and altered amyloid precursor protein cleavage pathway. Conclusions: Our results support a model in which mitochondrial dysfunction is not the cause of amyloid oligomer accumulation but rather a consequence of amyloid beta toxicity.

Coordination between plant development and nutrient availability ensures a suitable supply of macromolecules for growth and developmental programs. Nitrate is an important source of nitrogen (N) that acts as a signal molecule to modulate gene expression, physiological, growth and developmental responses throughout the life of the plant. New key players in the nitrate signaling pathway have been described and knowledge of the molecular mechanics of how it impacts growth and developmental processes is increasing fast. Importantly, mechanisms for nitrate-control of growth and developmental processes have been proposed for both local as well as systemic responses. This article provides a synthesis of recent insights into molecular mechanisms by which nitrate impacts growth and development over Arabidopsis life-cycle.

International audience; The environmental fluctuations of a constantly evolving world can mould a changing context, often unfavourable to sessile organisms that must adjust their resource allocation between both resistance or tolerance mechanisms and growth. Plants bear the fascinating ability to survive and thrive under extreme conditions, a capacity that has always attracted the curiosity of humans, who have discovered and improved species capable of meeting our physiological needs. In this context, plant research has produced a great wealth of knowledge on the responses of plants to a range of abiotic stresses, mostly considering model species and/or controlled conditions. However, there is still minimal comprehension of plant adaptations and acclimations to extreme environments, which cries out for future investigations. In this article, we examined the main advances in understanding the adapted traits fixed through evolution that allowed for plant resistance against abiotic stress in extreme natural ecosystems. Spatio-temporal adaptations from extremophile plant species are described from morpho-anatomical features to physiological function and metabolic pathways adjustments. Considering that metabolism is at the heart of plant adaptations, a focus is given to the study of primary and secondary metabolic adjustments as well as redox metabolism under extreme conditions. This article further casts a critical glance at the main successes in studying extreme environments and examines some of the challenges and opportunities this research offers, especially considering the possible interaction with ecology and metaphenomics.

Complex I (also known as NADH-ubiquinone oxidoreductase) deficiency is the most frequent mitochondrial disorder present in childhood. NADH-ubiquinone oxidoreductase iron-sulfur protein 3 (NDUFS3) is a catalytic subunit of the mitochondrial complex I; NDUFS3 is conserved from bacteria and essential for complex I function. Mutations affecting complex I, including in the Ndufs3 gene, cause fatal neurodegenerative diseases, such as Leigh syndrome. No treatment is available for these conditions. We developed and performed a detailed molecular characterization of a neuron-specific Ndufs3 conditional KO mouse model. We showed that deletion of Ndufs3 in forebrain neurons reduced complex I activity, altered brain energy metabolism, and increased locomotor activity with impaired motor coordination, balance, and stereotyped behavior. Metabolomics analyses showed an increase of glycolysis intermediates, suggesting an adaptive response to the complex I defect. Administration of metformin to these mice delayed the onset of the neurological symptoms but not of neuronal loss. This improvement was likely related to enhancement of glucose uptake and utilization, which are known effects of metformin in the brain. Despite reports that metformin inhibits complex I activity, our findings did not show worsening a complex I defect nor increases in lactic acid, suggesting that metformin should be further evaluated for use in patients with mitochondrial encephalopathies., Metformin delays onset of mitochondrial encephalopathy in a CNS model of mitochondrial oxidative phosphorylation defect.

The archaeological record shows that large pre-Inca agricultural systems supported settlements for centuries around the ravines and oases of northern Chile's hyperarid Atacama Desert. This raises questions about how such productivity was achieved and sustained, and its social implications. Using isotopic data of well-preserved ancient plant remains from Atacama sites, we show a dramatic increase in crop nitrogen isotope values (δ

Future climate change has the potential to alter the distribution and prevalence of plant pathogens, which may have significant implications for both agricultural crops and natural plant communities. However, there are few long-term datasets against which modelled predictions of pathogen responses to climate change can be tested. Here, we use 18S metabarcoding of 28 rodent middens (solidified deposits of rodent coprolites and nesting material) from the Central Atacama, spanning the last ca. 49 ka, to provide the first long-term late Quaternary record of change in plant pathogen communities in response to changing climate. Plant pathogen richness was significantly greater in middens deposited during the Central Andean Pluvial Event (CAPE); a period of increased precipitation between 17.5–8.5 ka. Moreover, the occurrence frequency of Pucciniaceae (rust fungi) was significantly greater during the CAPE, and the highest relative abundances for five additional potentially pathogenic taxa also occurred during this period. The results demonstrate the promising potential for ancient DNA analysis of late Quaternary samples to reveal insights into how plant pathogens responded to past climatic and environmental change, which could help predict how pathogens may responded to future change.

Carbonate clumped isotope thermometry provides a new method for investigating long-standing questions regarding seasonal biases in soil carbonate formation and the relationship between soil carbonate formation temperatures recorded by clumped isotopes ( T ( Δ 47 ) ) and surface temperatures. We address these questions by comparing C, O, and clumped isotope data from Holocene soil carbonates to meteorological and in situ soil monitoring data along a 170 km transect with >4 km of relief in Chile (30°S). This arid transect experiences a winter wet season, and a >20 °C range in mean annual air temperature. We test the hypothesis that, regardless of soil moisture conditions, soil carbonates from arid regions record warm season biases and form in isotopic equilibrium with soil water and soil CO2. Below 3200 m, precipitation falls as rain and soil carbonate T ( Δ 47 ) values at depths >40 cm resemble summer soil temperatures. Above 3200 m, precipitation falls as snow and T ( Δ 47 ) values resemble mean annual soil temperatures. Soil carbonates from the highest site yield anomalous δ 18 O , δ 13 C , and T ( Δ 47 ) values indicative of kinetic isotope effects consistent with cryogenic carbonate formation. Our findings (1) demonstrate that soil carbonate T ( Δ 47 ) values from shallow ( 40 cm; (3) highlight the role of the soil moisture regime in modulating the timing of soil carbonate formation, which affects the resulting carbonate T ( Δ 47 ) values; and (4) show that soil carbonates from high elevation or high latitude sites may form under non-equilibrium conditions. These findings underscore the importance of understanding past soil moisture conditions when attempting to reconstruct paleotemperatures using carbonate clumped isotope thermometry.

Paleoparasitology offers a window into prehistoric parasite faunas, and through studying time-series of parasite assemblages it may be possible to observe how parasites responded to past environmental or climate change, or habitat loss (host decline). Here, we use DNA metabarcoding to reconstruct parasite assemblages in twenty-eight ancient rodent middens (or paleomiddens) from the central Atacama Desert in northern Chile. The paleomiddens span the last 50,000 years, and include middens deposited before, during and after the Central Andean Pluvial Event (CAPE; 17.5–8.5 ka BP). The CAPE was a period of increased precipitation and vegetation change, which we also demonstrate was associated with changes in local rodent taxa. Thirteen parasite taxa (including lice, mites, ticks, nematodes and coccidians) were identified from the middens, nine of which were likely derived from rodent hosts and four from alternative (insect or avian) hosts. The former are consistent with parasites known to infect South American rodent hosts. At our conservative level of high taxonomic rank assignment, the parasites appear to have been resilient to the major perturbations in climate and host taxa associated with the CAPE, and finer taxonomic resolution would be required to detect whether any species turnover occurred within the identified parasite groups. Rodent paleomiddens are fast becoming an unrivaled source of genomic data that can be used to reconstruct past ecosystem change on multiple taxonomic, temporal and spatial scales providing new insights into ecological responses to global change.

Comprehending ecological dynamics requires not only knowledge of modern communities but also detailed reconstructions of ecosystem history. Ancient DNA (aDNA) metabarcoding allows biodiversity responses to major climatic change to be explored at different spatial and temporal scales. We extracted aDNA preserved in fossil rodent middens to reconstruct late Quaternary vegetation dynamics in the hyperarid Atacama Desert. By comparing our paleo-informed millennial record with contemporary observations of interannual variations in diversity, we show local plant communities behave differentially at different timescales. In the interannual (years to decades) time frame, only annual herbaceous expand and contract their distributional ranges (emerging from persistent seed banks) in response to precipitation, whereas perennials distribution appears to be extraordinarily resilient. In contrast, at longer timescales (thousands of years) many perennial species were displaced up to 1,000 m downslope during pluvial events. Given ongoing and future natural and anthropogenically induced climate change, our results not only provide baselines for vegetation in the Atacama Desert, but also help to inform how these and other high mountain plant communities may respond to fluctuations of climate in the future.

Understanding the factors that modulate bacterial community assembly in natural soils is a longstanding challenge in microbial community ecology. In this work, we compared two microbial co-occurrence networks representing bacterial soil communities from two different sections of a pH, temperature and humidity gradient occurring along a western slope of the Andes in the Atacama Desert. In doing so, a topological graph alignment of co-occurrence networks was used to determine the impact of a shift in environmental variables on OTUs taxonomic composition and their relationships. We observed that a fraction of association patterns identified in the co-occurrence networks are persistent despite large environmental variation. This apparent resilience seems to be due to: (1) a proportion of OTUs that persist across the gradient and maintain similar association patterns within the community and (2) bacterial community ecological rearrangements, where an important fraction of the OTUs come to fill the ecological roles of other OTUs in the other network. Actually, potential functional features suggest a fundamental role of persistent OTUs along the soil gradient involving nitrogen fixation. Our results allow identifying factors that induce changes in microbial assemblage configuration, altering specific bacterial soil functions and interactions within the microbial communities in natural environments.

Neuromuscular disorders with defects in the mitochondrial ATP-generating system affect a large number of children and adults worldwide, but remain without treatment. We used a mouse model of mitochondrial myopathy, caused by a cytochrome c oxidase deficiency, to evaluate the effect of induced mitochondrial biogenesis on the course of the disease. Mitochondrial biogenesis was induced either by transgenic expression of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator alpha (PGC-1alpha) in skeletal muscle or by administration of bezafibrate, a PPAR panagonist. Both strategies successfully stimulated residual respiratory capacity in muscle tissue. Mitochondrial proliferation resulted in an enhanced OXPHOS capacity per muscle mass. As a consequence, ATP levels were conserved resulting in a delayed onset of the myopathy and a markedly prolonged life span. Thus, induction of mitochondrial biogenesis through pharmacological or metabolic modulation of the PPAR/PGC-1alpha pathway promises to be an effective therapeutic approach for mitochondrial disorders.

Acute pharmacological activation of adenosine monophosphate (AMP)-kinase using 5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside (AICAR) has been shown to improve muscle mitochondrial function by increasing mitochondrial biogenesis. We asked whether prolonged AICAR treatment is beneficial in a mouse model of slowly progressing mitochondrial myopathy (Cox10-Mef2c-Cre), and whether the compensatory mechanism is indeed an increase in mitochondrial biogenesis. We treated the animals for 3 months and found that sustained AMP-dependent kinase activation improved cytochrome c oxidase activity, rescued the motor phenotype and delayed the onset of the myopathy. This improvement was observed whether treatment started before or after the onset of the disease. We found that AICAR increased skeletal muscle regeneration thereby decreasing the levels of deleted Cox10-floxed alleles. We conclude that although increase in mitochondrial biogenesis and other pathways may contribute, the main mechanism by which AICAR improves the myopathy phenotype is by promoting muscle regeneration.

Climate controls on the nitrogen cycle are suggested by the negative correlation between precipitation and δ15N values across different ecosystems. For arid ecosystems this is unclear, as water limitation among other factors can confound this relationship. We measured herbivore feces, foliar and soil δ15N and δ13C values and chemically characterized soils (pH and elemental composition) along an elevational/climatic gradient in the Atacama Desert, northern Chile. Although very positive δ15N values span the entire gradient, soil δ15N values show a positive correlation with aridity as expected. In contrast, foliar δ15N values and herbivore feces show a hump-shaped relationship with elevation, suggesting that plants are using a different N source, possibly of biotic origin. Thus at the extreme limits of plant life, biotic interactions may be just as important as abiotic processes, such as climate in explaining ecosystem δ15N values.

Aim To document the impact of late Quaternary pluvial events on plant movements between the coast and the Andes across the Atacama Desert, northern Chile. Location Sites are located along the lower and upper fringes of absolute desert (1100–2800 m a.s.l.), between the western slope of the Andes and the Coastal Ranges of northern Chile (24–26° S). Methods We collected and individually radiocarbon dated 21 rodent middens. Plant macrofossils (fruits, seeds, flowers and leaves) were identified and pollen content analysed. Midden assemblages afford brief snapshots of local plant communities that existed within the rodents’ limited foraging range during the several years to decades that it took the midden to accumulate. These assemblages were then compared with modern floras to determine the presence of extralocal species and species provenance. Results Five middens span the last glacial period (34–21 ka) and three middens are from the last glacial–interglacial transition (19–11 ka). The remaining 13 middens span the last 7000 years. Coastal hyperarid sites exhibit low taxonomic richness in middens at 19.3, 1.1, 1.0, 0.9, 0.5 ka and a modern sample. Middens are also dominated by the same plants that occur today. In contrast, middens dated to 28.1, 21.3, 17.3, 3.7 and 0.5 ka contain more species, including Andean extralocals. Precordillera middens (c. 2700 m) show a prominent increase in plant macrofossil richness, along with the appearance of Andean extralocals and sedges at 34.5 and 18.9 ka. Six younger middens dated to 6.1–0.1 ka are similar to the modern local vegetation. Main conclusions Increased species richness and Andean extralocal plants occurred along the current lower fringes of absolute desert during the last glacial–interglacial transition and late Holocene. The absence of soil carbonates indicates the persistence of absolute desert throughout the Quaternary. Colonization by Andean plants could have been accomplished through long-distance seed dispersal either by animals or floods that originated in the Andes. We postulate that dispersal would have been most frequent during regional pluvial events and associated increases in groundwater levels, forming local wetlands in the absolute desert, and generating large floods capable of crossing the Central Depression.

Although the role of cytochrome c in apoptosis is well established, details of its participation in signaling pathways in vivo are not completely understood. The knockout for the somatic isoform of cytochrome c caused embryonic lethality in mice, but derived embryonic fibroblasts were shown to be resistant to apoptosis induced by agents known to trigger the intrinsic apoptotic pathway. In contrast, these cells were reported to be hypersensitive to tumor necrosis factor alpha (TNF-alpha)-induced apoptosis, which signals through the extrinsic pathway. Surprisingly, we found that this cell line (CRL 2613) respired at close to normal levels because of an aberrant activation of a testis isoform of cytochrome c, which, albeit expressed at low levels, was able to replace the somatic isoform for respiration and apoptosis. To produce a bona fide cytochrome c knockout, we developed a mouse knockout for both the testis and somatic isoforms of cytochrome c. The mouse was made viable by the introduction of a ubiquitously expressed cytochrome c transgene flanked by loxP sites. Lung fibroblasts in which the transgene was deleted showed no cytochrome c expression, no respiration, and resistance to agents that activate the intrinsic and to a lesser but significant extent also the extrinsic pathways. Comparison of these cells with lines with a defective oxidative phosphorylation system showed that cells with defective respiration have increased sensitivity to TNF-alpha-induced apoptosis, but this process was still amplified by cytochrome c. These studies underscore the importance of oxidative phosphorylation and apoptosome function to both the intrinsic and extrinsic apoptotic pathways.

Deficiencies in the complex I (CI; NADH-ubiquinone oxidoreductase) of the respiratory chain are frequent causes of mitochondrial diseases and have been associated with other neurodegenerative disorders, such as Parkinson's disease. The NADH-ubiquinone oxidoreductase 1 alpha subcomplex subunit 5 (NDUFA5) is a nuclear-encoded structural subunit of CI, located in the peripheral arm. We inactivated Ndufa5 in mice by the gene-trap methodology and found that this protein is required for embryonic survival. Therefore, we have created a conditional Ndufa5 knockout (KO) allele by introducing a rescuing Ndufa5 cDNA transgene flanked by loxP sites, which was selectively ablated in neurons by the CaMKIIα-Cre. At the age of 11 months, mice with a central nervous system knockout of Ndufa5 (Ndufa5 CNS-KO) showed lethargy and loss of motor skills. In these mice cortices, the levels of NDUFA5 protein were reduced to 25% of controls. Fully assembled CI levels were also greatly reduced in cortex and CI activity in homogenates was reduced to 60% of controls. Despite the biochemical phenotype, no oxidative damage, neuronal death or gliosis were detected in the Ndufa5 CNS-KO brain at this age. These results showed that a partial defect in CI in neurons can lead to late-onset motor phenotypes without neuronal loss or oxidative damage.

Defects in the mitochondrial ATP-generating system are one of the most commonly inherited neurological disorders, but they remain without treatment. We have recently shown that modulation of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) level in skeletal muscle of a mitochondrial myopathy mouse model offers a therapeutic approach. Here we analyzed if endurance exercise, which is known to be associated with an increased PGC-1α level in muscle, offers the same beneficial effect. We subjected male and female mice that develop a severe mitochondrial myopathy due to a cytochrome- c oxidase deficiency at 3 mo of age to endurance exercise training and monitored phenotypical and metabolic changes. Sedentary myopathy and wild-type mice were used as controls. Exercise increased PGC-1α in muscle, resulting in increased mitochondrial biogenesis, and successfully stimulated residual respiratory capacity in muscle tissue. As a consequence, ATP levels were increased in exercised mice compared with sedentary myopathy animals, which resulted in a delayed onset of the myopathy and a prolonged lifespan of the exercised mice. As an added benefit, endurance exercise induced antioxidant enzymes. The overall protective effect of endurance exercise delayed the onset of the mitochondrial myopathy and increased life expectancy in the mouse model. Thus stimulating residual oxidative phosphorylation function in the affected muscle by inducing mitochondrial biogenesis through endurance exercise might offer a valuable therapeutic intervention for mitochondrial myopathy patients.

Members of the peroxisome proliferator-activated receptor gamma coactivator (PGC) family are potent inducers of mitochondrial biogenesis. We have tested the potential effect of increased mitochondrial biogenesis in cells derived from patients harboring oxidative phosphorylation defects due to either nuclear or mitochondrial DNA mutations. We found that the PGC-1 alpha and/or PGC-1 beta expression improved mitochondrial respiration in cells harboring a complex III or IV deficiency as well as in transmitochondrial cybrids harboring mitochondrial encephalomyopathy lactic acidosis and stroke A3243G tRNA((Leu)UUR) gene mutation. The respiratory function improvement was found to be associated with increased levels of mitochondrial components per cell, although this increase was not homogeneous. These results reinforce the concept that increased mitochondrial biogenesis is a promising venue for the treatment of mitochondrial diseases.

Defects in the mitochondrial cytochrome c oxidase (COX) have been associated with Alzheimer's Disease, in which the age-dependent accumulation of β-amyloid plays an important role in synaptic dysfunction and neurodegeneration. To test the possibility that age-dependent decline in the mitochondrial respiratory function, especially COX activity, may participate in the formation and accumulation of β-amyloid, we generated mice expressing mutant amyloid precursor protein and mutant presenilin 1 in a neuron-specific COX-deficient background. A neuron-specific COX-deficient mouse was generated by the Cre-loxP system, in which the COX10 gene was deleted by a CamKIIα promoter-driven Cre-recombinase. COX10 is a farnesyltransferase involved in the biosynthesis of heme a , required for COX assembly and function. These KO mice showed an age-dependent COX deficiency in the cerebral cortex and hippocampus. Surprisingly, COX10 KO mice exhibited significantly fewer amyloid plaques in their brains compared with the COX-competent transgenic mice. This reduction in amyloid plaques in the KO mouse was accompanied by a reduction in Aβ42 level, β-secretase activity, and oxidative damage. Likewise, production of reactive oxygen species from cells with partial COX activity was not elevated. Collectively, our results suggest that, contrary to previous models, a defect in neuronal COX does not increase oxidative damage nor predispose for the formation of amyloidgenic amyloid precursor protein fragments.