Past Fire and Vegetation Change in the Hyperdiverse Forests of the Ecuadorian Amazon.

The Ecuadorian Amazon holds more biodiversity than most other places on Earth. Palms are a particularly dominant component of the vegetation; however, it remains unknown to what degree the pattern has persisted through time. Here, we investigate the persistence of palm dominance through time and the degree to which past human activities (e.g., fire, cultivation, and forest opening) have affected changes in palm abundances across five regions of the Ecuadorian Amazon. We analyzed soil cores (40-80 cm depth) from each region for charcoal (evidence of past fire) and phytoliths (evidence of past vegetation change). The timings of fires (based on 14C radiocarbon dates), the occurrence, recurrence, and number of fires (based on charcoal presence and abundance in samples), and the amount of change in palm abundances (based on phytoliths) varied within and between the studied regions. The charcoal and phytolith results indicate the presence of low levels of past human activity at all sites. Our results show that patterns of modern palm hyperdominance found in Amazonian forests have not been persistent through time, and that even low levels of past human activities can affect palm abundance.

The Repurposing of FDA-Approved Drugs as FtsZ Inhibitors against Mycobacterium tuberculosis: An In Silico and In Vitro Study.

Mycobacterium tuberculosis (Mtb), the causative pathogen of tuberculosis, remains one of the leading causes of death from a single infectious agent. Furthermore, the growing evolution to multi-drug-resistant (MDR) strains requires de novo identification of drug targets for evaluating candidates or repurposing drugs. Hence, targeting FtsZ, an essential cell division protein, is a promising target. METHODS: Using an in silico pharmacological repositioning strategy, four FDA-based drugs that bind to the catalytic site FtsZ were selected. The Alamar Blue colorimetric assay was used to assess antimicrobial activity and the effect of drugs on Mtb growth through growth curves. Bacterial load was determined with an in vitro infection model using colony-forming units (CFU)/mL, and cytotoxicity on human monocyte-derived macrophages (MDMhs) was assessed by flow cytometry. RESULTS: Paroxetine and nebivolol exhibited antimycobacterial activity against both reference TB and MDR strains at a concentration of 25 µg/mL. Furthermore, both paroxetine and nebivolol demonstrated a significant reduction (p < 0.05) in viable bacteria compared to the untreated group in the in vitro infection model. CONCLUSIONS: Collectively, our findings demonstrate that the use of paroxetine and nebivolol is a promising strategy to help in the control of tuberculosis infection.

Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

Expert-based collaborative analysis of the situation and prospects of biomarker test implementation in oncology in Spain / Análisis colaborativo de expertos de la situación y perspectivas de la implementación de pruebas de biomarcadores en oncología en España

Purpose: Biomarkers as screening for precision medicine is a fundamental step. The purpose of this article is twofold. First, to highlight the existing barriers in the implementation of Precision Medicine in Spain, with a special emphasis on barriers in access to the determination of biomarkers. Second, to provide a Roadmap that can help implement Precision Medicine equitably at the national level and optimize the use of biomarkers. Methods: A systematic review of literature (SRL) and a focus group (FG) with multidisciplinary experts has been carried out in 2023. Participants were contacted individually, and discourse analysis was processed anonymously. Results: We carried out a quantitative (SRL) and a qualitative approach (FG). The discourse analysis and roadmap were sent individually to each expert for approval. Conclusions: The potential of Precision Medicine has not been fulfilled in Spain. While several regional initiatives are in place, a national plan or strategy around Precision Medicine and use of biomarkers is lacking. In a general context of rapid progress at a global and European level, including the 2021 Europe’s Beating Cancer Plan, it is time to define and implement a National Plan to make the promise come true. While some comparable countries within Europe – such as the UK or France – are mature enough to adopt such strategies, in Spain there is still a long way to go. We consider that the different strands of work outlined in the Roadmap can be used as basis for such purpose.(AU)

One sixth of Amazonian tree diversity is dependent on river floodplains.

Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.

Expert-based collaborative analysis of the situation and prospects of biomarker test implementation in oncology in Spain.

PURPOSE: Biomarkers as screening for precision medicine is a fundamental step. The purpose of this article is twofold. First, to highlight the existing barriers in the implementation of Precision Medicine in Spain, with a special emphasis on barriers in access to the determination of biomarkers. Second, to provide a Roadmap that can help implement Precision Medicine equitably at the national level and optimize the use of biomarkers. METHODS: A systematic review of literature (SRL) and a focus group (FG) with multidisciplinary experts has been carried out in 2023. Participants were contacted individually, and discourse analysis was processed anonymously. RESULTS: We carried out a quantitative (SRL) and a qualitative approach (FG). The discourse analysis and roadmap were sent individually to each expert for approval. CONCLUSIONS: The potential of Precision Medicine has not been fulfilled in Spain. While several regional initiatives are in place, a national plan or strategy around Precision Medicine and use of biomarkers is lacking. In a general context of rapid progress at a global and European level, including the 2021 Europe's Beating Cancer Plan, it is time to define and implement a National Plan to make the promise come true. While some comparable countries within Europe - such as the UK or France - are mature enough to adopt such strategies, in Spain there is still a long way to go. We consider that the different strands of work outlined in the Roadmap can be used as basis for such purpose.

HIV-1 Tat Induces Dysregulation of PGC1-Alpha and Sirtuin 3 Expression in Neurons: The Role of Mitochondrial Biogenesis in HIV-Associated Neurocognitive Disorder (HAND).

During the antiretroviral era, individuals living with HIV continue to experience milder forms of HIV-associated neurocognitive disorder (HAND). Viral proteins, including Tat, play a pivotal role in the observed alterations within the central nervous system (CNS), with mitochondrial dysfunction emerging as a prominent hallmark. As a result, our objective was to examine the expression of genes associated with mitophagy and mitochondrial biogenesis in the brain exposed to the HIV-1 Tat protein. We achieved this by performing bilateral stereotaxic injections of 100 ng of HIV-1 Tat into the hippocampus of Sprague-Dawley rats, followed by immunoneuromagnetic cell isolation. Subsequently, we assessed the gene expression of Ppargc1a, Pink1, and Sirt1-3 in neurons using RT-qPCR. Additionally, to understand the role of Tert in telomeric dysfunction, we quantified the activity and expression of Tert. Our results revealed that only Ppargc1a, Pink1, and mitochondrial Sirt3 were downregulated in response to the presence of HIV-1 Tat in hippocampal neurons. Interestingly, we observed a reduction in the activity of Tert in the experimental group, while mRNA levels remained relatively stable. These findings support the compelling evidence of dysregulation in both mitophagy and mitochondrial biogenesis in neurons exposed to HIV-1 Tat, which in turn induces telomeric dysfunction.

Mapping density, diversity and species-richness of the Amazon tree flora.

Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution.

More than 10,000 pre-Columbian earthworks are still hidden throughout Amazonia.

Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.

Micronuclei and nuclear buds in amniotic tissue of rats treated with cyclophosphamide.

Fetal development can be altered by DNA damage caused by maternal exposure to chemical, physical, or biological agents during gestation. One method of assessing genotoxicity is to detect micronuclei (MNs) and/or nuclear abnormalities. This can be performed in vivo and requires only frequently dividing tissues, such as amniotic tissue (AT), which is in contact with the fetal environment and is composed of very thin layers of cells. This study evaluated the presence of MNs, nucleoplasmic bridges, and nuclear buds (NBs) in the fetal AT following maternal exposure to cyclophosphamide (CP) during pregnancy. Pregnant Wistar rats were divided into a negative control group and an experimental group that was orally administered CP (10 mg/kg). Daily blood smears were obtained from pregnant rats on days 14-19 of gestation. The rats were dissected, and fetal ATs were obtained on the 19th day of gestation. The MN and NB frequencies in AT cells were analyzed using a fluorescence microscope (100 ×). Micronucleated erythrocytes in the peripheral blood of the control rats were also assessed. Micronucleated polychromatic erythrocyte frequencies were significantly higher than those in the controls. Polychromatic erythrocyte frequencies were lower in CP-treated rats than in controls at 48-120 h. Fetuses in the CP-treated group also showed a significant increase in MNs and NBs in AT cells. In conclusion, AT could be used for analyzing MNs and NBs in rats following maternal exposure to a genotoxic agent and as a viable alternative for analyzing the integrity of fetal DNA during gestation.

Niche breadth of Amazonian trees increases with niche optimum across broad edaphic gradients.

Understanding how biotic interactions and environmental filtering mediated by soil properties shape plant community assembly is a major challenge in ecology, especially when studying complex and hyperdiverse ecosystems like tropical forests. To shed light on the influence of both factors, we examined how the edaphic optimum of species (their niche position) related to their edaphic range (their niche breadth) along different environmental gradients and how this translates into functional strategies. Here we tested four scenarios describing the shape of the niche breadth-niche position relationship, including one neutral scenario and three scenarios proposing different relative influences of abiotic and biotic factors on community assembly along a soil resource gradient. To do so, we used soil concentration data for five key nutrients (N, P, Ca, Mg, and K), along with accurate measurements of 14 leaf, stem, and root traits for 246 tree species inventoried in 101 plots located across Eastern (French Guiana) and Western (Peru) Amazonia. We found that species niche breadth increased linearly with species niche position along each soil nutrient gradient. This increase was associated with more resource acquisitive traits in the leaves and the roots for soil N, Ca, Mg, and K concentration, while it was negatively associated with wood density for soil P concentration. These observations agreed with one of our hypothetical scenarios in which species with resource conservation traits are confined to the most nutrient-depleted soils (abiotic filter), but they are outperformed by faster-growing species in more fertile conditions (biotic filter). Our results refine and strengthen support for niche theories of species assembly while providing an integrated approach to improving forest management policies.

Evolutionary genomics of oceanic island radiations.

A recurring feature of oceanic archipelagos is the presence of adaptive radiations that generate endemic, species-rich clades that can offer outstanding insight into the links between ecology and evolution. Recent developments in evolutionary genomics have contributed towards solving long-standing questions at this interface. Using a comprehensive literature search, we identify studies spanning 19 oceanic archipelagos and 110 putative adaptive radiations, but find that most of these radiations have not yet been investigated from an evolutionary genomics perspective. Our review reveals different gaps in knowledge related to the lack of implementation of genomic approaches, as well as undersampled taxonomic and geographic areas. Filling those gaps with the required data will help to deepen our understanding of adaptation, speciation, and other evolutionary processes.

Unraveling Amazon tree community assembly using Maximum Information Entropy: a quantitative analysis of tropical forest ecology.

In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics.

Low-cost homemade cocktails for enzymatic conversion of sugarcane and cassava bagasses.

The agricultural industries generate lignocellulosic wastes that can be modified by fungi to generate high value-added products. This work aimed to analyze the efficiency and the cost-effectiveness of the bioconversion of sugarcane and cassava bagasses using low-cost homemade enzymatic cocktails from Aspergillus niger LBM 134. Both bagasses were pretreated with a soft alkaline solution without any loss of polysaccharides. After the hydrolysis, a 28% of conversion to glucose and 42% to xylose were reached in the hydrolysis of sugarcane bagasse while an 80% of saccharification yield, in the hydrolysis of cassava bagasse using the homemade enzymes. Furthermore, a more disorganised surface and no starch granules were observed in the sugarcane and cassava bagasses, respectively. The bioethanol yield from sugarcane and casava bagasses was predicted to be 4.16 mg mL-1 and 2.57 mg mL-1, respectively. A comparison of the cost of the homemade and the commercial enzymes was carried out. Similar hydrolysis percentages were achieved employing any enzyme; however, it was 1000-2000 times less expensive using the homemade cocktails than using the commercial enzymes. Therefore, the cost of obtaining glucose from bagasses was most expensive when applying the commercial enzymes. Moreover, the hydrolysis of the cassava bagasse was most efficient with the homemade cocktails. The importance and novelty of this work lie in the similar performance and the lower cost of the homemade cocktails from the fungus A. niger LBM 134 compared with the commercial enzymes on the hydrolysis of the sugarcane and cassava bagasses.

Climate Constrains Photosynthetic Strategies in Darwin's Daisies: A Test of the Climatic Variability and Jack-of-All-Trades Hypotheses.

AbstractEmpirical evidence for the climate variability and performance trade-off hypotheses is limited to animals, and it is unclear whether climate constrains the photosynthetic strategies of plants. The plant genus Scalesia Arn. ex Lindl (family Asteraceae), endemic to the Galápagos archipelago, provides an ideal study system to test these hypotheses because of its species with markedly different leaf morphologies that occupy distinct climatic zones. In this study we tested the classic hypotheses that (1) climate constrains leaf size, (2) high climatic temperature variability selects for thermal generalists (i.e., the climate variability hypothesis), and (3) there is a trade-off between the breadth and rate of photosynthetic performance (i.e., jack-of-all-trades but master of none hypothesis). To do this we measured the leaf morphologies and photosynthetic temperature response curves of 11 Scalesia species. In support of a priori predictions, we found that small-leaved Scalesia species were more likely to occupy hotter and drier climates than large-leaved species, there was a positive relationship between climatic temperature variability and the breadth of photosynthetic performance, and photosynthetic performance was negatively correlated with photosynthetic breadth. Our study is among the first to provide evidence for the performance-breadth trade-off hypothesis in photosynthesis, suggesting that climate change may select for photosynthetic thermal generalists.

Accelerating the discovery of rare tree species in Amazonian forests: integrating long monitoring tree plot data with metabolomics and phylogenetics for the description of a new species in the hyperdiverse genus Inga Mill.

In species-rich regions and highly speciose genera, the need for species identification and taxonomic recognition has led to the development of emergent technologies. Here, we combine long-term plot data with untargated metabolomics, and morphological and phylogenetic data to describe a new rare species in the hyperdiverse genus of trees Inga Mill. Our combined data show that Inga coleyana is a new lineage splitting from their closest relatives I. coruscans and I. cylindrica. Moreover, analyses of the chemical defensive profile demonstrate that I. coleyana has a very distinctive chemistry from their closest relatives, with I. coleyana having a chemistry based on saponins and I. cylindrica and I. coruscans producing a series of dihydroflavonols in addition to saponins. Finally, data from our network of plots suggest that I. coleyana is a rare and probably endemic taxon in the hyper-diverse genus Inga. Thus, the synergy produced by different approaches, such as long-term plot data and metabolomics, could accelerate taxonomic recognition in challenging tropical biomes.

Diagnostic Potential of the Serological Response to Synthetic Peptides from Mycobacterium tuberculosis Antigens for Discrimination Between Active and Latent Tuberculosis Infections.

Diagnosis and treatment of active tuberculosis (ATB) as well as latent tuberculosis infection (LTBI) are required for effective tuberculosis (TB) control, especially in TB endemic area. The usefulness of conventional tests to distinguish between ATB and LTBI has remained challenging. The present study was aimed to demonstrate the usefulness of the serological response to synthetic peptides from Mycobacterium tuberculosis (Mtb) antigens for discrimination between ATB and LTBI in Warao Amerindians. Serum IgG antibody levels were measured by the indirect ELISA assay using 22 designed and synthesized peptides derived from immunogenic Mtb ESAT-6 and Ag85A proteins. A total of 211 adult Warao Amerindians were included; cases with active TB (ATB, n = 75), latent TB infection (LTBI, n = 85) and non-infected (NI, n = 51). The approach's diagnostic information was compared using receiver operating characteristic (ROC) curves. For ATB diagnostic performance between ATB and NI; ESAT-6; P-12037 had 100% of sensitivity (AUC = 0.812; 0.733 to 0.891 95% CI); and Ag85A; P-10997 had 100% of specificity (AUC = 0.691; 0.597 to 0.785 95% CI); and ATB and LTBI; Ag85A; P-29878 had 100% of sensitivity (AUC = 0.741; 0.666-0.817 95% CI), and P-29879 had 99% of specificity (AUC = 0.679; 0.593-0.765 95% CI). While that ESAT-6 P-12037 also allowed differentiation between LTBI and NI or healthy ones. It had 98.8% of sensitivity and 98.0% of specificity (AUC = 0.640; 0.545-0.735 95% CI). The potential of combination-antigen immunoassays with peptides could discriminate between Warao Amerindians with ATB, LTBI and NI. Further validation of this approach could lead to developing a complementary tool for rapid diagnosis of TB infections.