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1.
ACS Synth Biol ; 13(4): 974-997, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38530077

RESUMO

The de novo construction of a living organism is a compelling vision. Despite the astonishing technologies developed to modify living cells, building a functioning cell "from scratch" has yet to be accomplished. The pursuit of this goal alone has─and will─yield scientific insights affecting fields as diverse as cell biology, biotechnology, medicine, and astrobiology. Multiple approaches have aimed to create biochemical systems manifesting common characteristics of life, such as compartmentalization, metabolism, and replication and the derived features, evolution, responsiveness to stimuli, and directed movement. Significant achievements in synthesizing each of these criteria have been made, individually and in limited combinations. Here, we review these efforts, distinguish different approaches, and highlight bottlenecks in the current research. We look ahead at what work remains to be accomplished and propose a "roadmap" with key milestones to achieve the vision of building cells from molecular parts.


Assuntos
Biotecnologia , Biologia Sintética
2.
Nature ; 627(8004): 564-571, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38418889

RESUMO

Numerous studies have shown reduced performance in plants that are surrounded by neighbours of the same species1,2, a phenomenon known as conspecific negative density dependence (CNDD)3. A long-held ecological hypothesis posits that CNDD is more pronounced in tropical than in temperate forests4,5, which increases community stabilization, species coexistence and the diversity of local tree species6,7. Previous analyses supporting such a latitudinal gradient in CNDD8,9 have suffered from methodological limitations related to the use of static data10-12. Here we present a comprehensive assessment of latitudinal CNDD patterns using dynamic mortality data to estimate species-site-specific CNDD across 23 sites. Averaged across species, we found that stabilizing CNDD was present at all except one site, but that average stabilizing CNDD was not stronger toward the tropics. However, in tropical tree communities, rare and intermediate abundant species experienced stronger stabilizing CNDD than did common species. This pattern was absent in temperate forests, which suggests that CNDD influences species abundances more strongly in tropical forests than it does in temperate ones13. We also found that interspecific variation in CNDD, which might attenuate its stabilizing effect on species diversity14,15, was high but not significantly different across latitudes. Although the consequences of these patterns for latitudinal diversity gradients are difficult to evaluate, we speculate that a more effective regulation of population abundances could translate into greater stabilization of tropical tree communities and thus contribute to the high local diversity of tropical forests.


Assuntos
Biodiversidade , Florestas , Mapeamento Geográfico , Árvores , Modelos Biológicos , Especificidade da Espécie , Árvores/classificação , Árvores/fisiologia , Clima Tropical
3.
Nat Ecol Evol ; 8(3): 400-410, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38200369

RESUMO

Mycorrhizae, a form of plant-fungal symbioses, mediate vegetation impacts on ecosystem functioning. Climatic effects on decomposition and soil quality are suggested to drive mycorrhizal distributions, with arbuscular mycorrhizal plants prevailing in low-latitude/high-soil-quality areas and ectomycorrhizal (EcM) plants in high-latitude/low-soil-quality areas. However, these generalizations, based on coarse-resolution data, obscure finer-scale variations and result in high uncertainties in the predicted distributions of mycorrhizal types and their drivers. Using data from 31 lowland tropical forests, both at a coarse scale (mean-plot-level data) and fine scale (20 × 20 metres from a subset of 16 sites), we demonstrate that the distribution and abundance of EcM-associated trees are independent of soil quality. Resource exchange differences among mycorrhizal partners, stemming from diverse evolutionary origins of mycorrhizal fungi, may decouple soil fertility from the advantage provided by mycorrhizal associations. Additionally, distinct historical biogeographies and diversification patterns have led to differences in forest composition and nutrient-acquisition strategies across three major tropical regions. Notably, Africa and Asia's lowland tropical forests have abundant EcM trees, whereas they are relatively scarce in lowland neotropical forests. A greater understanding of the functional biology of mycorrhizal symbiosis is required, especially in the lowland tropics, to overcome biases from assuming similarity to temperate and boreal regions.


Assuntos
Micorrizas , Árvores , Ecossistema , Solo , Nutrientes
4.
Ecology ; 104(9): e4140, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37461360

RESUMO

Tropical forests are well known for their high woody plant diversity. Processes occurring at early life stages are thought to play a critical role in maintaining this high diversity and shaping the composition of tropical tree communities. To evaluate hypothesized mechanisms promoting tropical tree species coexistence and influencing composition, we initiated a census of woody seedlings and small saplings in the permanent 50 ha Forest Dynamics Plot (FDP) on Barro Colorado Island (BCI), Panama. Situated in old-growth, lowland tropical moist forest, the BCI FDP was originally established in 1980 to monitor trees and shrubs ≥1 cm diameter at 1.3 m above ground (dbh) at ca. 5-year intervals. However, critical data on the dynamics occurring at earlier life stages were initially lacking. Therefore, in 2001 we established a 1-m2 seedling plot in the center of every 5 × 5 m section of the BCI FDP. All freestanding woody individuals ≥20 cm tall and <1 cm dbh (hereafter referred to as seedlings) were tagged, mapped, measured, and identified to species in 19,313 1-m2 seedling plots. Because seedling dynamics are rapid, we censused these seedling plots every 1-2 years. Here, we present data from the 14 censuses of these seedling plots conducted between the initial census in 2001 to the most recent census, in 2018. This data set includes nearly 1 M observations of ~185,000 individuals of >400 tree, shrub, and liana species. These data will permit spatially-explicit analyses of seedling distributions, recruitment, growth, and survival for hundreds of woody plant species. In addition, the data presented here can be linked to openly-available, long-term data on the dynamics of trees and shrubs ≥1 cm dbh in the BCI FDP, as well as existing data sets from the site on climate, canopy structure, phylogenetic relatedness, functional traits, soil nutrients, and topography. This data set can be freely used for non-commercial purposes; we request that users of these data cite this data paper in all publications resulting from the use of this data set.


Assuntos
Censos , Plântula , Humanos , Colorado , Filogenia , Clima Tropical , Florestas , Plantas , Panamá
5.
Glob Chang Biol ; 29(12): 3409-3420, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36938951

RESUMO

Accurate estimates of forest biomass stocks and fluxes are needed to quantify global carbon budgets and assess the response of forests to climate change. However, most forest inventories consider tree mortality as the only aboveground biomass (AGB) loss without accounting for losses via damage to living trees: branchfall, trunk breakage, and wood decay. Here, we use ~151,000 annual records of tree survival and structural completeness to compare AGB loss via damage to living trees to total AGB loss (mortality + damage) in seven tropical forests widely distributed across environmental conditions. We find that 42% (3.62 Mg ha-1 year-1 ; 95% confidence interval [CI] 2.36-5.25) of total AGB loss (8.72 Mg ha-1 year-1 ; CI 5.57-12.86) is due to damage to living trees. Total AGB loss was highly variable among forests, but these differences were mainly caused by site variability in damage-related AGB losses rather than by mortality-related AGB losses. We show that conventional forest inventories overestimate stand-level AGB stocks by 4% (1%-17% range across forests) because assume structurally complete trees, underestimate total AGB loss by 29% (6%-57% range across forests) due to overlooked damage-related AGB losses, and overestimate AGB loss via mortality by 22% (7%-80% range across forests) because of the assumption that trees are undamaged before dying. Our results indicate that forest carbon fluxes are higher than previously thought. Damage on living trees is an underappreciated component of the forest carbon cycle that is likely to become even more important as the frequency and severity of forest disturbances increase.


Assuntos
Árvores , Clima Tropical , Biomassa , Florestas , Carbono
6.
PLoS One ; 18(2): e0277786, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36802377

RESUMO

Kauffman picture of normal and tumor states as attractors in an abstract state space is used in order to interpret gene expression data for 15 cancer localizations obtained from The Cancer Genome Atlas. A principal component analysis of this data unveils the following qualitative aspects about tumors: 1) The state of a tissue in gene expression space can be described by a few variables. In particular, there is a single variable describing the progression from a normal tissue to a tumor. 2) Each cancer localization is characterized by a gene expression profile, in which genes have specific weights in the definition of the cancer state. There are no less than 2500 differentially-expressed genes, which lead to power-like tails in the expression distribution functions. 3) Tumors in different localizations share hundreds or even thousands of differentially expressed genes. There are 6 genes common to the 15 studied tumor localizations. 4) The tumor region is a kind of attractor. Tumors in advanced stages converge to this region independently of patient age or genetic characteristics. 5) There is a landscape of cancer in gene expression space with an approximate border separating normal tissues from tumors.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Transcriptoma , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica
7.
Medisur ; 20(6)dic. 2022.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1440607

RESUMO

Fundamento: la toma de decisiones como habilidad profesional en la formación del especialista en Pediatría es un aspecto que requiere atención desde el punto de vista didáctico. Objetivo presentar una estrategia didáctica para la toma de decisiones como habilidad profesional en la formación del especialista en Pediatría, así como un acercamiento a su implementación. Métodos se utilizaron métodos y técnicas de investigación cualitativa como la observación y el grupo de discusión mediante talleres para describir los resultados que se presentan en el artículo. Resultados se ofrecen acciones metodológicas llevadas a cabo mediante la ejecución de un taller de socialización, el registro de actividades prácticas con profesores/tutores y residentes en diferentes escenarios docente-asistenciales. Se muestran los resultados de la implementación de las acciones de la estrategia didáctica, así como las premisas y etapas que se determinaron durante su proceso de construcción. Se describen las principales regularidades. Conclusiones: la estrategia didáctica propuesta, y su carácter flexible, permiten su articulación durante los tres años de residencia de Pediatría, en beneficio de la toma de decisiones como habilidad profesional y asumiendo el principio de educación en el trabajo como la principal forma de enseñanza del especialista en formación.


Background: decision-making as a professional skill in the training of the Pediatrics specialist is an aspect that requires attention from the didactic point of view. Objective: to present a didactic strategy for decision making as a professional skill in the Pediatrics specialist training, as well as an approach to its implementation. Methods: Qualitative research methods and techniques such as observation and group discussion through workshops were used to describe the results presented in the article. Results: methodological actions carried out through the execution of a socialization workshop, the record of practical activities with teachers/tutors and residents in different teaching-assistance scenarios are offered. The results of the implementation of the actions of the didactic strategy are shown, as well as the premises and stages that were determined during its construction process. The main regularities are described. Conclusions: the proposed didactic strategy, and its flexible nature, allow its articulation during the three years of Pediatrics residency, to the benefit of decision-making as a professional skill and assuming the principle of education at work as the main way of teaching the pediatrician training specialist.

8.
J Breast Cancer ; 25(3): 218-232, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35657001

RESUMO

PURPOSE: The F3II cell line is a highly invasive variant of mammary carcinoma. Although it is frequently used as a model to evaluate the efficacy of immunotherapy, its impact on the immune system remains poorly understood. The main objectives of this study were to evaluate the effects of F3II tumors on the development of chronic inflammation and to characterize tumor-associated immunosuppression. METHODS: Following the experimental implantation of F3II tumors in BALB/c mice, alterations in the liver and spleen anatomy and the numbers of circulating leukocytes, myeloid-derived suppressor cells (MDSCs), and regulatory T cells were measured using hematological techniques, histopathological analysis, and flow cytometry. The capacity of the F3II tumor-bearing mice to reject MB16F10 allogeneic tumor transplantation was also evaluated. In addition, the restoration of immune parameters in tumor-bearing mice was evaluated after standard breast cancer chemotherapy and surgical tumor excision. RESULTS: F3II tumor implantation increased the levels of chronic inflammatory markers, such as the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, and caused myeloid alterations, including extramedullary granulopoiesis and megakaryopoiesis, along with the recruitment of MDSCs to the spleen. Chemotherapy or surgical F3II tumor removal completely rescued the tumor-associated extramedullary granulopoiesis and megakaryopoiesis. Notably, the presence of F3II tumors reduced the capacity of BALB/c mice to reject MB16F10 allogeneic tumor transplantation. CONCLUSION: These results support the occurrence of F3II tumor-mediated immune cell dysfunction, which mimics the immune alterations characterized by chronic systemic inflammation and immunosuppression observed in breast cancer in clinical settings. Thus, the F3II tumor model is relevant for evaluating novel breast cancer immunotherapies and combinations in preclinical studies. This model could also be useful for identifying appropriate therapeutic targets and developing proof-of-concept experiments in the future.

9.
New Phytol ; 234(5): 1664-1677, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35201608

RESUMO

Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4-52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1-10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.


Assuntos
Carbono , Clima Tropical , Biomassa , Temperatura , Madeira
10.
New Phytol ; 233(2): 705-721, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34716605

RESUMO

The relative importance of tree mortality risk factors remains unknown, especially in diverse tropical forests where species may vary widely in their responses to particular conditions. We present a new framework for quantifying the importance of mortality risk factors and apply it to compare 19 risks on 31 203 trees (1977 species) in 14 one-year periods in six tropical forests. We defined a condition as a risk factor for a species if it was associated with at least a doubling of mortality rate in univariate analyses. For each risk, we estimated prevalence (frequency), lethality (difference in mortality between trees with and without the risk) and impact ('excess mortality' associated with the risk, relative to stand-level mortality). The most impactful risk factors were light limitation and crown/trunk loss; the most prevalent were light limitation and small size; the most lethal were leaf damage and wounds. Modes of death (standing, broken and uprooted) had limited links with previous conditions and mortality risk factors. We provide the first ranking of importance of tree-level mortality risk factors in tropical forests. Future research should focus on the links between these risks, their climatic drivers and the physiological processes to enable mechanistic predictions of future tree mortality.


Assuntos
Árvores , Clima Tropical , Florestas , Fatores de Risco , Árvores/fisiologia
11.
Integr Comp Biol ; 61(6): 2294-2305, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34427632

RESUMO

The modern field of biology has its roots in the curiosity and skill of amateur researchers and has never been purely the domain of professionals. Today, professionals and amateurs contribute to biology research, working both together and independently. Well-targeted and holistic investment in amateur biology research could bring a range of benefits that, in addition to positive societal benefits, may help to address the considerable challenges facing our planet in the 21st century. We highlight how recent advances in amateur biology have been facilitated by innovations in digital infrastructure as well as the development of community biology laboratories, launched over the last decade, and we provide recommendations for how individuals can support the integration of amateurs into biology research. The benefits of investment in amateur biology research could be many-fold, however, without a clear consideration of equity, efforts to promote amateur biology could exacerbate structural inequalities around access to and benefits from STEM. The future of the field of biology relies on integrating a diversity of perspectives and approaches-amateur biology researchers have an important role to play.


Assuntos
Atletas , Biologia , Animais , Humanos
12.
Rev. cuba. pediatr ; 93(3): e1493, 2021.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1347546

RESUMO

La litiasis vesicular en la infancia y adolescencia ha acusado un notable incremento en los últimos años. En países europeos, como Inglaterra, las colecistectomías se han triplicado desde 1997 y en el 2012 en el Hospital Infantil de Santiago de Cuba representó el 96,4 por ciento de todas las operaciones mayores electivas. En el IV Simposio Nacional de Cirugía Pediátrica (Varadero, Matanzas, 1- 3 de julio de 2019) fue presentada, discutida y aprobada esta "Guía de Práctica Clínica de litiasis vesicular en niños y adolescentes" y se recomendó, al concluir dicho evento, compartir dicha guía a través de su publicación, para que los servicios de cirugía pediátrica la empleen como referencia y la apliquen en las instituciones del sistema cubano de salud encargadas de la atención sanitaria de niños y adolescentes(AU)


Vesicular lithiasis in childhood and adolescence has had a marked increase in recent years. In European countries such as England, cholecystectomies have tripled since 1997 and in 2012 at the Children's Hospital in Santiago de Cuba accounted for 96.4 percent of all major elective operations. At the IV National Symposium on Pediatric Surgery (Varadero, Matanzas, July 1-3, 2019) this " Clinical Practice Guidelines of Vesicular Lithiasis in Children and Adolescents" was presented, discussed and approved, and it was recommended, at the conclusion of that event, to share this guidelines through its publication, for pediatric surgery services to use it as a reference and to be applied in the institutions of the Cuban health system which are responsible for the health care of children and adolescents(AU)


Assuntos
Humanos , Criança , Adolescente , Colecistectomia/métodos , Cálculos da Bexiga Urinária/epidemiologia , Guia de Prática Clínica , Sistemas de Saúde , Atenção à Saúde/métodos
13.
New Phytol ; 231(5): 1798-1813, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33993520

RESUMO

Deep-water access is arguably the most effective, but under-studied, mechanism that plants employ to survive during drought. Vulnerability to embolism and hydraulic safety margins can predict mortality risk at given levels of dehydration, but deep-water access may delay plant dehydration. Here, we tested the role of deep-water access in enabling survival within a diverse tropical forest community in Panama using a novel data-model approach. We inversely estimated the effective rooting depth (ERD, as the average depth of water extraction), for 29 canopy species by linking diameter growth dynamics (1990-2015) to vapor pressure deficit, water potentials in the whole-soil column, and leaf hydraulic vulnerability curves. We validated ERD estimates against existing isotopic data of potential water-access depths. Across species, deeper ERD was associated with higher maximum stem hydraulic conductivity, greater vulnerability to xylem embolism, narrower safety margins, and lower mortality rates during extreme droughts over 35 years (1981-2015) among evergreen species. Species exposure to water stress declined with deeper ERD indicating that trees compensate for water stress-related mortality risk through deep-water access. The role of deep-water access in mitigating mortality of hydraulically-vulnerable trees has important implications for our predictive understanding of forest dynamics under current and future climates.


Assuntos
Secas , Árvores , Florestas , Folhas de Planta , Água , Abastecimento de Água , Xilema
14.
New Phytol ; 230(2): 485-496, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33449384

RESUMO

The effects of climate change on tropical forests will depend on how diverse tropical tree species respond to drought. Current distributions of evergreen and deciduous tree species across local and regional moisture gradients reflect their ability to tolerate drought stress, and might be explained by functional traits. We measured leaf water potential at turgor loss (i.e. 'wilting point'; πtlp ), wood density (WD) and leaf mass per area (LMA) on 50 of the most abundant tree species in central Panama. We then tested their ability to explain distributions of evergreen and deciduous species within a 50 ha plot on Barro Colorado Island and across a 70 km rainfall gradient spanning the Isthmus of Panama. Among evergreen trees, species with lower πtlp were associated with drier habitats, with πtlp explaining 28% and 32% of habitat association on local and regional scales, respectively, greatly exceeding the predictive power of WD and LMA. In contrast, πtlp did not predict habitat associations among deciduous species. Across spatial scales, πtlp is a useful indicator of habitat preference for tropical tree species that retain their leaves during periods of water stress, and holds the potential to predict vegetation responses to climate change.


Assuntos
Folhas de Planta , Árvores , Colorado , Secas , Panamá , Clima Tropical , Água
15.
In. Licea Puig, Manuel Emiliano. Diabetes mellitus. Una mirada integral. La Habana, Editorial Ciencias Médicas, 2021. , tab.
Monografia em Espanhol | CUMED | ID: cum-77337
16.
Medisur ; 18(6): 1145-1153, nov.-dic. 2020.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1149416

RESUMO

RESUMEN La formación del pediatra cubano ha transitado por diferentes momentos a través de los años. El objetivo de este artículo es caracterizar la enseñanza de la pediatría cubana en las diferentes etapas: colonia, neocolonia y Revolución en el poder, en que la enseñanza pasó de un carácter biologicista y expositivo a vincular la teoría con la práctica. El programa de la especialidad de pediatría expresa el sistema de habilidades y conocimientos que debe desarrollar el educando en cada módulo, estancia o asignatura. Se aplican tres tipos de evaluación: evaluación en el curso de la residencia, por año, evaluación de fin de año y examen estatal. Los nuevos tiempos enfrentan desafíos que requieren de un pediatra integral con alto grado de formación, autonomía y buenas decisiones, lo que implica la intencionalidad didáctica en su orientación, desarrollo y evaluación.


ABSTRACT The training of the Cuban pediatrician has gone through different moments through the years. The objective of this article is to characterize the teaching of Cuban pediatrics in the different stages: colony, neo-colony and Revolution in power, in which the teaching went from a biologists and expository character to linking theory with practice. The pediatrics specialty program expresses the system of skills and knowledge that the student must develop in each module, stay or subject. Three types of assessment are applied: assessment in the course of residency, per year, end-of-year assessment, and state examination. New times face challenges that require a comprehensive pediatrician with a high degree of training, autonomy and good decisions, which require didactic intentionality in their orientation, development and assessment.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32280481

RESUMO

Fungi have the ability to transform organic materials into a rich and diverse set of useful products and provide distinct opportunities for tackling the urgent challenges before all humans. Fungal biotechnology can advance the transition from our petroleum-based economy into a bio-based circular economy and has the ability to sustainably produce resilient sources of food, feed, chemicals, fuels, textiles, and materials for construction, automotive and transportation industries, for furniture and beyond. Fungal biotechnology offers solutions for securing, stabilizing and enhancing the food supply for a growing human population, while simultaneously lowering greenhouse gas emissions. Fungal biotechnology has, thus, the potential to make a significant contribution to climate change mitigation and meeting the United Nation's sustainable development goals through the rational improvement of new and established fungal cell factories. The White Paper presented here is the result of the 2nd Think Tank meeting held by the EUROFUNG consortium in Berlin in October 2019. This paper highlights discussions on current opportunities and research challenges in fungal biotechnology and aims to inform scientists, educators, the general public, industrial stakeholders and policymakers about the current fungal biotech revolution.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32206323

RESUMO

BACKGROUND: Lignocellulosic biomass could support a greatly-expanded bioeconomy. Current strategies for using biomass typically rely on single-cell organisms and extensive ancillary equipment to produce precursors for downstream manufacturing processes. Alternative forms of bioproduction based on solid-state fermentation and wood-degrading fungi could enable more direct means of manufacture. However, basic methods for cultivating wood-degrading fungi are often ad hoc and not readily reproducible. Here, we developed standard reference strains, substrates, measurements, and methods sufficient to begin to enable reliable reuse of mycological materials and products in simple laboratory settings. RESULTS: We show that a widely-available and globally-regularized consumer product (Pringles™) can support the growth of wood-degrading fungi, and that growth on Pringles™-broth can be correlated with growth on media made from a fully-traceable and compositionally characterized substrate (National Institute of Standards and Technology Reference Material 8492 Eastern Cottonwood Whole Biomass Feedstock). We also establish a Relative Extension Unit (REU) framework that is designed to reduce variation in quantification of radial growth measurements. So enabled, we demonstrate that five laboratories were able to compare measurements of wood-fungus performance via a simple radial extension growth rate assay, and that our REU-based approach reduced variation in reported measurements by up to ~ 75%. CONCLUSIONS: Reliable reuse of materials, measures, and methods is necessary to enable distributed bioproduction processes that can be adopted at all scales, from local to industrial. Our community-based measurement methods incentivize practitioners to coordinate the reuse of standard materials, methods, strains, and to share information supporting work with wood-degrading fungi.

19.
J Chem Inf Model ; 57(8): 2077-2088, 2017 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-28651433

RESUMO

While conventional random forest regression (RFR) virtual screening models appear to have excellent accuracy on random held-out test sets, they prove lacking in actual practice. Analysis of 18 historical virtual screens showed that random test sets are far more similar to their training sets than are the compounds project teams actually order. A new, cluster-based "realistic" training/test set split, which mirrors the chemical novelty of real-life virtual screens, recapitulates the poor predictive power of RFR models in real projects. The original Profile-QSAR (pQSAR) method greatly broadened the domain of applicability over conventional models by using as independent variables a profile of activity predictions from all historical assays in a large protein family. However, the accuracy still fell short of experiment on realistic test sets. The improved "pQSAR 2.0" method replaces probabilities of activity from naïve Bayes categorical models at several thresholds with predicted IC50s from RFR models. Unexpectedly, the high accuracy also requires removing the RFR model for the actual assay of interest from the independent variable profile. With these improvements, pQSAR 2.0 activity predictions are now statistically comparable to medium-throughput four-concentration IC50 measurements even on the realistic test set. Beyond the yes/no activity predictions from a typical high-throughput screen (HTS) or conventional virtual screen, these semiquantitative IC50 predictions allow for predicted potency, ligand efficiency, lipophilic efficiency, and selectivity against antitargets, greatly facilitating hitlist triaging and enabling virtual screening panels such as toxicity panels and overall promiscuity predictions.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Relação Quantitativa Estrutura-Atividade , Concentração Inibidora 50 , Aprendizado de Máquina , Análise de Regressão
20.
Front Immunol ; 7: 374, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27713745

RESUMO

Liposomes containing phosphatidylcholine have been widely used as adjuvants. Recently, we demonstrated that B-1 cells produce dipalmitoyl-phosphatidylcholine (DPPC)-specific IgM upon immunization of BALB/c mice with DPPC-liposomes encapsulating ovalbumin (OVA). Although this preparation enhanced the OVA-specific humoral response, the contribution of anti-DPPC antibodies to this effect was unclear. Here, we demonstrate that these antibodies are secreted by B-1 cells independently of the presence of OVA in the formulation. We also confirm that these antibodies are specific for phosphocholine. The anti-OVA humoral response was partially restored in B-1 cells-deficient BALB/xid mice by immunization with the liposomes opsonized with the serum total immunoglobulin (Ig) fraction containing anti-phosphocholine antibodies, generated in wild-type animals. This result could be related to the increased phagocytosis by peritoneal macrophages of the particles opsonized with the serum total Ig or IgM fractions, both containing anti-phosphocholine antibodies. In conclusion, in the present work, it has been demonstrated that phosphocholine-specific antibodies improve T-dependent antibody responses against OVA carried by DPPC-liposomes.

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