The intrinsic and extrinsic effects of TET proteins during gastrulation.

Mice deficient for all ten-eleven translocation (TET) genes exhibit early gastrulation lethality. However, separating cause and effect in such embryonic failure is challenging. To isolate cell-autonomous effects of TET loss, we used temporal single-cell atlases from embryos with partial or complete mutant contributions. Strikingly, when developing within a wild-type embryo, Tet-mutant cells retain near-complete differentiation potential, whereas embryos solely comprising mutant cells are defective in epiblast to ectoderm transition with degenerated mesoderm potential. We map de-repressions of early epiblast factors (e.g., Dppa4 and Gdf3) and failure to activate multiple signaling from nascent mesoderm (Lefty, FGF, and Notch) as likely cell-intrinsic drivers of TET loss phenotypes. We further suggest loss of enhancer demethylation as the underlying mechanism. Collectively, our work demonstrates an unbiased approach for defining intrinsic and extrinsic embryonic gene function based on temporal differentiation atlases and disentangles the intracellular effects of the demethylation machinery from its broader tissue-level ramifications.

A single-embryo, single-cell time-resolved model for mouse gastrulation.

Mouse embryonic development is a canonical model system for studying mammalian cell fate acquisition. Recently, single-cell atlases comprehensively charted embryonic transcriptional landscapes, yet inference of the coordinated dynamics of cells over such atlases remains challenging. Here, we introduce a temporal model for mouse gastrulation, consisting of data from 153 individually sampled embryos spanning 36 h of molecular diversification. Using algorithms and precise timing, we infer differentiation flows and lineage specification dynamics over the embryonic transcriptional manifold. Rapid transcriptional bifurcations characterize the commitment of early specialized node and blood cells. However, for most lineages, we observe combinatorial multi-furcation dynamics rather than hierarchical transcriptional transitions. In the mesoderm, dozens of transcription factors combinatorially regulate multifurcations, as we exemplify using time-matched chimeric embryos of Foxc1/Foxc2 mutants. Our study rejects the notion of differentiation being governed by a series of binary choices, providing an alternative quantitative model for cell fate acquisition.

Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision.

The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8+ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics, quantitative live imaging, and an acute infection model, we find that T cells will maintain or lose memory potential early after antigen recognition. However, following pathogen clearance, T cells may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by a stochastic cis-epigenetic switch that tunably and reversibly silences the memory regulator, TCF1, in response to stimulation. Mathematical modeling shows how this flexibility allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decisions ensure optimal immune responses against diverse threats.

Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response.

Cell fate decisions during early B cell activation determine the outcome of responses to pathogens and vaccines. We examined the early B cell response to T-dependent antigen in mice by single-cell RNA sequencing. Early after immunization, a homogeneous population of activated precursors (APs) gave rise to a transient wave of plasmablasts (PBs), followed a day later by the emergence of germinal center B cells (GCBCs). Most APs rapidly exited the cell cycle, giving rise to non-GC-derived early memory B cells (eMBCs) that retained an AP-like transcriptional profile. Rapid decline of antigen availability controlled these events; provision of excess antigen precluded cell cycle exit and induced a new wave of PBs. Fate mapping revealed a prominent contribution of eMBCs to the MBC pool. Quiescent cells with an MBC phenotype dominated the early response to immunization in primates. A reservoir of APs/eMBCs may enable rapid readjustment of the immune response when failure to contain a threat is manifested by increased antigen availability.

Deterministic and probabilistic fate decisions co-exist in a single retinal lineage.

Correct nervous system development depends on the timely differentiation of progenitor cells into neurons. While the output of progenitor differentiation is well investigated at the population and clonal level, how stereotypic or variable fate decisions are during development is still more elusive. To fill this gap, we here follow the fate outcome of single neurogenic progenitors in the zebrafish retina over time using live imaging. We find that neurogenic progenitor divisions produce two daughter cells, one of deterministic and one of probabilistic fate. Interference with the deterministic branch of the lineage affects lineage progression. In contrast, interference with fate probabilities of the probabilistic branch results in a broader range of fate possibilities than in wild-type and involves the production of any neuronal cell type even at non-canonical developmental stages. Combining the interference data with stochastic modelling of fate probabilities revealed that a simple gene regulatory network is able to predict the observed fate decision probabilities during wild-type development. These findings unveil unexpected lineage flexibility that could ensure robust development of the retina and other tissues.

Frequent winners explain apparent skewness preferences in experience-based decisions.

Do people's attitudes toward the (a)symmetry of an outcome distribution affect their choices? Financial investors seek return distributions with frequent small returns but few large ones, consistent with leading models of choice in economics and finance that assume right-skewed preferences. In contrast, many experiments in which decision-makers learn about choice options through experience find the opposite choice tendency, in favor of left-skewed options. To reconcile these seemingly contradicting findings, the present work investigates the effect of skewness on choices in experience-based decisions. Across seven studies, we show that apparent preferences for left-skewed outcome distributions are a consequence of those distributions having a higher value in most direct outcome comparisons, a "frequent-winner effect." By manipulating which option is the frequent winner, we show that choice tendencies for frequent winners can be obtained even with identical outcome distributions. Moreover, systematic choice tendencies in favor of right- or left-skewed options can be obtained by manipulating which option is experienced as the frequent winner. We also find evidence for an intrinsic preference for right-skewed outcome distributions. The frequent-winner phenomenon is robust to variations in outcome distributions and experimental paradigms. These findings are confirmed by computational analyses in which a reinforcement-learning model capturing frequent winning and intrinsic skewness preferences provides the best account of the data. Our work reconciles conflicting findings of aggregated behavior in financial markets and experiments and highlights the need for theories of decision-making sensitive to joint outcome distributions of the available options.

Self-organized BMP signaling dynamics underlie the development and evolution of digit segmentation patterns in birds and mammals.

Repeating patterns of synovial joints are a highly conserved feature of articulated digits, with variations in joint number and location resulting in diverse digit morphologies and limb functions across the tetrapod clade. During the development of the amniote limb, joints form iteratively within the growing digit ray, as a population of distal progenitors alternately specifies joint and phalanx cell fates to segment the digit into distinct elements. While numerous molecular pathways have been implicated in this fate choice, it remains unclear how they give rise to a repeating pattern. Here, using single-cell RNA sequencing and spatial gene expression profiling, we investigate the transcriptional dynamics of interphalangeal joint specification in vivo. Combined with mathematical modeling, we predict that interactions within the BMP signaling pathway-between the ligand GDF5, the inhibitor NOGGIN, and the intracellular effector pSMAD-result in a self-organizing Turing system that forms periodic joint patterns. Our model is able to recapitulate the spatiotemporal gene expression dynamics observed in vivo, as well as phenocopy digit malformations caused by BMP pathway perturbations. By contrasting in silico simulations with in vivo morphometrics of two morphologically distinct digits, we show how changes in signaling parameters and growth dynamics can result in variations in the size and number of phalanges. Together, our results reveal a self-organizing mechanism that underpins amniote digit segmentation and its evolvability and, more broadly, illustrate how Turing systems based on a single molecular pathway may generate complex repetitive patterns in a wide variety of organisms.

Validity of forensic cartridge-case comparisons.

This article presents key findings from a research project that evaluated the validity and probative value of cartridge-case comparisons under field-based conditions. Decisions provided by 228 trained firearm examiners across the US showed that forensic cartridge-case comparison is characterized by low error rates. However, inconclusive decisions constituted over one-fifth of all decisions rendered, complicating evaluation of the technique's ability to yield unambiguously correct decisions. Specifically, restricting evaluation to only the conclusive decisions of identification and elimination yielded true-positive and true-negative rates exceeding 99%, but incorporating inconclusives caused these values to drop to 93.4% and 63.5%, respectively. The asymmetric effect on the two rates occurred because inconclusive decisions were rendered six times more frequently for different-source than same-source comparisons. Considering probative value, which is a decision's usefulness for determining a comparison's ground-truth state, conclusive decisions predicted their corresponding ground-truth states with near perfection. Likelihood ratios (LRs) further showed that conclusive decisions greatly increase the odds of a comparison's ground-truth state matching the ground-truth state asserted by the decision. Inconclusive decisions also possessed probative value, predicting different-source status and having a LR indicating that they increase the odds of different-source status. The study also manipulated comparison difficulty by using two firearm models that produce dissimilar cartridge-case markings. The model chosen for being more difficult received more inconclusive decisions for same-source comparisons, resulting in a lower true-positive rate compared to the less difficult model. Relatedly, inconclusive decisions for the less difficult model exhibited more probative value, being more strongly predictive of different-source status.

The transcriptional portraits of the neural crest at the individual cell level.

Since the discovery of this cell population by His in 1850, the neural crest has been under intense study for its important role during vertebrate development. Much has been learned about the function and regulation of neural crest cell differentiation, and as a result, the neural crest has become a key model system for stem cell biology in general. The experiments performed in embryology, genetics, and cell biology in the last 150 years in the neural crest field has given rise to several big questions that have been debated intensely for many years: "How does positional information impact developmental potential? Are neural crest cells individually multipotent or a mixed population of committed progenitors? What are the key factors that regulate the acquisition of stem cell identity, and how does a stem cell decide to differentiate towards one cell fate versus another?" Recently, a marriage between single cell multi-omics, statistical modeling, and developmental biology has shed a substantial amount of light on these questions, and has paved a clear path for future researchers in the field.

Vaccination of household chickens results in a shift in young children's diet and improves child growth in rural Kenya.

Childhood growth faltering remains unacceptably high in sub-Saharan Africa. Rural communities dependent on household food production with limited off-farm income or liquid assets to bridge seasonal food availability are especially vulnerable. A cross-sectional survey in Siaya County, Kenya identified 23.5 and 4.8% of children under 5 y of age as stunted and wasted, respectively, using height-for-age Z (HAZ) scores to detect stunting and weight-for-height Z (WHZ) scores for wasting. Although these households are classified as living in poverty or extreme poverty with very limited off-farm income, households commonly have on-farm resources that could be developed to improve nutrition. While 95% of these households have chickens and consumption of eggs was shown to increase childhood growth by an average of 5%, the average flock size is small and constrained by high mortality due to infectious disease. We hypothesized that interventions to relieve this constraint would translate into household decisions influencing the diets and growth of children. Here, we show that vaccination of chickens against Newcastle disease has a causal impact on children's consumption of animal source foods rich in protein and micronutrients relative to a high-carbohydrate, grain-based diet. Children in treatment households (chicken vaccination) showed overall increases in scores for both HAZ and WHZ relative to control households, benefiting both girls and boys. The findings demonstrate the impact of directing interventions at common on-farm assets managed by women in rural communities and support programs to enhance productivity at the household level.

A framing effect in the judgment of discrimination.

Discrimination is not only an objective fact but also a subjective judgment. While extensive research has studied discrimination as an objective fact, we study the judgment of discrimination and show that it is malleable while holding objective discrimination constant. We focus on a common situation in real life: the constituent groups in a candidate pool are unequal (e.g., fewer female candidates than male candidates for tech jobs), and observers (e.g., the public) see only one side of the decision outcome (e.g., only the hired applicants, not the rejected ones). Ten experiments reveal a framing effect: people judge the decision-maker (e.g., the tech firm) as more discriminatory against the minority in the candidate pool if people see the composition of the accepted candidates than if they see the composition of the rejected candidates, even though the information in the two frames is equivalent (i.e., knowing the information in one frame is sufficient to infer the information in the other). The framing effect occurs regardless of whether the decision-maker is objectively discriminatory, replicates across diverse samples (Americans, Asians, and Europeans) and types of discrimination (e.g., gender, race, political orientation), and has significant behavioral consequences. We theorize and show that the framing effect arises because, when judging discrimination, people overlook information that they could infer but is not explicitly given, and they expect equality in the composition of the constituent groups in their given frame. This research highlights the fallibility of judged discrimination and suggests interventions to reduce biases and increase accuracy.

Olfactory Circuitry and Behavioral Decisions.

In mammals, odor information detected by olfactory sensory neurons is converted to a topographic map of activated glomeruli in the olfactory bulb. Mitral cells and tufted cells transmit signals sequentially to the olfactory cortex for behavioral outputs. To elicit innate behavioral responses, odor signals are directly transmitted by distinct subsets of mitral cells from particular functional domains in the olfactory bulb to specific amygdala nuclei. As for the learned decisions, input signals are conveyed by tufted cells as well as by mitral cells to the olfactory cortex. Behavioral scene cells link the odor information to the valence cells in the amygdala to elicit memory-based behavioral responses. Olfactory decision and perception take place in relation to the respiratory cycle. How is the sensory quality imposed on the olfactory inputs for behavioral outputs? How are the two types of odor signals, innate and learned, processed during respiration? Here, we review recent progress on the study of neural circuits involved in decision making in the mouse olfactory system.

Cardiac specification during gastrulation - The Yellow Brick Road leading to Tinman.

The question of how the heart develops, and the genetic networks governing this process have become intense areas of research over the past several decades. This research is propelled by classical developmental studies and potential clinical applications to understand and treat congenital conditions in which cardiac development is disrupted. Discovery of the tinman gene in Drosophila, and examination of its vertebrate homolog Nkx2.5, along with other core cardiac transcription factors has revealed how cardiac progenitor differentiation and maturation drives heart development. Careful observation of cardiac morphogenesis along with lineage tracing approaches indicated that cardiac progenitors can be divided into two broad classes of cells, namely the first and second heart fields, that contribute to the heart in two distinct waves of differentiation. Ample evidence suggests that the fate of individual cardiac progenitors is restricted to distinct cardiac structures quite early in development, well before the expression of canonical cardiac progenitor markers like Nkx2.5. Here we review the initial specification of cardiac progenitors, discuss evidence for the early patterning of cardiac progenitors during gastrulation, and consider how early gene expression programs and epigenetic patterns can direct their development. A complete understanding of when and how the developmental potential of cardiac progenitors is determined, and their potential plasticity, is of great interest developmentally and also has important implications for both the study of congenital heart disease and therapeutic approaches based on cardiac stem cell programming.

Affective valence does not reflect progress prediction errors in perceptual decisions.

Affective valence and intensity form the core of our emotional experiences. It has been proposed that affect reflects the prediction error between expected and actual states, such that better/worse-than-expected discrepancies result in positive/negative affect. However, whether the same principle applies to progress prediction errors remains unclear. We empirically and computationally evaluate the hypothesis that affect reflects the difference between expected and actual progress in forming a perceptual decision. We model affect within an evidence accumulation framework where actual progress is mapped onto the drift-rate parameter and expected progress onto an expected drift-rate parameter. Affect is computed as the difference between the expected and actual amount of accumulated evidence. We find that expected and actual progress both influence affect, but in an additive manner that does not align with a prediction error account. Our computational model reproduces both task behavior and affective ratings, suggesting that sequential sampling models provide a promising framework to model progress appraisals. These results show that although affect is sensitive to both expected and actual progress, it does not reflect the computation of a progress prediction error.

Tips for Testing Adults With Suspected Genetic Kidney Disease.

Genetic kidney disease is common but often unrecognized. It accounts for most cystic kidney diseases and tubulopathies, many forms of congenital abnormalities of the kidney and urinary tract (CAKUT), and some glomerulopathies. Genetic kidney disease is typically suspected where the disease usually has a genetic basis or there is another affected family member, a young age at onset, or extrarenal involvement, but there are also many exceptions to these "rules". Genetic testing requires the patient's written informed consent. When a patient declines testing, another later conversation may be worthwhile. Genetic testing not only indicates the diagnosis but also the inheritance pattern, likely at-risk family members, disease in other organs, clinical course, and possibly effective treatments. Sometimes genetic testing does not identify a pathogenic variant even where other evidence is strong. A variant of uncertain significance (VUS) may be reported but should not be used for clinical decision making. It may be reclassified after more information becomes available without necessarily retesting the patient. Patients should be provided with a copy of their genetic test report, the results explained, and at-risk family members offered "cascade" testing. A referral to a clinical geneticist or genetic counselor helps identify affected family members and in providing advice to assist with reproductive decisions.

Treatment decisions in axial spondyloarthritis daily clinical practice are more than treat-to-target.

OBJECTIVE: 'Treat-to-target principles' are advised for axial spondyloarthritis (axSpA), although a clear target is not yet defined and targets do not always reflect inflammation. Treat-to-target use and motives for treatment choices in clinics are unknown. Therefore, we studied the presence of residual disease activity according physician's opinion, patient's opinion and composite indices and compared them to the subsequent treatment decisions. METHODS: This cross-sectional multicentre study included 249 patients with a clinical diagnosis of axSpA ≥6 months. Remission and low disease activity according to the BASDAI (<1.9 and <3.5, respectively) and physician's and patient's opinion were assessed. Questionnaires included patient-reported outcomes and patients and physicians completed questions regarding treatment decisions. RESULTS: A total of 115/249 (46%) patients were in remission according to the physician and 37% (n = 43) of these patients reached remission according to the BASDAI. In 51/83 (60%) of the patients with residual disease activity according to the physician and a BASDAI >3.5 the treatment was left unchanged, either because of low disease activity as rated by the physician [n = 15 (29%)] or because of a combination of low disease activity with non-inflammatory complaints or comorbidities [n = 11 (25%)]. Retrospective treat-to-target evaluations showed that treatments were most frequently intensified in patients with arthritis or inflammatory back pain and less often in patients with other (non-inflammatory) musculoskeletal comorbidities. CONCLUSION: This study shows that physicians do not always strictly apply treat-to-target in case of residual disease activity in axSpA. Usually, they accept low disease activity as satisfactory.

Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny.

Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Mapping the chromatin dynamics of functionally defined cell populations will shed mechanistic insight into 2 major, unanswered questions in stem cell biology: how does epigenetic identity contribute to a cell type's lineage potential, and how do cascades of chromatin remodeling dictate ensuing fate decisions? Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. Oligopotent progenitor populations operating between the HSCs and unipotent cells play essential roles in effecting hematopoietic homeostasis. To test the hypothesis that selective HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during progenitor differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points. Additionally, quantification of genome-wide peak count and size revealed overall greater chromatin accessibility in HSCs, allowing us to identify HSC-unique peaks as putative regulators of self-renewal and multilineage potential. Finally, CRISPRi-mediated targeting of ATACseq-identified putative CREs in HSCs allowed us to demonstrate the functional role of selective CREs in lineage-specific gene expression. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.

Factors Affecting Post-trial Sustainment or De-implementation of Study Interventions: A Narrative Review.

In contrast to traditional randomized controlled trials, embedded pragmatic clinical trials (ePCTs) are conducted within healthcare settings with real-world patient populations. ePCTs are intentionally designed to align with health system priorities leveraging existing healthcare system infrastructure and resources to ease intervention implementation and increase the likelihood that effective interventions translate into routine practice following the trial. The NIH Pragmatic Trials Collaboratory, funded by the National Institutes of Health (NIH), supports the conduct of large-scale ePCT Demonstration Projects that address major public health issues within healthcare systems. The Collaboratory has a unique opportunity to draw on the Demonstration Project experiences to generate lessons learned related to ePCTs and the dissemination and implementation of interventions tested in ePCTs. In this article, we use case studies from six completed Demonstration Projects to summarize the Collaboratory's experience with post-trial interpretation of results, and implications for sustainment (or de-implementation) of tested interventions. We highlight three key lessons learned. First, ineffective interventions (i.e., ePCT is null for the primary outcome) may be sustained if they have other measured benefits (e.g., secondary outcome or subgroup) or even perceived benefits (e.g., staff like the intervention). Second, effective interventions-even those solicited by the health system and/or designed with significant health system partner buy-in-may not be sustained if they require significant resources. Third, alignment with policy incentives is essential for achieving sustainment and scale-up of effective interventions. Our experiences point to several recommendations to aid in considering post-trial sustainment or de-implementation of interventions tested in ePCTs: (1) include secondary outcome measures that are salient to health system partners; (2) collect all appropriate data to allow for post hoc analysis of subgroups; (3) collect experience data from clinicians and staff; (4) engage policy-makers before starting the trial.

What's in a sample? Epistemic uncertainty and metacognitive awareness in risk taking.

In a fundamentally uncertain world, sound information processing is a prerequisite for effective behavior. Given that information processing is subject to inevitable cognitive imprecision, decision makers should adapt to this imprecision and to the resulting epistemic uncertainty when taking risks. We tested this metacognitive ability in two experiments in which participants estimated the expected value of different number distributions from sequential samples and then bet on their own estimation accuracy. Results show that estimates were imprecise, and this imprecision increased with higher distributional standard deviations. Importantly, participants adapted their risk-taking behavior to this imprecision and hence deviated from the predictions of Bayesian models of uncertainty that assume perfect integration of information. To explain these results, we developed a computational model that combines Bayesian updating with a metacognitive awareness of cognitive imprecision in the integration of information. Modeling results were robust to the inclusion of an empirical measure of participants' perceived variability. In sum, we show that cognitive imprecision is crucial to understanding risk taking in decisions from experience. The results further demonstrate the importance of metacognitive awareness as a cognitive building block for adaptive behavior under (partial) uncertainty.

Community engagement and power dynamics in conservation philanthropy grant making.

Funding decisions influence where, how, and by whom conservation is pursued globally. In the context of growing calls for more participatory, Indigenous-led, and socially just conservation, we undertook the first empirical investigation of how philanthropic foundations working in marine conservation globally engage communities in grant-making decisions. We paid particular attention to whether and how community engagement practices reinforce or disrupt existing power dynamics. We conducted semistructured remote interviews with 46 individuals from 32 marine conservation foundations to identify how conservation foundations engage communities in setting their priorities and deciding which organizations and projects to fund. We found that community engagement in foundation decision-making was limited in practice. Eleven of the 32 foundations reported some form of community engagement in funding decisions. Two of these foundations empowered communities to shape funding priorities and projects through strong forms of engagement. Many engagement practices were one way, one time, or indirect and confined to certain points in decision-making processes. These weaker practices limited community input and reinforced unequal power relations, which may undermine the legitimacy, equity, and effectiveness of conservation efforts. We suggest that foundations aim for stronger forms of community engagement and reflect on how their grant-making practices affect power relations between foundations and communities.

Participación comunitaria y dinámicas de poder en la concesión de subsidios para la filantropía de la conservación Resumen Realizamos la primera investigación empírica sobre la forma en que las fundaciones filantrópicas que trabajan con la conservación marina a nivel mundial involucran a las comunidades en las decisiones para la concesión de subsidios. Prestamos especial atención a cómo y si las prácticas de participación ciudadana refuerzan o interrumpen las dinámicas de poder existentes. Entrevistamos de forma remota a 46 individuos de 32 fundaciones de conservación marina para identificar cómo las fundaciones de conservación involucran a las comunidades para establecer sus prioridades y decidir cuáles organizaciones y proyectos financiar. Encontramos que la participación comunitaria en las decisiones de financiamiento estaba limitada en la práctica. Once de las 32 fundaciones reportaron algún tipo de participación ciudadana en sus decisiones de financiamiento. Dos de estas fundaciones empoderaron a las comunidades para que formaran las prioridades de financiamiento y a los proyectos por medio de una participación sólida. Muchas de las prácticas de participación eran de una manera, de una vez o indirectas y confinadas a ciertos puntos en el proceso de decisión. Estas prácticas más débiles limitaron la aportación comunitaria y reforzaron las relaciones desiguales de poder, lo que puede debilitar la legitimidad, equidad y eficiencia de los esfuerzos de conservación. Sugerimos que las fundaciones busquen maneras más sólidas de involucrar a la comunidad y reflexionen sobre el efecto de sus prácticas de concesión de subsidios sobre las relaciones de poder entre las fundaciones y las comunidades.