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1.
bioRxiv ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38559159

RESUMO

AD related pathologies, such as beta-amyloid (Aß) and phosphorylated tau (pTau), are evident decades before any noticeable decline in memory occurs. Identifying individuals during this asymptomatic phase is crucial for timely intervention. The Mnemonic Similarity Task (MST), a modified recognition memory task, is especially relevant for early AD screening, as it assesses hippocampal integrity, a region affected (both directly and indirectly) early in the progression of the disease. Further, strong inferences on the underlying cognitive mechanisms that support performance on this task can be made using Bayesian cognitive modeling. We assessed whether analyzing MST performance using a cognitive model could detect subtle changes in cognitive function and AD biomarker status prior to overt cognitive decline. We analyzed MST data from >200 individuals (young, cognitively healthy older adults, and individuals with MCI), a subset of which also had existing CSF Aß and pTau data. Traditional performance scores and cognitive modeling using multinomial processing trees was applied to each participants MST data using Bayesian approaches. We assessed how well each could predict age group, memory ability, MCI status, Aß/pTau status using ROC analyses. Both approaches predicted age group membership equally, but cognitive modeling approaches exceeded traditional metrics in all other comparisons. This work establishes that cognitive modeling of the MST can detect individuals with AD prior to cognitive decline, making it a potentially useful tool for both screening and monitoring older adults during the asymptomatic phase of AD.

2.
Sci Rep ; 14(1): 344, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172509

RESUMO

Major depressive disorder (MDD) is a devastating and heterogenous disorder for which there are no approved biomarkers in clinical practice. We recently identified anticipatory hypo-arousal indexed by pupil responses as a candidate mechanism subserving depression symptomatology. Here, we conducted a replication and extension study of these findings. We analyzed a replication sample of 40 unmedicated patients with a diagnosis of depression and 30 healthy control participants, who performed a reward anticipation task while pupil responses were measured. Using a Bayesian modelling approach taking measurement uncertainty into account, we could show that the negative correlation between pupil dilation and symptom load during reward anticipation is replicable within MDD patients, albeit with a lower effect size. Furthermore, with the combined sample of 136 participants (81 unmedicated depressed and 55 healthy control participants), we further showed that reduced pupil dilation in anticipation of reward is inversely associated with anhedonia items of the Beck Depression Inventory in particular. Moreover, using simultaneous fMRI, particularly the right anterior insula as part of the salience network was negatively correlated with depressive symptom load in general and anhedonia items specifically. The present study supports the utility of pupillometry in assessing noradrenergically mediated hypo-arousal during reward anticipation in MDD, a physiological process that appears to subserve anhedonia.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Anedonia/fisiologia , Teorema de Bayes , Recompensa , Escalas de Graduação Psiquiátrica , Imageamento por Ressonância Magnética
3.
Proc Natl Acad Sci U S A ; 120(47): e2315701120, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37972069

RESUMO

The extent and ecological significance of intraspecific functional diversity within marine microbial populations is still poorly understood, and it remains unclear if such strain-level microdiversity will affect fitness and persistence in a rapidly changing ocean environment. In this study, we cultured 11 sympatric strains of the ubiquitous marine picocyanobacterium Synechococcus isolated from a Narragansett Bay (RI) phytoplankton community thermal selection experiment. Thermal performance curves revealed selection at cool and warm temperatures had subdivided the initial population into thermotypes with pronounced differences in maximum growth temperatures. Curiously, the genomes of all 11 isolates were almost identical (average nucleotide identities of >99.99%, with >99% of the genome aligning) and no differences in gene content or single nucleotide variants were associated with either cool or warm temperature phenotypes. Despite a very high level of genomic similarity, sequenced epigenomes for two strains showed differences in methylation on genes associated with photosynthesis. These corresponded to measured differences in photophysiology, suggesting a potential pathway for future mechanistic research into thermal microdiversity. Our study demonstrates that present-day marine microbial populations can harbor cryptic but environmentally relevant thermotypes which may increase their resilience to future rising temperatures.


Assuntos
Synechococcus , Synechococcus/metabolismo , Ecótipo , Temperatura , Temperatura Baixa , Nucleotídeos/metabolismo , Água do Mar/microbiologia
4.
Learn Mem ; 30(11): 296-309, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37923355

RESUMO

The mnemonic discrimination task (MDT) is a widely used cognitive assessment tool. Performance in this task is believed to indicate an age-related deficit in episodic memory stemming from a decreased ability to pattern-separate among similar experiences. However, cognitive processes other than memory ability might impact task performance. In this study, we investigated whether nonmnemonic decision-making processes contribute to the age-related deficit in the MDT. We applied a hierarchical Bayesian version of the Ratcliff diffusion model to the MDT performance of 26 younger and 31 cognitively normal older adults. It allowed us to decompose decision behavior in the MDT into different underlying cognitive processes, represented by specific model parameters. Model parameters were compared between groups, and differences were evaluated using the Bayes factor. Our results suggest that the age-related decline in MDT performance indicates a predominantly mnemonic deficit rather than differences in nonmnemonic decision-making processes. In addition, this mnemonic deficit might also involve a slowing in processes related to encoding and retrieval strategies, which are relevant for successful memory as well. These findings help to better understand what cognitive processes contribute to the age-related decline in MDT performance and may help to improve the diagnostic value of this popular task.


Assuntos
Memória Episódica , Teorema de Bayes , Técnicas de Apoio para a Decisão
5.
Biostatistics ; 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37897441

RESUMO

Microbiome scientists critically need modern tools to explore and analyze microbial evolution. Often this involves studying the evolution of microbial genomes as a whole. However, different genes in a single genome can be subject to different evolutionary pressures, which can result in distinct gene-level evolutionary histories. To address this challenge, we propose to treat estimated gene-level phylogenies as data objects, and present an interactive method for the analysis of a collection of gene phylogenies. We use a local linear approximation of phylogenetic tree space to visualize estimated gene trees as points in low-dimensional Euclidean space, and address important practical limitations of existing related approaches, allowing an intuitive visualization of complex data objects. We demonstrate the utility of our proposed approach through microbial data analyses, including by identifying outlying gene histories in strains of Prevotella, and by contrasting Streptococcus phylogenies estimated using different gene sets. Our method is available as an open-source R package, and assists with estimating, visualizing, and interacting with a collection of bacterial gene phylogenies.

6.
bioRxiv ; 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37645842

RESUMO

Microbiome scientists critically need modern tools to explore and analyze microbial evolution. Often this involves studying the evolution of microbial genomes as a whole. However, different genes in a single genome can be subject to different evolutionary pressures, which can result in distinct gene-level evolutionary histories. To address this challenge, we propose to treat estimated gene-level phylogenies as data objects, and present an interactive method for the analysis of a collection of gene phylogenies. We use a local linear approximation of phylogenetic tree space to visualize estimated gene trees as points in low-dimensional Euclidean space, and address important practical limitations of existing related approaches, allowing an intuitive visualization of complex data objects. We demonstrate the utility of our proposed approach through microbial data analyses, including by identifying outlying gene histories in strains of Prevotella, and by contrasting Streptococcus phylogenies estimated using different gene sets. Our method is available as an open-source R package, and assists with estimating, visualizing and interacting with a collection of bacterial gene phylogenies. dimension reduction, microbiome, non-Euclidean, statistical genetics, visualization.

7.
Proteins ; 91(9): 1298-1315, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37519023

RESUMO

Amyloid-based prions have simple structures, a wide phylogenetic distribution, and a plethora of functions in contemporary organisms, suggesting they may be an ancient phenomenon. However, this hypothesis has yet to be addressed with a systematic, computational, and experimental approach. Here we present a framework to help guide future experimental verification of candidate prions with conserved functions to understand their role in the early stages of evolution and potentially in the origins of life. We identified candidate prions in all high-quality proteomes available in UniProt computationally, assessed their phylogenomic distributions, and analyzed candidate-prion functional annotations. Of the 27 980 560 proteins scanned, 228 561 were identified as candidate prions (~0.82%). Among these candidates, there were 84 Gene Ontology (GO) terms conserved across the three domains of life. We found that candidate prions with a possible role in adaptation were particularly well-represented within this group. We discuss unifying features of candidate prions to elucidate the primeval roles of prions and their associated functions. Candidate prions annotated as transcription factors, DNA binding, and kinases are particularly well suited to generating diverse responses to changes in their environment and could allow for adaptation and population expansion into more diverse environments. We hypothesized that a relationship between these functions and candidate prions could be evolutionarily ancient, even if individual prion domains themselves are not evolutionarily conserved. Candidate prions annotated with these universally occurring functions potentially represent the oldest extant prions on Earth and are therefore excellent experimental targets.

8.
Biofilm ; 5: 100108, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36938359

RESUMO

Urine, humidity condensate, and other sources of non-potable water are processed onboard the International Space Station (ISS) by the Water Recovery System (WRS) yielding potable water. While some means of microbial control are in place, including a phosphoric acid/hexavalent chromium urine pretreatment solution, many areas within the WRS are not available for routine microbial monitoring. Due to refurbishment needs, two flex lines from the Urine Processor Assembly (UPA) within the WRS were removed and returned to Earth. The water from within these lines, as well as flush water, was microbially evaluated. Culture and culture-independent analysis revealed the presence of Burkholderia, Paraburkholderia, and Leifsonia. Fungal culture also identified Fusarium and Lecythophora. Hybrid de novo genome analysis of the five distinct Burkholderia isolates identified them as B. contaminans, while the two Paraburkholderia isolates were identified as P. fungorum. Chromate-resistance gene clusters were identified through pangenomic analysis that differentiated these genomes from previously studied isolates recovered from the point-of-use potable water dispenser and/or current NCBI references, indicating that unique populations exist within distinct niches in the WRS. Beyond genomic analysis, fixed samples directly from the lines were imaged by environmental scanning electron microscopy, which detailed networks of fungal-bacterial biofilms. This is the first evidence of biofilm formation within flex lines from the UPA onboard the ISS. For all bacteria isolated, biofilm potential was further characterized, with the B. contaminans isolates demonstrating the most considerable biofilm formation. Moreover, the genomes of the B. contaminans revealed secondary metabolite gene clusters associated with quorum sensing, biofilm formation, antifungal compounds, and hemolysins. The potential production of these gene cluster metabolites was phenotypically evaluated through biofilm, bacterial-fungal interaction, and hemolytic assays. Collectively, these data identify the UPA flex lines as a unique ecological niche and novel area of biofilm growth within the WRS. Further investigation of these organisms and their resistance profiles will enable engineering controls directed toward biofilm prevention in future space station water systems.

9.
Psychol Rev ; 130(4): 853-872, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36892901

RESUMO

Understanding model complexity is important for developing useful psychological models. One way to think about model complexity is in terms of the predictions a model makes and the ability of empirical evidence to falsify those predictions. We argue that existing measures of falsifiability have important limitations and develop a new measure. KL-delta uses Kullback-Leibler divergence to compare the prior predictive distributions of models to the data prior that formalizes knowledge about the plausibility of different experimental outcomes. Using introductory conceptual examples and applications with existing models and experiments, we show that KL-delta challenges widely held scientific intuitions about model complexity and falsifiability. In a psychophysics application, we show that hierarchical models with more parameters are often more falsifiable than the original nonhierarchical model. This counters the intuition that adding parameters always makes a model more complex. In a decision-making application, we show that a choice model incorporating response determinism can be harder to falsify than its special case of probability matching. This counters the intuition that if one model is a special case of another, the special case must be less complex. In a memory recall application, we show that using informative data priors based on the serial position curve allows KL-delta to distinguish models that otherwise would be indistinguishable. This shows the value in model evaluation of extending the notion of possible falsifiability, in which all data are considered equally likely, to the more general notion of plausible falsifiability, in which some data are more likely than others. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Memória , Modelos Psicológicos , Humanos , Probabilidade
10.
ISME Commun ; 3(1): 15, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823453

RESUMO

The colony-forming cyanobacteria Trichodesmium spp. are considered one of the most important nitrogen-fixing genera in the warm, low nutrient ocean. Despite this central biogeochemical role, many questions about their evolution, physiology, and trophic interactions remain unanswered. To address these questions, we describe Trichodesmium pangenomic potential via significantly improved genomic assemblies from two isolates and 15 new >50% complete Trichodesmium metagenome-assembled genomes from hand-picked, Trichodesmium colonies spanning the Atlantic Ocean. Phylogenomics identified ~four N2 fixing clades of Trichodesmium across the transect, with T. thiebautii dominating the colony-specific reads. Pangenomic analyses showed that all T. thiebautii MAGs are enriched in COG defense mechanisms and encode a vertically inherited Type III-B Clustered Regularly Interspaced Short Palindromic Repeats and associated protein-based immunity system (CRISPR-Cas). Surprisingly, this CRISPR-Cas system was absent in all T. erythraeum genomes, vertically inherited by T. thiebautii, and correlated with increased signatures of horizontal gene transfer. Additionally, the system was expressed in metaproteomic and transcriptomic datasets and CRISPR spacer sequences with 100% identical hits to field-assembled, putative phage genome fragments were identified. While the currently CO2-limited T. erythraeum is expected to be a 'winner' of anthropogenic climate change, their genomic dearth of known phage resistance mechanisms, compared to T. thiebautii, could put this outcome in question. Thus, the clear demarcation of T. thiebautii maintaining CRISPR-Cas systems, while T. erythraeum does not, identifies Trichodesmium as an ecologically important CRISPR-Cas model system, and highlights the need for more research on phage-Trichodesmium interactions.

11.
Psychol Methods ; 28(3): 558-579, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35298215

RESUMO

The last 25 years have shown a steady increase in attention for the Bayes factor as a tool for hypothesis evaluation and model selection. The present review highlights the potential of the Bayes factor in psychological research. We discuss six types of applications: Bayesian evaluation of point null, interval, and informative hypotheses, Bayesian evidence synthesis, Bayesian variable selection and model averaging, and Bayesian evaluation of cognitive models. We elaborate what each application entails, give illustrative examples, and provide an overview of key references and software with links to other applications. The article is concluded with a discussion of the opportunities and pitfalls of Bayes factor applications and a sketch of corresponding future research lines. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Teorema de Bayes , Pesquisa Comportamental , Psicologia , Humanos , Pesquisa Comportamental/métodos , Psicologia/métodos , Software , Projetos de Pesquisa
12.
Behaviormetrika ; 50(2): 517-539, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38481469

RESUMO

The Mnemonic Similarity Task (MST: Stark et al., 2019) is a modified recognition memory task designed to place strong demand on pattern separation. The sensitivity and reliability of the MST make it an extremely valuable tool in clinical settings. We develop new cognitive models, based on the multinomial processing tree framework, for two versions of the MST. The models are implemented as generative probabilistic models and applied to behavioral data using Bayesian graphical modeling methods. We demonstrate how the combination of cognitive modeling and Bayesian methods allows for flexible and powerful inferences about performance on the MST. These demonstrations include latent-mixture extensions for identifying individual differences in decision strategies, and hierarchical extensions that measure fine-grained differences in the ability to detect lures. One key finding is that the availability of a "similar" response in the MST reduces individual differences in decision strategies and allows for more direct measurement of recognition memory.

13.
J Math Psychol ; 1082022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36465949

RESUMO

The Mnemonic Similarity Task (MST: Stark et al., 2019) is a modified recognition memory task designed to place strong demand on pattern separation. The sensitivity and reliability of the MST make it an extremely valuable tool in clinical settings, where it has been used to identify hippocampal dysfunction associated with healthy aging, dementia, schizophrenia, depression, and other disorders. As with any test used in a clinical setting, it is especially important for the MST to be administered as efficiently as possible. We apply adaptive design optimization methods (Lesmes et al., 2015; Myung et al., 2013) to optimize the presentation of test stimuli in accordance with previous responses. This optimization is based on a signal-detection model of an individual's memory capabilities and decision-making processes. We demonstrate that the adaptive design optimization approach generally reduces the number of test stimuli needed to provide these measures.

14.
Sci Rep ; 12(1): 21125, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36476670

RESUMO

To better understand the potential relationship between COVID-19 disease and hologenome microbial community dynamics and functional profiles, we conducted a multivariate taxonomic and functional microbiome comparison of publicly available human bronchoalveolar lavage fluid (BALF) metatranscriptome samples amongst COVID-19 (n = 32), community acquired pneumonia (CAP) (n = 25), and uninfected samples (n = 29). We then performed a stratified analysis based on mortality amongst the COVID-19 cohort with known outcomes of deceased (n = 10) versus survived (n = 15). Our overarching hypothesis was that there are detectable and functionally significant relationships between BALF microbial metatranscriptomes and the severity of COVID-19 disease onset and progression. We observed 34 functionally discriminant gene ontology (GO) terms in COVID-19 disease compared to the CAP and uninfected cohorts, and 21 GO terms functionally discriminant to COVID-19 mortality (q < 0.05). GO terms enriched in the COVID-19 disease cohort included hydrolase activity, and significant GO terms under the parental terms of biological regulation, viral process, and interspecies interaction between organisms. Notable GO terms associated with COVID-19 mortality included nucleobase-containing compound biosynthetic process, organonitrogen compound catabolic process, pyrimidine-containing compound biosynthetic process, and DNA recombination, RNA binding, magnesium and zinc ion binding, oxidoreductase activity, and endopeptidase activity. A Dirichlet multinomial mixtures clustering analysis resulted in a best model fit using three distinct clusters that were significantly associated with COVID-19 disease and mortality. We additionally observed discriminant taxonomic differences associated with COVID-19 disease and mortality in the genus Sphingomonas, belonging to the Sphingomonadacae family, Variovorax, belonging to the Comamonadaceae family, and in the class Bacteroidia, belonging to the order Bacteroidales. To our knowledge, this is the first study to evaluate significant differences in taxonomic and functional signatures between BALF metatranscriptomes from COVID-19, CAP, and uninfected cohorts, as well as associating these taxa and microbial gene functions with COVID-19 mortality. Collectively, while this data does not speak to causality nor directionality of the association, it does demonstrate a significant relationship between the human microbiome and COVID-19. The results from this study have rendered testable hypotheses that warrant further investigation to better understand the causality and directionality of host-microbiome-pathogen interactions.


Assuntos
COVID-19 , Humanos , Líquido da Lavagem Broncoalveolar , Ontologia Genética
15.
J Exp Psychol Learn Mem Cogn ; 48(11): 1598-1617, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35084930

RESUMO

Much recent research and theorizing in the field of reasoning has been concerned with intuitive sensitivity to logical validity, such as the logic-brightness effect, in which logically valid arguments are judged to have a "brighter" typeface than invalid arguments. We propose and test a novel signal competition account of this phenomenon. Our account makes two assumptions: (a) as per the demands of the logic-brightness task, people attempt to find a perceptual signal to guide brightness judgments, but (b) when the perceptual signal is hard to discern, they instead attend to cues such as argument validity. Experiment 1 tested this account by manipulating the difficulty of the perceptual contrast. When contrast discrimination was relatively difficult, we replicated the logic-brightness effect. When the discrimination was easy, the effect was eliminated. Experiment 2 manipulated the ambiguity of the perceptual task, comparing discrimination performance when the perceptual contrast was labeled in terms of rating "brightness" or "darkness". When the less ambiguous darkness labeling was used, there was no evidence of a logic-brightness effect. In both experiments, individual sensitivity to the perceptual discrimination was negatively correlated with sensitivity to argument validity. Hierarchical latent mixture modeling revealed distinct individual strategies: responses based on perceptual cues, responses based on validity or guessing. Consistent with the signal competition account, the proportion of those responding to validity increased with perceptual discrimination difficulty or task ambiguity. The results challenge explanations of the logic-brightness effect based on parallel dual-process models of reasoning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Lógica , Pensamento , Humanos , Pensamento/fisiologia , Julgamento/fisiologia , Resolução de Problemas , Sinais (Psicologia)
16.
Environ Microbiol Rep ; 14(2): 203-217, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35023627

RESUMO

The globally dominant N2 -fixing cyanobacteria Trichodesmium and Crocosphaera provide vital nitrogen supplies to subtropical and tropical oceans, but little is known about how they will be affected by long-term ocean warming. We tested their thermal responses using experimental evolution methods during 2 years of selection at optimal (28°C), supra-optimal (32°C) and suboptimal (22°C) temperatures. After several hundred generations under thermal selection, changes in growth parameters, as well as N and C fixation rates, suggested that Trichodesmium did not adapt to the three selection temperature regimes during the 2-year evolution experiment, but could instead rapidly and reversibly acclimate to temperature shifts from 20°C to 34°C. In contrast, over the same timeframe apparent thermal adaptation was observed in Crocosphaera, as evidenced by irreversible phenotypic changes as well as whole-genome sequencing and variant analysis. Especially under stressful warming conditions (34°C), 32°C-selected Crocosphaera cells had an advantage in survival and nitrogen fixation over cell lines selected at 22°C and 28°C. The distinct strategies of phenotypic plasticity versus irreversible adaptation in these two sympatric diazotrophs are both viable ways to maintain fitness despite long-term temperature changes, and so could help to stabilize key ocean nitrogen cycle functions under future warming scenarios.


Assuntos
Cianobactérias , Nitrogênio , Aclimatação , Cianobactérias/genética , Cianobactérias/metabolismo , Nitrogênio/metabolismo , Fixação de Nitrogênio , Oceanos e Mares
17.
Comput Brain Behav ; 5(3): 261-278, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37873549

RESUMO

The n-back task is a widely used behavioral task for measuring working memory and the ability to inhibit interfering information. We develop a novel model of the commonly used 2-back task using the cognitive psychometric framework provided by Multinomial Processing Trees. Our model involves three parameters: a memory parameter, corresponding to how well an individual encodes and updates sequence information about presented stimuli; a decision parameter corresponding to how well participants execute choices based on information stored in memory; and a base-rate parameter corresponding to bias for responding "yes" or "no". We test the parameter recovery properties of the model using existing 2-back experimental designs, and demonstrate the application of the model to two previous data sets: one from social psychology involving faces corresponding to different races (Stelter and Degner, British Journal of Psychology 109:777-798, 2018), and one from cognitive neuroscience involving more than 1000 participants from the Human Connectome Project (Van Essen et al., Neuroimage 80:62-79, 2013). We demonstrate that the model can be used to infer interpretable individual-level parameters. We develop a hierarchical extension of the model to test differences between stimulus conditions, comparing faces of different races, and comparing face to non-face stimuli. We also develop a multivariate regression extension to examine the relationship between the model parameters and individual performance on standardized cognitive measures including the List Sorting and Flanker tasks. We conclude by discussing how our model can be used to dissociate underlying cognitive processes such as encoding failures, inhibition failures, and binding failures.

18.
J Proteome Res ; 21(1): 77-89, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34855411

RESUMO

Ocean microbial communities are important contributors to the global biogeochemical reactions that sustain life on Earth. The factors controlling these communities are being increasingly explored using metatranscriptomic and metaproteomic environmental biomarkers. Using published proteomes and transcriptomes from the abundant colony-forming cyanobacterium Trichodesmium (strain IMS101) grown under varying Fe and/or P limitation in low and high CO2, we observed robust correlations of stress-induced proteins and RNAs (i.e., involved in transport and homeostasis) that yield useful information on the nutrient status under low and/or high CO2. Conversely, transcriptional and translational correlations of many other central metabolism pathways exhibit broad discordance. A cellular RNA and protein production/degradation model demonstrates how biomolecules with small initial inventories, such as environmentally responsive proteins, achieve large increases in fold-change units as opposed to those with a higher basal expression and inventory such as metabolic systems. Microbial cells, due to their immersion in the environment, tend to show large adaptive responses in both RNA and protein that result in transcript-protein correlations. These observations and model results demonstrate multi-omic coherence for environmental biomarkers and provide the underlying mechanism for those observations, supporting the promise for global application in detecting responses to environmental stimuli in a changing ocean.


Assuntos
Cianobactérias , Trichodesmium , Cianobactérias/metabolismo , Biomarcadores Ambientais , Proteoma/genética , Proteoma/metabolismo , Transcriptoma , Trichodesmium/genética , Trichodesmium/metabolismo
19.
Behav Res Methods ; 54(2): 1010-1026, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34405388

RESUMO

The Balloon Analogue Risk Task (BART) is widely-used to measure risk propensity in theoretical, clinical, and applied research. In the task, people choose either to pump a balloon to increase its value at the risk of the balloon bursting and losing all value, or to bank the current value of the balloon. Risk propensity is most commonly measured as the average number of pumps on trials for which the balloon does not burst. Burst trials are excluded because they necessarily underestimate the number of pumps people intended to make. However, their exclusion discards relevant information about people's risk propensity. A better measure of risk propensity uses the statistical method of censoring to incorporate all of the trials. We develop a new Bayesian method, based on censoring, for measuring both risk propensity and behavioral consistency in the BART. Through applications to previous data we demonstrate how the method can be extended to consider the correlation of risk propensity with external measures, and to compare differences in risk propensity between groups. We provide implementations of all of these methods in R, MATLAB, and the GUI-based statistical software JASP.


Assuntos
Assunção de Riscos , Teorema de Bayes , Humanos
20.
Mol Pharm ; 18(9): 3464-3474, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34448393

RESUMO

Optimal cytoreduction for ovarian cancer is often challenging because of aggressive tumor biology and advanced stage. It is a critical issue since the extent of residual disease after surgery is the key predictor of ovarian cancer patient survival. For a limited number of cancers, fluorescence-guided surgery has emerged as an effective aid for tumor delineation and effective cytoreduction. The intravenously administered fluorescent agent, most commonly indocyanine green (ICG), accumulates preferentially in tumors, which are visualized under a fluorescent light source to aid surgery. Insufficient tumor specificity has limited the broad application of these agents in surgical oncology including for ovarian cancer. In this study, we developed a novel tumor-selective fluorescent agent by chemically linking ICG to mouse monoclonal antibody 10D7 that specifically recognizes an ovarian cancer-enriched cell surface receptor, CUB-domain-containing protein 1 (CDCP1). 10D7ICG has high affinity for purified recombinant CDCP1 and CDCP1 that is located on the surface of ovarian cancer cells in vitro and in vivo. Our results show that intravenously administered 10D7ICG accumulates preferentially in ovarian cancer, permitting visualization of xenograft tumors in mice. The data suggest CDCP1 as a rational target for tumor-specific fluorescence-guided surgery for ovarian cancer.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Moléculas de Adesão Celular/antagonistas & inibidores , Corantes Fluorescentes/administração & dosagem , Imagem Óptica/métodos , Neoplasias Ovarianas/diagnóstico , Animais , Anticorpos Monoclonais/química , Antígenos de Neoplasias , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/química , Humanos , Verde de Indocianina/administração & dosagem , Verde de Indocianina/química , Injeções Intravenosas , Camundongos , Neoplasias Ovarianas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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