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1.
Sci Rep ; 14(1): 5480, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443467

RESUMO

Earthquakes pose substantial threats to communities worldwide. Understanding how people respond to the fast-changing environment during earthquakes is crucial for reducing risks and saving lives. This study aims to study people's protective action decision-making in earthquakes by leveraging explainable machine learning and video data. Specifically, this study first collected real-world CCTV footage and video postings from social media platforms, and then identified and annotated changes in the environment and people's behavioral responses during the M7.1 2018 Anchorage earthquake. By using the fully annotated video data, we applied XGBoost, a widely-used machine learning method, to model and forecast people's protective actions (e.g., drop and cover, hold on, and evacuate) during the earthquake. Then, explainable machine learning techniques were used to reveal the complex, nonlinear relationships between different factors and people's choices of protective actions. Modeling results confirm that social and environmental cues played critical roles in affecting the probability of different protective actions. Certain factors, such as the earthquake shaking intensity and number of people shown in the environment, displayed evident nonlinear relationships with the probability of choosing to evacuate. These findings can help emergency managers and policymakers design more effective protective action recommendations during earthquakes.

2.
J Med Entomol ; 60(6): 1380-1387, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37963277

RESUMO

Haemaphysalis longicornis (Neumann) is an invasive ixodid tick originating from eastern Asia which recently has become established in the United States. In its native range, this tick can transmit several pathogens to animals and humans, but little is known about its ability to acquire and transmit pathogens native to the United States. Geographic overlap with ticks such as Dermacentor variabilis (Say), a known vector of Rickettsia rickettsii, makes investigation into the interactions between H. longicornis and D. variabilis of interest to the public health community. Previous studies have shown that H. longicornis can serve as a competent vector of R. rickettsii under laboratory settings, but there is little information on its ability to acquire this pathogen via other biologically relevant routes, such as co-feeding. Here, we assess the ability of H. longicornis nymphs to acquire R. rickettsii through co-feeding with infected D. variabilis adults on a vertebrate animal model under laboratory conditions. The median infection prevalence in engorged H. longicornis nymphs across 8 cohorts was 0% with an interquartile range (IQR) of 4.13%. Following transstadial transmission, the median infection prevalence in flat females was 0.7% (IQR = 2.4%). Our results show that co-feeding transmission occurs at low levels in the laboratory between these 2 species. However, based on the relatively low transmission rates, this may not be a likely mechanism of R. rickettsii introduction to H. longicornis.


Assuntos
Dermacentor , Ixodidae , Rickettsia , Rickettsiaceae , Febre Maculosa das Montanhas Rochosas , Feminino , Estados Unidos , Humanos , Animais , Rickettsia rickettsii , Ixodidae/microbiologia , Rickettsiales , Dermacentor/microbiologia , Ninfa/microbiologia
3.
J Med Entomol ; 60(1): 62-72, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36271802

RESUMO

National parks are unique and significant vector-borne pathogen transmission settings, engaging over 300 million people in outdoor recreation per year. In this study, we integrated vector surveys and ecological habitat feature data in spatial models to characterize tick-borne disease exposure risk in Acadia National Park (ANP), Maine. To determine the broad-scale patterns of blacklegged tick Ixodes scapularis Say (Acari: Ixodidae) densities in ANP, we conducted host-seeking tick collections at 114 sites across the park over two years. Using these tick survey data and geospatial landscape feature data (i.e., land cover, elevation, forest patch size, and aspect) we developed a random forest model of nymphal tick density. We found that host-seeking tick density varies significantly across the park and is particularly high in areas characterized by deciduous forest cover and relatively low elevation. To explore potential fine-scale ecological drivers of tick density spatial patterns, we quantified microclimate conditions, host activity, and vegetation characteristics at a subset of 19 sites. We identified significant differences in microclimate conditions but not host activity or vegetation metrics across broad-scale landscape feature classes. Mean temperature and mean humidity were correlated to nymphal densities and therefore may provide a mechanistic link between landscape features and blacklegged tick densities. Finally, we detected multiple tick-borne pathogens in both ticks and small mammals sampled in ANP, including Borrelia burgdorferi, Babesia microti, and Anaplasma phagocytophilum. Our findings demonstrate the value of using ecological metrics to estimate vector-borne disease exposure risk and provide insight into habitat characteristics that may drive tick-borne disease exposure risk.


Assuntos
Borrelia burgdorferi , Ixodes , Doença de Lyme , Doenças Transmitidas por Carrapatos , Estados Unidos , Animais , Parques Recreativos , Maine , Doenças Transmitidas por Carrapatos/epidemiologia , Doença de Lyme/epidemiologia , Mamíferos
4.
Artigo em Inglês | MEDLINE | ID: mdl-33649110

RESUMO

Enterococcus faecium, a commensal of the human intestine, has emerged as a hospital-adapted, multi-drug resistant (MDR) pathogen. Bacteriophages (phages), natural predators of bacteria, have regained attention as therapeutics to stem the rise of MDR bacteria. Despite their potential to curtail MDR E. faecium infections, the molecular events governing E. faecium-phage interactions remain largely unknown. Such interactions are important to delineate because phage selective pressure imposed on E. faecium will undoubtedly result in phage resistance phenotypes that could threaten the efficacy of phage therapy. In an effort to understand the emergence of phage resistance in E. faecium, three newly isolated lytic phages were used to demonstrate that E. faecium phage resistance is conferred through an array of cell wall-associated molecules, including secreted antigen A (SagA), enterococcal polysaccharide antigen (Epa), wall teichoic acids, capsule, and an arginine-aspartate-aspartate (RDD) protein of unknown function. We find that capsule and Epa are important for robust phage adsorption and that phage resistance mutations in sagA, epaR, and epaX enhance E. faecium susceptibility to ceftriaxone, an antibiotic normally ineffective due to its low affinity for enterococcal penicillin binding proteins. Consistent with these findings, we provide evidence that phages potently synergize with cell wall (ceftriaxone and ampicillin) and membrane-acting (daptomycin) antimicrobials to slow or completely inhibit the growth of E. faecium Our work demonstrates that the evolution of phage resistance comes with fitness defects resulting in drug sensitization and that lytic phages could serve as effective antimicrobials for the treatment of E. faecium infections.

5.
Sci Rep ; 12(1): 1634, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35102161

RESUMO

Online social networks (OSNs) have become a powerful tool to study collective human responses to extreme events such as earthquakes. Most previous research concentrated on a single platform and utilized users' behaviors on a single platform to study people's general responses. In this study, we explore the characteristics of people's behaviors on different OSNs and conduct a cross-platform analysis of public responses to earthquakes. Our findings support the Uses and Gratification theory that users on Reddit and Twitter are engaging with platforms that they may feel best reflect their sense of self. Using the 2019 Ridgecrest earthquakes as our study cases, we collected 510,579 tweets and 45,770 Reddit posts (including 1437 submissions and 44,333 comments) to answer the following research questions: (1) What were the similarities and differences between public responses on Twitter and Reddit? (2) Considering the different mechanisms of Twitter and Reddit, what unique information of public responses can we learn from Reddit as compared with Twitter? By answering these research questions, we aim to bridge the gap of cross-platform public responses research towards natural hazards. Our study evinces that the users on the two different platforms have both different topics of interest and different sentiments towards the same earthquake, which indicates the necessity of investigating cross-platform OSNs to reveal a more comprehensive picture of people's general public responses towards certain disasters. Our analysis also finds that r/conspiracy subreddit is one of the major venues where people discuss the 2019 Ridgecrest earthquakes on Reddit and different misinformation/conspiracies spread on Twitter and Reddit platforms (e.g., "Big one is coming" on Twitter and "Nuclear test" on Reddit).

6.
PLoS One ; 16(5): e0251497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33970975

RESUMO

The blacklegged tick (Ixodes scapularis) and the invasive European fire ant (Myrmica rubra) are both expanding throughout their sympatric range in coastal New England. Ixodes scapularis is the primary vector of the bacterium Borrelia burgdorferi, which is the causative agent of Lyme disease, and Mount Desert Island, Maine, home to Acadia National Park, currently is affected by a high Lyme disease burden. Ticks have many natural predators, including ants, although no previous studies have investigated interactions between these two species. To test the hypothesis that the presence of M. rubra alters I. scapularis abundance, we collected ticks by drag-sampling at eight ant-infested sites and eight uninfested control sites in Acadia National Park. We found that nymph density was significantly higher at ant-infested sites, while larval density was significantly higher at control sites. In addition, we conducted a laboratory bioassay to measure M. rubra aggression against I. scapularis larvae, nymphs, and adults and Dermacentor variabilis adults, and found that ant aggression was significantly higher against D. variabilis adults than I. scapularis adults. Our findings support the hypothesis that M. rubra has divergent effects across I. scapularis life stages, and we discuss possible ecological mechanisms, including optimal microclimate and predation, that could promote density of nymphs while inhibiting density of larvae.


Assuntos
Formigas/fisiologia , Espécies Introduzidas , Ixodes/fisiologia , Animais , Vetores Artrópodes/microbiologia , Vetores Artrópodes/fisiologia , Borrelia burgdorferi/isolamento & purificação , Feminino , Ixodes/microbiologia , Doença de Lyme/transmissão , New England , Simpatria
7.
J Med Entomol ; 57(1): 273-280, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502636

RESUMO

Lyme disease is the most commonly reported vector-borne illness and sixth most commonly reported notifiable infectious disease in the United States. The majority of cases occur in the Northeast and upper-Midwest, and the number and geographic distribution of cases is steadily increasing. The blacklegged tick (Ixodes scapularis Say) is the principal vector of the Lyme disease spirochete (Borrelia burgdorferi sensu stricto) in eastern North America. Although Lyme disease risk has been studied in residential and recreational settings across rural to urban landscapes including metropolitan areas, risk within U.S. cities has not been adequately evaluated despite the presence of natural and undeveloped public parkland where visitors could be exposed to B. burgdorferi-infected I. scapularis. We studied the occurrence of I. scapularis and infection prevalence of B. burgdorferi in four insular regional parks within the city of Pittsburgh to assess Lyme disease risk of exposure to infected adults and nymphs. We found that the density of I. scapularis adults (1.16 ± 0.21 ticks/100 m2) and nymphs (3.42 ± 0.45 ticks/100 m2), infection prevalence of B. burgdorferi in adults (51.9%) and nymphs (19.3%), and density of infected adults (0.60 ticks/100 m2) and nymphs (0.66 ticks/100 m2) are as high in these city parks as nonurban residential and recreational areas in the highly endemic coastal Northeast. These findings emphasize the need to reconsider, assess, and manage Lyme disease risk in greenspaces within cities, especially in high Lyme disease incidence states.


Assuntos
Borrelia burgdorferi/isolamento & purificação , Ixodes/microbiologia , Doença de Lyme/epidemiologia , Animais , Humanos , Ixodes/crescimento & desenvolvimento , Doença de Lyme/microbiologia , Ninfa/crescimento & desenvolvimento , Ninfa/microbiologia , Parques Recreativos , Pennsylvania/epidemiologia , Medição de Risco
8.
Artigo em Inglês | MEDLINE | ID: mdl-31527030

RESUMO

The innovation of new therapies to combat multidrug-resistant (MDR) bacteria is being outpaced by the continued rise of MDR bacterial infections. Of particular concern are hospital-acquired infections (HAIs) that are recalcitrant to antibiotic therapies. The Gram-positive intestinal pathobiont Enterococcus faecalis is associated with HAIs, and some strains are MDR. Therefore, novel strategies to control E. faecalis populations are needed. We previously characterized an E. faecalis type II CRISPR-Cas system and demonstrated its utility in the sequence-specific removal of antibiotic resistance determinants. Here, we present work describing the adaption of this CRISPR-Cas system into a constitutively expressed module encoded on a pheromone-responsive conjugative plasmid that efficiently transfers to E. faecalis for the selective removal of antibiotic resistance genes. Using in vitro competition assays, we show that these CRISPR-Cas-encoding delivery plasmids, or CRISPR-Cas antimicrobials, can reduce the occurrence of antibiotic resistance in enterococcal populations in a sequence-specific manner. Furthermore, we demonstrate that deployment of CRISPR-Cas antimicrobials in the murine intestine reduces the occurrence of antibiotic-resistant E. faecalis by several orders of magnitude. Finally, we show that E. faecalis donor strains harboring CRISPR-Cas antimicrobials are immune to uptake of antibiotic resistance determinants in vivo Our results demonstrate that conjugative delivery of CRISPR-Cas antimicrobials may be adaptable for future deployment from probiotic bacteria for exact targeting of defined MDR bacteria or for precision engineering of polymicrobial communities in the mammalian intestine.


Assuntos
Antibacterianos/farmacologia , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Farmacorresistência Bacteriana Múltipla/genética , Enterococcaceae/genética , Edição de Genes/métodos , Animais , Enterococcaceae/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/genética , Genes Bacterianos/genética , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Camundongos
9.
mSphere ; 4(4)2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31341074

RESUMO

CRISPR-Cas systems are barriers to horizontal gene transfer (HGT) in bacteria. Little is known about CRISPR-Cas interactions with conjugative plasmids, and studies investigating CRISPR-Cas/plasmid interactions in in vivo models relevant to infectious disease are lacking. These are significant gaps in knowledge because conjugative plasmids disseminate antibiotic resistance genes among pathogens in vivo, and it is essential to identify strategies to reduce the spread of these elements. We use enterococci as models to understand the interactions of CRISPR-Cas with conjugative plasmids. Enterococcus faecalis is a native colonizer of the mammalian intestine and harbors pheromone-responsive plasmids (PRPs). PRPs mediate inter- and intraspecies transfer of antibiotic resistance genes. We assessed E. faecalis CRISPR-Cas anti-PRP activity in the mouse intestine and under different in vitro conditions. We observed striking differences in CRISPR-Cas efficiency in vitro versus in vivo With few exceptions, CRISPR-Cas blocked intestinal PRP dissemination, while in vitro, the PRP frequently escaped CRISPR-Cas defense. Our results further the understanding of CRISPR-Cas biology by demonstrating that standard in vitro experiments do not adequately model the in vivo antiplasmid activity of CRISPR-Cas. Additionally, our work identifies several variables that impact the apparent in vitro antiplasmid activity of CRISPR-Cas, including planktonic versus biofilm settings, different donor-to-recipient ratios, production of a plasmid-encoded bacteriocin, and the time point at which matings are sampled. Our results are clinically significant because they demonstrate that barriers to HGT encoded by normal (healthy) human microbiota can have significant impacts on in vivo antibiotic resistance dissemination.IMPORTANCE CRISPR-Cas is a type of immune system in bacteria that is hypothesized to be a natural impediment to the spread of antibiotic resistance genes. In this study, we directly assessed the impact of CRISPR-Cas on antibiotic resistance dissemination in the mammalian intestine and under different in vitro conditions. We observed a robust effect of CRISPR-Cas on in vivo but not in vitro dissemination of antibiotic resistance plasmids in the native mammalian intestinal colonizer Enterococcus faecalis We conclude that standard in vitro experiments currently do not appropriately model the in vivo conditions where antibiotic resistance dissemination occurs between E. faecalis strains in the intestine. Moreover, our results demonstrate that CRISPR-Cas present in native members of the mammalian intestinal microbiota can block the spread of antibiotic resistance plasmids.


Assuntos
Sistemas CRISPR-Cas , Conjugação Genética , Farmacorresistência Bacteriana , Enterococcus faecalis/genética , Transferência Genética Horizontal , Intestinos/microbiologia , Animais , Antibacterianos/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos/genética
10.
Infect Immun ; 87(6)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30936157

RESUMO

Enterococcus faecalis is a human intestinal pathobiont with intrinsic and acquired resistance to many antibiotics, including vancomycin. Nature provides a diverse and virtually untapped repertoire of bacterial viruses, or bacteriophages (phages), that could be harnessed to combat multidrug-resistant enterococcal infections. Bacterial phage resistance represents a potential barrier to the implementation of phage therapy, emphasizing the importance of investigating the molecular mechanisms underlying the emergence of phage resistance. Using a cohort of 19 environmental lytic phages with tropism against E. faecalis, we found that these phages require the enterococcal polysaccharide antigen (Epa) for productive infection. Epa is a surface-exposed heteroglycan synthesized by enzymes encoded by both conserved and strain-specific genes. We discovered that exposure to phage selective pressure favors mutation in nonconserved epa genes both in culture and in a mouse model of intestinal colonization. Despite gaining phage resistance, epa mutant strains exhibited a loss of resistance to cell wall-targeting antibiotics. Finally, we show that an E. faecalisepa mutant strain is deficient in intestinal colonization, cannot expand its population upon antibiotic-driven intestinal dysbiosis, and fails to be efficiently transmitted to juvenile mice following birth. This study demonstrates that phage therapy could be used in combination with antibiotics to target enterococci within a dysbiotic microbiota. Enterococci that evade phage therapy by developing resistance may be less fit at colonizing the intestine and sensitized to vancomycin, preventing their overgrowth during antibiotic treatment.


Assuntos
Antibacterianos/farmacologia , Bacteriófagos/fisiologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/virologia , Enterococcus faecium/virologia , Infecções por Bactérias Gram-Positivas/terapia , Intestinos/microbiologia , Animais , Terapia Biológica , Enterococcus faecalis/imunologia , Enterococcus faecalis/fisiologia , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/imunologia , Enterococcus faecium/fisiologia , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Vancomicina/farmacologia
11.
Sci Rep ; 9(1): 2478, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30792471

RESUMO

We explore how accurate earthquake early warning (EEW) can be, given our limited ability to forecast expected shaking even if the earthquake source is known. Because of the strong variability of ground motion metrics, such as peak ground acceleration (PGA) and peak ground velocity (PGV), we find that correct alerts (i.e., alerts that accurately estimate the ground motion will be above a predetermined damage threshold) are not expected to be the most common EEW outcome even when the earthquake magnitude and location are accurately determined. Infrequently, ground motion variability results in a user receiving a false alert because the ground motion turned out to be significantly smaller than the system expected. More commonly, users will experience missed alerts when the system does not issue an alert but the user experiences potentially damaging shaking. Despite these inherit limitations, EEW can significantly mitigate earthquake losses for false-alert-tolerant users who choose to receive alerts for expected ground motions much smaller than the level that could cause damage. Although this results in many false alerts (unnecessary alerts for earthquakes that do not produce damaging ground shaking), it minimizes the number of missed alerts and produces overall optimal performance.

12.
Theor Issues Ergon Sci ; 15(6): 545-577, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25383042

RESUMO

Automation has the potential to aid humans with a diverse set of tasks and support overall system performance. Automated systems are not always reliable, and when automation errs, humans must engage in error management, which is the process of detecting, understanding, and correcting errors. However, this process of error management in the context of human-automation interaction is not well understood. Therefore, we conducted a systematic review of the variables that contribute to error management. We examined relevant research in human-automation interaction and human error to identify critical automation, person, task, and emergent variables. We propose a framework for management of automation errors to incorporate and build upon previous models. Further, our analysis highlights variables that may be addressed through design and training to positively influence error management. Additional efforts to understand the error management process will contribute to automation designed and implemented to support safe and effective system performance.

13.
Appl Ergon ; 45(6): 1687-99, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24958610

RESUMO

A human-systems perspective is a fruitful approach to understanding home health care because it emphasizes major individual components of the system - persons, equipment/technology, tasks, and environments - as well as the interaction between these components. The goal of this research was to apply a human-system perspective to consider the capabilities and limitations of the persons, in relation to the demands of the tasks and equipment/technology in home health care. Identification of challenges and mismatches between the person(s) capabilities and the demands of providing care provide guidance for human factors interventions. A qualitative study was conducted with 8 home health Certified Nursing Assistants and 8 home health Registered Nurses interviewed about challenges they encounter in their jobs. A systematic categorization of the challenges the care providers reported was conducted and human factors recommendations were proposed in response, to improve home health. The challenges inform a human-systems model of home health care.


Assuntos
Ergonomia , Serviços de Assistência Domiciliar , Equipamentos e Provisões , Humanos , Avaliação das Necessidades , Segurança do Paciente , Pesquisa Qualitativa , Garantia da Qualidade dos Cuidados de Saúde , Recursos Humanos
14.
Cell ; 155(7): 1451-63, 2013 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-24315484

RESUMO

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/microbiologia , Trato Gastrointestinal/microbiologia , Animais , Ansiedade/metabolismo , Ansiedade/microbiologia , Bacteroides fragilis , Comportamento Animal , Encéfalo/fisiologia , Criança , Transtornos Globais do Desenvolvimento Infantil/metabolismo , Modelos Animais de Doenças , Feminino , Trato Gastrointestinal/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Microbiota , Probióticos/administração & dosagem
15.
Proc Hum Factors Ergon Soc Annu Meet ; 57(1): 743-747, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31239608

RESUMO

In the United States, chronic pain affects at least 116 million Americans, differentially impacting older adults. One of the leading causes of pain for older adults is osteoarthritis. This disease affects approximately 14% of the United States population and can cause disability and mobility problems, in addition to having a high cost for the healthcare system. The methods individuals use to manage their pain are contingent upon their model of the disease (e.g., their beliefs about osteoarthritis pain management). The purpose of the present investigation was to: 1) understand what variables older adults with osteoarthritis believe impact pain, and 2) understand current approaches for self-management of osteoarthritis pain. We conducted structured interviews with eight older adults who have osteoarthritis. The interviews revealed current approaches in pain management, as well as gaps in knowledge. We propose an expansion of the idea of a general disease model for pain management that is patient-centered, allowing for personal customization of factors for reducing pain and increasing successful pain-management.

16.
PLoS One ; 7(9): e43601, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22970134

RESUMO

During mesenchymal condensation, the initial step of skeletogenesis, transduction of minute mechanical forces to the nucleus is associated with up or down-regulation of genes, ultimately resulting in formation of the skeletal template and appropriate cell lineage commitment. The summation of these biophysical cues affects the cell's shape and fate. Here, we predict and measure surface strain, in live stem cells, in response to controlled delivery of stresses, providing a platform to direct short-term structure--function relationships and long-term fate decisions. We measure local strains on stem cell surfaces using fluorescent microbeads coated with Concanavalin A. During delivery of controlled mechanical stresses, 4-Dimensional (x,y,z,t) displacements of the bound beads are measured as surface strains using confocal microscopy and image reconstruction. Similarly, micro-particle image velocimetry (µ-piv) is used to track flow fields with fluorescent microspheres. The measured flow velocity gradient is used to calculate stress imparted by fluid drag at the surface of the cell. We compare strain measured on cell surfaces with those predicted computationally using parametric estimates of the cell's elastic and shear modulus. Finally, cross-correlating stress--strain data to measures of gene transcription marking lineage commitment enables us to create stress--strain--fate maps, for live stem cells in situ. The studies show significant correlations between live stem cell stress--strain relationships and lineage commitment. The method presented here provides a novel means to probe the live stem cell's mechanome, enabling mechanistic studies of the role of mechanics in lineage commitment as it unfolds.


Assuntos
Reologia/métodos , Células-Tronco/citologia , Células-Tronco/fisiologia , Estresse Mecânico , Animais , Fenômenos Biomecânicos/fisiologia , Diferenciação Celular , Linhagem Celular , Sobrevivência Celular , Camundongos , Microesferas , Modelos Biológicos , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/metabolismo , Fatores de Tempo
17.
Proc Natl Acad Sci U S A ; 109(31): 12776-81, 2012 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-22802640

RESUMO

Increasing evidence highlights a role for the immune system in the pathogenesis of autism spectrum disorder (ASD), as immune dysregulation is observed in the brain, periphery, and gastrointestinal tract of ASD individuals. Furthermore, maternal infection (maternal immune activation, MIA) is a risk factor for ASD. Modeling this risk factor in mice yields offspring with the cardinal behavioral and neuropathological symptoms of human ASD. In this study, we find that offspring of immune-activated mothers display altered immune profiles and function, characterized by a systemic deficit in CD4(+) TCRß(+) Foxp3(+) CD25(+) T regulatory cells, increased IL-6 and IL-17 production by CD4(+) T cells, and elevated levels of peripheral Gr-1(+) cells. In addition, hematopoietic stem cells from MIA offspring exhibit altered myeloid lineage potential and differentiation. Interestingly, repopulating irradiated control mice with bone marrow derived from MIA offspring does not confer MIA-related immunological deficits, implicating the peripheral environmental context in long-term programming of immune dysfunction. Furthermore, behaviorally abnormal MIA offspring that have been irradiated and transplanted with immunologically normal bone marrow from either MIA or control offspring no longer exhibit deficits in stereotyped/repetitive and anxiety-like behaviors, suggesting that immune abnormalities in MIA offspring can contribute to ASD-related behaviors. These studies support a link between cellular immune dysregulation and ASD-related behavioral deficits in a mouse model of an autism risk factor.


Assuntos
Transtorno Autístico/imunologia , Comportamento Animal , Imunidade Celular , Complicações Infecciosas na Gravidez/imunologia , Linfócitos T Reguladores/imunologia , Animais , Antígenos de Diferenciação/imunologia , Transtorno Autístico/etiologia , Transtorno Autístico/patologia , Diferenciação Celular/imunologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/patologia , Humanos , Interleucina-17/imunologia , Interleucina-6/imunologia , Camundongos , Gravidez , Complicações Infecciosas na Gravidez/patologia , Fatores de Risco , Linfócitos T Reguladores/patologia , Transplante Homólogo
18.
Appl Ergon ; 43(6): 1122-30, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22591763

RESUMO

The design of and training for complex systems requires in-depth understanding of task demands imposed on users. In this project, we used the knowledge engineering approach (Bowles et al., 2004) to assess the task of mowing in a citrus grove. Knowledge engineering is divided into four phases: (1) Establish goals. We defined specific goals based on the stakeholders involved. The main goal was to identify operator demands to support improvement of the system. (2) Create a working model of the system. We reviewed product literature, analyzed the system, and conducted expert interviews. (3) Extract knowledge. We interviewed tractor operators to understand their knowledge base. (4) Structure knowledge. We analyzed and organized operator knowledge to inform project goals. We categorized the information and developed diagrams to display the knowledge effectively. This project illustrates the benefits of knowledge engineering as a qualitative research method to inform technology design and training.


Assuntos
Engenharia , Conhecimento , Análise e Desempenho de Tarefas , Adulto , Agricultura , Comunicação , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Pesquisa Qualitativa
19.
Gastroenterology ; 143(2): 418-28, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22522092

RESUMO

BACKGROUND & AIMS: Invariant natural killer T (iNKT) cells undergo canonical, Vα14-Jα18 rearrangement of the T-cell receptor (TCR) in mice; this form of the TCR recognizes glycolipids presented by CD1d. iNKT cells mediate many different immune reactions. Their constitutive activated and memory phenotype and rapid initiation of effector functions after stimulation indicate previous antigen-specific stimulation. However, little is known about this process. We investigated whether symbiotic microbes can determine the activated phenotype and function of iNKT cells. METHODS: We analyzed the numbers, phenotypes, and functions of iNKT cells in germ-free mice, germ-free mice reconstituted with specified bacteria, and mice housed in specific pathogen-free environments. RESULTS: Specific pathogen-free mice, obtained from different vendors, have different intestinal microbiota. iNKT cells isolated from these mice differed in TCR Vß7 frequency and cytokine response to antigen, which depended on the environment. iNKT cells isolated from germ-free mice had a less mature phenotype and were hyporesponsive to activation with the antigen α-galactosylceramide. Intragastric exposure of germ-free mice to Sphingomonas bacteria, which carry iNKT cell antigens, fully established phenotypic maturity of iNKT cells. In contrast, reconstitution with Escherichia coli, which lack specific antigens for iNKT cells, did not affect the phenotype of iNKT cells. The effects of intestinal microbes on iNKT cell responsiveness did not require Toll-like receptor signals, which can activate iNKT cells independently of TCR stimulation. CONCLUSIONS: Intestinal microbes can affect iNKT cell phenotypes and functions in mice.


Assuntos
Escherichia coli , Galactosilceramidas/imunologia , Intestinos/microbiologia , Ativação Linfocitária , Células T Matadoras Naturais/microbiologia , Sphingomonas , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Citometria de Fluxo , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Vida Livre de Germes , Intestinos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Fenótipo , Receptores de Antígenos de Linfócitos T/química , Organismos Livres de Patógenos Específicos
20.
Proc Hum Factors Ergon Soc Annu Meet ; 56(1): 2492-2496, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274972

RESUMO

The health care domain is experiencing a shift from traditional hospital-based care to care delivered in a patient's home setting. Although home health care provides many benefits, it creates new challenges and difficulties for professional caregivers (e.g., registered nurses) who are performing complex medical tasks without the support often present in a health care environment. In addition to performing these tasks themselves, registered nurses are also responsible for training patients to perform many of these tasks, which may include using medical devices and managing complex medication regimens. The purpose of this research was to identify and systematically categorize the issues facing registered nurses (RNs) when training older adult patients. Eight RNs participated in individual structured interviews wherein they were asked to describe the difficulties and frustrations associated with training older adult patients to use medical devices and manage medication independently. The data were categorized as patient-related, RN-related, or situation-related issues. The results highlight the complexity of training device use and medication management, as well as the needs of RNs for forms of additional support in training older adult patients.

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