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1.
Environ Sci Technol ; 56(6): 3514-3523, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35201763

RESUMEN

Fish swimming behavior is a commonly measured response in aquatic ecotoxicology because behavior is considered a whole organism-level effect that integrates many sensory systems. Recent advancements in animal behavior models, such as hidden Markov chain models (HMM), suggest an improved analytical approach for toxicology. Using both new and traditional approaches, we examined the sublethal effects of PCB126 and methylmercury on yellow perch (YP) larvae (Perca flavescens) using three doses. Both approaches indicate larvae increase activity after exposure to either chemical. The middle methylmercury-dosed larvae showed multiple altered behavior patterns. First, larvae had a general increase in activity, typically performing more behavior states, more time swimming, and more swimming bouts per second. Second, when larvae were in a slow or medium swimming state, these larvae tended to switch between these states more often. Third, larvae swam slower during the swimming bouts. The upper PCB126-dosed larvae exhibited a higher proportion and a fast swimming state, but the total time spent swimming fast decreased. The middle PCB126-dosed larvae transitioned from fast to slow swimming states less often than the control larvae. These results indicate that developmental exposure to very low doses of these neurotoxicants alters YP larvae overall swimming behaviors, suggesting neurodevelopment alteration.


Asunto(s)
Compuestos de Metilmercurio , Percas , Animales , Larva , Cadenas de Markov , Compuestos de Metilmercurio/toxicidad , Percas/fisiología , Natación
2.
Bull Environ Contam Toxicol ; 110(1): 32, 2022 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-36583746

RESUMEN

An accurate analytical method was developed to determine selected per- and polyfluorinated alkyl substances (PFAS) at the level of parts per trillion (ppt or ng/L) in drinking water. The method included a concentration step using solid phase extraction (SPE) approach in combination with a liquid chromatography-tandem mass spectrometry system (LC-MS/MS). This method was optimized and validated for the common PFAS contaminants in drinking water. An initial demonstration of capability was established with an acceptable initial calibration, minimum reporting limit (MRL), limit of detection (LOD), initial demonstration of low system background, and initial demonstration of precision (IDP). Isotopically labeled internal standards were used for quantification. Surrogate standards were used to monitor method performance. The current method will help in better understanding of PFAS crisis by providing an efficient measurement of PFAS in water. In this study, the recoveries of four surrogates were between 84 and 113%, and calculated limit of detection (DL) and minimum reporting limits (MRL) were generally 1.0-3.0 and 5-10 ng/L, respectively.


Asunto(s)
Agua Potable , Fluorocarburos , Contaminantes Químicos del Agua , Agua Potable/análisis , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Extracción en Fase Sólida/métodos , Fluorocarburos/análisis , Cromatografía Líquida de Alta Presión/métodos , Contaminantes Químicos del Agua/análisis
3.
Proc Natl Acad Sci U S A ; 114(5): 1135-1140, 2017 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-28096418

RESUMEN

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage of Klebsiella pneumoniae There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC (K. pneumoniae carbapenemases) beta-lactamases encoded by blaKPC2, blaKPC3, and blaKPC4, which were transferred between strains and species by seven distinct subgroups of the Tn4401 element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.


Asunto(s)
Carbapenémicos/farmacología , Elementos Transponibles de ADN/genética , Brotes de Enfermedades , Infecciones por Enterobacteriaceae/microbiología , Enterobacteriaceae/efectos de los fármacos , Factores R/genética , Resistencia betalactámica/genética , Proteínas Bacterianas/genética , Boston/epidemiología , Células Clonales , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/transmisión , Enterobacteriaceae/enzimología , Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/transmisión , Variación Genética , Genoma Bacteriano , Humanos , Estudios Prospectivos , Alineación de Secuencia , Transformación Bacteriana , Resistencia betalactámica/fisiología , beta-Lactamasas/genética
4.
BMC Genomics ; 17: 675, 2016 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-27558222

RESUMEN

BACKGROUND: The sea lamprey (Petromyzon marinus) is a jawless vertebrate that parasitizes fish as an adult and, with overfishing, was responsible for the decline in lake trout (Salvelinus namaycush) populations in the Great Lakes. While laboratory studies have looked at the rates of wounding on various fish hosts, there have been few investigations on the physiological effects of lamprey wounding on the host. In the current study, two morphotypes of lake trout, leans and siscowets, were parasitized in the laboratory by sea lampreys and the liver transcriptomes of parasitized and nonparasitized fish were analyzed by RNA-seq (DESeq2 and edgeR) to determine which genes and gene pathways (Ingenuity Pathway Analysis) were altered by lamprey parasitism. RESULTS: Overall, genes encoding molecules involved in catalytic (e.g., enzymatic) and binding activities (factors and regulators) predominated the regulated gene lists. In siscowets, the top upregulated gene was growth arrest and DNA-damage-inducible protein and for leans it was interleukin-18-binding protein. In leans, the most significantly downregulated gene was UDP-glucuronosyltransferase 2A2 - DESeq2 or phosphotriesterase related - edgeR. For siscowets, the top downregulated gene was C-C motif chemokine 19 - DESeq2 or GTP-binding protein Rhes - edgeR. Gene pathways associated with inflammatory-related responses or factors (cytokines, chemokines, oxidative stress, apoptosis) were regulated following parasitism in both morphotypes. However, pathways related to energy metabolism (glycolysis, gluconeogenesis, lipolysis, lipogenesis) were also regulated. These pathways or the intensity or direction (up/downregulation) of regulation were different between leans and siscowets. Finally, one of the most significantly downregulated pathways in both leans and siscowets was the kynurenine (tryptophan degradation) pathway. CONCLUSIONS: The results indicate a strong transcriptional response in the lake trout to lamprey parasitism that entails genes involved in the regulation of inflammation and cellular damage. Responses to energy utilization as well as hydromineral balance also occurred indicating an adjustment in the host to energy demands and osmotic imbalances during parasitism. Given the role of the kynurenine pathway in promoting immunotolerance in mammals, the downregulation observed in this pathway during parasitism may signify an attempt by the host to inhibit any feedback suppression of the immune response to the lamprey.


Asunto(s)
Proteínas de Peces/genética , Perfilación de la Expresión Génica/métodos , Petromyzon/fisiología , Análisis de Secuencia de ARN/métodos , Trucha/parasitología , Animales , Metabolismo Energético , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Quinurenina/metabolismo , Lagos , Trucha/genética
5.
Environ Sci Technol ; 50(9): 4808-16, 2016 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-27023211

RESUMEN

Methylmercury (MeHg) is an established neurotoxicant of concern to fish-eating organisms. While most studies have focused on the fish consumers, much less is known about the effects of MeHg on the fish themselves, especially following exposures to chronic and environmentally relevant scenarios. Here we evaluated the behavioral effects of developmental MeHg insult by exposing parental generations of zebrafish to an environmentally realistic MeHg dietary concentration (1 ppm) and two higher concentrations (3 and 10 ppm) throughout their whole life span. Upon reaching adulthood, their offspring were analyzed through a series of behavioral tests, including the visual-motor response (VMR) assay, analysis of spontaneous swimming and evaluation of foraging efficiency. The VMR assay identified decreased locomotor output in the 6 day postfertilization (dpf) offspring of fish exposed to 3 and 10 ppm MeHg. However, in a second test 7 dpf fish revealed an increase in locomotor activity in all MeHg exposures tested. Increases in locomotion continued to be observed until 16 dpf, which coincided with increased foraging efficiency. These results suggest an association between MeHg and hyperactivity, and imply that fish chronically exposed to MeHg in the wild may be vulnerable to predation.


Asunto(s)
Conducta Animal/efectos de los fármacos , Pez Cebra , Animales , Dieta , Compuestos de Metilmercurio/farmacología , Natación
6.
Ecotoxicology ; 25(6): 1136-49, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27154845

RESUMEN

A 4.1 million m(3) coal ash release into the Emory and Clinch rivers in December 2008 at the Tennessee Valley Authority's Kingston Fossil Plant in east Tennessee, USA, prompted a long-term, large-scale biological monitoring effort to determine if there are chronic effects of this spill on resident biota. Because of the magnitude of the ash spill and the potential for exposure to coal ash-associated contaminants [e.g., selenium (Se), arsenic (As), and mercury (Hg)] which are bioaccumulative and may present human and ecological risks, an integrative, bioindicator approach was used. Three species of fish were monitored-bluegill (Lepomis macrochirus), redear sunfish (L. microlophus), and largemouth bass (Micropterus salmoides)-at ash-affected and reference sites annually for 5 years following the spill. On the same individual fish, contaminant burdens were measured in various tissues, blood chemistry parameters as metrics of fish health, and various condition and reproduction indices. A multivariate statistical approach was then used to evaluate relationships between contaminant bioaccumulation and fish metrics to assess the chronic, sub-lethal effects of exposure to the complex mixture of coal ash-associated contaminants at and around the ash spill site. This study suggests that while fish tissue concentrations of some ash-associated contaminants are elevated at the spill site, there was no consistent evidence of compromised fish health linked with the spill. Further, although relationships between elevated fillet burdens of ash-associated contaminants and some fish metrics were found, these relationships were not indicative of exposure to coal ash or spill sites. The present study adds to the weight of evidence from prior studies suggesting that fish populations have not incurred significant biological effects from spilled ash at this site: findings that are relevant to the current national discussions on the safe disposal of coal ash waste.


Asunto(s)
Liberación de Peligros Químicos , Ceniza del Carbón , Monitoreo del Ambiente , Reproducción/fisiología , Contaminantes Químicos del Agua/toxicidad , Animales , Arsénico , Peces , Mercurio , Perciformes , Ríos/química , Selenio , Tennessee , Contaminantes Químicos del Agua/análisis
7.
Proc Natl Acad Sci U S A ; 109(8): 3065-70, 2012 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-22315421

RESUMEN

The degree to which molecular epidemiology reveals information about the sources and transmission patterns of an outbreak depends on the resolution of the technology used and the samples studied. Isolates of Escherichia coli O104:H4 from the outbreak centered in Germany in May-July 2011, and the much smaller outbreak in southwest France in June 2011, were indistinguishable by standard tests. We report a molecular epidemiological analysis using multiplatform whole-genome sequencing and analysis of multiple isolates from the German and French outbreaks. Isolates from the German outbreak showed remarkably little diversity, with only two single nucleotide polymorphisms (SNPs) found in isolates from four individuals. Surprisingly, we found much greater diversity (19 SNPs) in isolates from seven individuals infected in the French outbreak. The German isolates form a clade within the more diverse French outbreak strains. Moreover, five isolates derived from a single infected individual from the French outbreak had extremely limited diversity. The striking difference in diversity between the German and French outbreak samples is consistent with several hypotheses, including a bottleneck that purged diversity in the German isolates, variation in mutation rates in the two E. coli outbreak populations, or uneven distribution of diversity in the seed populations that led to each outbreak.


Asunto(s)
Brotes de Enfermedades/estadística & datos numéricos , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Escherichia coli/genética , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/genética , Europa (Continente)/epidemiología , Humanos , Modelos Genéticos , Filogenia , Polimorfismo de Nucleótido Simple/genética
9.
Acad Psychiatry ; 39(3): 246-52, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25583402

RESUMEN

OBJECTIVE: There is a projected shortage of psychiatrists in Canada in forthcoming years. This study assessed factors in medical school education that are associated with students selecting psychiatry first and matching as a discipline. METHOD: The Canadian Organization of Undergraduate Psychiatry Educators (COUPE) conducted telephone interviews and sent e-mail questionnaires to the 17 medical schools across Canada; all schools provided data for 2012. Relevant data were obtained from the Canadian Resident Matching Service. Statistics were performed using v12 STATA program, and significance was set at a p value of <0.05. RESULTS: Medical student enrollment ranged from 54 to 266 students (mean = 158 ± 16). Of these students, 4.9 ± 0.6 % ranked psychiatry as their first choice for residency. Final match results yielded similar numbers at 5.0 ± 0.6 %. Ten out of 17 programs filled all psychiatry residency positions, whereas the remaining 7 programs had vacancy rates from 5 to 100 % (mean = 43.4 ± 15.1 %). Medical students were exposed to an average of 2.8 ± 0.5 pre-clerkship psychiatry weeks and 6.2 ± 0.3 clerkship weeks. Linear regression analysis demonstrated that the percentage of graduating medical students entering a psychiatry residency program could be predicted from the number of weeks of pre-clerkship exposure (p = 0.01; R(2) = 0.36) but not from the number of clerkship weeks (p = 0.74). CONCLUSIONS: This study indicates that the duration of pre-clerkship exposure to psychiatry predicts the number of students selecting psychiatry as their first choice as a discipline. Thus, increasing the duration of pre-clerkship exposure may increase the enrollment of medical students into psychiatry.


Asunto(s)
Selección de Profesión , Prácticas Clínicas/estadística & datos numéricos , Curriculum/estadística & datos numéricos , Internado y Residencia/estadística & datos numéricos , Psiquiatría/estadística & datos numéricos , Adulto , Canadá , Femenino , Humanos , Masculino , Psiquiatría/educación , Adulto Joven
10.
Antimicrob Agents Chemother ; 58(2): 936-49, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24277043

RESUMEN

Whole-genome sequencing of a collection of 103 Acinetobacter strains belonging to 22 validly named species and another 16 putative species allowed detection of genes for 50 new class D ß-lactamases and 65 new Acinetobacter-derived cephalosporinases (ADC). All oxacillinases (OXA) contained the three typical motifs of class D ß-lactamases, STFK, (F/Y)GN, and K(S/T)G. The phylogenetic tree drawn from the OXA sequences led to an increase in the number of OXA groups from 7 to 18. The topologies of the OXA and RpoB phylogenetic trees were similar, supporting the ancient acquisition of blaOXA genes by Acinetobacter species. The class D ß-lactamase genes appeared to be intrinsic to several species, such as Acinetobacter baumannii, Acinetobacter pittii, Acinetobacter calcoaceticus, and Acinetobacter lwoffii. Neither blaOXA-40/143- nor blaOXA-58-like genes were detected, and their origin remains therefore unknown. The phylogenetic tree analysis based on the alignment of the sequences deduced from blaADC revealed five main clusters, one containing ADC belonging to species closely related to A. baumannii and the others composed of cephalosporinases from the remaining species. No indication of blaOXA or blaADC transfer was observed between distantly related species, except for blaOXA-279, possibly transferred from Acinetobacter genomic species 6 to Acinetobacter parvus. Analysis of ß-lactam susceptibility of seven strains harboring new oxacillinases and cloning of the corresponding genes in Escherichia coli and in a susceptible A. baumannii strain indicated very weak hydrolysis of carbapenems. Overall, this study reveals a large pool of ß-lactamases in different Acinetobacter spp., potentially transferable to pathogenic strains of the genus.


Asunto(s)
Acinetobacter/genética , Cefalosporinasa/clasificación , Cefalosporinasa/genética , Filogenia , Acinetobacter/clasificación , Acinetobacter/efectos de los fármacos , Acinetobacter/enzimología , Secuencias de Aminoácidos , Antibacterianos/metabolismo , Antibacterianos/farmacología , Cefalosporinasa/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Datos de Secuencia Molecular , Plásmidos , Proteínas Recombinantes/clasificación , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , beta-Lactamas/metabolismo , beta-Lactamas/farmacología
11.
Acad Psychiatry ; 38(3): 350-3, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24664612

RESUMEN

OBJECTIVES: There is a lack of information regarding interventions for undergraduate students at Canadian medical schools who require remediation during their psychiatric training. The need for a theoretical framework to guide remediation has been identified. In this study, we sought to characterize remediation taking place in undergraduate psychiatry education, particularly during clerkship. A secondary goal was to ascertain whether those responsible for remediation were aware of the stages of change (transtheoretical) model, and whether they formally incorporated this framework (or another) into their remediation processes. METHODS: A short six-question survey on remediation practices was e-mailed to educators responsible for undergraduate psychiatry education at all 17 Canadian medical schools as identified through the Canadian Organization of Undergraduate Psychiatry Educators (COUPE). RESULTS: The response rate was 67 %. Respondents' overall impressions of their school's remediation process were that it was "highly effective" (25 %), or "somewhat effective" (67 %); 8 % reported being unsure of its effectiveness. While 75 % of survey respondents were aware of the stages of change model, only 17 % reported using this framework: no alternate theoretical frameworks were reported. CONCLUSIONS: The most common form of evaluation was multiple-choice question (MCQ) exams, and the most common form of remediation was exam rewrites. There is little information regarding the long-term outcomes of remediation, and further research would be useful in formulating recommendations regarding best practices.


Asunto(s)
Prácticas Clínicas/organización & administración , Psiquiatría/educación , Educación Compensatoria/organización & administración , Canadá , Prácticas Clínicas/métodos , Recolección de Datos , Evaluación Educacional/métodos , Humanos , Educación Compensatoria/métodos , Facultades de Medicina/organización & administración
12.
J Transl Med ; 11: 218, 2013 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-24047116

RESUMEN

BACKGROUND: Targeted therapies directed at commonly overexpressed pathways in melanoma have clinical activity in numerous trials. Little is known about how these therapies influence microRNA (miRNA) expression, particularly with combination regimens. Knowledge of miRNAs altered with treatment may contribute to understanding mechanisms of therapeutic effects, as well as mechanisms of tumor escape from therapy. We analyzed miRNA expression in metastatic melanoma tissue samples treated with a novel combination regimen of Temsirolimus and Bevacizumab. Given the preliminary clinical activity observed with this combination regimen, we hypothesized that we would see significant changes in miRNA expression with combination treatment. METHODS: Using microarray analysis we analyzed miRNA expression levels in melanoma samples from a Cancer Therapy Evaluation Program-sponsored phase II trial of combination Temsirolimus and Bevacizumab in advanced melanoma, which elicited clinical benefit in a subset of patients. Pre-treatment and post-treatment miRNA levels were compared using paired t-tests between sample groups (patients), using a p-value < 0.01 for significance. RESULTS: microRNA expression remained unchanged with Temsirolimus alone; however, expression of 15 microRNAs was significantly upregulated (1.4 to 2.5-fold) with combination treatment, compared to pre-treatment levels. Interestingly, twelve of these fifteen miRNAs possess tumor suppressor capabilities. We identified 15 putative oncogenes as potential targets of the 12 tumor suppressor miRNAs, based on published experimental evidence. For 15 of 25 miRNA-target mRNA pairings, changes in gene expression from pre-treatment to post-combination treatment samples were inversely correlated with changes in miRNA expression, supporting a functional effect of those miRNA changes. Clustering analyses based on selected miRNAs suggest preliminary signatures characteristic of clinical response to combination treatment and of tumor BRAF mutational status. CONCLUSIONS: To our knowledge, this is the first study analyzing miRNA expression in pre-treatment and post-treatment human metastatic melanoma tissue samples. This preliminary investigation suggests miRNAs that may be involved in the mechanism of action of combination Temsirolimus and Bevacizumab in metastatic melanoma, possibly through inhibition of oncogenic pathways, and provides the preliminary basis for further functional studies of these miRNAs.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Melanoma/tratamiento farmacológico , Melanoma/genética , MicroARNs/genética , Terapia Molecular Dirigida , Sirolimus/análogos & derivados , Anticuerpos Monoclonales Humanizados/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab , Línea Celular Tumoral , Análisis por Conglomerados , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Melanoma/patología , MicroARNs/metabolismo , Proyectos Piloto , Proteínas Proto-Oncogénicas B-raf/genética , Reproducibilidad de los Resultados , Sirolimus/farmacología , Sirolimus/uso terapéutico
13.
Conserv Physiol ; 11(1): coad006, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36911047

RESUMEN

Parasitism is an energetically costly event for host species. Dynamic energy budget (DEB) theory describes the metabolic dynamics of an individual organism through its lifetime. Models derived from DEB theory specify how an organism converts food to reserves (maintenance-free energy available for metabolism) and allocates mobilized reserves to maintenance, growth (increase of structural body mass) and maturation or reproduction. DEB models thus provide a useful approach to describe the consequences of parasitism for host species. We developed a DEB model for siscowet lake trout and modeled the impact of sea lamprey parasitism on growth and reproduction using data collected from studies documenting the long-term effects following a non-lethal sea lamprey attack. The model was parameterized to reflect the changes in allocation of energy towards growth and reproduction observed in lake trout following sea lamprey parasitism and includes an estradiol module that describes the conversion of reproductive reserves to ovarian mass based on estradiol concentration. In our DEB model, parasitism increased somatic and maturity maintenance costs, reduced estradiol and decreased the estradiol-mediated conversion efficiency of reproductive reserves to ovarian mass. Muscle lipid composition of lake trout influenced energy mobilization from the reserve (efficiency of converting reserves allocated to reproduction into eggs) and reproductive efficiency. These model changes accurately reflect observed empirical changes to ovarian mass and growth. This model provides a plausible explanation of the energetic mechanisms that lead to skipped spawning following sea lamprey parasitism and could be used in population models to explore sublethal impacts of sea lamprey parasitism and other stressors on population dynamics.

14.
Integr Comp Biol ; 62(1): 104-120, 2022 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-35026028

RESUMEN

The energetic demands of stressors like parasitism require hosts to reallocate energy away from normal physiological processes to survive. Life history theory provides predictions about how hosts will reallocate energy following parasitism, but few studies provide empirical evidence to test these predictions. We examined the sub-lethal effects of sea lamprey parasitism on lean and siscowet lake charr, two ecomorphs with different life history strategies. Leans are shorter lived, faster growing, and reach reproductive maturity earlier than siscowets. Following a parasitism event of 4 days, we assessed changes to energy allocation by monitoring endpoints related to reproduction, energy storage, and growth. Results indicate that lean and siscowet lake charr differ considerably in their response to parasitism. Severely parasitized leans slightly increased their reproductive effort and maintained growth and energy storage, consistent with expectations based on life history that leans are less likely to survive parasitism and have shorter lifespans than siscowets making investing in immediate reproduction more adaptive. Siscowets nearly ceased reproduction following severe parasitism and showed evidence of altered energy storage, consistent with a strategy that favors maximizing long-term reproductive success. These findings suggest that life history can be used to generalize stressor response between populations and can aid management efforts.


Asunto(s)
Petromyzon , Trucha , Animales , Lagos , Reproducción/fisiología , Simbiosis
15.
Integr Comp Biol ; 61(6): 1991-2010, 2022 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-34021749

RESUMEN

Many biological systems across scales of size and complexity exhibit a time-varying complex network structure that emerges and self-organizes as a result of interactions with the environment. Network interactions optimize some intrinsic cost functions that are unknown and involve for example energy efficiency, robustness, resilience, and frailty. A wide range of networks exist in biology, from gene regulatory networks important for organismal development, protein interaction networks that govern physiology and metabolism, and neural networks that store and convey information to networks of microbes that form microbiomes within hosts, animal contact networks that underlie social systems, and networks of populations on the landscape connected by migration. Increasing availability of extensive (big) data is amplifying our ability to quantify biological networks. Similarly, theoretical methods that describe network structure and dynamics are being developed. Beyond static networks representing snapshots of biological systems, collections of longitudinal data series can help either at defining and characterizing network dynamics over time or analyzing the dynamics constrained to networked architectures. Moreover, due to interactions with the environment and other biological systems, a biological network may not be fully observable. Also, subnetworks may emerge and disappear as a result of the need for the biological system to cope with for example invaders or new information flows. The confluence of these developments renders tractable the question of how the structure of biological networks predicts and controls network dynamics. In particular, there may be structural features that result in homeostatic networks with specific higher-order statistics (e.g., multifractal spectrum), which maintain stability over time through robustness and/or resilience to perturbation. Alternative, plastic networks may respond to perturbation by (adaptive to catastrophic) shifts in structure. Here, we explore the opportunity for discovering universal laws connecting the structure of biological networks with their function, positioning them on the spectrum of time-evolving network structure, that is, dynamics of networks, from highly stable to exquisitely sensitive to perturbation. If such general laws exist, they could transform our ability to predict the response of biological systems to perturbations-an increasingly urgent priority in the face of anthropogenic changes to the environment that affect life across the gamut of organizational scales.


Asunto(s)
Algoritmos , Animales , Homeostasis
16.
Artículo en Inglés | MEDLINE | ID: mdl-36325881

RESUMEN

Problem formulation (PF) is a critical initial step in planning risk assessments for chemical exposures to wildlife, used either explicitly or implicitly in various jurisdictions to include registration of new pesticides, evaluation of new and existing chemicals released to the environment, and characterization of impact when chemical releases have occurred. Despite improvements in our understanding of the environment, ecology, and biological sciences, few risk assessments have used this information to enhance their value and predictive capabilities. In addition to advances in organism-level mechanisms and methods, there have been substantive developments that focus on population- and systems-level processes. Although most of the advances have been recognized as being state-of-the-science for two decades or more, there is scant evidence that they have been incorporated into wildlife risk assessment or risk assessment in general. In this article, we identify opportunities to consider elevating the relevance of wildlife risk assessments by focusing on elements of the PF stage of risk assessment, especially in the construction of conceptual models and selection of assessment endpoints that target population- and system-level endpoints. Doing so will remain consistent with four established steps of existing guidance: (1) establish clear protection goals early in the process; (2) consider how data collection using new methods will affect decisions, given all possibilities, and develop a decision plan a priori; (3) engage all relevant stakeholders in creating a robust, holistic conceptual model that incorporates plausible stressors that could affect the targets defined in the protection goals; and (4) embrace the need for iteration throughout the PF steps (recognizing that multiple passes may be required before agreeing on a feasible plan for the rest of the risk assessment). Integr Environ Assess Manag 2022;00:1-16. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

17.
Int J Cancer ; 129(12): 2807-15, 2011 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-21544800

RESUMEN

Vascular endothelial growth factor (VEGF) is an angiogenic factor that also functions as an autocrine growth factor for VEGF receptor (VEGFR)-2(+) melanomas. In multiple studies, VEGFR-2 was detected by immunostaining in 78-89% of human melanoma cells, suggesting that most patients with melanoma would benefit from anti-VEGF therapy. Here, we evaluated 167 human melanoma specimens in a tissue microarray to verify the presence of VEGFR-2, but found disparities in staining with commercial antibodies A-3 and 55B11. Antibody A-3 stained melanoma cells in 79% of specimens, consistent with published results; however, we noted extensive nonspecific staining of other cells such as smooth muscle and histiocytes. In contrast, antibody 55B11 stained melanoma cells in only 7% (95% confidence interval: 3.3-11.5) of specimens. As an internal positive control for VEGFR-2 detection, vascular endothelial cells were stained with antibody 55B11 in all specimens. We compared VEGFR-2(+) and VEGFR-2(-) melanoma cell lines by immunoblotting and immunohistochemistry after small interfering RNA (siRNA) knockdown and transient overexpression of VEGFR-2 to validate antibody specificity. Immunoblotting revealed that A-3 primarily cross-reacted with several proteins in both cell lines and these were unaffected by siRNA knockdown of VEGFR-2. In contrast, 55B11 staining of VEGFR-2(+) cells was mostly eliminated by siRNA knockdown of VEGFR-2 and increased in VEGFR-2(-) melanoma cell lines following transfection to express ectopic VEGFR-2. Our results show that relatively few melanoma cells (<10%) express detectable levels of VEGFR-2, and therefore, the majority of patients with melanoma are unlikely to benefit from antiproliferative effects of anti-VEGF therapy.


Asunto(s)
Melanoma/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Anticuerpos/farmacología , Línea Celular Tumoral , Humanos , Immunoblotting , Inmunohistoquímica , Melanoma/patología , Metástasis de la Neoplasia , Análisis de Matrices Tisulares , Receptor 2 de Factores de Crecimiento Endotelial Vascular/inmunología
18.
Mol Ecol ; 19 Suppl 1: 176-96, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20331779

RESUMEN

In Lake Superior there are three principal forms of lake trout (Salvelinus namaycush): lean, siscowet and humper. Wild lean and siscowet differ in the shape and relative size of the head, size of the fins, location and size of the eyes, caudal peduncle shape and lipid content of the musculature. To investigate the basis for these phenotypic differences, lean and siscowet lake trout, derived from gametes of wild populations in Lake Superior, were reared communally under identical environmental conditions for 2.5 years. Fish were analysed for growth, morphometry and lipid content, and differences in liver transcriptomics were investigated using Roche 454 GS-FLX pyrosequencing. The results demonstrate that key phenotypic differences between wild lean and siscowet lake trout such as condition factor, morphometry and lipid levels, persist in these two forms when reared in the laboratory under identical environmental conditions. This strongly suggests that these differences are genetic and not a result of environmental plasticity. Transcriptomic analysis involving the comparison of hepatic gene frequencies (RNA-seq) and expression (quantitative reverse transcription-polymerase chain reaction (qPCR)) between the two lake trout forms, indicated two primary gene groups that were differentially expressed; those involving lipid synthesis, metabolism and transport (acyl-CoA desaturase, acyl-CoA binding protein, peroxisome proliferator-activated receptor gamma, and apolipoproteins), and those involved with immunity (complement component C3, proteasome, FK506 binding protein 5 and C1q proteins). The results demonstrate that RNA-seq can be used to identify differentially expressed genes; however, some discrepancies between RNA-seq analysis and qPCR indicate that methods for deep sequencing may need to be refined and/or different RNA-seq platforms utilized.


Asunto(s)
Perfilación de la Expresión Génica , Fenotipo , Trucha/genética , Animales , Ambiente , Frecuencia de los Genes , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Trucha/anatomía & histología , Trucha/crecimiento & desarrollo
19.
Ecology ; 91(7): 2003-12, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20715623

RESUMEN

We used a field experiment, population modeling, and an analysis of 30 years of data from walleye (Sander vitreus; a freshwater fish) in Lake Erie to show that maternal influences on offspring survival can affect population dynamics. We first demonstrate experimentally that the survival of juvenile walleye increases with egg size (and, to a lesser degree, female energy reserves). Because egg size in this species tends to increase with maternal age, we then model these maternal influences on offspring survival as a function of maternal age to show that adult age structure can affect the maximum rate at which a population can produce new adults. Consistent with this hypothesis, we present empirical evidence that the maximum reproductive rate of an exploited population of walleye was approximately twice as high when older females were abundant as compared to when they were relatively scarce. Taken together, these results indicate that age- or size-based maternal influences on offspring survival can be an important mechanism driving population dynamics and that exploited populations could benefit from management strategies that protect, rather than target, reproductively valuable individuals.


Asunto(s)
Agua Dulce , Perciformes/fisiología , Animales , Conservación de los Recursos Naturales , Ecosistema , Femenino , Masculino , Modelos Biológicos , Dinámica Poblacional , Reproducción , Razón de Masculinidad
20.
Environ Toxicol Chem ; 39(10): 1998-2007, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32667689

RESUMEN

Coal ash contains numerous contaminants and is the focus of regulatory actions and risk assessments due to environmental spills. We exposed Daphnia magna to a gradient of coal ash contamination under high and low food rations to assess the sublethal effects of dietary exposures. Whereas exposure to contaminants resulted in significant reductions in growth and reproduction in daphnids, low, environmentally relevant food rations had a much greater effect on these endpoints. Environ Toxicol Chem 2020;39:1998-2007. © 2020 SETAC.


Asunto(s)
Ceniza del Carbón/toxicidad , Daphnia/efectos de los fármacos , Exposición Dietética/efectos adversos , Contaminantes Químicos del Agua/toxicidad , Animales , Bioacumulación/efectos de los fármacos , Ceniza del Carbón/metabolismo , Daphnia/crecimiento & desarrollo , Exposición Dietética/análisis , Modelos Teóricos , Reproducción/efectos de los fármacos , Contaminantes Químicos del Agua/metabolismo
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