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1.
J Exp Biol ; 223(Pt 10)2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32321748

RESUMO

Group-living animals must communicate to stay in contact. In long-finned pilot whales, there is a trade-off between the benefits of foraging individually at depth and the formation of tight social groups at the surface. Using theoretical modelling and empirical data of tagged pairs within a group, we examined the potential of pilot whale social calls to reach dispersed group members during foraging periods. Both theoretical predictions and empirical data of tag pairs showed a potential for communication between diving and non-diving group members over separation distances up to 385 m (empirical) and 1800 m (theoretical). These distances match or exceed pilot whale dive depths recorded across populations. Call characteristics and environmental characteristics were analysed to investigate determinants of call detectability. Longer calls with a higher sound pressure level (SPL) that were received in a quieter environment were more often detected than their shorter, lower SPL counterparts within a noisier environment. In a noisier environment, calls were louder and had a lower peak frequency, indicating mechanisms for coping with varying conditions. However, the vulnerability of pilot whales to anthropogenic noise is still of concern as the ability to cope with increasing background noise may be limited. Our study shows that combining propagation modelling and actual tag recordings provides new insights into the communicative potential for social calls in orientation and reunion with group members for deep-diving pilot whales.


Assuntos
Baleia Comum , Baleias Piloto , Animais , Vocalização Animal
2.
Biochem Biophys Res Commun ; 496(3): 858-864, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29374508

RESUMO

A key challenge in the development of novel chemotherapeutics is the design of molecules capable of selective toxicity to cancer cells. Antibodies have greater target specificity compared to small molecule drugs, but most are unable to penetrate cells, and predominantly target extracellular antigens. A nuclear-penetrating anti-DNA autoantibody isolated from the MRL/lpr lupus mouse model, 3E10, preferentially localizes to tumors, inhibits DNA repair, and selectively kills cancer cells with defects in DNA repair. A murine divalent single chain variable fragment of 3E10 with mutations for improved DNA binding affinity, 3E10 (D31N) di-scFv, has previously been produced in P. pastoris and yielded promising pre-clinical findings, but is unsuitable for clinical testing. The present study reports the design, expression and testing of a panel of humanized 3E10 (D31N) di-scFvs, some of which contain CDR substitution. These variants were expressed in a modified CHO system and evaluated for their physicochemical attributes and ability to penetrate nuclei to selectively cause DNA damage accumulation in and kill cancer cells with DNA repair defects. Secondary structure was conserved and most variants retained the key characteristics of the murine 3E10 (D31N) di-scFv produced in P. pastoris. Moreover, several variants with CDR substitutions outperformed the murine prototype. In conclusion, we have designed several humanized variants of 3E10 (D31N) di-scFv that have potential for application as monotherapy or conjugates for targeted nuclear drug delivery.


Assuntos
Anticorpos Antinucleares/genética , Anticorpos Antinucleares/imunologia , Autoanticorpos/genética , Autoanticorpos/imunologia , DNA/genética , DNA/imunologia , Engenharia de Proteínas/métodos , Animais , Anticorpos Antinucleares/uso terapêutico , Autoanticorpos/uso terapêutico , Dano ao DNA/imunologia , Camundongos
3.
Anal Chem ; 88(5): 2614-21, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26823002

RESUMO

Electrospray ionization-mass spectrometry (ESI-MS) was tested for its use in monitoring spent nuclear fuel (SNF) constituents including U, Pu, dibutyl phosphate (DBP), and tributyl phosphate (TBP). Both positive and negative ion modes were used to evaluate the speciation of U and Pu with TBP and DBP. Furthermore, apparent stability constants were determined for U complexed to TBP and DBP. In positive ion mode, TBP produced a strong signal with and without complexation to U or Pu, but, in negative ion mode, no TBP, U-TBP, or Pu-TBP complexes were observed. Apparent stability constants were determined for [UO2(NO3)2(TBP)2], [UO2(NO3)2(H2O)(TBP)2], and [UO2(NO3)2(TBP)3]. In contrast DBP, U-DBP, and Pu-DBP complexes were observed in both positive and negative ion modes. Apparent stability constants were determined for the species [UO2(DBP)], [UO2(DBP)3], and [UO2(DBP)4]. Analyzing mixtures of U or Pu with TBP and DBP yielded the formation of ternary complexes whose stoichiometry was directly related to the ratio of TBP to DBP. The ESI-MS protocols used in this study will further demonstrate the utility of ESI-MS and its applicability to process control monitoring in SNF reprocessing facilities.

5.
Avian Dis ; 59(4): 548-53, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26629631

RESUMO

Single swabs (cultured individually) are currently used in the Food and Drug Administration (FDA) official method for sampling the environment of commercial laying hens for the detection of Salmonella enterica ssp. serovar Enteritidis (Salmonella Enteritidis). The FDA has also granted provisional acceptance of the National Poultry Improvement Plan's (NPIP) Salmonella isolation and identification methodology for samples taken from table-egg layer flock environments. The NPIP method, as with the FDA method, requires single-swab culturing for the environmental sampling of laying houses for Salmonella Enteritidis. The FDA culture protocol requires a multistep culture enrichment broth, and it is more labor intensive than the NPIP culture protocol, which requires a single enrichment broth. The main objective of this study was to compare the FDA single-swab culturing protocol with that of the NPIP culturing protocol but using a four-swab pool scheme. Single and multi-laboratory testing of replicate manure drag swab sets (n  =  525 and 672, respectively) collected from a Salmonella Enteritidis-free commercial poultry flock was performed by artificially contaminating swabs with either Salmonella Enteritidis phage type 4, 8, or 13a at one of two inoculation levels: low, x¯  = 2.5 CFU (range 2.5-2.7), or medium, x¯  = 10.0 CFU (range 7.5-12). For each replicate, a single swab (inoculated), sets of two swabs (one inoculated and one uninoculated), and sets of four swabs (one inoculated and three uninoculated), testing was conducted using the FDA or NPIP culture method. For swabs inoculated with phage type 8, the NPIP method was more efficient (P < 0.05) for all swab sets at both inoculation levels than the reference method. The single swabs in the NPIP method were significantly (P < 0.05) better than four-pool swabs in detecting Salmonella Enteritidis at the lower inoculation level. In the collaborative study (n  =  13 labs) using Salmonella Enteritidis phage type 13a inoculated swabs, there was no significant difference (P > 0.05) between the FDA method (single swabs) and the pooled NPIP method (four-pool swabs). The study concludes that the pooled NPIP method is not significantly different from the FDA method for the detection of Salmonella Enteritidis in drag swabs in commercial poultry laying houses. Consequently based on the FDA's Salmonella Enteritidis rule for equivalency of different methods, the pooled NPIP method should be considered equivalent. Furthermore, the pooled NPIP method was more efficient and cost effective.


Assuntos
Criação de Animais Domésticos/métodos , Técnicas Bacteriológicas/veterinária , Galinhas , Doenças das Aves Domésticas/diagnóstico , Salmonelose Animal/diagnóstico , Salmonella enteritidis/isolamento & purificação , Manejo de Espécimes/veterinária , Animais , Técnicas Bacteriológicas/instrumentação , Esterco/microbiologia , Doenças das Aves Domésticas/microbiologia , Salmonelose Animal/microbiologia , Sensibilidade e Especificidade , Manejo de Espécimes/instrumentação
6.
Anal Chem ; 86(2): 1023-9, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24350789

RESUMO

Electrospray ionization-mass spectrometry (ESI-MS) shows great promise as a rapid method to identify metal-ligand complexes in solution. However, its application for quantitative determination of the distribution of species present in complicated equilibria is still in its infancy, and a direct correlation between ions observed in the gas phase and species expected in solution must be made with caution. The present work focuses on a seemingly simple system; the complexation of lanthanide cations with the acetate ligand. Using a high resolution quadrupole time-of-flight mass spectrometer, ions created by electrospray of solutions containing trivalent neodymium and acetate were identified. The gas phase distribution of species was compared to the solution phase speciation predicted using thermodynamic complexation constants. Apparent gas phase speciation diagrams were constructed as a function of solution conditions and fragmentation potential. Despite the expected variability of metal-ligand complexes as solution conditions change, the observed gas phase speciation was independent of the metal to ligand ratio but dependent on the operating conditions of the ESI-MS.

7.
Food Chem Toxicol ; 191: 114878, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067742

RESUMO

Renoliths were removed at necropsy from dogs that had died from acute kidney injury in Asia in 2004 and submitted to our laboratories for analysis including elemental composition, mass spectrometry, and nuclear magnetic resonance spectroscopy. The presence of a mixed s-triazine matrix comprising melamine, cyanuric acid, and ammelide, but no detectable ammeline, was found in the stone samples we analyzed. The unusual and unique green coloration of these stones was determined to be due to the presence of biliverdin. The occurrence of these green stones distinguished the 2004 incident from another incident in 2007 in the USA and other reported cases. The presence of crystals was reported in renal tubules and collecting ducts in both outbreaks, but no stones were reported in the 2007 incident. This difference suggested a variation in the disease process caused by mixed s-triazine ingestion. Careful monitoring of food additives is warranted to prevent future problems in animals and humans.


Assuntos
Ração Animal , Surtos de Doenças , Doenças do Cão , Contaminação de Alimentos , Cálculos Renais , Triazinas , Animais , Triazinas/análise , Triazinas/toxicidade , Cães , Contaminação de Alimentos/análise , Surtos de Doenças/veterinária , Doenças do Cão/epidemiologia , Ração Animal/análise , Cálculos Renais/epidemiologia , Cálculos Renais/química , Insuficiência Renal/epidemiologia
8.
ACS Cent Sci ; 10(8): 1562-1572, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39220699

RESUMO

Some antinuclear antibodies (ANAs) bind extracellular nucleic acids released into tumor environments and are pulled into the nuclei of live cancer cells through nucleoside salvage pathways, independent of tumor-specific surface antigens. Here we show that ANA nuclear penetration induces nuclear flux by the lysosomal protease cathepsin B and leverage this mechanism to design an antinuclear antibody-drug conjugate (ANADC) with cathepsin B-labile drug linker. The ANADC targets nucleic acid exhaust from necrotic tumors and crosses membrane barriers through nucleoside salvage as a DNA-seeking and tumor agnostic "antinuclear missile" cancer therapy.

9.
Nat Commun ; 15(1): 258, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225272

RESUMO

There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer's disease. The role of amyloid beta 42 (Aß42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aß42, which is increased from adipose tissue of male mice with obesity and is associated with higher plasma Aß42. Increasing circulating Aß42 levels in male mice without obesity has no effect on systemic glucose homeostasis but has obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. The closely related Aß40 isoform does not have these same effects on the heart. Administration of an Aß-neutralising antibody prevents obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aß-neutralising antibody administration in established obesity prevents further deterioration of cardiac function. Multi-contrast transcriptomic analyses reveal that Aß42 impacts pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aß42 inhibits mitochondrial complex I. These data reveal a role for systemic Aß42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer's disease could be effective in combating obesity-induced heart failure.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Masculino , Camundongos , Animais , Peptídeos beta-Amiloides , Diabetes Mellitus Tipo 2/complicações , Anticorpos Neutralizantes , Obesidade/complicações , Glucose , Fragmentos de Peptídeos
10.
Immunohorizons ; 6(6): 356-365, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697479

RESUMO

Nuclear-penetrating anti-DNA autoantibodies have therapeutic potential as delivery agents and in targeting DNA and the DNA damage response (DDR). Derivatives of such Abs have advanced to human testing in genetic disease and are in preparation for oncology clinical trials. DNA release associated with neutrophil extracellular traps (NETs) contributes to immunity, inflammation, and the pathophysiology of multiple diseases. The DDR contributes to mechanisms of NETosis, and we hypothesize that anti-DNA autoantibodies that localize into live cell nuclei and inhibit DNA repair will suppress release of NETs by activated neutrophils. In the current study we evaluated the impact of a nuclear-penetrating anti-DNA autoantibody that interferes with the DDR on decondensation and release of DNA and NETs by activated human granulocyte-like differentiated PLB-985 cells and neutrophils isolated from C57BL/6 mice. The response of cells pretreated with control or autoantibody to subsequent stimulators of NETosis, including PMA and the calcium ionophore ionomycin, was evaluated by DAPI and SYTOX Green stains, measurement of DNA release, analysis of histone citrullination by Western blot, or visualization of NETs by immunostaining and confocal fluorescence microscopy. Autoantibody treatment of the cells yielded significant inhibition of NADPH oxidase-dependent and independent NETosis. These findings establish the concept of nuclear-penetrating anti-DNA autoantibodies as modulators of neutrophil biology with potential for use in strategies to suppress NETosis.


Assuntos
Armadilhas Extracelulares , Animais , Autoanticorpos , Núcleo Celular , DNA , Camundongos , Camundongos Endogâmicos C57BL
11.
PeerJ ; 9: e10720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614274

RESUMO

Elasmosaurid plesiosaurian remains have been documented from non-marine to paralic (fluvial to estuarine) sediments of the upper Campanian Dinosaur Park Formation (DPF) of southern Alberta since 1898. Despite this long collection history, this material has received relatively little research attention, largely due to the highly fragmentary nature of most recovered specimens. However, this assemblage is significant, as it constitutes a rare occurrence of plesiosaurian remains in a non-marine depositional environment. This study reports on a recently collected and prepared specimen, which represents the most complete elasmosaurid yet collected from the DPF. This specimen preserves the trunk region, the base of the neck and tail, a partial fore and hind limb, and tooth, and is sufficiently complete to be assigned as the holotype of a new genus and species. This new taxon is diagnosed by a distinctive character state combination including a boomerang-shaped clavicular arch with acute anterior process, convex anterolateral margin, deeply embayed posterior margin, and pronounced ventral keel, together with the presence of 22 dorsal vertebrae, and the anterior dorsal centra bearing a ventral notch. The DPF plesiosaurian fossils were recovered from both estuarine/bay and fluvial palaeochannel sediments. The holotype skeleton represents an osteologically mature individual with an estimated body length of around 5 m, although the largest referred DPF elasmosaurid might have been closer to 7 m, which is considerably larger than other plesiosaurians reported from non-marine deposits. This suggests small-body lengths relative to typical elasmosaurids from marine settings, but is consistent with other plesiosaurians recovered from non-marine sediments. The identification of a distinct elasmosaurid taxon in the DPF might be evidence of niche-partitioning among the predominantly oceanic members of the ubiquitous plesiosaurian clade.

12.
JCI Insight ; 6(14)2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34128837

RESUMO

The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response. We found that DX1 penetrated brain endothelial cells and crossed the BBB, and mechanistic studies identify ENT2 as the key transporter. In efficacy studies, DX1 crosses the BBB to suppress orthotopic glioblastoma and breast cancer brain metastases. ENT2-linked transport of autoantibodies across the BBB has potential to be exploited in brain tumor immunotherapy, and its discovery raises hypotheses on actionable mechanisms of CNS penetration by neurotoxic autoantibodies in CNS lupus.


Assuntos
Anticorpos Antinucleares/farmacologia , Autoanticorpos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Transportador Equilibrativo 2 de Nucleosídeo/metabolismo , Glioblastoma/tratamento farmacológico , Animais , Anticorpos Antinucleares/uso terapêutico , Autoanticorpos/uso terapêutico , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/patologia , Células CHO , Linhagem Celular , Cricetulus , Células Endoteliais , Transportador Equilibrativo 2 de Nucleosídeo/genética , Técnicas de Silenciamento de Genes , Glioblastoma/patologia , Humanos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Mutat Res ; 695(1-2): 2-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19800024

RESUMO

Arsenic is a human carcinogen, and only recently animal models have been developed that are useful in investigating its carcinogenic mode of action (MOA). However, how arsenic induces cancer is still an open question. In a previous paper, we proposed a model detailing how arsenic might induce DNA lesions leading to cytogenetic damage [A.D. Kligerman, A.H. Tennant, Toxicol. Appl. Pharmacol. 222 (2007) 281-288]. In this model we hypothesized that arsenic does not induce chromosome damage via DNA adduction but induces short-lasting lesions from the action of reactive oxygen species (ROS). These lesions cause single-strand breaks (SSB) that induce chromosome breakage when treatment is in late G(1)- or S-phase. However, if treatment is confined to the G(0)- or early G(1)-phase of the cell cycle, it is predicted that little or no cytogenetic damage will result at the subsequent metaphase. Here, we describe the results from testing this model using monomethylarsonous acid (MMA(III)) and cytosine arabinoside (araC), a DNA chain terminator, to extend the time that DNA lesions remain open during repair to allow the lesions to reach S-phase or interact to form DNA exchanges that would lead to exchange aberrations at metaphase. The results of our study only partially confirmed our hypothesis. Instead, the results indicated that the lesions induced by MMA(III) are quickly repaired through base excision repair, that there is little chance for araC to extend the life of the lesions, and thus the DNA damage induced by arsenicals that leads to chromosome aberrations is very short lived.


Assuntos
Arsênio/toxicidade , Quebra Cromossômica/efeitos dos fármacos , Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Animais , Antimetabólitos Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Citarabina/farmacologia , Reparo do DNA/genética , Feminino , Masculino , Metanossulfonato de Metila/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Baço/citologia , Baço/efeitos dos fármacos
14.
PeerJ ; 6: e5194, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30002987

RESUMO

Chasmosaurine ceratopsids are well documented from the Upper Cretaceous (Campanian) Dinosaur Park Formation (DPF) of southern Alberta and Saskatchewan, and include Chasmosaurus belli, Chasmosaurus russelli, Mercuriceratops gemini, Vagaceratops irvinensis, and material possibly referable to Spiclypeus shipporum. In this study, we describe three recently prepared chasmosaurine skulls (CMN 8802, CMN 34829, and TMP 2011.053.0046) from the DPF, and age-equivalent sediments, of Alberta. CMN 8802 and CMN 34829 are both referred to Chasmosaurus sp. based on the size and shape of the preserved parietal fenestrae. TMP 2011.053.0046 is referred to Vagaceratops sp. based on the position and orientation of its preserved epiparietals. Each skull is characterized by the presence of an accessory fenestra in either the squamosal (CMN 8802 and TMP 2011.053.0046) or parietal (CMN 34829). Such fenestrae are common occurrences in chasmosaurine squamosals, but are rare in the parietal portion of the frill. The origin of the fenestrae in these three specimens is unknown, but they do not appear to exhibit evidence of pathology, as has been previously interpreted for the accessory fenestrae in most other chasmosaurine frills. These three skulls contribute to a better understanding of the morphological variation, and geographic and stratigraphic distribution, of chasmosaurines within the DPF and age-equivalent sediments in Western Canada.

15.
Toxicology ; 237(1-3): 145-157, 2007 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-17590257

RESUMO

Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of metabolism and of environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. However, because these same chemicals can result from metabolism or by biodegradation, monitoring total urinary metabolite levels may be reflective of not only an individual's contact with the parent pesticide, but also exposure with the metabolites, which are present in the environment. The objective of the current study was to compare the pharmacokinetics of orally administered DEP, DETP and TCPy with their kinetics following oral dosing with the parent insecticide CPF in the rat. Groups of rats were orally administered CPF, DEP, TCPy or DETP at doses of 140mumol/kg body weight, and the time-courses of the metabolites were evaluated in blood and urine. Following oral administration, all three metabolites were well absorbed with peak blood concentrations being attained between 1 and 3h post-dosing. In the case of DEP and TCPy virtually all the administered dose was recovered in the urine by 72h post-dosing, suggesting negligible, if any, metabolism; whereas with DETP, approximately 50% of the orally administered dose was recovered in the urine. The CPF oral dose was likewise rapidly absorbed and metabolized to DEP, TCPy and DETP, with the distribution of metabolites in the urine followed the order: TCPy (22+/-3mumol)>DETP (14+/-2mumol)>DEP (1.4+/-0.7mumol). Based upon the total amount of TCPy detected in the urine a minimum of 63% of the oral CPF dose was absorbed. These studies support the hypotheses that DEP, DETP and TCPy present in the environment can be readily absorbed and eliminated in the urine of rats and potentially humans.


Assuntos
Clorpirifos/farmacocinética , Inseticidas/farmacocinética , Organofosfatos/metabolismo , Fosfatos/metabolismo , Piridonas/metabolismo , Administração Oral , Animais , Biotransformação , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Organofosfatos/sangue , Organofosfatos/farmacocinética , Organofosfatos/urina , Fosfatos/sangue , Fosfatos/farmacocinética , Fosfatos/urina , Piridonas/sangue , Piridonas/farmacocinética , Piridonas/urina , Ratos , Ratos Sprague-Dawley
16.
PLoS One ; 11(1): e0145805, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26726769

RESUMO

BACKGROUND: The chasmosaurine ceratopsid Chasmosaurus is known from the Upper Cretaceous (Campanian) Dinosaur Park Formation of southern Alberta and Saskatchewan. Two valid species, Chasmosaurus belli and C. russelli, have been diagnosed by differences in cranial ornamentation. Their validity has been supported, in part, by the reported stratigraphic segregation of chasmosaurines in the Dinosaur Park Formation, with C. belli and C. russelli occurring in discrete, successive zones within the formation. RESULTS/CONCLUSIONS: An analysis of every potentially taxonomically informative chasmosaurine specimen from the Dinosaur Park Formation indicates that C. belli and C. russelli have indistinguishable ontogenetic histories and overlapping stratigraphic intervals. Neither taxon exhibits autapomorphies, nor a unique set of apomorphies, but they can be separated and diagnosed by a single phylogenetically informative character-the embayment angle formed by the posterior parietal bars relative to the parietal midline. Although relatively deeply embayed specimens (C. russelli) generally have relatively longer postorbital horncores than specimens with more shallow embayments (C. belli), neither this horncore character nor epiparietal morphology can be used to consistently distinguish every specimen of C. belli from C. russelli. STATUS OF KOSMOCERATOPS IN THE DINOSAUR PARK FORMATION: Kosmoceratops is purportedly represented in the Dinosaur Park Formation by a specimen previously referred to Chasmosaurus. The reassignment of this specimen to Kosmoceratops is unsupported here, as it is based on features that are either influenced by taphonomy or within the realm of individual variation for Chasmosaurus. Therefore, we conclude that Kosmoceratops is not present in the Dinosaur Park Formation, but is instead restricted to southern Laramidia, as originally posited.


Assuntos
Dinossauros/classificação , Fósseis , Alberta , Animais , Filogenia , Saskatchewan
17.
Cortex ; 75: 204-219, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26026707

RESUMO

Competitive Scrabble players devote considerable time to studying words and practicing Scrabble-related skills (e.g., anagramming). This training is associated with extraordinary performance in lexical decision, the standard visual word recognition task (Hargreaves, Pexman, Zdrazilova & Sargious, 2012). In the present study we investigated the neural consequences of this lexical expertise. Using both event-related and resting-state fMRI, we compared brain activity and connectivity in 12 competitive Scrabble experts with 12 matched non-expert controls. Results showed that when engaged in the lexical decision task (LDT), Scrabble experts made use of brain regions not generally associated with meaning retrieval in visual word recognition, but rather those associated with working memory and visual perception. The analysis of resting-state data also showed group differences, such that a different network of brain regions was associated with higher levels of Scrabble-related skill in experts than in controls.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiologia , Percepção Visual/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Semântica
18.
J Toxicol Environ Health A ; 67(8-10): 635-50, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15192859

RESUMO

There is a need to develop approaches for assessing risk associated with acute exposures to a broad range of metals and chemical agents and to rapidly determine the potential implications to human health. Noninvasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants, including heavy metals and pesticides. To advance the application of noninvasive biomonitoring a microfluidic/electrochemical device has also been developed for the analysis of lead (Pb), using square-wave anodic stripping voltametry. The system demonstrates a linear response over a broad concentration range (1-2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for noninvasive biomonitoring can provide a sensitive and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these noninvasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for evaluating acute exposure and health risk.


Assuntos
Exposição Ambiental , Monitoramento Ambiental/métodos , Substâncias Perigosas/toxicidade , Inseticidas/toxicidade , Compostos Organometálicos/toxicidade , Compostos Organofosforados , Saliva/química , Animais , Substâncias Perigosas/farmacocinética , Inseticidas/farmacocinética , Compostos Organometálicos/farmacocinética , Ratos , Saliva/metabolismo
19.
Nat Prod Commun ; 9(1): 91-4, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24660472

RESUMO

Licorice root (Glycyrrhiza glabra), an herbal Chinese medicine, has shown medicinal uses in therapeutics and cancer prevention. Dibenzoylmethane (DBM; 1, 3-diphenyl-1, 3-propadinedione), a small beta-diketone, has been reported to be a minor constituent of licorice and a known deregulator of the human prostate cancer cell cycle. Characterization of the phytochemical profiles of licorice root forms including commercially available DBM will advance our search in identifying novel reagents for prostate cancer therapeutics. Gas chromatography- triple quadrupole-mass spectrometric analysis was used for detecting DBM in licorice root extracts. DBM and all licorice forms exhibited a component with a retention time of 14.5 minutes. The major fragment ions detected were at m/z 77, 105, 147, 223 and 224 at the identified retention time by selected reaction monitoring/SRM. These data confirm the presence of DBM from its natural source (G. glabra), and the GC-MS/SRM method helps in the identification of this minor component in a complex biological matrix.


Assuntos
Chalconas/análise , Glycyrrhiza/química , Medicamentos de Ervas Chinesas/química , Cromatografia Gasosa-Espectrometria de Massas , Raízes de Plantas/química
20.
J Clin Exp Neuropsychol ; 35(10): 1071-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24215387

RESUMO

The Balloon Analogue Risk Task (BART) is an experimental measure of risk taking that has commonly been employed to measure the risk taking behavior of nonclinical populations. Previous research has indicated that the task measures a unique aspect of behavioral disinhibition, but there has not as yet been focus upon the possible impact of other aspects of cognitive processing on performance. The current study investigated the cognitive factors related to performance of the BART in an alcohol-using sample. Seventeen individuals with long-term alcohol use were matched for age and education to a group of 17 nonusing participants. The results indicated that the alcohol-using group pumped the balloons on the BART to a lesser extent than did the nonusing group across all trials on the task. The results indicate that the alcohol-using group made less "optimal" decisions on the BART most notably due to neuropsychological impairment in the domains of immediate memory and executive functioning.


Assuntos
Transtornos Relacionados ao Uso de Álcool/complicações , Transtornos Relacionados ao Uso de Álcool/psicologia , Transtornos Cognitivos/etiologia , Tomada de Decisões/fisiologia , Assunção de Riscos , Análise de Variância , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Inventário de Personalidade , Escalas de Graduação Psiquiátrica , Estatística como Assunto , Escalas de Wechsler
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