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1.
Int J Mol Sci ; 24(10)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37239972

RESUMO

Variations in vascular wall shear stress are often presumed to result in the formation of atherosclerotic lesions at specific arterial regions, where continuous laminar flow is disturbed. The influences of altered blood flow dynamics and oscillations on the integrity of endothelial cells and the endothelial layer have been extensively studied in vitro and in vivo. Under pathological conditions, the Arg-Gly-Asp (RGD) motif binding integrin αvß3 has been identified as a relevant target, as it induces endothelial cell activation. Animal models for in vivo imaging of endothelial dysfunction (ED) mainly rely on genetically modified knockout models that develop endothelial damage and atherosclerotic plaques upon hypercholesterolemia (ApoE-/- and LDLR-/-), thereby depicting late-stage pathophysiology. The visualization of early ED, however, remains a challenge. Therefore, a carotid artery cuff model of low and oscillating shear stress was applied in CD-1 wild-type mice, which should be able to show the effects of altered shear stress on a healthy endothelium, thus revealing alterations in early ED. Multispectral optoacoustic tomography (MSOT) was assessed as a non-invasive and highly sensitive imaging technique for the detection of an intravenously injected RGD-mimetic fluorescent probe in a longitudinal (2-12 weeks) study after surgical cuff intervention of the right common carotid artery (RCCA). Images were analyzed concerning the signal distribution upstream and downstream of the implanted cuff, as well as on the contralateral side as a control. Subsequent histological analysis was applied to delineate the distribution of relevant factors within the carotid vessel walls. Analysis revealed a significantly enhanced fluorescent signal intensity in the RCCA upstream of the cuff compared to the contralateral healthy side and the downstream region at all time points post-surgery. The most obvious differences were recorded at 6 and 8 weeks after implantation. Immunohistochemistry revealed a high degree of αv-positivity in this region of the RCCA, but not in the left common carotid artery (LCCA) or downstream of the cuff. In addition, macrophages could be detected by CD68 immunohistochemistry in the RCCA, showing ongoing inflammatory processes. In conclusion, MSOT is capable of delineating alterations in endothelial cell integrity in vivo in the applied model of early ED, where an elevated expression of integrin αvß3 was detected within vascular structures.


Assuntos
Aterosclerose , Células Endoteliais , Animais , Camundongos , Células Endoteliais/metabolismo , Aterosclerose/diagnóstico por imagem , Aterosclerose/metabolismo , Tomografia Computadorizada por Raios X , Oligopeptídeos/metabolismo , Integrinas/metabolismo
2.
Am Nat ; 198(6): 750-758, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34762568

RESUMO

AbstractThe impact of pollinator community diversity on trait matching in plant-pollinator interactions is poorly studied, even though many mutualisms involve multiple interaction partners. We studied 10 communities in which one to three species of oil-collecting Rediviva bees pollinate the long-spurred, oil-producing flowers of Diascia "floribunda" to examine how pollinator diversity affects covariation of functional traits across sites and trait matching within sites. Floral spur length was significantly correlated with weighted grand mean foreleg length of the local bee community but not with foreleg length of individual bee species. The closeness of trait matching varied among populations and was inversely related to pollinator community diversity. For all bee species, trait matching was closest at sites characterized by exclusive pairwise interactions. Reduced trait matching associated with increased community diversity for individual pollinator species but close matching at the community level supports the importance of community context for shaping interacting traits of flowers and pollinators.


Assuntos
Flores , Polinização , Animais , Abelhas , Fenótipo , Simbiose
3.
Mol Pharm ; 17(1): 109-117, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31816245

RESUMO

The endothelin (ET) axis plays a pivotal role in cardiovascular diseases. Enhanced levels of circulating ET-1 have been correlated with an inferior clinical outcome after myocardial infarction (MI) in humans. Thus, the evaluation of endothelin-A receptor (ETAR) expression over time in the course of myocardial injury and healing may offer valuable information toward the understanding of the ET axis involvement in MI. We developed an approach to track the expression of ETAR with a customized molecular imaging probe in a murine model of MI. The small molecular probe based on the ETAR-selective antagonist 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]-2(5H)-furanone (PD156707) was labeled with fluorescent dye, IRDye800cw. Mice undergoing permanent ligation of the left anterior descending artery (LAD) were investigated at day 1, 7, and 21 post surgery after receiving an intravenous injection of the ETAR probe. Cryosections of explanted hearts were analyzed by cryotome-based CCD, and fluorescence reflectance imaging (FRI) and fluorescence signal intensities (SI) were extracted. Fluorescence-mediated tomography (FMT) imaging was performed to visualize probe distribution in the target region in vivo. An enhanced fluorescence signal intensity in the infarct area was detected in cryoCCD images as early as day 1 after surgery and intensified up to 21 days post MI. FRI was capable of detecting significantly enhanced SI in infarcted regions of hearts 7 days after surgery. In vivo imaging by FMT localized enhanced SI in the apex region of infarcted mouse hearts. We verified the localization of the probe and ETAR within the infarct area by immunohistochemistry (IHC). In addition, neovascularized areas were found in the affected myocardium by CD31 staining. Our study demonstrates that the applied fluorescent probe is capable of delineating ETAR expression over time in affected murine myocardium after MI in vivo and ex vivo.


Assuntos
Dioxóis/metabolismo , Antagonistas dos Receptores de Endotelina/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Infarto do Miocárdio/metabolismo , Receptores de Endotelina/metabolismo , Animais , Crioultramicrotomia , Dioxóis/química , Modelos Animais de Doenças , Antagonistas dos Receptores de Endotelina/análise , Antagonistas dos Receptores de Endotelina/química , Feminino , Corantes Fluorescentes/análise , Imuno-Histoquímica , Indóis/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/diagnóstico por imagem , Neovascularização Fisiológica , Imagem Óptica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo
4.
Mol Ecol ; 28(17): 4118-4133, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31232488

RESUMO

Plant-pollinator interactions are often highly specialised, which may be a consequence of co-evolution. Yet when plants and pollinators co-evolve, it is not clear if this will also result in frequent cospeciation. Here, we investigate the mutual evolutionary history of South African oil-collecting Rediviva bees and their Diascia host plants, in which the elongated forelegs of female Rediviva have been suggested to coevolve with the oil-producing spurs of their Diascia hosts. After controlling for phylogenetic nonindependence, we found Rediviva foreleg length to be significantly correlated with Diascia spur length, suggestive of co-evolution. However, as trait correlation could also be due to pollinator shifts, we tested if cospeciation or pollinator shifts have dominated the evolution of Rediviva-Diascia interactions by analysing phylogenies in a cophylogenetic framework. Distance-based cophylogenetic analyses (PARAFIT, PACo) indicated significant congruence of the two phylogenies under most conditions. Yet, we found that phylogenetic relatedness was correlated with ecological similarity (the spectrum of partners that each taxon interacted with) only for Diascia but not for Rediviva, suggesting that phylogenetic congruence might be due to phylogenetic tracking by Diascia of Rediviva rather than strict (reciprocal) co-evolution. Furthermore, event-based reconciliation using a parsimony approach (CORE-PA) on average revealed only 11-13 cospeciation events but 58-80 pollinator shifts. Probabilistic cophylogenetic analyses (COALA) supported this trend (8-29 cospeciations vs. 40 pollinator shifts). Our study suggests that diversification of Diascia has been largely driven by Rediviva (phylogenetic tracking, pollinator shifts) but not vice versa. Moreover, our data suggest that, even in co-evolving mutualisms, cospeciation events might occur only infrequently.


Assuntos
Abelhas/genética , Evolução Biológica , Especiação Genética , Interações Hospedeiro-Parasita/genética , Polinização/fisiologia , Scrophulariaceae/parasitologia , Animais , Filogenia , Característica Quantitativa Herdável
5.
BMC Evol Biol ; 18(1): 196, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30567486

RESUMO

Adaptation to local host plants may impact a pollinator's population genetic structure by reducing gene flow and driving population genetic differentiation, representing an early stage of ecological speciation. South African Rediviva longimanus bees exhibit elongated forelegs, a bizarre adaptation for collecting oil from floral spurs of their Diascia hosts. Furthermore, R. longimanus foreleg length (FLL) differs significantly among populations, which has been hypothesised to result from selection imposed by inter-population variation in Diascia floral spur length. Here, we used a pooled restriction site-associated DNA sequencing (pooled RAD-seq) approach to investigate the population genetic structure of R. longimanus and to test if phenotypic differences in FLL translate into increased genetic differentiation (i) between R. longimanus populations and (ii) between phenotypes across populations. We also inferred the effects of demographic processes on population genetic structure and tested for genetic markers underpinning local adaptation. RESULTS: Populations showed marked genetic differentiation (average FST = 0.165), though differentiation was not statistically associated with differences between populations in FLL. All populations exhibited very low genetic diversity and were inferred to have gone through recent bottleneck events, suggesting extremely low effective population sizes. Genetic differentiation between samples pooled by leg length (short versus long) rather than by population of origin was even higher (FST = 0.260) than between populations, suggesting reduced interbreeding between long and short-legged individuals. Signatures of selection were detected in 1119 (3.8%) of a total of 29,721 SNP markers, CONCLUSIONS: Populations of R. longimanus appear to be small, bottlenecked and isolated. Though we could not detect the effect of local adaptation (FLL in response to floral spurs of host plants) on population genetic differentiation, short and long legged bees appeared to be partially differentiated, suggesting incipient ecological speciation. To test this hypothesis, greater resolution through the use of individual-based whole-genome analyses is now needed to quantify the degree of reproductive isolation between long and short legged bees between and even within populations.


Assuntos
Abelhas/genética , Genética Populacional , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Animais , Marcadores Genéticos , Genoma de Inseto , Geografia , Polimorfismo de Nucleotídeo Único/genética , África do Sul
6.
Am J Pathol ; 187(2): 268-279, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28088288

RESUMO

Staphylococcus aureus causes very serious infections of vascular grafts. Knowledge of the molecular mechanisms of this disease is largely lacking because of the absence of representable models. Therefore, the aim of this study was to set up a mouse model of vascular graft infections that closely mimics the human situation. A catheter was inserted into the right carotid artery of mice, which acted as a vascular graft. Mice were infected i.v. using 8 different S. aureus strains, and development of the infection was followed up. Although all strains had varying abilities to form biofilm in vitro and different levels of virulence in mice, they all caused biofilm formation on the grafts. This graft infection was monitored using magnetic resonance imaging (MRI) and 18F-fluordeoxyglucose positron emission tomography (FDG-PET). MRI allowed the quantification of blood flow through the arteries, which was decreased in the catheter after infection. FDG-PET revealed high inflammation levels at the site of the catheter after infection. This model closely resembles the situation in patients, which is characterized by a tight interplay between pathogen and host, and can therefore be used for the testing of novel treatment, diagnosis, and prevention strategies. In addition, combining MRI and PET with microscopic techniques provides an appropriate way to characterize the course of these infections and to precisely analyze biofilm development.


Assuntos
Biofilmes/crescimento & desenvolvimento , Infecções Relacionadas a Cateter/diagnóstico por imagem , Modelos Animais de Doenças , Infecções Estafilocócicas/diagnóstico por imagem , Animais , Prótese Vascular/microbiologia , Ensaio de Imunoadsorção Enzimática , Hibridização in Situ Fluorescente , Imageamento por Ressonância Magnética , Camundongos , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Tomografia por Emissão de Pósitrons , Staphylococcus aureus
7.
Proc Biol Sci ; 284(1862)2017 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-28904147

RESUMO

Adaptation is evolution in response to natural selection. Hence, an adaptation is expected to originate simultaneously with the acquisition of a particular selective environment. Here we test whether long legs evolve in oil-collecting Rediviva bees when they come under selection by long-spurred, oil-secreting flowers. To quantify the selective environment, we drew a large network of the interactions between Rediviva species and oil-secreting plant species. The selective environment of each bee species was summarized as the average spur length of the interacting plant species weighted by interaction frequency. Using phylogenetically independent contrasts, we calculated divergence in selective environment and evolutionary divergence in leg length between sister species (and sister clades) of Rediviva We found that change in the selective environment explained 80% of evolutionary change in leg length, with change in body size contributing an additional 6% of uniquely explained variance. The result is one of four proposed steps in testing for plant-pollinator coevolution.


Assuntos
Adaptação Biológica , Abelhas/genética , Coevolução Biológica , Estruturas Animais/anatomia & histologia , Animais , Abelhas/anatomia & histologia , Tamanho Corporal , Flores , Polinização , Seleção Genética
8.
Mol Phylogenet Evol ; 115: 95-105, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28757446

RESUMO

Despite close ecological interactions between plants and their pollinators, only some highly specialised pollinators adapt to a specific host plant trait by evolving a bizarre morphology. Here we investigated the evolution of extremely elongated forelegs in females of the South African bee genus Rediviva (Hymenoptera: Melittidae), in which long forelegs are hypothesised to be an adaptation for collecting oils from the extended spurs of their Diascia host flowers. We first reconstructed the phylogeny of the genus Rediviva using seven genes and inferred an origin of Rediviva at around 29MYA (95% HPD=19.2-40.5), concurrent with the origin and radiation of the Succulent Karoo flora. The common ancestor of Rediviva was inferred to be a short-legged species that did not visit Diascia. Interestingly, all our analyses strongly supported at least two independent origins of long legs within Rediviva. Leg length was not correlated with any variable we tested (ecological specialisation, Diascia visitation, geographic distribution, pilosity type) but seems to have evolved very rapidly. Overall, our results indicate that foreleg length is an evolutionary highly labile, rapidly evolving trait that might enable Rediviva bees to respond quickly to changing floral resource availability.


Assuntos
Abelhas/classificação , Membro Posterior/fisiologia , Animais , Evolução Biológica , Complexo IV da Cadeia de Transporte de Elétrons/classificação , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Membro Posterior/anatomia & histologia , Fenótipo , Filogenia , RNA Polimerase II/classificação , RNA Polimerase II/genética , RNA Ribossômico 28S/classificação , RNA Ribossômico 28S/genética
9.
Eur J Neurosci ; 43(10): 1352-65, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26950181

RESUMO

Parkinson's disease is a slowly progressing neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra (SN), leading to severe impairment in motor and non-motor functions. Endogenous subventricular zone (SVZ) neural stem cells constantly give birth to new cells that might serve as a possible source for regeneration in the adult brain. However, neurodegeneration is accompanied by neuroinflammation and dopamine depletion, potentially compromising regeneration. We therefore employed in vivo imaging methods to study striatal deafferentation (N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-[(123) I]iodophenyl)nortropane single photon emission computed tomography, DaTscan(™) ) and neuroinflammation in the SN and striatum (N,N-diethyl-2-(2-(4-(2-[(18) F]fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide positron emission tomography, [(18) F]DPA-714 PET) in the intranigral 6-hydroxydopamine Parkinson's disease mouse model. Additionally, we transduced cells in the SVZ with a lentivirus encoding firefly luciferase and followed migration of progenitor cells in the SVZ-olfactory bulb axis via bioluminescence imaging under disease and control conditions. We found that activation of microglia in the SN is an acute process accompanying the degeneration of dopaminergic cell bodies in the SN. Dopaminergic deafferentation of the striatum does not influence the generation of doublecortin-positive neuroblasts in the SVZ, but generates chronic astrogliosis in the nigrostriatal system.


Assuntos
Corpo Estriado/patologia , Neurônios Dopaminérgicos/patologia , Encefalite/patologia , Gliose/complicações , Neurogênese , Doença de Parkinson/patologia , Substância Negra/patologia , Animais , Astrócitos/patologia , Proliferação de Células , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Encefalite/complicações , Células HEK293 , Humanos , Medições Luminescentes , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Microglia/patologia , Vias Neurais/patologia , Vias Neurais/fisiologia , Células-Tronco Neurais/patologia , Células-Tronco Neurais/fisiologia , Oxidopamina/toxicidade , Doença de Parkinson/complicações , Tomografia por Emissão de Pósitrons , Substância Negra/efeitos dos fármacos
11.
MAGMA ; 28(4): 315-27, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25381179

RESUMO

OBJECTIVES: In this study, we established and validated a time-resolved three-dimensional phase-contrast magnetic resonance imaging method (4D PC MRI) on a 9.4 T small-animal MRI system. Herein we present the feasibility of 4D PC MRI in terms of qualitative and quantitative flow pattern analysis in mice with transverse aortic constriction (TAC). MATERIALS AND METHODS: 4D PC FLASH images of a flow phantom and mouse heart were acquired at 9.4 T using a four-point phase-encoding scheme. The method was compared with slice-selective PC FLASH and ultrasound using Bland-Altman analysis. Advanced 3D streamlines were visualized utilizing Voreen volume-rendering software. RESULTS: In vitro, 4D PC MRI flow profiles showed the transition between laminar and turbulent flow with increasing velocities. In vivo, 4D PC MRI data of the ascending aorta and the pulmonary artery were confirmed by ultrasound, resulting in linear regressions of R (2) > 0.93. Magnitude- and direction-encoded streamlines differed substantially pre- and post-TAC surgery. CONCLUSIONS: 4D PC MRI is a feasible tool for in vivo velocity measurements on high-field small-animal scanners. Similar to clinical measurement, this method provides a complete spatially and temporally resolved dataset of the murine cardiovascular blood flow and allows for three-dimensional flow pattern analysis.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Insuficiência Cardíaca/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Animais , Aorta , Estenose da Valva Aórtica/diagnóstico por imagem , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Aumento da Imagem/métodos , Imageamento Tridimensional , Imageamento por Ressonância Magnética/instrumentação , Camundongos , Camundongos Endogâmicos C57BL , Imagens de Fantasmas , Ultrassonografia
12.
Behav Res Methods ; 47(1): 275-94, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24853832

RESUMO

Research on emotional speech often requires valid stimuli for assessing perceived emotion through prosody and lexical content. To date, no comprehensive emotional speech database for Persian is officially available. The present article reports the process of designing, compiling, and evaluating a comprehensive emotional speech database for colloquial Persian. The database contains a set of 90 validated novel Persian sentences classified in five basic emotional categories (anger, disgust, fear, happiness, and sadness), as well as a neutral category. These sentences were validated in two experiments by a group of 1,126 native Persian speakers. The sentences were articulated by two native Persian speakers (one male, one female) in three conditions: (1) congruent (emotional lexical content articulated in a congruent emotional voice), (2) incongruent (neutral sentences articulated in an emotional voice), and (3) baseline (all emotional and neutral sentences articulated in neutral voice). The speech materials comprise about 470 sentences. The validity of the database was evaluated by a group of 34 native speakers in a perception test. Utterances recognized better than five times chance performance (71.4 %) were regarded as valid portrayals of the target emotions. Acoustic analysis of the valid emotional utterances revealed differences in pitch, intensity, and duration, attributes that may help listeners to correctly classify the intended emotion. The database is designed to be used as a reliable material source (for both text and speech) in future cross-cultural or cross-linguistic studies of emotional speech, and it is available for academic research purposes free of charge. To access the database, please contact the first author.


Assuntos
Emoções , Idioma , Psicolinguística , Reconhecimento Psicológico , Fala , Percepção Auditiva , Bases de Dados Factuais , Feminino , Humanos , Irã (Geográfico) , Masculino , Psicolinguística/métodos , Psicolinguística/normas , Reprodutibilidade dos Testes , Percepção da Fala , Comportamento Verbal , Vocabulário
13.
Mol Phylogenet Evol ; 70: 412-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23994491

RESUMO

New molecular studies suggested that the family Melittidae is either a paraphyletic group from which all the other bees are derived, or the sister clade to all other existing bees. Studying the historical biogeography and evolution of each major lineage within this group is a key step to understand the origin and early radiation of bees. Melitta is the largest genus of melittid bees, for which a robust molecular phylogeny and a biogeographic analysis are still lacking. Here, we derive a phylogenetic hypothesis from the sequences of seven independent DNA fragments of mitochondrial and nuclear origin. This phylogenetic hypothesis is then used to infer the evolution of the species range and of the host-plant shifts in Melitta. Our results confirmed the monophyly of Melitta, but did not recover all previously defined clades within the genus. We propose new taxa by splitting the genus in three subgenera (including two new subgenera described in the Appendix: Afromelitta subgen. nov., Plesiomelitta subgen. nov.) and describe two new species: Melitta avontuurensis sp. n. and M. richtersveldensis sp. n. Regarding the evolution of host-plant use, our analysis suggests that all species currently specialized on one plant family originated from an ancestor that was specialized on Fabaceae plants. The inferred biogeographic history for the genus supported an African origin. In concordance with previous studies identifying Africa as the geographic origin for many clades of bees, our data bring new evidence for an African origin of melittid bees.


Assuntos
Himenópteros/genética , Magnoliopsida/genética , Filogenia , África , Animais , Flores/genética , Himenópteros/classificação , Filogeografia , Análise de Sequência de DNA
14.
Mol Pharm ; 11(5): 1415-23, 2014 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-24641497

RESUMO

The noninvasive imaging of matrix metalloproteinases (MMPs) activity in postischemic myocardial tissue holds great promise to predict cardiac function post-myocardial infarction. Consequently, development of MMP specific molecular imaging probes for noninvasive visualization and quantification of MMP activity is of great interest. A novel MMP imaging strategy is based on activatable cell-penetrating peptide probes (ACPP) that are sensitive to the proteolytic activity of MMP-2 and -9. The MMP-mediated activation of these ACPPs drives probe accumulation at the target site. The aim of this study was the development and characterization of radiolabeled MMP-2/9 sensitive ACPPs to assess MMP activity in myocardial remodeling in vivo. Specifically, a short and long-circulating MMP activatable cell-penetrating imaging probe (ACPP and Alb-ACPP, respectively; the latter is an ACPP modified with an albumin binding ligand that prolongs blood clearance) were successfully synthesized and radiolabeled. Subsequently, their biodistributions were determined in vivo in a Swiss mouse model of myocardial infarction. Both peptide probes showed a significantly higher uptake in infarcted myocardium compared to remote myocardium. The biodistribution for dual-isotope radiolabeled probes, which allowed us to discriminate between uncleaved ACPP and activated ACPP, showed increased retention of activated ACPP and activated Alb-ACPP in infarcted myocardium compared to remote myocardium. The enhanced retention correlated to gelatinase levels determined by gelatin zymography, whereas no correlation was found for the negative control: an MMP-2/9 insensitive non-ACPP. In conclusion, radiolabeled MMP sensitive ACPP probes enable to assess MMP activity in the course of remodeling post-myocardial infarction in vivo. Future research should evaluate the feasibility and the predictive value of the ACPP strategy for assessing MMP activity as a main player in postinfarction myocardial remodeling in vivo.


Assuntos
Metaloproteinase 2 da Matriz/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinases da Matriz/química , Metaloproteinases da Matriz/metabolismo , Sondas Moleculares , Peptídeos , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Sondas Moleculares/química , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Peptídeos/química
15.
Mol Ther ; 21(3): 570-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23319055

RESUMO

Despite treatments combining surgery, radiation-, and chemotherapy, patients affected by glioblastoma (GBM) have a limited prognosis. Addition of temozolomide (TMZ) to radiation therapy is the standard therapy in clinical application, but effectiveness of TMZ is limited by the tumor's overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). The goal of this study was to use the highly specific and efficient RNA interference (RNAi) pathway to modulate MGMT expression to increase TMZ efficiency in chemotherapy resistant GBM. Using lentiviral-based anti-MGMT small hairpin RNA (shRNA) technology we observed a specific inhibition of the MGMT expression in GBM cell lines as well as in subcutaneous tumors. Tumor growth inhibition was observed following TMZ treatment of xenografts with low MGMT expression in contrast to xenografts with high MGMT expression. Bioluminescence imaging (BLI) measurements indicated that luciferase and shRNA-expressing lentiviruses were able to efficiently transduce the GBM xenografts in vivo. Treatment combining injection of a lentivirus expressing an anti-MGMT shRNA and TMZ induced a reduction of the size of the tumors, in contrast with treatment combining the lentivirus expressing the control shRNA and TMZ. Our data suggest that anti-MGMT shRNA therapy could be used in combination with TMZ chemotherapy in order to improve the treatment of resistant GBM.


Assuntos
Metilases de Modificação do DNA/antagonistas & inibidores , Enzimas Reparadoras do DNA/antagonistas & inibidores , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Lentivirus/genética , RNA Interferente Pequeno/uso terapêutico , Proteínas Supressoras de Tumor/antagonistas & inibidores , Animais , Antineoplásicos Alquilantes/uso terapêutico , Linhagem Celular Tumoral , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Dacarbazina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação da Expressão Gênica , Vetores Genéticos , Glioblastoma/radioterapia , Humanos , Camundongos , Camundongos Nus , Temozolomida , Transdução Genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Zootaxa ; 3780: 534-46, 2014 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-24871849

RESUMO

Two species of the Colletes flavicornis-group from China are treated in this paper. C. vestitus sp. n. from Xinjiang is illustrated and described, and C. popovi Noskiewicz, 1936 is illustrated and redescribed. Both sexes of the two species are in addition characterized by DNA barcodes. The type specimens of the new species are deposited in the Insect Collection of Institute of Zoology, Chinese Academy of Sciences, Beijing, China.


Assuntos
Abelhas/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Estruturas Animais/crescimento & desenvolvimento , Animais , Abelhas/anatomia & histologia , Abelhas/crescimento & desenvolvimento , Tamanho Corporal , China , Feminino , Masculino , Dados de Sequência Molecular , Filogenia
17.
J Cardiovasc Magn Reson ; 15: 59, 2013 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-23826850

RESUMO

BACKGROUND: To overcome flow and electrocardiogram-trigger artifacts in cardiovascular magnetic resonance (CMR), we have implemented a cardiac and respiratory self-gated cine ultra-short echo time (UTE) sequence. We have assessed its performance in healthy mice by comparing the results with those obtained with a self-gated cine fast low angle shot (FLASH) sequence and with echocardiography. METHODS: 2D self-gated cine UTE (TE/TR = 314 µs/6.2 ms, resolution: 129 × 129 µm, scan time per slice: 5 min 5 sec) and self-gated cine FLASH (TE/TR = 3 ms/6.2 ms, resolution: 129 × 129 µm, scan time per slice: 4 min 49 sec) images were acquired at 9.4 T. Volume of the left and right ventricular (LV, RV) myocardium as well as the end-diastolic and -systolic volume was segmented manually in MR images and myocardial mass, stroke volume (SV), ejection fraction (EF) and cardiac output (CO) were determined. Statistical differences were analyzed by using Student t test and Bland-Altman analyses. RESULTS: Self-gated cine UTE provided high quality images with high contrast-to-noise ratio (CNR) also for the RV myocardium (CNRblood-myocardium = 25.5 ± 7.8). Compared to cine FLASH, susceptibility, motion, and flow artifacts were considerably reduced due to the short TE of 314 µs. The aortic valve was clearly discernible over the entire cardiac cycle. Myocardial mass, SV, EF and CO determined by self-gated UTE were identical to the values measured with self-gated FLASH and showed good agreement to the results obtained by echocardiography. CONCLUSIONS: Self-gated UTE allows for robust measurement of cardiac parameters of diagnostic interest. Image quality is superior to self-gated FLASH, rendering the method a powerful alternative for the assessment of cardiac function at high magnetic fields.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca , Frequência Cardíaca , Imagem Cinética por Ressonância Magnética/métodos , Taxa Respiratória , Função Ventricular Esquerda , Função Ventricular Direita , Animais , Artefatos , Ecocardiografia Doppler , Feminino , Interpretação de Imagem Assistida por Computador , Camundongos Endogâmicos C57BL , Modelos Animais , Contração Miocárdica , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Volume Sistólico , Fatores de Tempo
18.
Zootaxa ; 3693: 267-92, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-26185847

RESUMO

The Ethiopian species of the bee genus Colletes are revised and redescribed to facilitate their identification and future research. Colletes langano Kuhlmann sp. n., C. aethiopicus Kuhlmann sp. n. and C. senkelensis Kuhlmann sp. n. are described as new. The females of C. abessinicus Friese 1915 and C. microdontus Cockerell 1937 and the males of C. rothschildi Vachal 1909 and C. somereni Cockerell 1947 are described for the first time. Colletes rufitarsis Friese 1909 is removed from the list of Ethiopian species so currently a total of eight Colletes species are known from this country. A key is provided to facilitate species identification.


Assuntos
Distribuição Animal/fisiologia , Abelhas/anatomia & histologia , Abelhas/classificação , Animais , Abelhas/fisiologia , Etiópia , Feminino , Masculino , Especificidade da Espécie
19.
Zootaxa ; 3750: 401-49, 2013 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-25113710

RESUMO

Available information about bees of the genus Colletes in Central Asia is summarized. Eighty species are currently known from this area. Six new species are described: Colletes transitus sp. nov., C. askhabadoides sp. nov., C. kaline sp. nov., C. muellermotzfeldi sp. nov., C. pesenkoi sp. nov., and C. mirabilis sp. nov. Five species are newly recorded from Central Asia: Colletes idoneus Cockerell 1922, C. cunicularius (Linnaeus 1761), C. ebmeri Kuhlmann 2002, C. friesei Cockerell 1918, and C. impunctatus Nylander 1852. The subspecies C. tuberculatus anatolicus Noskiewicz 1959 syn. nov. and C. t. siculus Noskiewicz 1959 syn. nov. are synonymized with C. tuberculatus Morawitz 1894. Lectotypes are designated for Colletes arenarius Morawitz 1876 and C. flavicornis Morawitz 1876. Additionally one new species from Turkey and Iran, Colletes comatoides sp. nov., is here described as new and included due to its close relationship to the Central Asian C. bernadettae Kuhlmann and C. comatus Noskiewicz.


Assuntos
Abelhas/classificação , Distribuição Animal , Estruturas Animais/anatomia & histologia , Animais , Ásia Central , Abelhas/anatomia & histologia , Ecossistema , Feminino , Masculino
20.
Zootaxa ; 3626: 173-87, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-26176131

RESUMO

Four species of the Colletes succinctus-group known from China are reviewed and a key to species is provided. Colletes gigas Cockerell, 1918 is recognized as a member of the Colletes succinctus-group for the first time based on a redescription of the male.


Assuntos
Abelhas/anatomia & histologia , Abelhas/classificação , Distribuição Animal , Animais , Abelhas/genética , Abelhas/fisiologia , China , Código de Barras de DNA Taxonômico , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Proteínas de Insetos/genética , Masculino , Proteínas Mitocondriais/genética , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Especificidade da Espécie
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