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1.
Phys Rev Lett ; 125(2): 025101, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32701353

RESUMO

In many physics fields, the radio emission of a composite system composed of a large number of randomly occurring but similar emission sources is encountered. In general, the composite system lasts longer than each individual component and individual source currents vary much more rapidly. This Letter presents a theory to understand the electromagnetic radiation spectrum of such a system. If the temporal distribution of the random occurrence of the component and the distribution to describe the relevant emission source properties are known, the spectrum of the composite system can be readily found from this theory. There are two main terms that define the spectrum: one term results from the coherent summation of the contributions from individual sources and is proportional to the square of the total number of the components in the system; the other term results from an incoherent summation and is proportional to the first power of that number. This can lead to drastically different spectral magnitudes in different spectral regions, typically with the spectral magnitude in the lower frequency region many orders of magnitude stronger than that in the higher frequency region.

2.
Zoo Biol ; 39(5): 297-303, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32785969

RESUMO

Prior research into the conceptual underpinnings of the public's institutional trust in zoos and aquariums has suggested a range of ethical dimensions that set these types of cultural institutions apart from others in the museum sector. As the recognized holders, care-takers, and nurturers of wild animals, zoos and aquariums are sustained at least in part by the public's perception that these activities are legitimate pursuits and essential to the long-term conservation of the natural world. This paper builds on recent research that identified the ethical dimensions of trust in zoos and aquariums and assessed their distribution among the U.S. public by analyzing survey responses with respect to the importance of trust criteria. We hypothesized that distinct clusters of individuals, as defined by their response to trust criteria items, would emerge and that these clusters would prioritize different dimensions in their trust of zoos and aquariums. Using k-means clustering, we identified four relevant clusters of individuals on seven dimensions of institutional trust in zoos and aquariums. Based on these clusters, we suggest strategies for addressing what may be necessary for zoos and aquariums to claim authority as agents promoting conservation behaviors in society.


Assuntos
Criação de Animais Domésticos/normas , Bem-Estar do Animal/normas , Conservação dos Recursos Naturais , Confiança , Animais , Animais de Zoológico , Educação/métodos , Humanos
3.
J Urol ; 195(2): 460-4, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26408416

RESUMO

PURPOSE: Although the Clavien-Dindo classification of surgical complications has been evaluated using adult surgical patients, it is being applied to pediatric populations. We hypothesized that this instrument is not well suited to children and sought to determine the reliability of the tool in a pediatric urological population. MATERIALS AND METHODS: We replaced adult surgical cases in the "Survey to Assess Acceptability and Reproducibility of the Classification" from the original Clavien-Dindo study with pediatric urology cases and mimicked original study methods. The survey was distributed with the REDCap (Research Electronic Data Capture) tool, and Krippendorff α coefficients of reliability were calculated from the responses. RESULTS: There were 51 respondents and 40 complete responses. The Krippendorff α coefficient of reliability for the Clavien-Dindo classification (α = 0.487) did not achieve the minimum level of acceptable agreement (α = 0.667) with the pediatric urological cases, even when the disability suffix (α = 0.266) was excluded from the analysis (α = 0.632). The accuracy of the grading system with the pediatric urological surgical cases when excluding the disability suffix (410 of 550, 75%) was significantly less than the accuracy had been with the original adult cases (1,816 of 2,016, 90%, p <0.0001). While 89% of respondents (32 of 36) thought the system was appropriate for adults, only 49% (17 of 35) found it appropriate for children (p <0.001). CONCLUSIONS: The Clavien-Dindo classification of surgical complications is not a reliable tool for use in pediatric urology, where its accuracy is significantly decreased compared to adult surgical cases. Further study is needed to determine if findings are similar across all pediatric surgical groups.


Assuntos
Complicações Intraoperatórias/classificação , Complicações Pós-Operatórias/classificação , Procedimentos Cirúrgicos Urológicos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários
4.
J Hand Surg Am ; 40(4): 701-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25648783

RESUMO

PURPOSE: To determine the accuracy of digital palpation for clinical assessment of elevated intracompartmental pressure compared with needle manometry in a simulated compartment syndrome of the hand. METHODS: Three cadaveric hands were configured with interstitial fluid infusion and an arterial line pressure monitor to create and continuously measure intracompartmental pressure in the thenar and hypothenar compartments. Seventeen assessors clinically judged the presence or absence of compartment syndrome based on digital palpation for firmness and then measured pressures with a handheld manometer. An intracompartmental pressure threshold of 30 mm Hg or greater was used to diagnose compartment syndrome. RESULTS: The sensitivity and specificity of digital palpation of the thenar eminence were 49% and 79%, respectively, with a positive predictive value (PPV) of 86% and negative predictive value (NPV) of 37%. Using the handheld manometer, the sensitivity and specificity increased to 97% and 86% with a PPV of 95% and NPV of 92%. The sensitivity and specificity of digital palpation of the hypothenar eminence were 62% and 83%, respectively, with improvement of 100% and 100%, respectively, with a handheld manometer. For the hypothenar compartment, use of a handheld manometer improved the PPV from 92% to 100% and the NPV from 40% to 100% compared with digital palpation. CONCLUSIONS: Digital palpation alone was insufficient to detect elevated compartment pressures in hands at risk for compartment syndrome. Handheld invasive pressure measurement was a useful adjunct for detecting elevated interstitial tissue pressures and may aid in diagnosing compartment syndrome. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.


Assuntos
Síndromes Compartimentais/diagnóstico , Mãos , Palpação , Cadáver , Síndromes Compartimentais/fisiopatologia , Humanos , Manometria , Sensibilidade e Especificidade
5.
Thromb J ; 12: 10, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24891841

RESUMO

BACKGROUND: Platelet inhibitors are commonly used to reduce the risk of atherothrombotic events. The aim of this study was to determine the impact of platelet inhibitors, specifically clopidogrel and aspirin, on clot kinetics, strength, and/or structure during the use of thrombin based gelatin matrices and fibrin sealants. METHODS: Blood was collected and heparinized from donors on clopidogrel (and aspirin) and age matched control donors. Blood component analysis, whole blood platelet aggregometry, and activated clotting time (ACT) were used to monitor compliance to therapy and identify any differences between donor groups. Clot kinetics and strength were analyzed using thrombelastography (TEG). Field Emission Scanning Electron Microscopy (FESEM) was used to analyze clot structure. RESULTS: Blood component profiles were similar for both donor groups. Aggregometry indicated that aggregation response to adenosine diphosphate (ADP) for clopidogrel donors was 12% of that for the controls (p = 0.0021), an expected result of clopidogrel induced platelet inhibition. However, blood from both donor groups had an elevated thrombin induced aggregation response. Heparinization of donor blood resulted in similarly elevated ACTs for both donor groups. TEG results indicated similar clot kinetics and strength between clopidogrel and control donor groups for blood alone and when clotting was induced using thrombin based gelatin matrices and fibrin sealants. FESEM images supported TEG findings in that similar morphologies were observed in ex vivo formed clots from both donor groups when thrombin based gelatin matrices and fibrin sealants were used. CONCLUSION: These results suggest that platelet inhibitors do not negatively impact clot kinetics, strength, and structure when clotting is initiated with thrombin based gelatin matrices and fibrin sealants.

6.
Cell Mol Life Sci ; 70(5): 893-908, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23052206

RESUMO

Posttranslational modifications such as phosphorylation are universally acknowledged regulators of protein function. Recently we characterised a striated muscle-specific isoform of the formin FHOD3 that displays distinct subcellular targeting and protein half-life compared to its non-muscle counterpart and which is dependent on phosphorylation by CK2 (formerly casein kinase 2). We now show that the two isoforms of FHOD3 are already expressed in the vertebrate embryonic heart. Analysis of CK2 alpha knockout mice showed that phosphorylation by CK2 is also required for proper targeting of muscle FHOD3 to the myofibrils in embryonic cardiomyocytes in situ. The localisation of muscle FHOD3 in the sarcomere varies depending on the maturation state, being either broader or restricted to the Z-disc proper in the adult heart. Following myofibril disassembly, such as that in dedifferentiating adult rat cardiomyocytes in culture, the expression of non-muscle FHOD3 is up-regulated, which is reversed once the myofibrils are reassembled. The shift in expression levels of different isoforms is accompanied by an increased co-localisation with p62, which is involved in autophagy, and affects the half-life of FHOD3. Phosphorylation of three amino acids in the C-terminus of FHOD3 by ROCK1 is sufficient for activation, which results in increased actin filament synthesis in cardiomyocytes and also a broader localisation pattern of FHOD3 in the myofibrils. ROCK1 can directly phosphorylate FHOD3, and FHOD3 seems to be the downstream mediator of the exaggerated actin filament formation phenotype that is induced in cardiomyocytes upon the overexpression of constitutively active ROCK1. We conclude that the expression of the muscle FHOD3 isoform is characteristic of the healthy mature heart and that two distinct phosphorylation events are crucial to regulate the activity of this isoform in thin filament assembly and maintenance.


Assuntos
Proteínas Aviárias/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Proteínas Aviárias/genética , Células COS , Caseína Quinase II/genética , Células Cultivadas , Embrião de Galinha/embriologia , Embrião de Galinha/metabolismo , Galinhas , Chlorocebus aethiops , Forminas , Regulação da Expressão Gênica no Desenvolvimento , Células HeLa , Coração/embriologia , Humanos , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/análise , Proteínas dos Microfilamentos/genética , Proteínas Musculares/análise , Proteínas Musculares/genética , Miócitos Cardíacos/citologia , Miofibrilas/metabolismo , Miofibrilas/ultraestrutura , Isoformas de Proteínas/análise , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratos , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo
7.
J Mol Cell Cardiol ; 55: 27-30, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23277191

RESUMO

Perhexiline is a potent anti-anginal drug used for treatment of refractory angina and other forms of heart disease. It provides an oxygen sparing effect in the myocardium by creating a switch from fatty acid to glucose metabolism through partial inhibition of carnitine palmitoyltransferase 1 and 2. However, the precise molecular mechanisms underlying the cardioprotective effects elicited by perhexiline are not fully understood. The present study employed a combined proteomics, metabolomics and computational approach to characterise changes in murine hearts upon treatment with perhexiline. According to results based on difference in-gel electrophoresis, the most profound change in the cardiac proteome related to the activation of the pyruvate dehydrogenase complex. Metabolomic analysis by high-resolution nuclear magnetic resonance spectroscopy showed lower levels of total creatine and taurine in hearts of perhexiline-treated mice. Creatine and taurine levels were also significantly correlated in a cross-correlation analysis of all metabolites. Computational modelling suggested that far from inducing a simple shift from fatty acid to glucose oxidation, perhexiline may cause complex rebalancing of carbon and nucleotide phosphate fluxes, fuelled by increased lactate and amino acid uptake, to increase metabolic flexibility and to maintain cardiac output. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".


Assuntos
Fármacos Cardiovasculares/farmacologia , Coração/efeitos dos fármacos , Metaboloma , Miocárdio/metabolismo , Perexilina/farmacologia , Proteoma , Animais , Análise por Conglomerados , Simulação por Computador , Masculino , Metabolômica , Camundongos , Modelos Biológicos , Proteômica
8.
Phys Rev Lett ; 109(2): 025002, 2012 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-23030169

RESUMO

This Letter reports a modeling study on the formation of streamer discharges from an isolated ionization column under subbreakdown condition. Numerical simulations show that positive streamers are able to form from the tip of an ionization column in a uniform applied electric field well below the breakdown threshold field. However, even when the applied field approaches the breakdown threshold field, negative streamers fail to originate from the other tip of the ionization column after the positive streamer has propagated a certain distance. The results reported explain some puzzling observations on streamer discharges in nature such as the predominant initiation of sprites by downward propagating positive streamers and help advance the initiation theories of sprites and lightning.

9.
eNeuro ; 9(2)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35074828

RESUMO

Here, we reveal an unbiased view of the brain regions that provide specific inputs to aromatase-expressing cells in the medial amygdala, neurons that play an outsized role in the production of sex-specific social behaviors, using rabies tracing and light sheet microscopy. While the downstream projections from these cells are known, the specific inputs to the aromatase-expressing cells in the medial amygdala remained unknown. We observed established connections to the medial amygdala (e.g., bed nucleus of the stria terminalis and accessory olfactory bulb) indicating that aromatase neurons are a major target cell type for efferent input including from regions associated with parenting and aggression. We also identified novel and unexpected inputs from areas involved in metabolism, fear and anxiety, and memory and cognition. These results confirm the central role of the medial amygdala in sex-specific social recognition and social behavior, and point to an expanded role for its aromatase-expressing neurons in the integration of multiple sensory and homeostatic factors, which are likely used to modulate many other social behaviors.


Assuntos
Aromatase , Complexo Nuclear Corticomedial , Tonsila do Cerebelo/fisiologia , Aromatase/metabolismo , Feminino , Humanos , Masculino , Neurônios/metabolismo , Comportamento Social
10.
Sci Rep ; 11(1): 16462, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385489

RESUMO

Techniques used to clear biological tissue for fluorescence microscopy are essential to connect anatomical principles at levels ranging from subcellular to the whole animal. Here we report a simple and straightforward approach to efficiently render opaque tissue samples transparent and show that this approach can be modified to rapidly label intact tissue samples with antibodies for large volume fluorescence microscopy. This strategy applies a magnetohydrodynamic (MHD) force to accelerate the removal of lipids from tissue samples at least as large as an intact adult mouse brain. We also show that MHD force can be used to accelerate antibody penetration into tissue samples. This strategy complements a growing array of tools that enable high-resolution 3-dimensional anatomical analyses in intact tissues using fluorescence microscopy. MHD-accelerated clearing is simple, fast, reliable, inexpensive, provides good thermal regulation, and is compatible with existing strategies for high-quality fluorescence microscopy of intact tissues.


Assuntos
Encéfalo/metabolismo , Hidrodinâmica , Magnetismo , Animais , Camundongos , Microscopia de Fluorescência/métodos
11.
Nat Commun ; 10(1): 1648, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967558

RESUMO

Thunderstorms are natural laboratories for studying electrical discharges in air, where the vast temporal, spatial, and energy scales available can spawn surprising phenomena that reveal deficiencies in our understanding of dielectric breakdown. Recent discoveries, such as sprites, jets, terrestrial gamma ray flashes, and fast positive breakdown, highlight the diversity of complex phenomena that thunderstorms can produce, and point to the possibility for electrical breakdown/discharge mechanisms beyond dielectric breakdown theory based mainly on laboratory experiments. Here we present one such confounding discovery, termed fast negative breakdown, that does not fit with our current understanding of dielectric breakdown. Our adaptation of radio astronomy imaging techniques to study extremely transient lightning-associated events confirms that electrical breakdown in thunderstorms can begin with oppositely-directed fast breakdown of negative polarity, similar and in addition to fast positive breakdown expected from conventional dielectric theory and recent observations. The discovery of fast negative breakdown calls for an addendum to the physical description of electrical discharges in air.

12.
Sci Am ; 307(2): 54-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22844853
13.
Hand (N Y) ; 12(2): 119-126, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28344521

RESUMO

Background: Literature on open fracture infections has focused primarily on long bones, with limited guidelines available for open hand fractures. In this study, we systematically review the available hand surgery literature to determine infection rates and the effect of debridement timing and antibiotic administration. Methods: Searches of the MEDLINE, EMBASE, and Cochrane computerized literature databases and manual bibliography searches were performed. Descriptive/quantitative data were extracted, and a meta-analysis of different patient cohorts and treatment modalities was performed to compare infection rates. Results: The initial search yielded 61 references. Twelve articles (4 prospective, 8 retrospective) on open hand fractures were included (1669 open fractures). There were 77 total infections (4.6%): 61 (4.4%) of 1391 patients received preoperative antibiotics and 16 (9.4%) of 171 patients did not receive antibiotics. In 7 studies (1106 open fractures), superficial infections (requiring oral antibiotics only) accounted for 86%, whereas deep infections (requiring operative debridement) accounted for 14%. Debridement within 6 hours of injury (2 studies, 188 fractures) resulted in a 4.2% infection rate, whereas debridement within 12 hours of injury (1 study, 193 fractures) resulted in a 3.6% infection rate. Two studies found no correlation of infection and timing to debridement. Conclusions: Overall, the infection rate after open hand fracture remains relatively low. Correlation does exist between the administration of antibiotics and infection, but the majority of infections can be treated with antibiotics alone. Timing of debridement, has not been shown to alter infection rates.


Assuntos
Desbridamento/métodos , Fraturas Expostas/cirurgia , Traumatismos da Mão/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Antibacterianos/administração & dosagem , Esquema de Medicação , Fraturas Expostas/epidemiologia , Traumatismos da Mão/epidemiologia , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Fatores de Tempo
14.
Hand (N Y) ; 11(3): 341-346, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27698638

RESUMO

Background: Posttraumatic finger stiffness can occur as a result of hand fractures. The purpose was to assess and quantify the improvement in range of motion (ROM) after surgical management of the stiff finger in patients who developed loss of motion following treatment for a metacarpal or phalangeal fracture. In addition, an aim was to identify possible risk factors for suboptimal improvement in ROM postoperatively. Methods: A retrospective review was performed on 18 patients who underwent surgery to improve finger stiffness following metacarpal or phalangeal fracture. Demographic data including age, initial diagnosis and treatment, health history, and worker's compensation status were collected. We determined the number of specific procedures performed at the time of surgery, the number of days between surgical release and initiation of therapy, and the total active motion (TAM) prior to surgical release and at the patient's last follow-up. Results: Mean TAM improved from 150° preoperatively (range 60°-241°) to 191° postoperatively (range 61°-271°). Most patients required multiple anatomic structures released concomitantly, with an average of 3.1. Patients who started physical therapy within 7 days of the release improved by 59°, whereas those who started physical therapy after 7 days (average 11.5 days) lost 19° of motion. Patients who had filed a worker's compensation claim improved an average of 9°, whereas nonworker's compensation patients improved an average of 58°. Degree of TAM improvement had a weak correlation with patient age or preoperative TAM. Conclusions: Surgical release for stiff fingers following hand fractures can offer modest improvements in ROM in some patients. Although the overall increase in motion as a result of these operations is generally limited, functional improvement can be obtained. Delay in initiating physical therapy is a risk factor for persistent or worsened stiffness. Patients involved in worker's compensation claims demonstrated significantly lower TAM improvement after surgical intervention.


Assuntos
Falanges dos Dedos da Mão/lesões , Fraturas Ósseas/complicações , Traumatismos da Mão/complicações , Artropatias/cirurgia , Ossos Metacarpais/lesões , Amplitude de Movimento Articular , Adolescente , Adulto , Criança , Feminino , Humanos , Artropatias/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
15.
Sci Am ; 292(5): 64-71, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15882023

RESUMO

Lightning is a particularly unsettling product of bad weather. It causes more deaths and injuries in the U.S. than either hurricanes or tornadoes do, and it strikes without warning, sometimes with nothing but blue sky overhead. In central Florida, where I live, thunderstorms are a daily occurrence during the summer, and so, ironically, people in the Sunshine State often spend their afternoons indoors to avoid the risk of death from the sky. Worldwide, lightning flashes about four million times a day, and bolts have even been observed on other planets. Yet despite its familiarity, we still do not know what causes lightning. It is a misconception that Benjamin Franklin solved the puzzle when he conducted his famous kite experiment in 1752.

16.
Nat Commun ; 6: 7540, 2015 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-26118893

RESUMO

Sprites are large, luminous electrical discharges in the upper atmosphere caused by intense cloud-to-ground lightning flashes, manifesting an impulsive coupling mechanism between lower and upper atmospheric regions. Their dynamics are governed by filamentary streamer discharges whose propagation properties have been well studied by past work. However, how they are initiated is still under active debate. It has recently been concluded that ionospheric/mesospheric inhomogeneities are required for their initiation, but it is an open question as to what the sources of those inhomogeneities are. Here we present numerical simulation results to demonstrate that naturally-existing, small-scale mesospheric structures such as those created by gravity waves via instability and breaking are viable sources. The proposed theory is supported by a recent, unique high-speed observation from aircraft flying at 14-km altitude. The theory naturally explains many aspects of observed sprite streamer initiation and has important implications for future observational work.

17.
Nat Commun ; 6: 5995, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25607345

RESUMO

Observation of upward electrical discharges from thunderstorms has been sporadically reported in the scientific literature. According to their terminal altitudes, they are classified as starters (20-30 km), jets (40-50 km) and gigantic jets (70-90 km). They not only have a significant impact on the occupied atmospheric volumes but also electrically couple different atmospheric regions. However, as they are rare and unpredictable, our knowledge of them has been built on observations that typically record only one type of such discharges. Here we report a close-distance observation of seven upward discharges including one starter, two jets and four gigantic jets above Tropical Depression Dorian. Our optical and electromagnetic data indicate that all events are of negative polarity, suggesting they are initiated in the same thundercloud charge region. The data also indicate that the lightning-like discharge channel can extend above thunderclouds by about 30 km, but the discharge does not emit low-frequency electromagnetic radiation as normal lightning.

18.
Nat Commun ; 6: 7845, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26263880

RESUMO

Gamma-ray 'glows' are long duration (seconds to tens of minutes) X-ray and gamma-ray emission coming from thunderclouds. Measurements suggest the presence of relativistic runaway electron avalanches (RREA), the same process underlying terrestrial gamma-ray flashes. Here we demonstrate that glows are relatively a common phenomena near the tops of thunderstorms, when compared with events such as terrestrial gamma-ray flashes. Examining the strongest glow measured by the airborne detector for energetic emissions, we show that this glow is measured near the end of a downward RREA, consistent with occurring between the upper positive charge layer and the negative screening layer above it. The glow discharges the upper positive layer by ≥9.6 mA, strong enough to be an important charging mechanism of the storm. For this glow, the gamma-ray flux observed is close to the value at which relativistic feedback processes become important, with an avalanche multiplication factor of 4,500.

19.
Anat Rec (Hoboken) ; 297(9): 1560-70, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25125170

RESUMO

Members of the formin family are known to be involved in the regulation of the actin cytoskeleton. We have recently identified a muscle specific splice variant of the formin FHOD3 and demonstrated its role in the maintenance of the contractile filaments of cardiomyocytes. Here, we characterize the expression and subcellular localization of FHOD3's closest relative, FHOD1, in the heart. Confocal microscopy shows that FHOD1 is mainly located at the intercalated disc, the special type of cell-cell contact between cardiomyocytes, but also partially associated with the myofibrils. Subcellular targeting of FHOD1 is probably mediated by its N-terminal domain, since expression constructs lacking this domain show aberrant localization in primary cultures of neonatal rat cardiomyocytes. Finally, we show that in contrast to FHOD3, FHOD1 shows increased expression levels in dilated cardiomyopathy, suggesting that the two formins play distinct roles and are differentially regulated in cardiomyocytes.


Assuntos
Proteínas Fetais/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Nucleares/metabolismo , Animais , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Modelos Animais de Doenças , Proteínas Fetais/genética , Forminas , Humanos , Proteínas com Domínio LIM/deficiência , Proteínas com Domínio LIM/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Musculares/deficiência , Proteínas Musculares/genética , Mutação , Miofibrilas/metabolismo , Proteínas Nucleares/genética , Estrutura Terciária de Proteína , Ratos Wistar , Transfecção , Regulação para Cima
20.
Cardiovasc Res ; 97(4): 612-22, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23180722

RESUMO

The conventional reductionist approach to cardiovascular research investigates individual candidate factors or linear signalling pathways but ignores more complex interactions in biological systems. The advent of molecular profiling technologies that focus on a global characterization of whole complements allows an exploration of the interconnectivity of pathways during pathophysiologically relevant processes, but has brought about the issue of statistical analysis and data integration. Proteins identified by differential expression as well as those in protein-protein interaction networks identified through experiments and through computational modelling techniques can be used as an initial starting point for functional analyses. In combination with other '-omics' technologies, such as transcriptomics and metabolomics, proteomics explores different aspects of disease, and the different pillars of observations facilitate the data integration in disease-specific networks. Ultimately, a systems biology approach may advance our understanding of cardiovascular disease processes at a 'biological pathway' instead of a 'single molecule' level and accelerate progress towards disease-modifying interventions.


Assuntos
Proteômica/métodos , Cromatografia Líquida , Humanos , Metabolômica , Proteínas/análise , Biologia de Sistemas , Espectrometria de Massas em Tandem , Transcriptoma
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