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1.
J Acoust Soc Am ; 151(1): 180, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35105033

ABSTRACT

This paper investigates the performance of one-eighth Spherical Fraction Microphone Array through experimental measurement to analyze acoustic scenes in one-eighth of space. The array geometry is designed to be placed in a room corner at the junction of three acoustically rigid walls. Two prototypes are built with 8 and 16 microphones, respectively. The sampling strategy is discussed and a spatial aliasing analysis is carried out both analytically and by numerical simulations. The array performances are evaluated through Spherical Fraction Beamforming (SFB). This approach is based on the decomposition of the acoustic pressure field in a rigid bounded domain. The localization angular error and Directivity Index criterion are evaluated for both arrays. In a first experiment, the arrays are mounted in an eighth of space built inside an anechoic room. The results are compared with simulation and show consistency. The theoretical limitations of SFB in a rigid bounded one-eighth of space are retrieved experimentally. These limitations are also observed in a real configuration: an office room. Further investigations on SFB are also conducted in the case of a virtual scene constructed with two sound sources.

2.
Educ Technol Res Dev ; 69(1): 123-126, 2021.
Article in English | MEDLINE | ID: mdl-33199950

ABSTRACT

Borup et al. (Educ Technol Res Dev 63: 161-184. 10.1007/s11423-015-9367-8, 2015) examined teacher candidate and instructor perceptions of feedback in blended learning environments. Their work juxtaposed two different modalities of learning and feedback; it serves as a critical anchor to support future efforts to ensure students and instructors are engaged in an efficient feedback experience that offers affective benefits in digital learning spaces. In this article, I offer applicable feedback delivery strategies for educators as an extension of Borup et al.'s work.

3.
Article in English | MEDLINE | ID: mdl-37547748

ABSTRACT

In this position paper, we advocate for the use of equity-focused teaching and learning as an essential practice within computer science classrooms. We provide an overview of the theoretical underpinnings of various equity pedagogies (Banks & Banks, 1995), such as culturally relevant pedagogy (Ladson-Billings, 1995, 2006) and share how they have been utilized in CS classrooms. First, we provide a brief history of CS education and issues of equity within public schools in the United States. In sharing our definition of equity, along with our rationale for how and why these strategies can be taken up in computer science (CS) learning environments, we demonstrate how researchers and educators can shift the focus from access and achievement to social justice. After explaining the differences between the relevant theoretical frameworks, we provide practical examples from research of how both practitioners and researchers might use and/or examine equity-focused teaching practices. Resources for further learning are also included.

4.
Clin Oncol (R Coll Radiol) ; 28(8): e61-7, 2016 08.
Article in English | MEDLINE | ID: mdl-26876458

ABSTRACT

AIMS: To determine the toxicity and tumour control rates after chemo-intensity-modulated radiotherapy (chemo-IMRT) for locally advanced nasopharyngeal cancers (LA-NPC). MATERIALS AND METHODS: Patients with LA-NPC were enrolled in a trial to receive induction chemotherapy followed by parotid-sparing chemo-IMRT. The primary site and involved nodal levels received 65 Gy in 30 fractions and at risk nodal levels received 54 Gy in 30 fractions. Incidence of ≥grade 2 subjective xerostomia was the primary end point. Secondary end points included incidences of acute and late toxicities and survival outcomes. RESULTS: Forty-two patients with American Joint Committee on Cancer stages II (12%), III (26%) and IV (62%) (World Health Organization subtype: I [5%]; II [40%]; III [55%]) completed treatment between January 2006 and April 2010 with a median follow-up of 32 months. Incidences of ≥grade 2 acute toxicities were: dysphagia 83%; xerostomia 76%; mucositis 97%; pain 76%; fatigue 99% and ototoxicity 12%. At 12 months, ≥grade 2 subjective xerostomia was observed in 31%, ototoxicitiy in 13% and dysphagia in 4%. Two year locoregional control was 86.2% (95% confidence interval: 70.0-94.0) with 2 year progression-free survival at 78.4% (61.4-88.6) and 2 year overall survival at 85.9% (69.3-93.9). CONCLUSIONS: Chemo-IMRT for LA-NPC is feasible with good survival outcomes. At 1 year, 31% experience ≥grade 2 subjective xerostomia.


Subject(s)
Chemoradiotherapy/methods , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Adult , Aged , Chemoradiotherapy/adverse effects , Disease-Free Survival , Female , Follow-Up Studies , Humans , Induction Chemotherapy/adverse effects , Induction Chemotherapy/methods , Male , Middle Aged , Nasopharyngeal Neoplasms/mortality , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods
5.
Appl Microbiol Biotechnol ; 93(5): 1865-75, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22322872

ABSTRACT

The production of synthetic glycerol from petrochemical feedstocks has been decreasing in recent years. This is largely due to increasing supplies of crude glycerol derived as a co-product from the oleochemical industry, especially biodiesel production. The price of glycerol is at historic lows, and the supply of crude glycerol is projected to grow faster than its industrial uses. This oversupply is driving the transition from glycerol as a product to glycerol as a precursor for new industrial applications, including its use as a substrate for bioconversion. This article reviews the use of fungi for the bioconversion of crude glycerol to the value-added products 1,2-propanediol, ethanol, single cell oil, specialty polyunsaturated fatty acids, biosurfactants, and organic acids. Information on the impurities of crude glycerol from different industrial processes is also included.


Subject(s)
Fungi/metabolism , Glycerol/metabolism , Biotechnology/methods , Biotransformation
6.
Phys Rev Lett ; 103(24): 241101, 2009 Dec 11.
Article in English | MEDLINE | ID: mdl-20366193

ABSTRACT

Extended or generalized similarity is a ubiquitous but not well understood feature of turbulence that is realized over a finite range of scales. The ULYSSES spacecraft solar polar passes at solar minimum provide in situ observations of evolving anisotropic magnetohydrodynamic turbulence in the solar wind under ideal conditions of fast quiet flow. We find a single generalized scaling function characterizes this finite range turbulence and is insensitive to plasma conditions. The recent unusually inactive solar minimum--with turbulent fluctuations down by a factor of approximately 2 in power--provides a test of this invariance.

7.
Phys Rev Lett ; 98(21): 211101, 2007 May 25.
Article in English | MEDLINE | ID: mdl-17677760

ABSTRACT

We quantify the scaling of magnetic energy density in the inertial range of solar-wind turbulence seen in situ at 1 AU with respect to solar activity. At solar maximum, when the coronal magnetic field is dynamic and topologically complex, we find self-similar scaling in the solar wind, whereas at solar minimum, when the coronal fields are more ordered, we find multifractality. This quantifies the solar-wind signature that is of direct coronal origin and distinguishes it from that of local MHD turbulence, with quantitative implications for coronal heating of the solar wind.

9.
J Econ Entomol ; 97(4): 1390-403, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15384353

ABSTRACT

Extracts from three species of the plant family Piperaceae, Piper nigrum [L.], Piper guineense [Schum & Thonn, and Piper tuberculatum [Jacq.], were tested for efficacy against insects from five orders. All three species contain isobutyl amides, plant secondary compounds that act as neurotoxins in insects. These materials are considered safe to mammals because Piper spp. were used for centuries for spice and medicinal purposes. When 24-h P. nigrum LC50 values were compared between common insect pests from eastern Canada and the northeastern United States, the most sensitive species in order of increasing lethal concentration were eastern tent caterpillar, Malacosoma americanum (F.) < European pine sawfly larvae, Neodiprion sertifer (Geoffroy) < spindle ermine moth larvae, Yponomeuta cagnagella [Hübner] < viburnum leaf beetle larvae, Pyrrhalta viburni [Paykull] < stripped cucumber beetle adults, Acalymma vittatum (F.) < Colorado potato beetle adults, Leptinotarsa decemlineata (Say) < Japanese beetle adults, Popillia japonica [Newman] < hairy chinch bug, Blissus leucopterus hirtis [Montandon]. The life stage tested was the point at which each species causes the greatest amount of damage to the host plant and the point at which most gardeners would likely choose to treat with a conventional synthetic insecticide. Greenhouse trials revealed that the pepper formulations also had a repellent activity, thus protecting plant leaves from 1) herbivory (lily leaf beetle, Lilioceris lilii [Scopoli], adults and larvae and stripped cucumber beetle adults) and 2) oviposition [European corn borer, Ostrinia nubilalis (Hübner)]. Combinations with other botanical extracts were additive at best in toxicity and repellent trials. Nontarget toxicity to beneficial invertebrates is a possibility because the P. nigrum LC50 for beneficial ladybird beetles was 0.2%. P. nigrum extracts can provide a reasonable level of control against lepidopteran and European pine sawfly larvae and also will work as a short-term repellent and feeding deterrent. It is recommended that the use of Piper extracts be restricted to small-scale spot treatments in residential areas where insect pest outbreaks have occurred.


Subject(s)
Insecticides , Piper/chemistry , Plant Extracts/chemistry , Animals , Coleoptera , Hemiptera , Hymenoptera , Insect Repellents , Lepidoptera , Oviposition , Piper nigrum/chemistry , Plant Leaves , Sunlight , Ultraviolet Rays
10.
Int J Food Microbiol ; 93(3): 305-18, 2004 Jun 15.
Article in English | MEDLINE | ID: mdl-15163587

ABSTRACT

A pilot plant-scale cheese-milk pasteurisation plant was designed and constructed to study the development of biofilms of Streptococcus thermophilus during pasteurisation of milk, and to investigate methods for preventing this growth from occurring. Under base run conditions, S. thermophilus grew on surfaces in the cool-down sections of the pilot plant, between 50 and 35 degrees C (bulk milk temperature), and could be detected in the product stream after 8-10 h production, reaching levels of 10(6) CFU ml-1 after 16 h. Thermoduric bacteria also grew in the heating sections of the pilot plant, although to a lesser extent, as did non-thermoduric bacteria that originated in the raw milk. The novel application of temperature step changes, implemented periodically to the growth region of S. thermophilus, successfully controlled the development of biofilms of these organisms. The growth of bacteria on the heating side of the pilot plant was also prevented by the implementation of these same step changes. The optimum step change conditions required to achieve a 20-h production run without detectable growth of S. thermophilus comprised a step change to 55 degrees C, applied for 10 min, with a 60-min interval between step changes.


Subject(s)
Biofilms/growth & development , Cheese/microbiology , Milk/microbiology , Streptococcus/physiology , Temperature , Animals , Colony Count, Microbial , Food Handling/methods , Pilot Projects , Time Factors
11.
Clin Orthop Relat Res ; (402): 245-50, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12218490

ABSTRACT

Forty-nine children with diaphyseal both-bone forearm fractures were treated with either both-bone intramedullary wire fixation (24), single ulnar intramedullary wire fixation (22), or single radial intramedullary wire fixation (3). Six fractures were open and 43 were closed. A limited open approach to one or both bones was necessary for insertion of the intramedullary wire in 10 of 43 closed fractures. All both-bone and single radial intramedullary wire fixations healed with less than 5 degrees angulation. Progressive reangulation of the nonfixed radial fracture after an initial satisfactory reduction was seen in seven of the 22 fractures treated with single ulnar intramedullary wire fixation. In four patients, the reangulation was controlled by a change of cast and molding of the fracture and was between 8 degrees and 12 degrees at union. In two other patients a second operative procedure was required to reduce and internally fix the radius. One fracture healed with a radial angulation of 25 degrees. Three fractures in older patients showed late reangulation after early removal of intramedullary wires at 5 weeks. The results of the current study suggest that the radius and ulna should be stabilized with intramedullary wires and that the wires should be buried to reduce the need for early removal.


Subject(s)
Fracture Fixation, Intramedullary/methods , Radius Fractures/surgery , Ulna Fractures/surgery , Adolescent , Child , Female , Fracture Fixation, Intramedullary/instrumentation , Fractures, Closed/surgery , Fractures, Open/surgery , Humans , Male , Radiography , Radius Fractures/diagnostic imaging , Retrospective Studies , Treatment Outcome , Ulna Fractures/diagnostic imaging
12.
Phytopathology ; 92(5): 534-41, 2002 May.
Article in English | MEDLINE | ID: mdl-18943028

ABSTRACT

ABSTRACT Fusarium spp. in maize can contaminate the grain with mycotoxins if environmental conditions are favorable for fungal growth. To quantify the relationship between growth of Fusarium spp. and environmental conditions, a mathematical model was developed to simulate growth of F. graminearum and F. verticillioides on maize ears following silk inoculation in field experiments from 1992 to 1995. Each species was inoculated separately and as a mixture of the two for 3 of the 4 years on one maize hybrid. Disease progress in ears was measured by a visual rating scale that was converted to percent visual infection. Measurements were made at regular time intervals after silks were inoculated 5 days after silk emergence. Differential equations were used to relate growth rates of Fusarium spp. in maize ears to hourly air temperature and relative humidity and to daily precipitation. Integration of these equations over time produced quantitative estimates of fungal growth. Model calculations compared well with measurements (R(2) = 0.931, standard error of estimate [SEE] = 2.11%) of percent visual disease infection of maize ears over 3 years. The model was tested against a second set of data (R(2) = 0.89, SEE = 5.9%) in which silks were inoculated at nine different times after first silk emergence for each of 2 years (1994 and 1995) with the two species of fungi on the same maize hybrid. At this time, a silk function was developed to account for changes in the susceptibility of silks to disease. F. graminearum responded to wet conditions more than F. verticillioides, and for the conditions of this experiment, grew much faster than F. verticillioides when inoculated separately. When they were inoculated together, F. graminearum growth rates were much lower, indicating some interference by F. verticillioides. During 1993, weather conditions before inoculation reduced the growth of both species in silks.

13.
EMBO J ; 20(11): 2757-67, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11387209

ABSTRACT

Mitogen-activated protein kinase (MAPK) pathways couple intrinsic and extrinsic signals to hypertrophic growth of cardiomyocytes. The MAPK kinase MEK5 activates the MAPK ERK5. To investigate the potential involvement of MEK5-ERK5 in cardiac hypertrophy, we expressed constitutively active and dominant-negative forms of MEK5 in cardiomyocytes in vitro. MEK5 induced a form of hypertrophy in which cardiomyocytes acquired an elongated morphology and sarcomeres were assembled in a serial manner. The cytokine leukemia inhibitory factor (LIF), which stimulates MEK5 activity, evoked a similar response. Moreover, a dominant-negative MEK5 mutant specifically blocked LIF-induced elongation of cardiomyocytes and reduced expression of fetal cardiac genes without blocking other aspects of LIF-induced hypertrophy. Consistent with the ability of MEK5 to induce serial assembly of sarcomeres in vitro, cardiac-specific expression of activated MEK5 in transgenic mice resulted in eccentric cardiac hypertrophy that progressed to dilated cardiomyopathy and sudden death. These findings reveal a specific role for MEK5-ERK5 in the induction of eccentric cardiac hypertrophy and in transduction of cytokine signals that regulate serial sarcomere assembly.


Subject(s)
Cardiomyopathy, Dilated/physiopathology , Heart/physiopathology , Interleukin-6 , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinases/metabolism , Myocardium/enzymology , Sarcomeres/physiology , Animals , Animals, Newborn , Apoptosis , COS Cells , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/pathology , Cells, Cultured , Chlorocebus aethiops , Enzyme Activation , Growth Inhibitors/pharmacology , Heart Ventricles , Humans , Leukemia Inhibitory Factor , Lymphokines/pharmacology , MAP Kinase Kinase 5 , Mice , Mice, Transgenic , Mitogen-Activated Protein Kinase 7 , Mitogen-Activated Protein Kinase Kinases/genetics , Myocardium/cytology , Myocardium/pathology , Rats , Recombinant Proteins/metabolism , Sequence Deletion , Transfection
14.
Proc Natl Acad Sci U S A ; 98(6): 3328-33, 2001 Mar 13.
Article in English | MEDLINE | ID: mdl-11248078

ABSTRACT

Signaling events controlled by calcineurin promote cardiac hypertrophy, but the degree to which such pathways are required to transduce the effects of various hypertrophic stimuli remains uncertain. In particular, the administration of immunosuppressive drugs that inhibit calcineurin has inconsistent effects in blocking cardiac hypertrophy in various animal models. As an alternative approach to inhibiting calcineurin in the hearts of intact animals, transgenic mice were engineered to overexpress a human cDNA encoding the calcineurin-binding protein, myocyte-enriched calcineurin-interacting protein-1 (hMCIP1) under control of the cardiac-specific, alpha-myosin heavy chain promoter (alpha-MHC). In unstressed mice, forced expression of hMCIP1 resulted in a 5-10% decline in cardiac mass relative to wild-type littermates, but otherwise produced no apparent structural or functional abnormalities. However, cardiac-specific expression of hMCIP1 inhibited cardiac hypertrophy, reinduction of fetal gene expression, and progression to dilated cardiomyopathy that otherwise result from expression of a constitutively active form of calcineurin. Expression of the hMCIP1 transgene also inhibited hypertrophic responses to beta-adrenergic receptor stimulation or exercise training. These results demonstrate that levels of hMCIP1 producing no apparent deleterious effects in cells of the normal heart are sufficient to inhibit several forms of cardiac hypertrophy, and suggest an important role for calcineurin signaling in diverse forms of cardiac hypertrophy. The future development of measures to increase expression or activity of MCIP proteins selectively within the heart may have clinical value for prevention of heart failure.


Subject(s)
Calcineurin Inhibitors , Cardiomyopathy, Dilated/prevention & control , Muscle Proteins/physiology , Animals , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/pathology , DNA-Binding Proteins , Female , Gene Expression , Humans , Intracellular Signaling Peptides and Proteins , Mice , Mice, Inbred C57BL , Mice, Transgenic , Models, Genetic , Muscle Proteins/genetics , Myosin Heavy Chains/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/physiology
15.
J Med Genet ; 37(9): 680-3, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10978359

ABSTRACT

The role of major gene and multifactorial inheritance in the aetiology of club foot in the New Zealand Polynesian population was studied using 287 New Zealand Maori and Pacific club foot families. The club foot family data were analysed by complex segregation analysis under the mixed model using the computer program POINTER. This analysis shows that the best genetic model for club foot in this population is a single dominant gene with a penetrance of 33% and a predicted gene frequency of 0.9%. These data provide a scientific foundation for molecular studies in the Maori and Polynesian population to identify putative club foot genes.


Subject(s)
Clubfoot/genetics , Alleles , Clubfoot/ethnology , Family Health , Female , Gene Frequency , Humans , Male , New Zealand/epidemiology , Pedigree , Penetrance , Polynesia/ethnology
16.
J Adolesc ; 23(3): 243-61, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10837105

ABSTRACT

Penal, social services, special education and health agencies in one National Health Service Region were screened for severely troubled and troublesome young people in need of mental health services. One hundred and sixteen detailed assessments were undertaken on young people: 57 in "penal" and 59 in "welfare" establishments. Little difference was found between those in these two types of setting except that the "penal group" were much more likely to have high levels of violent behaviour and to have had more changes of placement. The needs for mental health care greatly outstripped supply. As part of this overall neglect, 11 of 15 young people with serious mental illnesses and all 13 who had suffered sexual abuse in the sample were not receiving appropriate treatment. A tentative estimate of the size of the problem in the region yielded a rate of around 11.4 per million with very severe disorder but this is probably an under estimate. The effectiveness of treatment for the problems of these young people is discussed and a possible structure for a service is explored.


Subject(s)
Adolescent Health Services/supply & distribution , Juvenile Delinquency/psychology , Mental Disorders/diagnosis , Mental Health Services/supply & distribution , Needs Assessment , Adolescent , Catchment Area, Health , Child , Female , Humans , Male , Mental Disorders/epidemiology , Prevalence , Social Adjustment , State Medicine , United Kingdom/epidemiology
17.
J Clin Invest ; 105(10): 1395-406, 2000 May.
Article in English | MEDLINE | ID: mdl-10811847

ABSTRACT

Hypertrophic growth is an adaptive response of the heart to diverse pathological stimuli and is characterized by cardiomyocyte enlargement, sarcomere assembly, and activation of a fetal program of cardiac gene expression. A variety of Ca(2+)-dependent signal transduction pathways have been implicated in cardiac hypertrophy, but whether these pathways are independent or interdependent and whether there is specificity among them are unclear. Previously, we showed that activation of the Ca(2+)/calmodulin-dependent protein phosphatase calcineurin or its target transcription factor NFAT3 was sufficient to evoke myocardial hypertrophy in vivo. Here, we show that activated Ca(2+)/calmodulin-dependent protein kinases-I and -IV (CaMKI and CaMKIV) also induce hypertrophic responses in cardiomyocytes in vitro and that CaMKIV overexpressing mice develop cardiac hypertrophy with increased left ventricular end-diastolic diameter and decreased fractional shortening. Crossing this transgenic line with mice expressing a constitutively activated form of NFAT3 revealed synergy between these signaling pathways. We further show that CaMKIV activates the transcription factor MEF2 through a posttranslational mechanism in the hypertrophic heart in vivo. Activated calcineurin is a less efficient activator of MEF2-dependent transcription, suggesting that the calcineurin/NFAT and CaMK/MEF2 pathways act in parallel. These findings identify MEF2 as a downstream target for CaMK signaling in the hypertrophic heart and suggest that the CaMK and calcineurin pathways preferentially target different transcription factors to induce cardiac hypertrophy.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cardiomegaly/etiology , Cardiomegaly/metabolism , DNA-Binding Proteins/metabolism , Nuclear Proteins , Transcription Factors/metabolism , Animals , Atrial Natriuretic Factor/genetics , Calcineurin/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 4 , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Cardiomegaly/genetics , Gene Expression Regulation , Genes, Reporter , Humans , Luciferases/genetics , MEF2 Transcription Factors , Mice , Mice, Transgenic , Myocardium/metabolism , Myogenic Regulatory Factors , Myosin Heavy Chains/genetics , NFATC Transcription Factors , Promoter Regions, Genetic , Rats , Signal Transduction
18.
J Pediatr Orthop ; 20(2): 189-92, 2000.
Article in English | MEDLINE | ID: mdl-10739280

ABSTRACT

The purpose of this prospective study was to document results of early spica casting in treating all children aged 10 years or younger presenting during a 30-month period with a femoral shaft fracture. The outcome of 101 femoral shaft fractures thus treated demonstrated excellent results with few complications. Four spicas had to be removed at 7 to 10 days for unacceptable shortening and an additional four probably should have been. Control of alignment was not a problem, with only one patient's femur on cast removal being in a position different from that accepted at 7 to 10 days. An age older than 7 to 8 years is the only variable that might be used to predict the need for a change in treatment at 7 to 10 days.


Subject(s)
Casts, Surgical , Femoral Fractures/therapy , Hip , Child , Child, Preschool , Female , Femoral Fractures/diagnosis , Follow-Up Studies , Fracture Healing/physiology , Humans , Male , Prospective Studies , Treatment Outcome
19.
Proc Natl Acad Sci U S A ; 97(8): 4070-5, 2000 Apr 11.
Article in English | MEDLINE | ID: mdl-10737771

ABSTRACT

Myocyte enhancer factor-2 (MEF2) transcription factors control muscle-specific and growth factor-inducible genes. We show that hypertrophic growth of cardiomyocytes in response to phenylephrine and serum is accompanied by activation of MEF2 through a posttranslational mechanism mediated by calcium, calmodulin-dependent protein kinase (CaMK), and mitogen-activated protein kinase (MAPK) signaling. CaMK stimulates MEF2 activity by dissociating class II histone deacetylases (HDACs) from the DNA-binding domain. MAPKs, which activate MEF2 by phosphorylation of the transcription activation domain, maximally stimulate MEF2 activity only when repression by HDACs is relieved by CaMK signaling to the DNA-binding domain. These findings identify MEF2 as an endpoint for hypertrophic stimuli in cardiomyocytes and demonstrate that MEF2 mediates synergistic transcriptional responses to the CaMK and MAPK signaling pathways by signal-dependent dissociation from HDACs.


Subject(s)
DNA-Binding Proteins/metabolism , Histone Deacetylases/metabolism , Signal Transduction , Transcription Factors/metabolism , Animals , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cells, Cultured , MEF2 Transcription Factors , Mice , Myogenic Regulatory Factors , Rats , Transcription, Genetic
20.
Annu Rev Genomics Hum Genet ; 1: 179-223, 2000.
Article in English | MEDLINE | ID: mdl-11701629

ABSTRACT

The identification of genetic mutations underlying familial structural heart disease has provided exciting new insights into how alterations in structural components of the cardiomyocyte lead to different forms of cardiomyopathy. Specifically, mutations in components of the sarcomere are frequently associated with hypertrophic cardiomyopathy, whereas mutations in cytoskeletal proteins lead to dilated cardiomyopathy. In addition, extrinsic stresses such as hypertension and valvular disease can produce myocardial remodeling that is very similar to that observed in genetic cardiomyopathy. For myocardial remodeling to occur, changes in gene expression must occur; therefore, changes in contractile function or wall stress must be communicated to the nucleus via signal transduction pathways. The identity of these signaling pathways has become a key question in molecular biology. Numerous signaling molecules have been implicated in the development of hypertrophy and failure, including the beta-adrenergic receptor, G alpha(q) and downstream effectors, mitogen-activated protein kinase pathways, and the Ca(2+)-regulated phosphatase, calcineurin. In the past it has been difficult to discern which signaling molecules actually contributed to disease progression in vivo; however, the development of numerous transgenic and knockout mouse models of cardiomyopathy is now allowing the direct testing of stimulatory and inhibitory molecules in the mouse heart. From this work it has been possible to identify signaling molecules and pathways that are required for different aspects of disease progression in vivo. In particular, a number of signaling pathways have now been identified that may be key regulators of changes in myocardial structure and function in response to mutations in structural components of the cardiomyocyte. Myocardial structure and signal transduction are now merging into a common field of research that will lead to a more complete understanding of the molecular mechanisms that underly heart disease.


Subject(s)
Cardiomyopathies/genetics , Animals , Apoptosis , Calcium Signaling , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Hypertrophic, Familial/genetics , Cell Nucleus/physiology , Cell Survival , GTP-Binding Proteins/physiology , Gene Expression , Humans , Mice , Mitogen-Activated Protein Kinases/physiology , Protein Kinase C/physiology , Receptors, Cell Surface/physiology , Sarcomeres/physiology , Signal Transduction
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