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Search Results: 1 - 10 of 503779 matches for " David A. Wassarman "
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The Drosophila Translational Control Element (TCE) Is Required for High-Level Transcription of Many Genes That Are Specifically Expressed in Testes
Rebeccah J. Katzenberger,Elizabeth A. Rach,Ashley K. Anderson,Uwe Ohler,David A. Wassarman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045009
Abstract: To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE). The TCE functions in the 5′ untranslated region of Mst(3)CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300–400 bp) genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID) subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and understanding the dual role of the TCE in translational and transcriptional regulation.
动物学杂志 , 1988,
Sequence similarity between stereocilin and otoancorin points to a unified mechanism for mechanotransduction in the mammalian inner ear
Luca Jovine, Jong Park, Paul M Wassarman
BMC Cell Biology , 2002, DOI: 10.1186/1471-2121-3-28
Abstract: We report that the inner ear protein stereocilin is related in sequence to otoancorin and, based on its localisation and predicted GPI-anchoring, may mediate attachment of the tectorial and otoconial membranes to sensory hair bundles.It is expected that antibodies directed against stereocilin would specifically label sites of contact between sensory hair cells and tectorial/otoconial membranes of the inner ear.Our findings support a unified molecular mechanism for mechanotransduction, with stereocilin and otoancorin defining a new protein family responsible for the attachment of acellular gels to both sensory and nonsensory cells of the inner ear.The cochlea and the vestibule, respectively, are responsible for hearing and balance in the mammalian inner ear. The tectorial membrane, an acellular gel, covers the surface of the organ of Corti within the cochlea. Similarly, otoconial and cupula membranes overlie sensory regions of the five organs constituting the vestibule. Sound-induced motion of the basilar membrane in the cochlea or head motion in the vestibule generates shear between the acellular gels and the apical surface of the sensory epithelia; the latter consist of both hair (sensory) and supporting (nonsensory) cells. Deflection of stereocilia bundles on sensory hair cells causes membrane potential alterations that transduce mechanical information into electrical signals [1-3]. Mutations in genes encoding protein components of the acellular gels result in hearing and balance defects, highlighting the importance of these structures in mechanotransduction [2-10]. Therefore, there is considerable interest in identifying molecules that are responsible for attachment of the gels to the sensory epithelia.Recently, two new genes specifically expressed in the human inner ear were described. STRC, a chromosome 15q15 gene mutated in families affected by non-syndromic deafness at the DFNB16 locus, was predicted to encode a polypeptide of 1778 amino acids of unknown func
Treatments for fibrosis development and progression: Lessons learned from preclinical models and potential impact on human conditions such as scleroderma, pulmonary fibrosis, hypertrophic scarring and tendinopathies  [PDF]
David A. Hart
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.68A2001
Abstract: Progressive fibrosis of a tissue or organ in response to a damaging insult may result in loss of organ function if the acute response is excessive, or a chronic fibrotic response is initiated due to the persistence of the insult. In the author’s laboratory over the past several years, a number of preclinical models of fibrosis or fibrogenic responses have been characterized for the effectiveness of various treatment approaches to either prevent or impede fibrosis development and progression to identify commonalities and translatable research directions that could provide insights into human diseases. These have mainly included either chemically induced pulmonary fibrosis models or overt physical injury models in rats, pigs and rabbits. Some preliminary studies in human populations have also been undertaken. The interventions evaluated have included fibrinolytic agents and drugs targeting specific cell populations. The results indicate that some approaches lend themselves to modifying fibrotic reactions in some models and not others, while others may have a more generalized impact on fibrogenic responses due to interference with abnormal cell functions in the injury environment.
Source-to-Source Translation and Software Engineering  [PDF]
David A. Plaisted
Journal of Software Engineering and Applications (JSEA) , 2013, DOI: 10.4236/jsea.2013.64A005
Abstract: Source-to-source translation of programs from one high level language to another has been shown to be an effective aid to programming in many cases. By the use of this approach, it is sometimes possible to produce software more cheaply and reliably. However, the full potential of this technique has not yet been realized. It is proposed to make source-to-source translation more effective by the use of abstract languages, which are imperative languages with a simple syntax and semantics that facilitate their translation into many different languages. By the use of such abstract languages and by translating only often-used fragments of programs rather than whole programs, the need to avoid writing the same program or algorithm over and over again in different languages can be reduced. It is further proposed that programmers be encouraged to write often-used algorithms and program fragments in such abstract languages. Libraries of such abstract programs and program fragments can then be constructed, and programmers can be encouraged to make use of such libraries by translating their abstract programs into application languages and adding code to join things together when coding in various application languages. This approach can also improve program reliability, because it is only necessary to verify the abstract programs once instead of verifying them separately in each application language. Also, this approach makes it possible to generate code faster than programming from scratch each time. This approach is compared to the use of libraries and to other methods in current use for communication between programming languages and translation between languages.
Perspectives on endogenous and exogenous tissue engineering following injury to tissues of the knee  [PDF]
David A. Hart
Journal of Biomedical Science and Engineering (JBiSE) , 2014, DOI: 10.4236/jbise.2014.72009
Abstract: The knee is a multi-component organ system comprised of several tissues which function coordinately to provide mobility. Injury to any one component compromises the integrity of the system and leads to adaptation of the other components. Over time, such events often lead to dysfunction and degeneration of the knee. Therefore, there has been considerable research emphasis to repair injured components in the knee including cartilage, menisci, and ligaments. Approaches to improving healing and repair/regeneration of knee tissues have included surgery, anti-sense gene therapy, injection of growth factors and inflammatory cytokine antagonists, transplantation of in vitro expanded chondrocytes, enhancement of endogenous cells via microfracture, injection of mesenchymal stem cells, and implantation of in vitro tissue engineered constructs. Some of these approaches have lead to temporary improvement in knee functioning, while others offer the potential to restore function and tissue integrity for longer periods of time. This article will review the status of many of these approaches, and provide a perspective on their limitations and potential to contribute to restoration of knee function across the lifespan.
Why Mesenchymal Stem/Progenitor Cell Heterogeneity in Specific Environments?
—Implications for Tissue Engineering Applications Following Injury or Degeneration of Connective Tissues

David A. Hart
Journal of Biomedical Science and Engineering (JBiSE) , 2014, DOI: 10.4236/jbise.2014.78054
Abstract: Mesenchymal stem/progenitor cells (MSC/MPC) from a variety of tissue sources (bone marrow, adipose tissue, fat pads, synovial membranes, synovial fluid, skin, muscle and periosteal tissue) have been widely applied for tissue engineering applications to generate replacements for injured or degenerated tissues. Alternatively, they have also been injected as free cells in an attempt to facilitate in vivo repair. Nearly all studies reported have used mixed cell populations of MSC/MPC, usually defined by cell surface phenotypes and/or functional ability to differentiate towards multiple cell lineages. Using more detailed cell surface phenotyping and limiting dilution approaches to isolate individual MSC/MPC clones have indicated that such mixed cell populations are very heterogeneous. In addition subsets of cells from different sources may have epigenetic modifications. While it is clear that MSC/MPC cells exhibit heterogeneity, the question of why this is the case has not been well addressed. This review will address some of these issues, as well as provide some insights into the implications when using such diverse cells for tissue engineering applications.
Is Adipocyte Differentiation the Default Lineage for Mesenchymal Stem/Progenitor Cells after Loss of Mechanical Loading? A Perspective from Space Flight and Model Systems  [PDF]
David A. Hart
Journal of Biomedical Science and Engineering (JBiSE) , 2014, DOI: 10.4236/jbise.2014.710079
Abstract: Mesenchymal stem/progenitor cells (MSC/MPC) are found in many tissues and fluids including bone marrow, adipose tissues, muscle, synovial membranes, synovial fluid, and blood. Such cells from different sources can proliferate and differentiate into different lineages (e.g. osteogenic, chondrogenic and adipogenic) after suitable stimulation. However, details regarding the regulation of MSC/MPC proliferation and differentiation status are still unclear and it is likely that regulation involves both biological and mechanical influences in the different environments. It has been noted that in humans and preclinical animal models that exposure to microgravity/space flight or prolonged bed rest (a surrogate for microgravity) can lead to infiltration of skeletal muscle and bone marrow with fat. Similarly, in preclinical models treated with multiple intramuscular injections of Botulinum Toxin A to induce muscle weakness and atrophy, there is also an infiltration of the muscle with fat. The origins and basis for these fat deposits are largely unknown, but there is a possibility that the altered mechanical and biological environments lead to dysregulation of MSC/MPC and progression to preferential differentiation towards the adipocyte lineage. Furthermore, loss of MSC regulatory control by either mechanical and/or biological factors may also contribute to their involvement in obesity development and progression. Thus, the utility of using MSC/MPC from some sources for tissue engineering purposes may be compromised and further research regarding optimal loading for tissue engineering purposes is likely warranted.
Coupled-Nonlinear Elastic Structure: An Innovative Parameterization Scheme of the Motion Equations  [PDF]
S. A. David
Applied Mathematics (AM) , 2014, DOI: 10.4236/am.2014.521324
Abstract: In this paper, I applied the Euler-Lagrange equations in order to obtain the coupled-nonlinear motion equations for an elastic structure. The model is composed of six coupled and strongly nonlinear ordinary differential equations. The new contribution of this work arises from the fact that a convenient and innovative parameterization of the motion equations for the elastic system was developed with all mathematical nonlinearities taken into account, without the usage of any simplifying linearization procedure, as found in most of the works presented in the literature. The results can be used as a source for conducting experiments and can be useful for a better understanding and control of such nonlinear elastic systems.
Would Adding Low Doses of Lithium Salts and/or Prebiotic Fibre Interventions to an Effective Exercise Protocol Further Enhance Retention of Cognitive Integrity? Potential for Preventing Loss of Cognition with Aging Using Combinations of Low Cost Regimens  [PDF]
David A. Hart
Journal of Biomedical Science and Engineering (JBiSE) , 2018, DOI: 10.4236/jbise.2018.111001
Abstract: It is clear that loss of cognition is becoming epidemic in our aging society. Onset of dementia and diseases such as Alzheimer’s are very prevalent and the prognosis is not optimistic that numbers will decrease in the coming decades. Thus, this epidemic is impacting the quality of life of a large number of people, primarily females, as well as the health care systems of many countries. Of relevance is the fact that large clinical trials of candidate drugs to treat these conditions have not been overwhelming successes, indicating that we may need to take new directions or focus on prevention. One conservative approach in this regard has been the use of exercise protocols to both retain cognition and inhibit progression of loss. With the optimization of exercise protocols, it may be time to step back and ask “how can these successes be augmented to further inhibit risk and stabilize loss early in the development of these conditions?” An example of how this could be approached is via supplementation with low doses of minerals such as lithium salts, or supplementation of the diet with prebiotics in patients with obesity and metabolic syndrome. Regarding the former, recent epidemiological studies have indicated that the content of Li in the drinking water is associated with lower incidences of cognitive diseases/conditions. While not definitive, such clues may warrant performing controlled studies using low doses of lithium salts plus exercise to further optimize impact on retention of cognition in those at risk, or those with early disease. Similarly, patients with obesity are at higher risk to develop dementia, and prebiotics can correct some of the metabolic derangements associated with the microbiome in such patients to impact risk. Thus, multiple low cost interventions plus exercise could further enhance retention of cognitive integrity in specific populations.
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