Biomedical subjects

D Auerbach

Publications and source records attributed to D Auerbach.

At least 19 recordsLinked to original sources

PubMed2006

Positron production by x rays emitted by betatron motion in a plasma wiggler.

Positrons in the energy range of 3-30 MeV, produced by x rays emitted by betatron motion in a plasma wiggler of 28.5 GeV electrons from the SLAC accelerator, have been measured. The extremely high-strength plasma wiggler is an ion column induced by the electron beam as it propagates through and ionizes dense lithium vapor. X rays in the range of 1-50 MeV in a forward cone angle of 0.1 mrad collide with a 1.7 mm thick tungsten target to produce electron-positron pairs. The positron spectra are found to be strongly influenced by the plasma density and length as well as the electron bunch length. By characterizing the beam propagation in the ion column these influences are quantified and result in excellent agreement between the measured and calculated positron spectra.

Journal Article↗

PubMed2003

Observation of terahertz emission from a laser-plasma accelerated electron bunch crossing a plasma-vacuum boundary.

Coherent radiation in the 0.3-3 THz range has been generated from femtosecond electron bunches at a plasma-vacuum boundary via transition radiation. The bunches produced by a laser-plasma accelerator contained 1.5 nC of charge. The THz energy per pulse within a limited 30 mrad collection angle was 3-5 nJ and scaled quadratically with bunch charge, consistent with coherent emission. Modeling indicates that this broadband source produces about 0.3 microJ per pulse within a 100 mrad angle, and that increasing the transverse plasma size and electron beam energy could provide more than 100 microJ/pulse.

Journal Article↗

PubMed2000

Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin.

gamma-Filamin, also called ABP-L, is a filamin isoform that is specifically expressed in striated muscles, where it is predominantly localized in myofibrillar Z-discs. A minor fraction of the protein shows subsarcolemmal localization. Although gamma-filamin has the same overall structure as the two other known isoforms, it is the only isoform that carries a unique insertion in its immunoglobulin (Ig)-like domain 20. Sequencing of the genomic region encoding this part of the molecule shows that this insert is encoded by an extra exon. Transient transfections of the insert-bearing domain in skeletal muscle cells and cardiomyocytes show that this single domain is sufficient for targeting to developing and mature Z-discs. The yeast two-hybrid method was used to identify possible binding partners for the insert-bearing Ig-like domain 20 of gamma-filamin. The two Ig-like domains of the recently described alpha-actinin-binding Z-disc protein myotilin were found to interact directly with this filamin domain, indicating that the amino-terminal end of gamma-filamin may be indirectly anchored to alpha-actinin in the Z-disc via myotilin. Since defects in the myotilin gene were recently reported to cause a form of autosomal dominant limb-girdle muscular dystrophy, our findings provide a further contribution to the molecular understanding of this disease.

Adult↗

PubMed2000

A novel marker for vertebrate embryonic heart, the EH-myomesin isoform.

Myomesin is a structural component of the M-band that is expressed in all types of striated muscle. Its primary function may be the maintenance of the thick filament lattice and its anchoring to the elastic filament system composed of titin. Different myomesin isoforms have been described in chicken and mice, but no particular function has been assigned to them. Here we investigate the spatio-temporal expression pattern of myomesin isoforms by means of reverse transcriptase-polymerase chain reaction and isoform-specific antibodies. We find that two alternative splicing events give rise to four myomesin isoforms in chicken contrary to only one splicing event with two possible isoforms in mice. A splicing event at the C terminus results in two splice variants termed H-myomesin and S-myomesin, which represent the major myomesin species in heart and skeletal muscle of avian species, respectively. In contrast, in mammalian heart and skeletal muscle only S-myomesin is expressed. In embryonic heart of birds and mammals, alternative splicing in the central part of the molecule gives rise to the isoform that we termed EH-myomesin. It represents the major myomesin isoform at early embryonic stages of heart but is rapidly down-regulated around birth. Thus, the strict developmental regulation of the EH-myomesin makes it an ideally suited marker for embryonic heart.

Alternative Splicing↗

PubMed1999

Different domains of the M-band protein myomesin are involved in myosin binding and M-band targeting.

Myomesin is a 185-kDa protein located in the M-band of striated muscle where it interacts with myosin and titin, possibly connecting thick filaments with the third filament system. By using expression of epitope-tagged myomesin fragments in cultured cardiomyocytes and biochemical binding assays, we could demonstrate that the M-band targeting activity and the myosin-binding site are located in different domains of the molecule. An N-terminal immunoglobulin-like domain is sufficient for targeting to the M-band, but solid-phase overlay assays between individual N-terminal domains and the thick filament protein myosin revealed that the unique head domain contains the myosin-binding site. When expressed in cardiomyocytes, the head domains of rat and chicken myomesin showed species-specific differences in their incorporation pattern. The head domain of rat myomesin localized to a central area within the A-band, whereas the head domain of chicken myomesin was diffusely distributed in the cytoplasm. We therefore conclude that the head domain of myomesin binds to myosin but that this affinity is not sufficient for the restriction of the domain to the M-band in vivo. Instead, the neighboring immunoglobulin-like domain is essential for the precise incorporation of myomesin into the M-band, possibly because of interaction with a yet unknown protein of the sarcomere.

Animals↗

PubMed1999

Slow growth in the United States of the number of minorities in the RN workforce.

PURPOSE: To assess the extent to which the number of minority RNs has grown during the past 20 years, and to identify and compare key trends in personal and professional characteristics among minority groups and between minority and majority populations of RNs. Nursing education programs, employers, philanthropic organizations, and governments have expended considerable effort and resources to increase the number of minorities in nursing. DESIGN: Longitudinal analysis of trends in the number, education, employment, and earnings of minority RNs from 1977 to 1997. METHODS: Descriptive analysis of data from the U.S. National Sample Surveys of the Population of Registered Nurses, 1977-1996; and data from the U.S. Bureau of the Census Current Population Survey (CPS) Outgoing Rotation Group Annual Merged Files, 1977-1997. FINDINGS: In the past 20 years, the number of minority RNs has grown from 87,386 (or 6.3% of the total supply of RNs) in 1977 to 246,364 RNs (9.7%) in 1996. The number of Black (nonHispanic), Asian Pacific/Islanders, and American Indian/Alaskan Native nurses nearly tripled in this period while the number of Hispancis doubled. Although these rates of growth are impressive, the percentage of minorities in nursing lags considerably behind the percentage (18.3%) who are teachers, and the percentage (28.2%) in the U.S. population. CONCLUSIONS: Studies are needed to determine the barriers that exist in nursing education programs, health care organizations, and society in general that deter minorities from a nursing career. Without this understanding, efforts to design and implement ideas to attract, educate, and retain minorities in nursing education and later in the workplace are hampered.

Humans↗

PubMed1999

Effects of eyelid scrubbing on the lid margin.

PURPOSE: To compare the effects of eyelid scrubbing with an eyelid cleansing solution (ECS) to eyelid scrubbing with ECS and the addition of antibacterial or anti-inflammatory pharmaceuticals on the clinical appearance, microbial status, tissue histology, and the inflammatory cell profile of the normal eyelid margin. METHODS: Eyelid scrubbing was performed twice daily using ECS; ECS with the antibacterial sulfacetamide (ECS+); and ECS with sulfacetamide and prednisolone acetate (ECS++) over a 21 day period on three groups of 16 rabbits with clinically normal eyelids. RESULTS: Significant hyperemia of the margin occurred in all three groups over the 3 week period; however, the degree of hyperemia was less with ECS+ (P<0.05) and ECS++ (P<0.05). Chemosis, tearing, mucus discharge, and the microbial status were not significantly different than controls. There were no marked histologic differences in the tissues, except for increased red blood cell packing in the small vessels near the lid margins in scrubbed eyelids, consistent with hyperemia. The inflammatory cell profile showed minimal changes that were not statistically significant in any of the three groups, except that >50% of mast cells showed evidence of degranulation. CONCLUSIONS: Use of ECS with an antibiotic, or an antibiotic and steroid solution, resulted in less inflammation than scrubbing with ECS alone.

Administration, Topical↗

PubMed1997

Molecular mechanisms of myofibril assembly in heart.

We investigated the assembly of the first sarcomeres in chicken embryos by confocal microscopy of immunofluorescently stained whole mount rudiments of early chicken hearts isolated around the onset of beating. In embryos with merely 9 somites, myomesin was found to be present in a cross striated pattern, indicating that myomesin is expressed rather early during development. RNA studies confirmed these findings and RT-PCR revealed the presence of myomesin mRNA already in the 7 somite embryo. The expression of myomesin mRNA coding for the skeletal isoform preceded the heart specific transcript. In the adult heart, however, only the heart isoform was detectable. The interaction of myomesin domains with the sarcomere was investigated by transfection of epitope tagged constructs into cultured cardiomyocytes. The second domain of myomesin, an immunoglobulin-like domain, was found to specifically bind to the M-band region of chicken cardiomyocytes. All constructs containing this domain also showed M-band localization. Additionally, constructs consisting of either the second domain of myomesin or the myosin light chain isoform MLC 3f fused to the green fluorescent protein (eGFP) were expressed in rat cardiomyocytes and were found to be distributed in the same manner as the expression constructs tagged only with the much shorter VSV epitope. Transfected cells did not show any alteration in beating activity and no alteration of myofibrillar structure, as judged by simultaneous staining for the Z-disc protein alpha-actinin and other sarcomeric markers. Apparently, the addition of eGFP did not disturb the assembly properties or the function of the two proteins and therefore allowed the easy visualization of assembly and contraction processes directly in the living cardiomyocyte.

Animals↗

PubMed1997

Chaos in protein dynamics.

MD simulations, currently the most detailed description of the dynamic evolution of proteins, are based on the repeated solution of a set of differential equations implementing Newton's second law. Many such systems are known to exhibit chaotic behavior, i.e., very small changes in initial conditions are amplified exponentially and lead to vastly different, inherently unpredictable behavior. We have investigated the response of a protein fragment in an explicit solvent environment to very small perturbations of the atomic positions (10(-3)-10(-9) A). Independent of the starting conformation (native-like, compact, extended), perturbed dynamics trajectories deviated rapidly, leading to conformations that differ by approximately 1 A RMSD within 1-2 ps. Furthermore, introducing the perturbation more than 1-2 ps before a significant conformational transition leads to a loss of the transition in the perturbed trajectories. We present evidence that the observed chaotic behavior reflects physical properties of the system rather than numerical instabilities of the calculation and discuss the implications for models of protein folding and the use of MD as a tool to analyze protein folding pathways.

Bacterial Proteins↗

PubMed1996

Tissue-specific isoforms of chicken myomesin are generated by alternative splicing.

Myomesin is a high molecular weight protein that is present in the M-band of all fiber types of cross-striated skeletal muscle and heart. We have isolated two cDNAs encoding tissue-specific isoforms of chicken myomesin with calculated molecular masses of 174 kDa in skeletal muscle and 182 kDa in heart. Distinct sequences are found at the 3'-end of the two cDNAs, giving rise to different C-terminal domains. Partial analysis of the gene structure has shown that in chicken, both isoforms are generated by alternative splicing of a composite exon. Amino acid sequences show that the main body of myomesin consists of five fibronectin type III (class I motifs) and seven immunoglobulin-like domains (class II motifs). An identical structure was found in M-protein and human 190K protein (the human counterpart of chicken myomesin), and a comparable domain arrangement occurs in the M-band-associated protein skelemin. We postulate that myomesin, M-protein, and skelemin belong to the same subfamily of high molecular weight M-band-associated proteins of the immunoglobulin superfamily and that they probably have the same ancestor in evolution.

Alternative Splicing↗

PubMed1996