Ruth Hogue Angeletti

Bio: Ruth Hogue Angeletti is an academic researcher from Albert Einstein College of Medicine. The author has contributed to research in topics: Peptide & Peptide sequence. The author has an hindex of 41, co-authored 131 publications receiving 6211 citations. Previous affiliations of Ruth Hogue Angeletti include Yeshiva University & University of Pennsylvania.

A common open representation of mass spectrometry data and its application to proteomics research

Abstract: A broad range of mass spectrometers are used in mass spectrometry (MS)-based proteomics research. Each type of instrument possesses a unique design, data system and performance specifications, resulting in strengths and weaknesses for different types of experiments. Unfortunately, the native binary data formats produced by each type of mass spectrometer also differ and are usually proprietary. The diverse, nontransparent nature of the data structure complicates the integration of new instruments into preexisting infrastructure, impedes the analysis, exchange, comparison and publication of results from different experiments and laboratories, and prevents the bioinformatics community from accessing data sets required for software development. Here, we introduce the 'mzXML' format, an open, generic XML (extensible markup language) representation of MS data. We have also developed an accompanying suite of supporting programs. We expect that this format will facilitate data management, interpretation and dissemination in proteomics research.

Nerve growth factor from mouse submaxillary gland: amino acid sequence.

Abstract: The complete amino-acid sequence of the 2.5S nerve growth factor from male-mouse submaxillary glands has been determined. The unambiguous alignment of peptides derived from tryptic, chymotryptic, thermolytic, and peptic digestion of S-carboxymethyl-, S-aminoethyl-, and native growth factor indicates that the primary subunit is composed of 118 amino acids, with amino-terminal serine and carboxyl-terminal arginine. The molecular weight of this subunit, calculated from the primary sequence, is 13,259. Thus, the native protein, which is composed of two of the subunits, has a molecular weight of 26,518. These values, as well as the final amino-acid composition, are in excellent agreement with those determined by direct measurement with undigested growth factor. The alignment of the three disulfide bonds, determined from a combination of peptic and thermolytic digestions, is I-IV, II-V, and III-VI. The latter two pairs are located in a closed loop of 14 amino acids, by virtue of the fact that half-cystinyl residues V and VI are separated by only a single residue in the linear sequence. Assignment of the side-chain amides showed that 7 of 11 aspartic acid residues and 2 of 8 glutamic acid residues are present as amides. This distribution of charged residues is entirely consistent with the observed isoelectric point of 9.3.

Insights into the mechanism of microtubule stabilization by Taxol

Abstract: The antitumor drug Taxol stabilizes microtubules and reduces their dynamicity, promoting mitotic arrest and cell death. Upon assembly of the α/β-tubulin heterodimer, GTP bound to β-tubulin is hydrolyzed to GDP reaching a steady-state equilibrium between free tubulin dimers and microtubules. The binding of Taxol to β-tubulin in the polymer results in cold-stable microtubules at the expense of tubulin dimers, even in the absence of exogenous GTP. However, there is little biochemical insight into the mechanism(s) by which Taxol stabilizes microtubules. Here, we analyze the structural changes occurring in both β- and α-tubulin upon microtubule stabilization by Taxol. Hydrogen/deuterium exchange (HDX) coupled to liquid chromatography–electrospray ionization MS demonstrated a marked reduction in deuterium incorporation in both β-and α-tubulin when Taxol was present. Decreased local HDX in peptic peptides was mapped on the tubulin structure and revealed both expected and new dimer–dimer interactions. The increased rigidity in Taxol microtubules was distinct from and complementary to that due to GTP-induced polymerization. The Taxol-induced changes in tubulin conformation act against microtubule depolymerization in a precise directional way. These results demonstrate that HDX coupled to liquid chromatography–electrospray ionization MS can be effectively used to study conformational effects induced by small ligands on microtubules. The present study also opens avenues for locating drug and protein binding sites and for deciphering the mechanisms by which their interactions alter the conformation of microtubules and tubulin dimers.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

Microtubules as a target for anticancer drugs.

Abstract: Highly dynamic mitotic-spindle microtubules are among the most successful targets for anticancer therapy. Microtubule-targeted drugs, including paclitaxel and Vinca alkaloids, were previously considered to work primarily by increasing or decreasing the cellular microtubule mass. Although these effects might have a role in their chemotherapeutic actions, we now know that at lower concentrations, microtubule-targeted drugs can suppress microtubule dynamics without changing microtubule mass; this action leads to mitotic block and apoptosis. In addition to the expanding array of chemically diverse antimitotic agents, some microtubule-targeted drugs can act as vascular-targeting agents, rapidly depolymerizing microtubules of newly formed vasculature to shut down the blood supply to tumours.

The nerve growth factor 35 years later

Abstract: "Embryogenesis is in some way a model system. It has always been distinguished by the exactitude even punctitio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves . . . one too often feels that they might have been delivered five years beforehand without making anyone much the wiser, or deferred for five years without making anyone conscious of a great loss" (1). This feeling of frustration so incisively conveyed by these considerations by P. Medawar, pervaded, in the forties, the field of experimental embryology which had been enthusiastically acclaimed in the mid-thirties, when the upper lip of the amphibian blastopore brought this area of research to the forefront of the biological stage. The side branch of experimental neuroembryology, which had stemmed out from the common tree and was entirely devoted to the study of the tropic interrelations between neuronal cell populations and between these and the innervated organs and tissues, was then in its initial vigorous growth phase. It in turn suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R. G. Harrison delivered his celebrated lecture on this topic at the Royal Society in London in 1935 (2). Although the alternate "wax and wane" cycles are the rule rather than the exception in all fields of human endeavor, in that of biological sciences the "wane" is all too often indicative of a justified loss of faith in the rational and methodical approach that had at first raised so much hope. A brief account of the state-of-the-art of experimental neuroembryology in the

Epidermal growth factor

Abstract: During the course of purifying nerve growth factor from the submaxillary gland of the mouse, Cohen (1960) and Levi-Montalcini and Cohen (1960) noticed that daily injections of certain gland extract fractions into newborn mice produced developmental changes that could not be ascribed to nerve growth factor. These changes included precocious opening of the eyelids (7 days compared to the usual 14 days) and a similar early eruption of the incisors. Using these gross anatomical changes as an assay, Cohen (1962) proceeded to isolate the active factor — a polypeptide which he termed epidermal growth factor (EGF).