Science Research In 1992: What Fields Were The Hottest Of The Hot?

RANK PAPER CITATIONS 1 M. Leid, et al., "Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently," Cell, 68(2): 377- 95, 24 January 1992. 58 2 J.D. Brook, et al., "Molecular basis of myotonic dystrophy; Expansion of a trinucleotide (CTG) repeat at the 3 end of a transcript encoding a protein kinase family member," Cell, 68(4):799-808, 20 February 1992. 47 3 W.O. Spitzer, et al., "The use of beta-agonists and the risk of death and near death from asthma," NEJM, 326(8):501-6, 20 February 1992. 42 4 H.G. Harley, et al., "Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy," Nature, 355(6360):545-6, 6 February 1992. 41 5 T.E. Golde, et al., "Processing of the amyloid protein precursor to potentially amyloidogenic derivatives," Science, 255(5045):728-30, 7 February 1992. 41 6 C.E. Bear, et al., "Purification and and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR)," Cell, 68(4):809-18, 21 February 1992. 39 7 C. Aslanidis, et al., "Cloning of the essential myotonic dystrophy region and mapping of the putative defect," Nature, 355(6360):548-51, 6 February 1992. 39 8 J. Buxton, et al., "Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy," Nature, 355(6360):547-8, 6 February 1992. 37 9 Y. Tanabe, et al., "A family of metabotropic glutamate receptors," Neuron, 8(1):169-79, January 1992. 36 10 F. Abe, et al., "Lower limit on the top-quark mass from events with two leptons in pp collisions at = 1.8 TeV," Phys. Rev. Lett., 68(4):447-51, 27 January 1992. 35 11 R.A. Heyman, et al., "9-Cis retinoic acid is a high affinity ligand for the retinoid X receptor," Cell, 68(2):397-406, 24 January 1992. 33 12 Y.-H. Fu, et al., "An unstable triplet repeat in a gene related to myotonic muscular dystrophy," Science, 255(5049):1256-8, 6 March 1992. 31 13 K.W. Wood, et al., "ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK," Cell, 68(6):1041- 50, 20 March 1992. 28 14 H.Y. Lin, et al., "Expression cloning of the TGF-beta Type II receptor, a function transmembrane serine/ threonine kinase," Cell, 68(4):775-85, 21 February 1992. 27 15 M.D. Adams, et al., "Sequence identification of 2,375 human brain genes," Nature, 355(6361):632-4, 13 February 1992. 27 16 S. Matsuda, et al., "Xenopus MAP kinase activator: identification and function as a key intermediate in the phosphorylation cascade," EMBO J., 11(3):973-82, March 1992. 27 17 M. Mahadevan, et al., "Myotonic dystrophy mutation: an unstable CTG repeat in the 3 untranslated region of the gene," Science, 255(5049):1253-5, 6 March 1992. 26 18 Q.-W. Xie, et al., "Cloning and characterization of inducible nitric oxide synthase from mouse macrophages," Science, 256(5054):225-8, 10 April 1992. 25 19 A.D. Federman, et al., "Hormonal stimulation of adenylyl cyclase through Gi-protein beta gamma subunits," Nature, 356(6365):159-61, 12 March 1991. 24 20 L.A. Donehower, et al., "Mice deficient for the p53 are developmentally normal but susceptible to spontaneous tumours," Nature, 356(6366):215-21, 19 March 1992. 24 21 W.I.F. David, et al., "Structural phase transitions in the fullerene C60," Europhys. Lett., 18(3):219-225, 21 February 1992. 24 22 M.S. Brandt, et al., "The origin of visible luminescence from `porous silicon': a new interpretation," Solid State Comm., 81(4):307-12, January 1992. 23 23 C.R. Lyons, G.J. Orloff, J. M. Cunningham, "Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line," J. Biol. Chem., 267(9):6370-4, 25 March 1992. 23 24 S.M. Thomas, et al., "Ras is essential for nerve growth factor and phorbol ester-induced tyrosine phosphorylation of MAP kinases," Cell, 68(6):1031-40, 20 March 1992. 22 25 C.T. Baldwin, et al., "An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome," Nature, 355(6361):637-8, 13 February 1992. 22 26 M.P. Mattson, et al., "Beta-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity," J. Neurosci., 12(2):376- 89, February 1992. 21 27 W.J. Fanti, et al., "Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways," Cell, 69(3):413- 23, 1 May 1992. 21 28 D.P. Gearing, et al., "The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity coverter for the LIF receptor," Science, 255(5050): 1434-7, 13 March 1992. 21 29 C.A. Midgley, et al., "Analysis of p53 expression in human tumors: an antibody raised against human p53 expressed in Escherichia coli," J. Cell. Sci., 101(1):183-9, January 1992. 21 30 A. Kashishian, A. Kazlauskas, J.A. Cooper, "Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo," EMBO J., 11(4):1373-82, April 1992. 20 31 S. Dalton, R. Treisman, "Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element," Cell, 68(3):597-612, 7 February 1992. 20 SOURCE: Science Watch/Institute for Scientific Information Editor's Note: Among all research fields last year, papers addressing the role of beta-agonist bronchodilators, such as albuterol, in the treatment of asthma attracted a higher bimonthly average of citations than did any other single area of scientific investigation, according to data from the Philadelphia-based Institute for Scientific Information (ISI). Based on this criterion, ISI's monthly newsletter Science Watch put this area of scientific study at the top of its list of last year's seven hottest research fields, and--using citation analysis--also identified the 31 most cited research papers of the year. Examined together, the lists provide a fascinating glimpse of where the world of science has been heading in the recent past--and where it may be heading in the near future. In a December 1992 article, Science Watch presented the lists along with an illuminating commentary on them. Following is the article, reprinted with the permission of ISI. Science Watch searched ISI's exclusive "Hot Papers" database to compile a list of 31 of 1992's superstar papers; all had attracted at least 20 citations by the end of the year. From this group, seven red-hot fields emerged: six in the biological sciences and one in the physical sciences (see accompanying chart). The fields identified in the chart are ranked by the average bimonthly citations of the hot paper or papers in each field. This measure allows reports published later in the year to compete with those that appeared earlier and had more time to collect citations. Still and all, most are from the first half of the year. Each of the 31 papers in the group is listed in the table on page 15, ranked by total citations. As usual, Science Watch elected to pass over the year's highly cited reviews, electing to focus instead on the year's most-cited discovery accounts. In last year's study of the hottest papers, research on C60 and the other fullerenes all but stole the show. Buckyball papers, in fact, accounted for nearly half of the 23 papers that were then highlighted (Science Watch, 3[1]:1-2, January 1992). The current crop, however, produced no buckyball battalion. In fact, only one C60 paper managed to make the list of 1992's most cited reports. According to the measure of average bimonthly citations, 1992's hottest paper was a Canadian study (see item No. 3 in the table) on the use of inhaled beta-agonist bronchodilators in the treatment of asthma. The study compared a group of patients who had suffered fatal or near-fatal asthmatic events with a control group of asthmatics who had not experienced such adverse events. The regular use of inhaled beta-agonists, such as albuterol and fenoterol, was associated with an increased risk of death from asthma. According to lead author Walter O. Spitzer, McGill University, Montreal, the study has had a major impact on asthma treatment. "This paper very clearly showed that the first line of defense in the management of asthma should be topical steroids, and not beta-agonists. Beta-agonists should be a backup drug for breakthrough symptoms and should be used parsimoniously," he says. Another of 1992's hottest hits reported further research on the cystic fibrosis gene (No. 6). The cloning of this gene in 1989 attracted wide and sustained interest (Science Watch, 2[1]:5, January/ February 1991). As part of the continuing effort to understand the structural and functional properties of the gene, researchers in Toronto and Birmingham, Ala., purified its protein product, known as cystic fibrosis transmembrane regulator (CFTR). Previously, it was not entirely clear whether regulated ion channel activity was a property of the CFTR molecule itself; results in this paper suggest that it is. The authors note that the purified protein should be very useful for subsequent research: "We will be able to directly assess the functional consequences of biochemical and genetic modification of CFTR. A completely in vitro system for the study of CFTR should also prove useful for study of drugs that may alter the activity of the protein." A Japanese team fielded another of 1992's hottest papers (No. 9), which discusses a family of metabotropic glutamate receptors. Glutamate acts as a major excitatory neurotransmitter, and the neurotransmission of glutamate is believed to play a central role in many neuronal functions, including memory and learning, as well as in conditions such as epilepsy and stroke. Researchers at Kyoto University isolated three novel metabotropic glutamate receptors from rat brain, bringing the known membership of this receptor family to four. The family's unique structural architecture, the authors note, includes a large extracellular domain. "No functional role of this conserved domain has been elucidated yet," they point out, "but it may have some important functions such as interaction with a specific protein involved in the regulation of glutamate neurotransmission." Six papers in all (Nos. 2, 4, 7, 8, 12, and 17) pertain to still another of 1992's hot areas: identifying and characterizing the genetic flaw in myotonic dystrophy. Seven different research groups--six working in concert under the auspices of the Muscular Dystrophy Association, and another group that took up the chase independently--were pursuing the defect. All the groups published their results within a month of one another in Nature, Cell, and Science. The defect, a repeating triplet of cytosine, thymine, and guanine on chromosome 19, proved to be very similar to the expanding nucleotide triplet repeat seen in another genetic disorder, Fragile X syndrome (Science Watch, 3[7]:5, September 1992). Suspecting the possibility that a similar mechanism might underlie other heritable diseases, geneticists are beginning to scrutinize diabetes, Huntington's disease, and Alzheimer's, among others (R. Nowak, Journal of NIH Research, 4[4]: 49-55, April 1992). The next hottest subject of 1992 involved nuclear retinoid receptors. In fact, in terms of total citations, this topic accounted for 1992's most cited paper. Published in Cell, the No.1 paper, by Pierre Chambon and colleagues, reports the purification and cloning of a retinoid X receptor (RXR) protein that stimulates binding of thyroid hormone receptors and retinoic acid receptors (RAR) to various response elements. The authors also comment on the contributions of RAR-RXT heterodimers to such functions as transcription and signaling. The other hot 1992 paper on this topic (No. 11) discusses a specific retinoic acid that acts as a ligand for RXR. "Our observations suggest that a better understanding of retinoid metabolism may provide new insights into physiology," note the authors. After turning up in the 1991 list, amyloid proteins stayed near the top of the hot topics in 1992, with two papers weighing in. One paper (No. 5) reported on the processing of the amyloid beta precursor protein (betaAPP) by the endosomal-lysosomal system. Results supported the hypothesis that dysfunctional processing in this system may play a role in the pathogenesis of Alzheimer's (Diana Steele, The Scientist, April 5, 1992, page 15). The second paper (No. 26) examined the activity of beta-amyloid in human cortical neurons. Among the other topics treated by 1992's red-hot biomedical reports: the cloning of the transforming growth factor-beta type II receptor, a sequence identification of human brain genes, and the cloning of inducible nitric oxide (NO) synthase from mouse macrophages. The role of Ras in nerve growth factor function was another hot topic, as was that perennial favorite, the tumor suppressor gene p53. The physical sciences, despite the falloff in fullerene fervor, still managed a respectable showing in this 1992 tally. At the top for physics, quite suitably, is a paper discussing the top quark. The hunt for this elusive particle--the last of 12 fundamental units of matter recognized by physicists--has been going on for more than a decade. In paper No. 10, the Collision Detector Facility (CDF) Collaboration at the Fermi National Accelerator Laboratory's Tevatron Collider presented its analysis of data collected during 1988-89. Although the CDF team failed to cop the top quark, it was able to posit a lower limit on the particle's mass. A year later, the world still awaits confirmation of the top quark, although events in the CDF in the fall of 1992 had physicists buzzing. Other heavy hitters in physics included 1992's sole entry from the buckyball brigade: a report (No. 21) on structural phase transitions in C60. Physicists also sought enlightenment concerning the source of visible photoluminescence in porous silicon. A paper on this topic by a German team (No. 22) burned brightly in 1992. A key 1990 paper on photoluminescence in silicon recently arose as a fixture in Science Watch's physics Top 10, as well (Science Watch, 3[6]:6, August 1992).

Science Research In 1992: What Fields Were The Hottest Of The Hot?

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