Interpolation coding: A representation for numbers in neural models

A central task of perception can be defined as one of computing hierarchies of invariants. One way of representing such invariants in intermediate levels of abstraction in this hierarchy is to use discrete units. These have been termed value units. A problem with such an encoding is that there has not been a good way to represent accurate numerical quantities using these units. This paper remedies the deficiency by describing a scheme that interpolates values between units representing fixed numerical quantities. The scheme has nice properties: it extends across functional mappings and it allows different sources of evidence to be combined.This work was supported in part by the National Science Foundation under Grant DCR-8405720 and the National Institutes of Health under Public Health Service Grant 1R01NS22407-01     

Interspecies transmission and host restriction of avian H5N1 influenza virus

Long-term endemicity of avian H5N1 influenza virus in poultry and continuous sporadic human infections in several countries has raised the concern of another potential pandemic influenza. Suspicion of the avian origin of the previous pandemics results in the close investigation of the mechanism of interspecies transmission. Entry and fusion is the first step for the H5N1 influenza virus to get into the host cells affecting the host ranges. Therefore receptor usage study has been a major focus for the last few years. We now know the difference of the sialic acid structures and distributions in different species, even in the different parts of the same host. Many host factors interacting with the influenza virus component proteins have been identified and their role in the host range expansion and interspecies transmission is under detailed scrutiny. Here we review current progress in the receptor usage and host factors. Supported by the National Basic Research Program of China (Grant Nos. 2005CB523001, 2005CB523002), National Key Technologies Research & Development Program (Grant 2006BAD06A01/2006BAD06A04); US National Institutes of Health (NIH) (Grant 3 U19 AI051915-05S1), the National Natural Science Foundation of China (Grant 30599434). GAO FG is a distinguished young investigator of the NSFC (Grant No. 30525010).     

Biological properties of human melanoma cells in culture

Summary Three human melanoma cell lines derived from one primary and two metastatic tumors from three different patients were characterized for growth properties usually associated with malignant transformation; these include cell morphology, growth rate, saturation density, growth in semisolid media, colony-forming ability on contact-inhibited monolayers of normal fibroblasts and epithelial cells, and tumorigenicity in immunosuppressed mice. Variations in expression of aberrant properties were evident among the lines. One of the metastatic lines satisfied all the parameters of malignancy tested and the other showed a number of these properties, whereas the primary essentially fulfilled only one. These results suggest that cultured melanoma cells reflect the clinical variability often observed among melanoma patients and the metastatic melanoma seems to display a higher degree of malignant transformation than the primary. THis work was supported in part by USPHS Grant No. 5 T01 AI00332-06 from the National Institutes of Health, Contract E73-2001-N01-CP-3-3237 from the Virus Cancer Program of the National Cancer Institute, and USPHS Grant No. 0H00714-02 from the National Institute for Occupational Safety and Health.     

Human carbonic anhydrases. VII. A new C type isozyme in erythrocytes of American Negroes

An unusual erythrocyte carbonic anhydrase C type isozyme tentatively designated as H has been found in American Negroes. It has an electrophoretic mobility near that of carbonic anhydrase B. In about 18% of the individuals studied the H isozyme replaces half of the normal C isozyme, and in about 1% of this population only the H isozyme is present.This work was supported in part by Grant CA-01786 from the United States Public Health Service. One of us (M.J.M.) is a recipient of a National Institutes of Health predoctoral traineeship on U.S. Public Health Training Grant No. 5-T01-GM0125-05 to the Department of Anthropology.     

Normal murine melanocytes in culture

Summary A major obstacle to applying the techniques of molecular biology to the genetics and cell biology of pigmentation has been our inability to grow normal murine melanocytes in culture. We report here the establishment and characterization of continuously proliferating cultures of cutaneous pigment cells from seven strains of mice. Melanocytes were grown from the dermis of newborn mice in medium containing 12-0-tetradecanoyl-13-phorbol-acetate; a substance, such as melanotropin, that raises intracellular levels of cyclic AMP; and an extract made from human placenta. This work was supported by Grant R01 CA04679 from the U.S. National Institutes of Health and a fellowship to Dr. A. Tamura from Mr. and Mrs. Allen Locklin. The chromosome studies were carried out in the laboratory of Dr. Uta Francke, Department of Human Genetics, Yale University. JCM was supported by NIH contract number N01-CP-21037.     

Fine structure of the pterin layer in the dermis of Rana pipiens

Summary The fine structure of the pterin layer was investigated in both wild type Rana pipiens and Rana pipiens homozygous for the speckle mutant gene. No difference in morphology of the layer was noted between the wild type and mutant. The layer lines the outer surface of the stratum compactum of the dermis and separates this stratum from the stratum spongiosum. The pterin layer consists of extra-cellular material and contains membrane-bounded granules filled with fine spicules. Many of the spicules are somewhat similar in appearance to the initial calcification loci present in developing membrane bone. The layer first appears in the tadpole at approximately stage 14 (Taylor and Kollros, 1946); subsequent developmental stages are described.This work was supported by United States Public Health Service Fellowships (to G.E.W.) 1-FO2-CA32869-01 and 5-FO2-CA32869-02; (to L.W.B.) 1-FO2-GM-32, 906-01 and 1-FO2-GM-32-906-02; by funds from an Institutional Grant to the University of Colorado from the American Cancer Society (L.W.B.); by National Research Council (Canada) Grant # A6209 (L.W.B.); by Program Project HD-02282 of the National Institutes of Health; and by Health Sciences Advancement Award FR-02084 from the National Institutes of Health.     

Sex differences in activity of glucose 6-phosphate dehydrogenase from cultured human fetal lung cells despite X-inactivation

In a previous report, it was noted that glucose 6-phosphate dehydrogenase (G6PD) specific activity was approximately 45% higher in fibroblasts cultured from female fetal lung than in fibroblasts from male fetal lung. This sex difference was nullified during the first postnatal weeks by an abrupt rise in G6PD activity in cultured male lung rather than by any changes in G6PD activity in cultured female lung. No sex differences for G6PD activity were found in fetal or postnatal cultured skin (Steele and Owens, 1973). In the present report, analysis of the G6PD phenotype of clones derived from skin and lung fibroblasts from a 14-week fetus heterozygous for the AB electrophoretic variants of G6PD indicates that in these fetal cells only one X chromosome is active. Therefore, the sex differences in the specific activity of G6PD in fetal lung cells cannot be attributed to lack of X-inactivation in the female but must result from yet undefined regulatory mechanisms operative in the male.This work was supported in part by HRSF of Pittsburgh Grant No. L-22, NIH GRS Grant No. 5-S01FR05507, National Cancer Institute Grant No. R01 CA12113, and NIH Grant No. HD 05465.     

Chromosome 7 short arm deletion and craniosynostosis a 7p-syndrome

Summary A patient with craniosynostosis and a small deletion of part of the short arm of chromosome 7 is described. A review of the literature indicates that craniosynostosis has occurred in at least four of the five infants (the fifth having microcephaly) affected by structural changes (resulting in deletion) within the terminal region of the short arm of chromosome 7.Supported by: National Foundation March of Dimes Grant CA-90, National Institutes of Health Grants, No. 5S01 RR05655-07 and No. P01 GM 15 253-08     

Computer simulation of diffusely-connected neuronal populations

This paper describes computer simulations of diffusely-connected neuronal populations. Main findings are that diffuse monosynaptic linkages between populations are selectively sensitive to synchronized clusters of action potentials in the pre-synaptic population; that diffusely-connected excitatory recurrent collaterals tend to produce rhythmic series of synchronized clusters; and that diffusely-connected inhibition (both recurrent and afferent) tend to reduce the number of cells participating in a given synchronized cluster and thereby the overall transfer rate. However, recurrent inhibition tends to increase the rate at which synchronized clusters are produced by recurrent excitation. These results suggest the speculation that diffusely connected neuronal populations are particularly prone to deal with synchronized clusters of action potentials.This work has been supported by Grant GB 33687 of the National Science Foundation, Grant 1-R01-NS-10781-01 COM of the National Institutes of Health, and by a fellowship from Zonta, International     

Isolation,characterization, and long-term culture of fetal bovine tracheal epithelial cells

Summary Epithelial cells were isolated from fetal bovine trachea by exposing and stripping the mucosal epithelium from the adjacent connective tissue. The tissue was minced and enzymically dissociated in Ca-Mg-free medium containing dispase and dithiothreitol. The stripping procedure and selective trypsinization produced epithelial cell cultures free of fibroblasts. Seeded on plastic, the plating efficiency was 21.5% with a doubling time of 24 h. Dome formation, evidence of occluding junctions and active ion transport characteristic of epithelial cells, was common. Growth of the cells on glass, collagen, and Engelbreth-Holm-Swarm (EHS) substrate demonstrated a striking difference in morphology. Cells grown on EHS presented a more distinctly three-dimensional growth pattern and many more microvilli when compared to cells grown on glass or collagen. The cells retained their epithelioid characteristics through more than 30 passages as shown by the presence of distinct apical and basolateral membranes, tight junctions, and positive keratin staining. This study was supported in part by grants BRSG S07 RR05408-25, Biomedical Research Support Grant Program, Division of Research Resources, by ES 00159, Center Grant, National Institutes of Environmental Health Sciences, by R23-HL37621, New Investigator Award, National Heart, Lung and Blood Institutes, National Institutes of Health, and by the Health Effects Institute, an organization jointly funded by the U.S. Environmental Protection Agency (Assistance Agreement X-8120059) and automotive manufactures. The contents do not necessarily reflect the views of policies of HEI, EPA, or automotive manufacturers.     

Fine structural study of a possible mechanism of secretion by the interrenal cells of the brown pelican

Summary In the deeper zones of the adrenal gland of the brown pelican, small dense bodies have been observed in the subendothelial space and between adjacent interrenal cells. They appear to be extruded from the interrenal cell by reverse pinocytosis. Intracellularly, similar appearing dense bodies, bounded by a single membrane, are sometimes evident. An interpretation of the foregoing is presented and discussed which suggests that this material may be hormone which is synthesized or organized into droplet form by the agranular endoplasmic reticulum and extruded from the cell either apically or apico-laterally, to be dispersed or rendered soluble in the subendothelial space.Supported in part by the Comly Fund of the Ohio State University, by Grant AM 09658-01 from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health and Grant DT-8 from the National Institute of Dental Research.Deceased January, 1965.     

Optimal strategies in immunology III. The IgM-IgG switch

Summary During a primary immune response generally two classes of antibody are produced, immunoglobulin M (IgM) and immunoglobulin G (IgG). It is currently thought that some lymphocytes which initially produce IgM switch to the production of IgG with the same specificity for antigen. During a secondary immune response IgG is the predominant antibody made throughout the response. In this paper we address the question of why such apparently complicated modes of response should have been adapted by evolution.We construct mathematical models of the immune response to growing antigens which incorporate complement dependent cell lysis. By comparing the times required to eliminate antigen we show that under certain conditions it is advantageous for an animal to switch some of its lymphocytes from IgM to IgG production during a primary response, but yet to secrete only IgG during a secondary response. The sensitivity of such a conclusion to parameter variations is studied and the biological basis and implications of our models are fully discussed.Portions of this work were performed under the auspices of the U.S. Department of Energy. A.S.P. was also supported by the National Science Foundation under Grant No. ENG-7904852 and BRSG grant S07 RR05664-11 awarded by the Biomedical Research Support Grant Program, Division of Research Resources, National Institute of Health. A.S.P. is the recepient of an NIH Research Career Development Award 1K04 AI 00357-01. S.R. was a recipient of NIH Fellowship 5 F32 AI05107-02     

A model of the peripheral auditory system

Summary Recent electrophysiological data obtained from auditory nerve fibers of cats have made possible the formulation of a model of the peripheral auditory system that relates the all-or-none activity of these fibers to acoustic stimulation. The components of the model are intended to represent the major functional components of the peripheral system. These components are: (i) a linear mechanical system intended to represent the outer, middle, and mechanical parts of the inner ear; (ii) a transducer intended to represent the action of the sensory cells; and (iii) a model neuron whose properties are intended to represent the nerve excitation process. A general-purpose digital computer has been used to determine the response of the model to a variety of acoustic stimuli. These results have been compared with data obtained from auditory nerve fibers.This work was supported in part by the Joint Services Electronics Program (Contract DA 36-039-AMC-03200(E); and in part by the National Science Foundation (Grant GP-2495), the National Institutes of Health (Grant MH-04737-05), the National Aeronautics and Space Administration (Grant NsG-496); and by Research Grant NB-01344, National Institute of Neurological Diseases and Blindness of the National Institutes of Health, Public Health Service.     

An endonuclease fromCaenorhabditis elegans: Partial purification and characterization

A deoxyribonuclease was partially purified from the free-living nematodeCaenorhabditis elegans. The DNase functioned as an endonuclease and introduced both single-strand nicks and double-strand breaks into DNA. The enzyme hydrolyzed double-stranded DNA seven times more rapidly than single-stranded DNA. DNase activity was not affected by the addition of divalent cations below 1mm but was inhibited at higher ionic concentrations. In addition, the enzyme was not inhibited in the presence of 10mm EDTA. The enzyme was inhibited by salt concentrations greater than 20mm. Three independent mutations in thenuc-1 gene were shown to reduce nuclease activity to less than 1% of that seen in wild-type organisms. This work was supported by National Institutes of Health Grant AG03161 and a TCU Research Foundation Grant. Some stocks used in these experiments were obtained from theCaenorhabditis Genetics Center, which is supported by Contract NOI-AG-9-2113 between the NIH and the curators of the University of Missouri.     

Transformed phenotype conferred to NIH/3T3 cells by ectopic expression of heparin-binding growth factor 1/acidic fibroblast growth factor

Summary Heparin-binding growth factor 1 (HBGF-1), also known as acidic fibroblast growth factor, is a potent mitogen and angiogenic factor found in tissues such as brain, kidney and heart. The genomic and cDNA sequences indicate that HBGF-1 does not have a typical signal peptide sequence. HBGF-1 was shown to be localized to the extracellular matrix of cardiac myocytes, but the mechanism of secretion is not presently known. We have cloned the HBGF-1 cDNA which allowed us to directly test the biological activity, mechanism of secretion and transforming potential of the recombinant protein. A previous report showed that the truncated HBGF-1 confers partial transformed phenotype to the recipient fibroblasts. However, expression of full-length HBGF-1 has not been reported. The HBGF-1 coding sequence was cloned into the retroviral expression vector, SVX, and transfected into NIH/3T3 cells. Transfectants expressing full-length HBGF-1 protein at high levels form foci and grow to a higher cell density than the parental NIH/3T3 cells. Western blotting analysis showed that the recombinant HBGF-1 is a unique band of approximately 20 kDa and can be detected in the cell homogenate but not in the conditioned medium. NIH/3T3 cells were conferred anchorage independence when HBGF-1 was provided exogenously. We showed the transformed cells are capable of growing on soft agar even in the absence of exogenously-provided HBGF-1. Transfected cells expressing HBGF-1 also induced tumor formation when injected into nude mice. Thus, NIH/3T3 cells acquired a full spectrum of transformed phenotype when full length HBGF-1 was expressed at high levels. This work was supported by grants from the National Cancer Institute (RO1 CA45611), The March of Dimes Birth Defects Foundation (No. 6-549) and The Ohio Cancer Research Associates, Inc. I.-M.C. is a recipient of The Research Career Development Award (KO4 CA01369) from the National Institutes of Health.     

Uroporphyrinogen III cosynthetase activity in fibroblasts from patients with congenital erythropoietic porphyria

The activity of uroporphyrinogen III cosynthetase is lower in extracts of fibroblasts from patients with congenital erythropoietic porphyria than in extracts of fibroblasts from control subjects. The porphyric extracts do not inhibit the cosynthetase activity of control extracts. The genetically determined enzymatic defect in this disease can thus occur in other tissues besides bone marrow.Supported in part by a National Institutes of Health Grant (NB-05367).     

Species identity of insect cell lines

Summary Three mosquito cell cultures designated as Suitor's clone ofAedes aegypti, Culiseta inornata, andAedes vexans were shown to be moth by immunological, karyological, and isozyme analyses. The cells reacted with rabbit antimoth serum but not rabbit antimosquito serum. Chromosome analyses indicated Lepidopteran rather than Dipteran morphology, and three isozyme systems were confirmative. Any one of these assays would be sufficient to indicate that contamination had occurred and could be used as a periodic check for identity of cell cultures. Morphology and growth characteristics are also valid criteria to distinguish between these particular orders of insect cells. These studies were supported by Grant CA-04953-12 from the National Cancer Institute; General Research Support Grant FR-5582 from the National Institutes of Health; and Grant-in-Aid Contract M-43 from the State of New Jersey. Recipient of Research Career Award 5-K3-16,749 from the National Institutes of Health.     

Nonsecreting myeloma variants with heavy-chain carbohydrate deficiencies

Light- and heavy-chain synthesis was studied in six previously isolated S194-2 mouse myeloma variant lines and in the parent from which they were derived. Serological data and comparative analysis of the cyanogen bromide fragments obtained from variant and parent intracellular immunoglobulin showed that five variants which failed to secrete detectable amounts of IgA synthesized both heavy- and light-chain subunits. Whereas at least two heavy-chain populations were resolved in the parent line, one containing carbohydrate and one devoid of carbohydrate, only the heavy-chain fraction devoid of carbohydrate was detected in the variant lines. The correlation between carbohydrate deficiencies on the heavy chains and lack of immunoglobulin secretion in five independent subclones is discussed in terms of possible primary lesions and the role of carbohydrate in secretion.This work was supported by National Institutes of Health Grant A 109595 and National Science Foundation Grant GB-37495 to Charles Kimmel and by Public Health Service Training Grant 5T01 GM00715 to the Institute of Molecular Biology.     

Proline endopeptidase and exopeptidase activity in polymorphonuclear granulocytes

Summary Peptidases capable of releasing proline residues from polypeptides are present in the cytoplasmic fraction of rabbit polymorphonuclear granulocytes. This was shown with peptide substrates where proline is present either at the carboxy-terminal or within the polypeptide chain. Lysosomal and plasma membrane enzymes were inactive towards such polypeptides. The proline residue was hydrolyzed at either its amino end or its carboxy end. It is noteworthy that a Pro:Pro bond was cleaved both in the pentapeptide Thr-Lys-Pro-Pro-Arg and the dipeptide Pro:Pro.Supported by Grant AI-09116 from the National Institutes of Health, U.S. Public Health Service and Grant BMS72-01469 AO3 from the National Science Foundation.     

Nitrogen regulation of amino acid catabolism in Neurospora crassa

Neurospora crassa can utilize numerous compounds including certain amino acids as a sole nitrogen source. Mutants of the nit-2 locus, a regulatory gene which is postulated to mediate nitrogen catabolite repression, are deficient in the ability to utilize several amino acids as well as other nitrogen sources used by wild type. Various enzymes involved in amino acid catabolism were found to be regulated in distinct ways. Arginase, ornithine transaminase, and pyrroline-5-carboxylate dehydrogenase are all inducible enzymes but are not subject to nitrogen catabolite repression. By contrast, proline oxidase and the amino acid transport system(s) are controlled by nitrogen repression and their synthesis is increased markedly when nitrogen source is limiting. Unlike wild type, the nit-2 mutant cannot derepress amino acid transport, although proline oxidase is regulated in a normal fashion.This work was supported by Grant R01 GM-23367 from the National Institutes of Health. T. J. F. was supported by an NIH Predoctoral Traineeship in Developmental Biology; G. A. M. is supported by NIH Career Development Award GM-00052.