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SummaryNeoplastic transformation of rat embryo cells in vitro by an osteosarcoma (FBJ) virus is reported. Foci of transformed cells consisted largely of spindle-shaped cells which stained vividly with acridine orange. The transformed cells produced virus and complement-fixing (CF) antigen characteristic of the murine leukemia-sarcoma virus complex. Tumors were produced when transformed cells were injected into newborn mice and rats. The mouse tumors had the histologic pattern of osteosarcoma, which was transmissible in cell-free passages in newborn mice. Cell-free extracts of the mouse tumors also produced transformed foci in vitro. The rat rumors were undifferentiated sarcomas, also yielding virus and CF antigens.

Background Reactive oxygen species, ionizing radiation, and other free radical generators initiate the conversion of guanine (G) residues in DNA to 8-oxoguanine ( O G), which is highly mutagenic as it preferentially mispairs with adenine (A) during replication. Bacteria counter this threat with a multicomponent system that excises the lesion, corrects O G:A mispairs and cleanses the nucleotide precursor pool of d O GTP. Although biochemical evidence has suggested the existence of base-excision DNA repair proteins specific for O G in eukaryotes, little is known about these proteins. Results Using substrate-mimetic affinity chromatography followed by a mechanism-based covalent trapping procedure, we have isolated a base-excision DNA repair protein from Saccharomyces cerevisiae that processes O G opposite cytosine ( O G:C) but acts only weakly on O G:A. A search of the yeast genome database using peptide sequences from the protein identified a gene, OGG1 , encoding a predicted 43 kDa (376 amino acid) protein, identical to one identified independently by complementation cloning. Ogg1 has O G:C-specific base-excision DNA repair activity and also intrinsic β -lyase activity, which proceeds through a Schiff base intermediate. Targeted disruption of the OGG1 gene in yeast revealed a second O G glycosylase/lyase protein, tentatively named Ogg2, which differs from Ogg1 in that it preferentially acts on O G:G. Conclusions S. cerevisiae has two O G-specific glycosylase/lyases, which differ significantly in their preference for the base opposite the lesion. We suggest that one of these, Ogg1, is closely related in overall three-dimensional structure to Escherichia coli endonuclease III (endo III), a glycosylase/lyase that acts on fragmented and oxidatively damaged pyrimidines. We have recently shown that AlkA, a monofunctional DNA glycosylase that acts on alkylated bases, is structurally homologous to endo III. We have now identified a shared active site motif amongst these three proteins. Using this motif as a protein database searching tool, we find that it is present in a number of other base-excision DNA repair proteins that process diverse lesions. Thus, we propose the existence of a DNA glycosylase superfamily, members of which possess a common fold yet act upon remarkably diverse lesions, ranging from UV photoadducts to mismatches to alkylated or oxidized bases.

Background: Transversion mutations are caused by 8-oxoguanine ( O G), a DNA lesion produced by the spontaneous oxidation of guanine nucleotides, which mis-pairs with adenine during replication. Resistance to this mutagenic threat is mediated by the GO system, the components of which are functionally conserved in bacteria and mammals. To date, only one of three GO system components has been identified in the budding yeast Saccharomyces cerevisiae , namely the O G:C-specific glycosylase/lyase yOgg1. Furthermore, S. cerevisiae has been reported to contain a unique glycosylase/lyase activity, yOgg2, which excises O G residues opposite adenines. Paradoxically, according to the currently accepted model, yOgg2 activity should increase the mutagenicity of O G lesions. Here we report the isolation of yOgg2 and the elucidation of its role in oxidative mutagenesis. Results: Borohydride-dependent cross-linking using an O G-containing oligonucleotide substrate led to the isolation of yOgg1 and a second protein, Ntg1, which had previously been shown to process oxidized pyrimidines in DNA. We demonstrate that Ntg1 has O G-specific glycosylase/lyase activity indistinguishable from that of yOgg2. Targeted disruption of the NTG1 gene resulted in complete loss of yOgg2 activity and yeast lacking NTG1 had an elevated rate of A:T to C:G transversions. Conclusions: The Ntg1 and yOgg2 activities are encoded by a single gene. We propose that yOgg2 has evolved to process O G:A mis-pairs that have arisen through mis-incorporation of 8-oxo-dGTP during replication. Thus, the GO system in S. cerevisiae is fundamentally distinct from that in bacteria and mammals.

This Classic article is a reprint of the original work by William Arbuthnot Lane, The Operative Treatment of Fractures. An accompanying biographical sketch on William Arbuthnot Lane, M.S., F.R.C.S., is available at DOI 10.1007/s11999-009-0861-3. The Classic Article is ©1909 by Wolters Kluwer Health-Lippincott Williams & Wilkins and is reprinted with permission from Lane WA. The operative treatment of fractures. Ann Surg. 1909;50:1106.

Here, we report the identification of a new E1A binding protein complex that is essential for E1A-mediated transformation. Its core component is a SWI2/SNF2-related, 400 kDa protein (p400). Other components include the myc- and p/CAF-associated cofactor, TRRAP/PAF400, the DNA helicases TAP54α/β, actin-like proteins, and the human homolog of the Drosophila Enhancer of Polycomb protein. An E1A mutant, defective in p400 binding, is also defective in transformation. Certain p400 fragments partially rescued this phenotype, underscoring the role of E1A-p400 complex formation in the E1A transforming process. Furthermore, E1A and c- myc each alter the subunit composition of p400 complexes, implying that physiological p400 complex formation contributes to transformation suppression.

SummaryWe have identified a protein, Kif24, that shares homology with the kinesin-13 subfamily of motor proteins and specifically interacts with CP110 and Cep97, centrosomal proteins that play a role in regulating centriolar length and ciliogenesis. Kif24 preferentially localizes to mother centrioles. Loss of Kif24 from cycling cells resulted in aberrant cilia assembly but did not promote growth of abnormally long centrioles, unlike CP110 and Cep97 depletion. We found that loss of Kif24 leads to the disappearance of CP110 from mother centrioles, specifically in cycling cells able to form cilia. Kif24 is able to bind and depolymerize microtubules in vitro. Remarkably, ectopically expressed Kif24 specifically remodels centriolar microtubules without significantly altering cytoplasmic microtubules. Thus, our studies have identified a centriolar kinesin that specifically remodels a subset of microtubules, thereby regulating cilia assembly. These studies also suggest mechanistic differences between the regulation of microtubule elongation associated with centrioles and cilia.

Background: Base-excision DNA repair (BER) is the principal pathway responsible for the removal of aberrant, genotoxic bases from the genome and restoration of the original sequence. Key components of the BER pathway are DNA glycosylases, enzymes that recognize aberrant bases in the genome and catalyze their expulsion. One major class of such enzymes, glycosylase/lyases, also catalyze scission of the DNA backbone following base expulsion. Recent studies indicate that the glycosylase and lyase functions of these enzymes are mechanistically unified through a common amine-bearing residue on the enzyme, which acts as both the electrophile that displaces the aberrant base and an electron sink that facilitates DNA strand scission through imine (Schiff base)/conjugate elimination chemistry. The identity of this critical amine-bearing residue has not been rigorously established for any member of a superfamily of BER glycosylase/lyases. Results: Here, we report the identification of the active-site amine of the human 8-oxoguanine DNA glycosylase (hOgg1), a human BER superfamily protein that repairs the mutagenic 8-oxoguanine lesion in DNA. We employed Edman sequencing of an active-site peptide irreversibly linked to substrate DNA to identify directly the active-site amine of hOgg1 as the ϵ-NH 2 group of Lys249. In addition, we observed that the repair-inactive but recognition-competent Cys249 mutant (Lys249→Cys) of hOgg1 can be functionally rescued by alkylation with 2-bromoethylamine, which functionally replaces the lysine residue by generating a γ-thia-lysine. Conclusions: This study provides the first direct identification of the active-site amine for any DNA glycosylase/lyase belonging to the BER superfamily, members of which are characterized by the presence of a helix-hairpin-helix-Gly/Pro-Asp active-site motif. The critical lysine residue identified here is conserved in all members of the BER superfamily that exhibit robust glycosylase/lyase activity. The ability to trigger the catalytic activity of the Lys249→4Cys mutant of hOgg1 by treatment with the chemical inducer 2-bromoethylamine may permit snapshots to be taken of the enzyme acting on its substrate and could represent a novel strategy for conditional activation of catalysis by hOgg1 in cells.

SummaryIn the course of screening for new small-molecule modulators of cell motility, we discovered that quinocarmycin (also known as quinocarcin) analog DX-52-1 is an inhibitor of epithelial cell migration. While it has been assumed that the main target of DX-52-1 is DNA, we identified and confirmed radixin as the relevant molecular target of DX-52-1 in the cell. Radixin is a member of the ezrin/radixin/moesin family of membrane-actin cytoskeleton linker proteins that also participate in signal transduction pathways. DX-52-1 binds specifically and covalently to the C-terminal region of radixin, which contains the domain that interacts with actin filaments. Overexpression of radixin in cells abrogates their sensitivity to DX-52-1's antimigratory activity. Small interfering RNA-mediated silencing of radixin expression reduces the rate of cell migration. Finally, we found that DX-52-1 disrupts radixin's ability to interact with both actin and the cell adhesion molecule CD44.

Recent surveys show that there are unlimited opportunities in the food, dairy, and regulatory agency fields. An entire new food product development program has started with the space age. It has become imperative to consider anew universal nutrition problems. Industry and educational institutions, as well as the individual himself have a responsibility to develop present opportunities through recruitment programs, training programs, research projects, and incentive plans. The future holds higher technological demands which must: be developed to meet the food needs of the world's population.

The breakdown mechanism for SOI (silicon-on-insulator) n-type MOSFETs is discussed. It is proposed that by reducing the channel lateral electric field at the drain that breakdown can be increased. A two-dimensional finite-element modeling program was used to design a treble diffused drain-sources (TDD) implant profile which would increase the breakdown voltage. The modeling showed that a linearly graded structure would lower the electric field in the channel and would subsequently increase drain-source breakdown voltage by over 20%. Transistors fabricated in e-beam recrystallized material verified these predictions. >

Hamster tumors transplanted subcutaneously from primary intracranial tumors which developed after inoculation of the Bryan strain of Rous sarcoma virus, contained virusspecific tumor antigens indistinguishable from those induced by the Schmidt-Ruppin strain.

Chemical and physical aspects of a program to formulate radioactive aerosols, to design exposure chambers, and to assess the biological hazards by sacrificing exposed animals and analyzing organs and tissues for internally deposited radionuclides are discussed. (C.J.G.)

The word pim in I Samuel 13: 21 was unintelligible until Raffaeli identified it 1 with the pym which is inscribed on small weights from Palestine.2 This identification is now almost universally accepted. The word is thus the name of a weight. The context of the Biblical passage shows that it was used for measuring silver. Clermont-Ganneau had pointed out the purely consonantal Hebrew orthography at the time of the weights. He thought that the word was a dual, to be vocalized *payim, and suggested that it was the dual of Hebrew pe (h), "mouth" or "fraction," assigning to it the specific meaning "two-thirds." 3 It must be admitted that the Hebrew word p (h) can have the meaning "one-third." This meaning is clear in Zechariah 13: 8, where a whole is divided into pi-9nayim and Peldt. The same meaning is found in the cognate Akkadian .in 2pi, " two-thirds," and Ugaritic inpt. Additional weight is given to Clermont-Ganneau's suggestion by the fact that the weight of a pym is two-thirds that of a shekel.4 It is, therefore, not surprising that although scholars have expressed reservations about this explanation none has completely rejected it. However, there are references from outside Palestine which appear to be allusions to this weight and which are, therefore, pertinent, The first is the Phoenician inscription from Kition found in CIS I, 87; a transcription of it follows.

SummaryAmantadine hydrochloride (1 adamantanamine hydrochloride), a compound reported to be active against influenza viruses and Rous sarcoma viruses, inhibited the in vitro cellular transformation induced by Murine sarcoma viruses. The antiviral activity is not due to direct inactivation of the virus.

RAT embryo cells infected with either CF-1 or Rauscher C-type RNA murine leukaemia virus, when treated with diethylnitrosamine (DENA), undergo morphological transformation and become aneuploid1. Untreated cells and cells treated with either virus or chemical alone do not transform. We describe here a similar effect of 3-methylcholanthrene (3 MC) on rat cells infected with Rauscher leukaemia virus.

This paper reviews two of the major sociological theories of modernization, the consensus and conflict perspectives. These two theories are used to analyze some aspects of the economic and political situation in Chile. The international stratification approach is then presented as a third theory. Based upon criteria developed during the critique of the consensus and conflict theories, it is argued that the international stratification paradigm offers a synthesis of these two approaches which may be able to fulfill the requirements for a comprehensive sociological theory of modernization. From the classical period to the present sociologists have been con cerned with social change and development. Comte, Spencer and others, under the influence of Darwin, were particularly concerned with social progress. Social progress has been defined as "attempts to trace the evo lution of specific social forms or entire societies from some earlier, less advanced state to a terminal, advanced state . . (Apelbaum, 1970:18). While sociologists no longer discuss social progress, they are concerned with development and, the more inclusive process, modernization. This interest in modernization became an urgent area of study at the end of the Second World War as a result of the changing international situation, particularly in relationship to the colonial countries (Bernstein, 1971). This paper examines two general approaches to the sociology of modernization, the consensus and conflict theories. The work of Smelser and Marx will be examined as important and representative examples of each of the respective theories. Data on social change in Chile is then used to examine the explanatory abilities of each theory. The interna tional stratification approach, an alternative model to the conflict and consensus models, will be discussed. Based upon the evaluation of each of these approaches, some requirements for a sociological theory of modernization will be presented.

Immunization of crossbred and F1 mice with combined killed and live Gross leukemia virus AKR type-C viral vaccines suppressed endogeneous N-type AKR virus up to 10,000-fold for significant periods during early life. Since several previous studies in the same and similar crossbred systems revealed direct correlations between low and high levels of type-C virus early in life with low and high incidences of leukemia and other cancers later in life, we believe that prospects for suppression of spontaneous neoplasms are good; however, 8-14 months will be required to achieve the final results. Should cancers be prevented by serotype-specific vaccines, such evidence would provide conclusive proof of endogenous viral etiology.

Eight food dyes or commercial color mixtures certified for use in the United States were tested for their ability to transform in vitro a serial line of Fischer rat embryo cells previously reported to be a sensitive indicator of chemicals having carcinogenic potential. Malignant cell transformation was induced by a commercial mixture (G2024) of two of these dyes (Blue 1 and Yellow 5) and by Blue 2, Green 3 (one of two experiments) and Red 4. Food dyes Blue 1, Red 3, Yellow 5 and Yellow 6 did not induce cell transformation. One to 1.5 mg of each dye was injected into suckling LVG or Graffi hamsters which were monitored for tumor induction and/or death over a 330-day period. None of the non-transforming dyes (Blue 1, Red 3, Yellow 5, Yellow 6) or Green 3 induced a significant increase in tumor (mostly lymphoma) incidence or animal mortality. Three of the transforming dyes (Blue 2, Green 2024, Red 4) did increase tumor incidence and/or mortality in at least one strain of hamster. We conclude the the in vitro assay suggested that certain food dyes were carcinogens and that in vivo studies in hamsters supported this interpretation.

Our previous work has shown that, in the yeast Saccharomyces cerevisiae, any of the eight stabilizing amino-terminal residues confers a long (> 20 h) half-life on a test protein β-galactosidase (β gal), whereas 12 destabilizing amino-terminal residues confer on β gal half-lives from less than 3 min to 30 min. We now show that an analogous single-residue code (the N-end rule) operates in an in vitro system derived from mammalian reticulocytes. We also show that the N-end rule has a hierarchical structure. Specifically, amino-terminal Glu and Asp (and also Cys in reticulocytes) are secondary destabilizing residues in that they are destabilizing through their ability to be conjugated to primary destabilizing residues such as Arg. Amino-terminal Gln and Asn are tertiary destabilizing residues in that they are destabilizing through their ability to be converted, via selective deamidation, into secondary destabilizing residues Glu and Asp. Furthermore, in reticulocytes, distinct types of the N-end-recognizing activity are shown to be specific for three classes of primary destabilizing residues: basic (Arg, Lys, His), bulky hydrophobic (Phe, Leu, Trp, Tyr), and small uncharged (Ala, Ser, Thr). Features of the N-end rule in reticulocytes suggest that the exact form of the N-end rule may depend on the cell's physiological state, thereby providing a mechanism for selective destruction of preexisting proteins upon cell differentiation.

A glial hyaluronate-binding protein (GHAP) with an isoelectric point of 4.3-4.4 was isolated from human brain white matter. The 60-kDa glycoprotein appeared to be quite resistant to proteolysis, and comparison with GHAP from a viable glioma removed at surgery showed that the protein isolated from autopsy material was not a degradation product resulting from postmortem autolysis. The protein was localized immunohistochemically with mouse monoclonal and rabbit polyclonal antibodies in cerebral white matter. Only small amounts could be found in the gray matter. After enzymatic deglycosylation, an immunoreactive 47-kDa polypeptide was obtained. Two amino acid sequences of GHAP showed a striking similarity (up to 89%) with a highly conserved region of cartilage proteins (bovine nasal cartilage proteoglycan and rat and chicken link protein). However, the amino acid composition and other amino acid sequences suggested that there are also differences between brain-specific GHAP and cartilage proteins.

SummaryAdenovirus type 3 strain JF was propagated in its early passage history in rhesus monkey kidney cell cultures. Upon discovery of infectious SV40 in the adenovirus, further passages were carried out in African green monkey kidney cell cultures in the presence of SV40 antiserum. Following this procedure, two separate passage lines of the adenovirus were free of detectable infectious SV40, but vaccine seeds prepared from these lines (JF-1 and JF-2) induced in hamsters tumors which contained CF antigens identical to those found in tumors induced by SV40. These tumors, in turn, elicited serum antibodies that fixed complement with SV40 tumor and T antigens. In addition, both lots of adenovirus 3 strain JF induced the formation in human embryo kidney cells of SV40 antigen which was detected by the immuno-fluorescent technique. The induction of fluo-rescent-stainable SV40 T antigen in tissue culture was prevented by treatment of the virus with adenovirus type 3 neutralizing antiserum but not by treatment w...

The uptake of five radionuclides (Sr-85, Zr-Nb-95, Ru-106, Cs-137, and Ce-144) was measured for seven plants (bean, carrot, clover, lettuce, radish, tomato, and wheat) grown in three different soil types (sand, loam, and clay). Plants were grown in large soil containers that allowed most of the root system to develop under normal field conditions. Sampling started as soon as the plants sprouted and continued at frequent intervals depending on growth characteristics of the plant. Plant uptake contamination factors (a sub SU) were calculated for each of the samples harvested. Comparisons of the uptake for various plant part-soil-radionuclide combinations at crop maturity show that the a sub SU values for Sr-85 are the largest in all instances, usually by an order of magnitude. The a sub SU value for the edible portion of each plant was lowest in every case, and usually the leafy portion of the plant had the largest a sub SU value.

When newborn hamsters were inoculated subcutaneously with chicken-embryo lethal orphan virus, tumnors developed at the site of inoculation in 23 out of 69 hamsters within 88 to 195 days of inoculation. These tutlnors and tissue cultures, prepared from a primary tumor, were transplantable to newborn and weanling hamsters. The primary tumnors and tissue cultures of a primary tumor were free of demnonstrable infectious virus. The virus is the first "nonhuman" adenovirus found to induce tumors in hamsters.

Tests for the group-specific antigen of the C-type RNA tumor virus showed that mouse embryos of all strains tested, at some stage of development in utero , revealed detectable titers of group-specific antigen in one or more of their tissues; younger, rather than older, embryos were likely to be positive, particularly in those strains which normally reveal little or no expression of the RNA genome postnatally. The antigens were found in embryos of low-leukemia strains, free of infectious virus. These new findings support a previously stated hypothesis that the genome of RNA tumor viruses, mostly switched off for infectious virus expression, is vertically transmitted as part of the natural genetic apparatus of normal mouse cells. Since group-specific antigens have also been described in chick embryos and immunological tolerance to homologous group-specific antigens has been demonstrated in hamsters and cats as well as in mice and chickens, the hypothesis has been extended to include vertebrate cells in general. Finally, the high incidence and titers of the group-specific antigen suggest that the genes for RNA tumor virus, which later in life act as determinants of cancer, may be important also as gene determinants in the developing embryo.

The toxicity of pyrolysis products (550°C) of polytetrafluoroethylene (PTFE) was evaluated by exposure of dogs, rabbits, guinea pigs, rats and mice. Carbonyl fluoride (COF2) was identified as the principal toxic component. One-hour exposures of rats showed a 24-hour LC50 of 370 ppm for the pyrolysis products and an LC50 of 360 ppm for COF2. When PTFE is pyrolyzed in the absence of silica, the products are less toxic to a slight degree. Pathology revealed changes in the lungs and livers of exposed animals. Irritation of the lungs may persist for some days.

Rafter, Gale W. (The Johns Hopkins School of Medicine and School of Hygiene and Public Health, Baltimore, Md.) and William C. Lane . Phosphoproteins in Escherichia coli . J. Bacteriol. 83: 1077–1083. 1962.—The identification and metabolism of phosphoprotein were investigated in Escherichia coli . Hydrolysis of bacterial protein fractions with barium hydroxide or with phosphoprotein phosphatase released acid-soluble phosphorus. Chromatography of acid-hydrolyzed and incubated fractions also indicated the presence of phospho-amino acids. Turnover of phosphate in protein of growing cells was not observed, but incorporation of phosphate into protein of nongrowing cells was found. The protein-phosphate content decreased as organisms passed from the growing to the nongrowing state. The phosphoprotein composition, as revealed by paper electrophoresis, was heterogeneous. No protein phosphokinase or protein-phosphate phosphatase was detected in cell-free extracts, but an active principle which catalyzed the formation of acid-soluble phosphate from bacterial protein fractions was found.

Over the years there has been a continual increase in the rating requirements for metal-clad switchgear. Both the continuous ratings and the interrupting values have been pushed upwards in order to keep pace with the growing needs of industrial and utility electric power systems. Each rating increase has generally led to the need for better insulation for one or more of the following reasons: higher voltage, increased operating temperature, greater short-circuit forces, improved reliability, and increased operator safety.

HaItley aind Rtowel reported that the in vitro focus-formiing effects of Moloney sarcoma virus (iMISV)2 I depended on the presence in the same cells of two virus particles, a defective M/ISV particle and a fully infectious M\/Ioloney leukemia particle. Superinfection with additional Moloney leukemia virus potentiated focus formation by 1MISV, converting a "two-hit" dose response curve to a one-hit curve; preliminary experiments also suggested a two-hit requirement for sarcoma induction in vivo by M\SV.4 These experiments suggested that murine leukemia viruses serve as "helpers" for a defective MSV particle in much the same way that avian leukosis viruses help to complete defective Rous sarcoma virus (RSV) infectious particles, but with the difference that in the I\/ISV system in mouse cells helper virus may be required for cellular alteration as well. 1 Sarma, Vass, and Huebner5 described a virus-free sarcoma induced in hamsters by the defective Bryan strain of RSV, the cells from which when propagated in mixed tissue cultures with chicken embryo fibroblasts transferred the noninfectious RSV genome to the latter. When the mixed cultures were superinfected with avian leukosis viruses, fully infectious RSV was released. On the other hand, when uninfected, mixed cultures were implanted in the wing web of leukosis-free chicks, virus-free sarcomas having the avian karyotype were produced. When cells from these sarcomas were grown in tissue cultures, they behaved as typical nonproducer (NP) sarcoma cells. The addition of avian leukosis viruses to these avian cells yielded infectious RSV. In this system, the "nonproducer" hamster and chick cells contain large amounts of complement-fixing (CF) and immunofluorescentstainable antigens believed to represent the internal protein moiety of the virus,6' but the genetic information for the outer envelope must be supplied by the helper virus. In this communication we describe fibrosarcomas induced in hamsters by the M\XIoloney sarcoma virus which carry the defective I\/iSV genome but not infectious MVISV or murine leukemia virus nor mouse leukemia group reactive CF antigen. By adding various standard murine leukemia viruses such as the Rauscher, Friend, ilioloney, and Gross strains to mixed cultures of MSV-induced hamster tumor cells and normal mouse embryo fibroblasts, we obtained fully infectious pseudotypes of MSV having the immunological characteristics of the helper leukemia viruses. Sarcomas containing the infectious pseudotype viruses were also readily produced when newborn Swiss mice were injected with 1\4ISV h -amster tuimor cells nmixed with various murine leukemia viruses.

Cell cultures of Syrian hamster embryo were treated for 7 days with selected chemicals. Certain cultures were morphologically transformed by three different chemical preparations and yielded cell lines that subsequently produced malignant tumors in hamsters. Although the cell lines were negative for infectious virus before inoculation into animals, hamster-specific C-type RNA virus was isolated from tumors or from cell lines derived from the tumors. Since infectious C-type viruses are usually not demonstrable in hamster tissues of normal or tumor origin, we conclude that the chemical treatment and activation of the viruses are related events.

Long-term (five-year) studies of the storage life of bulgur wafers and adjuncts (food to serve with the wafers to vary fall out shelter menus) are in progress. Taste panel results after 16 months of storage indicate that the shelf-life of bulgur wafers may be increased by nitrogen-gas packing and by use of malt sirup rather than corn sirup in the formulation. Chemical-physical analyses are being made on duplicate samples of wafers in a search for a test that correlates with organoleptic evaluation. Trends are not yet well enough developed to permit meaningful correlation. Identify of components of the vapors from rancidifying bulgur and from a model compound, methyl linoleate (linoleic acid comprises more than half of the fatty acids in wheat), is being sought by means of a new technique which combines gas-liquid chromatography and rapid-scan mass spectrometry. Wheat products prepared by hot-air puff-drying and by gun puffing have been evaluated as wafer ingredients potentially cheaper than regular puffed bulgur. Material obtained by hot-air puff-drying shows some promise as a suitable alternate wheat ingredient for wafers. Several new adjuncts have been proposed, including a pectin jelly prepared with cold water to replace the originally developed jellies requiring hot water for preparation.

Striatin and S/G(2) nuclear autoantigen (SG2NA) are related proteins that contain membrane binding domains and associate with protein phosphatase 2A (PP2A) and many additional proteins that may be PP2A regulatory targets. Here we identify a major member of these complexes as class II mMOB1, a mammalian homolog of the yeast protein MOB1, and show that its phosphorylation appears to be regulated by PP2A. Yeast MOB1 is critical for cytoskeletal reorganization during cytokinesis and exit from mitosis. We show that mMOB1 associated with PP2A is not detectably phosphorylated in asynchronous murine fibroblasts. However, treatment with the PP2A inhibitor okadaic acid induces phosphorylation of PP2A-associated mMOB1 on serine. Moreover, specific inhibition of PP2A also results in hyperphosphorylation of striatin, SG2NA, and three unidentified proteins, suggesting that these proteins may also be regulated by PP2A. Indirect immunofluorescence produced highly similar staining patterns for striatin, SG2NA, and mMOB1, with the highest concentrations for each protein adjacent to the nuclear membrane. We also present evidence that these complexes may interact with each other. These data are consistent with a model in which PP2A may regulate mMOB1, striatin, and SG2NA to modulate changes in the cytoskeleton or interactions between the cytoskeleton and membrane structures.

Transcribing low resource languages can be challenging in the absence of a good lexicon and trained transcribers. Accordingly, we seek a way to enable interactive transcription whereby the machine amplifies human efforts. This paper presents a data model and a system architecture for interactive transcription, supporting multiple modes of interactivity, increasing the likelihood of finding tasks that engage local participation in language work. The approach also supports other applications which are useful in our context, including spoken document retrieval and language learning.

The Rel family of transcription factors serve as terminal messengers in a variety of developmental and receptor-mediated signaling pathways. These proteins are related by a domain of approximately 280 amino acids, the Rel homology region, which mediates dimerization and sequence-specific binding to DNA. Here we report the use of photocrosslinking and site-directed mutagenesis to identify specific contact partners in a Rel protein-DNA interface. Within the Rel homology region of NF-kappa B p50 (also known as KBF1), two amino acid residues were identified by photocrosslinking to adjacent bases in a beta-interferon regulatory element. Secondary structure analysis suggests that the DNA-binding motif of the Rel homology region comprises a beta-turn-beta structure, in contrast to the alpha-helical motifs so commonly observed in transcription factors.

Drosophila Enhancer of Polycomb, E(Pc), is a suppressor of position-effect variegation and an enhancer of both Polycomb and trithorax mutations. A homologous yeast protein, Epl1, is a subunit of the NuA4 histone acetyltransferase complex. Epl1 depletion causes cells to accumulate in G2/M and global loss of acetylated histones H4 and H2A. In relation to theDrosophilaprotein, mutation of Epl1 suppresses gene silencing by telomere position effect. Epl1 protein is found in the NuA4 complex and a novel highly active smaller complex named Piccolo NuA4 (picNuA4). The picNuA4 complex contains Esa1, Epl1, and Yng2 as subunits and strongly prefers chromatin over free histones as substrate. Epl1 conserved N-terminal domain bridges Esa1 and Yng2 together, stimulating Esa1 catalytic activity and enabling acetylation of chromatin substrates. A recombinant picNuA4 complex shows characteristics similar to the native complex, including strong chromatin preference. Cells expressing only the N-terminal half of Epl1 lack NuA4 HAT activity, but possess picNuA4 complex and activity. These results indicate that the essential aspect of Esa1 and Epl1 resides in picNuA4 function. We propose that picNuA4 represents a nontargeted histone H4/H2A acetyltransferase activity responsible for global acetylation, whereas the NuA4 complex is recruited to specific genomic loci to perturb locally the dynamic acetylation/deacetylation equilibrium.

Maximal human immunodeficiency virus type 1 (HIV-1) gene expression requires specific cellular factors in addition to the virus-encoded trans-activator protein Tat and the RNA element TAR. We developed a functional assay, based on transcriptional activation in vitro, to identify these cellular factors. Here, we describe the purification and molecular cloning of CA150, a nuclear protein that is associated with the human RNA polymerase II holoenzyme and is involved in Tat-dependent HIV-1 transcriptional activation. The sequence of CA150 contains an extensive glutamine- and alanine-rich repeat that is found in transcriptional modulators such as GAL11 and SSN6 in Saccharomyces cerevisiae and Zeste in Drosophila melanogaster. Immunodepletion of CA150 abolished Tat trans activation in vitro. Moreover, overexpression of a mutant CA150 protein specifically and dramatically decreased Tat-mediated activation of the HIV-1 promoter in vivo, strongly suggesting a role for CA150 in HIV-1 gene regulation. Immunoprecipitation experiments demonstrated that both CA150 and Tat associate with the RNA polymerase II holoenzyme. Furthermore, we found that functional Tat associates with the holoenzyme whereas activation-deficient Tat mutants do not. Thus, we propose that Tat action is transduced via an RNA polymerase II holoenzyme that contains CA150.

The corepressor SMRT mediates repression by thyroid hormone receptor (TR) as well as other nuclear hormone receptors and transcription factors. Here we report the isolation of a novel SMRT-containing complex from HeLa cells. This complex contains transducin β-like protein 1 (TBL1), whose gene is mutated in human sensorineural deafness. It also contains HDAC3, a histone deacetylase not previously thought to interact with SMRT. TBL1 displays structural and functional similarities to Tup1 and Groucho corepressors, sharing their ability to interact with histone H3. In vivo, TBL1 is bridged to HDAC3 through SMRT and can potentiate repression by TR. Intriguingly, loss-of-function TRβ mutations cause deafness in mice and humans. These results define a new TR corepressor complex with a physical link to histone structure and a potential biological link to deafness.