Miracle-dz/UniFAR-FTUs huggingface dataset:
Cooperativity between two NF-kappa B complexes, mediated by high-mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter

Cytokine-induced expression of the E-selectin gene requires the promoter binding and interaction of the transcription factors NF-kappa B and ATF. Here we have further analyzed the E-selectin promoter and revealed an additional region (nucleotides -140 to -105 [-140/-105]) which is essential in controlling promoter activation by cytokines. We identified high-mobility-group protein I(Y) [HMG-I(Y)] interacting specifically at two sites within this region. We noted that one of the HMG-I(Y)-binding sites overlaps a sequence element (-127/-118) diverging at only one position from the NF-kappa B consensus binding sequence. This led us to ask whether the -127/-118 element represents a second functional NF-kappa B-binding site within the E-selectin promoter. Using specific antisera, we show that p50, p65, and, interestingly, RelB are components of the complex interacting at this site. Mutational analysis of the -127/-118 NF-kappa B site indicates that both NF-kappa B and HMG-I(Y) binding at this site are essential for interleukin-1 induction of the promoter. We demonstrate that the binding affinity of the p50 subunit of NF-kappa B to both NF-kappa B sites within the E-selectin promoter is significantly enhanced by HMG-I(Y). In addition, an essential role for cooperative interaction between the two NF-kappa B complexes is shown by the requirement for both NF-kappa B sites to mediate E-selectin promoter activation by interleukin-1 and p50/p65 expression. We conclude that HMG-I(Y) mediates binding of a distinct NF-kappa B complex at two sites within the E-selectin promoter. Furthermore, a unique cooperativity between these NF-kappa B complexes is essential for induced E-selectin expression. These results suggest mechanisms by which NF-kappa B complexes are involved in specific gene activation.
The Drosophila melanogaster gypsy transposable element encodes putative gene products homologous to retroviral proteins

We determined the complete nucleotide sequence of the gypsy element present at the forked locus of Drosophila melanogaster in the f1 allele. The gypsy element shares more homology with vertebrate retroviruses than with the copia element of D. melanogaster or the Ty element of Saccharomyces cerevisiae, both in overall organization and at the DNA sequence level. This transposable element is 7,469 base pairs long and encodes three putative protein products. The long terminal repeats are 482 nucleotides long and contain transcription initiation and termination signals; sequences homologous to the polypurine tract and tRNA primer binding site of retroviruses are located adjacent to the long terminal repeats. The central region of the element contains three different open reading frames. The second one encodes a putative protein which shows extensive amino acid homology to retroviral proteins, including gag-specific protease, reverse transcriptase, and DNA endonuclease.
Integrating CUREs in Ongoing Research: Undergraduates as Active Participants in the Discovery of Biodegrading Thermophiles

Research-based courses are a powerful way to engage undergraduates in the scientific process while simultaneously teaching participants relevant laboratory, analysis, and scientific communication skills. In most programs, students conduct a simulated project which effectively improves student conceptions of scientific thinking but does not produce research-quality data. ABSTRACT Research-based courses are a powerful way to engage undergraduates in the scientific process while simultaneously teaching participants relevant laboratory, analysis, and scientific communication skills. In most programs, students conduct a simulated project which effectively improves student conceptions of scientific thinking but does not produce research-quality data. The course described here delivered an authentic research experience by assigning undergraduates an objective from an active grant-funded project. Participants contributed to research aimed at culturing biodegrading thermophiles from hot springs in Yellowstone National Park. Students participated in a backcountry field experience, collecting environmental samples of their choosing and determining appropriate culturing conditions. Following high-temperature incubations, 16S rRNA gene sequencing identified enriched microbial populations, with analytical and microscopy methods tracking degradation and growth. Importantly, several teams successfully cultivated thermophilic plastic-degrading consortia. Student learning was assessed using several methods, including grade distributions on assignments and statistical comparisons of pre- and posttests. A consistent and, in most cases, statistically significant increase was observed in the students’ posttest scores. The grade distribution on summative assessments also suggests that students achieved the desired learning outcomes. Student perceptions of their learning and experience gains were high, with participants reporting improvements in components emphasized in the research activities. Overall, the findings highlight how involving undergraduates in real-world research projects can enhance student interest and ownership of scientific research, along with contributing quality data that inform active studies.
A Study on Diagnostic Assist Systems of Chronic Obstructive Pulmonary Disease from Medical Images by Deep Learning

In this paper, we propose new diagnostic assist systems of medical images using deep learning algorithms. Specifically, we aim to develop a diagnostic support system for the very early stage of chronic obstructive pulmonary disease (COPD) based on the CT images. It is said that COPD is a disease that develops due to long-term smoking, and it is said that there are a large number of latent onset reserve forces. By discovering this COPD in the very early period 0 and improving the living conditions, subsequent severity can be avoided in many cases, so a system that will help diagnosis by professional radiologists is needed. We show the some experimental results examined by the constructed system.
Distal protein sequences can affect the function of a nuclear localization signal

The major DNA-binding protein, or infected-cell protein 8 (ICP8), encoded by herpes simplex virus can localize to the cell nucleus independently of other viral proteins. To define the nuclear localization signals within ICP8, we performed several forms of mutagenesis on the cloned ICP8 gene. Deletion analysis of the ICP8 gene showed that several portions of ICP8 are involved in its nuclear localization. To determine whether these regions were independent localization signals, we introduced various portions of the ICP8 gene into a series of cassette plasmids which allowed expression of fusion proteins containing pyruvate kinase, normally a cytoplasmic protein, fused to various portions of ICP8. These results showed that the carboxyl-terminal 28 residues are the only portion of ICP8 capable of targeting protein kinase into the nucleus. However, inclusion of certain additional regions of ICP8 into the fusion protein led to an inhibition of nuclear localization. Therefore, the carboxyl-terminal 28 residues of ICP8 can act independently as a nuclear localization signal, but certain conformational constraints or folding or assembly requirements in the remainder of the protein can affect the nuclear localization of the protein. Our results demonstrate that sequences distant from a nuclear localization signal can affect its ability to function. A set of fusion vectors has been isolated which should be of general use for making 5' or 3' fusions in any reading frame to rapidly map localization signals.
Application of Sampling Algorithms in the Problem of Classification of User Requests *

The article discusses the application of methods for reducing the size of majority classes (undersampling) in unbalanced samples to the problem of processing and classifying user requests sent to the technical support of the portal of the Center for Industry Information and Analytical Systems. Sampling meth-ods are investigated, indicators of the classification quality are given - F1-meas-ure for macro and micro averaging. The paper considers a sample consisting of user requests to the technical support service, which has a highly unbalanced form - volume of some classes in the sample exceeds the volume of others by several times. On this sample, various undersampling algorithms are used, a conclusion is made about the advisability of using certain algorithms. A study of the influence of undersampling and oversampling methods on the accuracy of classification of user requests to the portal's technical support service when using gradient boosting on decision trees was carried out. The results obtained showed that an increase in F1-measure compared to the base model was achieved only with the use of the Tomek Links undersampling method; other methods for reducing the size of majority classes did not give an increase inaccuracy, and in most cases even worsened the result.
Molecular basis of bacterial outer membrane permeability

INTRODUCTION Bacteria produce cell walls with the exception of mycoplasmas, and the cell wall component common to all eubacteria is the murein, or the peptidoglycan, which contributes mechanical rigidity. All gram-negative bacteria contain an additional layer in the cell wall structure, i.e., the outer membrane, which is located outside the peptidoglycan layer and shows up as a trilaminar structure on the electron micrographs of thin sections of these bacteria (84). It is becoming increasingly clear that the outer membrane is very important in the physiology of gram-negative bacteria in making them resistant to host defense factors such as lysozyme, P-lysin, and various leukocyte proteins, which
Targeting proteins into mitochondria

From the pioneering insights of the microscopists, spectroscopists, and cell physiologists almost a century ago (16) to the elucidation of intracellular organelle-organelle communication by cell and molecular biologists today, mitochondria continue to be the focal point for biochemical analysis of many intracellular processes. This organelle is now poised with its wealth of biophysical, cell biological, and structural knowledge to complement the tools of the molecular geneticist. This is most evident in the analysis of intracellular protein targeting and the translocation mechanism of proteins across a cellular membrane. It has been known since the early 1950s that the development of functional mitochondria in yeasts requires Mendelian genes; however, the extent to which nuclear deoxyribonucleic acid (DNA) contributed to mitochondrial development was not appreciated until 20 years later. Indeed, the few mitochondrially encoded proteins in yeasts and higher eucaryotes are subunits of oligomeric enzymes which consist for the most part of proteins encoded by nuclear DNA (13). Based on labeling and genetic studies, the amount of protein contributed by the nuclear and mitochondrial genomes has been evaluated. It has been conservatively estimated that the nucleocytoplasmic system contributes greater than 90% of the protein mass to the organelle. During the past 8 years considerable effort has gone into analysis of the delivery and localization mechanisms for mitochondrial proteins (53, 67). Our current understanding of the events required to correctly deliver a protein into mitochondria has come largely from studies in Saccharomyces cerevisiae and Neurospora crassa, which trace the fate of mitochondrial precursors in vivo compared to their behavior in in vitro import assays. The recent explosion of data bearing on the mechanism of import of proteins into
Functional expression of the cre-lox site-specific recombination system in the yeast Saccharomyces cerevisiae

The procaryotic cre-lox site-specific recombination system of coliphage P1 was shown to function in an efficient manner in a eucaryote, the yeast Saccharomyces cerevisiae. The cre gene, which codes for a site-specific recombinase, was placed under control of the yeast GALI promoter. lox sites flanking the LEU2 gene were integrated into two different chromosomes in both orientations. Excisive recombination at the lox sites (as measured by loss of the LEU2 gene) was promoted efficiently and accurately by the Cre protein and was dependent upon induction by galactose. These results demonstrate that a procaryotic recombinase can enter a eucaryotic nucleus and, moreover, that the ability of the Cre recombinase to perform precise recombination events on the chromosomes of S. cerevisiae is unimpaired by chromatin structure.
Hemin-induced transcriptional activation of the HSP70 gene during erythroid maturation in K562 cells is due to a heat shock factor-mediated stress response

Hemin-induced differentiation of the human erythroleukemia cell line K562 results in the expression and accumulation of erythroid-specific gene products such as embryonic and fetal hemoglobins and the elevated synthesis of the major heat shock protein HSP70. This activity was suggested to represent activation of a heat shock gene during erythroid maturation independent of stress induction. In this study, we demonstrate that hemin induces the transcription of two members of the human HSP70 gene family, HSP70 and GRP78 (BiP). However, the induction of HSP70 by hemin showed characteristics consistent with the molecular events associated with a heat shock or stress response. The increase in HSP70 gene transcription was accompanied by induction of the stress-induced form of the heat shock transcription factor. Moreover, a heat shock element was required for the hemin responsiveness of chimeric heat shock promoter-chloramphenicol acetyltransferase genes transiently expressed in transfected K562 cells.
Interactions of bacteriophage and host macromolecules in the growth of bacteriophage lambda

DAVID I. FRIEDMAN,'* ERIC R. OLSON,2 COSTA GEORGOPOULOS,3 KIT TILLY,4 IRA HERSKOWITZ,5 AND FLORA BANUETT5 Department of Microbiology, The University of Michigan Medical School, Ann Arbor, Michigan 481091; Biology Department, McGill University, Montreal, Quebec, Canada H3A LBI2; Department of Cellular, Viral, and Molecular Biology, University of Utah College of Medicine, Salt Lake City, Utah 841323; Department ofBiochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 021384; and Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco, California 941435
Opposite replication polarities of transcribed and nontranscribed histone H5 genes

We used an in vitro nuclear runoff replication assay to analyze the direction of replication of the active and inactive histone H5 genes in avian cells. In embryonic erythrocytes the transcribed histone H5 gene displayed sensitivity to endogenous nuclease cleavage. In contrast, this gene was insensitive to endogenous nuclease digestion under the same conditions in nuclei of the lymphoblastoid cell line MSB-1, and histone H5 gene transcripts were not detectable by dot-blot analysis of MSB-1 cell RNA. When nuclei were isolated from embryonic erythrocytes and incubated with bromodeoxyuridine triphosphate, runoff replication from endogenous nuclease cleavage sites led to a relative enrichment for fragments near the 3' end of the histone H5 gene in the density-labeled DNA. In nuclei of MSB-1 cells or chicken embryo fibroblasts, however, runoff replication from restriction enzyme-cut sites (or induced endogenous nuclease-cut sites in MSB-1 nuclei) led to a relative enrichment for fragments near the 5' end of the H5 gene in dense DNA. Based on the enhanced incorporation of bromodeoxyuridine into origin-distal regions of DNA during the in vitro runoff replication assay, we conclude that the active histone H5 gene in embryonic erythrocytes is preferentially replicated in the transcriptional direction from an origin in the 5'-flanking DNA, whereas its inactive counterparts in MSB-1 cells and chicken embryo fibroblasts are preferentially replicated in the opposite direction.
Field evaluations of marine oil spill bioremediation

Bioremediation is defined as the act of adding or improving the availability of materials (e.g., nutrients, microorganisms, or oxygen) to contaminated environments to cause an acceleration of natural biodegradative processes. The results of field experiments and trials following actual spill incidents have been reviewed to evaluate the feasibility of this approach as a treatment for oil contamination in the marine environment. The ubiquity of oil-degrading microorganisms in the marine environment is well established, and research has demonstrated the capability of the indigenous microflora to degrade many components of petroleum shortly after exposure. Studies have identified numerous factors which affect the natural biodegradation rates of oil, such as the origin and concentration of oil, the availability of oil-degrading microorganisms, nutrient concentrations, oxygen levels, climatic conditions, and sediment characteristics. Bioremediation strategies based on the application of fertilizers have been shown to stimulate the biodegradation rates of oil in aerobic intertidal sediments such as sand and cobble. The ratio of oil loading to nitrogen concentration within the interstitial water has been identified to be the principal controlling factor influencing the success of this bioremediation strategy. However, the need for the seeding of natural environments with hydrocarbon-degrading bacteria has not been clearly demonstrated under natural environmental conditions. It is suggested that bioremediation should now take its place among the many techniques available for the treatment of oil spills, although there is still a clear need to set operational limits for its use. On the basis of the available evidence, we have proposed preliminary operational guidelines for bioremediation on shoreline environments.
Detailed analysis of the higher-order structure of 16S-like ribosomal ribonucleic acids

INTRODUCTION. 622 PART 1. DETAILED CONSIDERATION OF THE VARIOUS HELICAL ELEMENTS . 627 Helix 9-13/21-25 (Table 1) . 628 Helix 17-20/915-918 (Table 2) . 628 Helix 27-37/547-556 (Table 3) . 628 Helix 39-47/394-403 (Table 4) . 629 Helix 52-58/354-359 (Table 5) . 630 Helix 73-82/87-97 Table 6). 630 Helix 113-115/312-314. 630 Helices 122-128/233-239 and 136-142/221-227 (Table 7) . 631 Helices 144-147/175-178 and 153-158/163-168 (Table 8) . 631 The 180 to 220 Region (Table 9) . 632 Helix 240-259/267-286 (Table 10) . 632 Helix 289-292/308-311 (Table 11) . 634 Helices 316-322/331-337 and 339-342/347-350 (Table12). 634 Helices 368-371/390-393 and 375-379/384-388 (Table 13) . 636 Helices 406-409/433-436 and 416-419/424-427 (Table 14) . 636 Helices 437-446/488-497 and 455-462/470-477 (Table 15) . 637 Helix 500-517/534-545 (Table 16) . 637 Helices 576-580/761-765 and 584-587/754-757 (Table 17) . 639 Helix 588-617/623-651 (Table 18) . 640 Helices 655-672/734-751 and 677-684/706-713 (Table 19) . 640 Helices 769-775/804-810 and 783-786/796-799 (Table 20) . 640 Helices 821-828/872-879 and 829-840/846-857 (Table 21) . 642 Helices 888-891/909-912 and 893-897/902-906 (Table 22) . 642 Helix 926-933/1384-1391 (Table 23) . 644 Helix 938-943/1340-1345 (Table 24) . 644 Helices 946-955/1225-1235 and 984-990/1215-1221 (Table 25) . 645 Helix 960-963/972-975 (Table 26) . 645 Helix 997-1012/1017-1044 (Table 27) . 645 Helix 1046-1067/1189-1211 (Table 28) . 648 Helix 1068-1071/1104-1107 (Table 29) . 649 Helices 1072-1076/1081-1085 and 1086-1089/1096-1099 (Table 30) . 649 Helices 1113-1117/1183-1187 and 1118-1124/1149-1155 (Table 31) . 650 Helix 1161-1165/1171-1175 (Table 32) . 650 Helix 1241-1247/1290-1296 (Tables 33 and 34). 650 Helix 1308-1314/1323-1329 (Table 35) . 651 Helix 1350-1356/1366-1372 (Table 36) . 651 Helices 1409-1430/1470-1491 and 1435-1445/1457-1466 (Table 37) . 654 Helix 1506-1515/1520-1529 (Table 38) . 655 Comparison with Other Models . 656 PART 2. BEYOND SECONDARY STRUCTURE . 656 G-U, G-A, and Other Noncanonical Base Pairs . 657 Modified Residues. 658 Single Unpaired Residues Within a Helix. 658 Coaxial Helices . 659 Energetics of Helices (from a Biological Perspective) . 659 Ribosomal Protein Binding Sites . 660 Overall Shape of 16S-Like rRNA. 660 Ribosome Evolution and Essential Core 16S rRNA Structure . 660 Molecular Mechanics of Translation . 665 CONCLUSION . 666 ACKNOWLEDGMENTS . 666 LITERATURE CITED . 666
Structure of transcripts from the homeotic Antennapedia gene of Drosophila melanogaster: two promoters control the major protein-coding region

The Antennapedia (Antp) homeotic gene of Drosophila melanogaster regulates segmental identity in the thorax. Loss of Antp function results in altered development of the embryonic thoracic segments or can cause legs to be transformed into antennae. Certain combinations of Antp recessive lethal alleles complement to permit normal development. The structure of the Antp gene, analyzed by sequencing cDNA clones and exons and by transcript mapping, revealed some of the basis for its genetic complexity. It has two promoters governing two nested transcription units, one unit 36 and one 103 kilobase pairs (kb) long. Both units incorporated the same protein-coding exons, all of which are located in the 3'-most 13 kb of the gene. The two promoters resulted in the attachment of either of two long noncoding leader sequences (1.5 and 1.7 kb) to a 1.1-kb open reading frame. Both transcription units used the same pair of alternative polyadenylation sites 1.4 kb apart; the choice of sites was developmentally regulated. Some of the mutations that disrupt the larger transcription unit complemented a mutation affecting the smaller one. Dominant mutations that transform antennae into legs split the gene but left the coding exons intact. The encoded protein has unusually long runs of glutamine and a homeodomain near the C terminus.
Identification of an essential site for transcriptional activation within the human T-cell receptor delta enhancer

A T-cell-specific transcriptional enhancer was previously identified within the J delta 3-C delta intron of the human T-cell receptor (TCR) delta gene, and seven distinct binding sites for nuclear factors (delta E1 to delta E7) were defined by DNase I footprinting. In this study, we conducted a detailed functional analysis of the various cis-acting DNA sequence elements of the enhancer and show that a 60-bp fragment encompassing delta E3 and delta E4 displays potent enhancer activity, as judged by its ability to activate transcription from the V delta 1 promoter. We show that the interaction of nuclear factors with the delta E3 site is essential for enhancer activity. This element displays significant activity in the absence of additional segments of the enhancer. Further, methylation interference and in vitro mutagenesis identify a site within delta E3 that mediates the binding of two nuclear factors (NF-delta E3A and NF-delta E3C) and that is required for significant transcriptional activation by the enhancer. NF-delta E3C is ubiquitous and may be identical to a previously characterized microE3-binding factor. NF-delta E3A is preferentially expressed in T lymphocytes, and we suggest that this factor may play the dominant role in transcriptional activation through the delta E3 site. This factor interacts with the sequence TGTGGTTT, a motif that is also found within the enhancers of additional TCR and CD3 genes. Nuclear factor binding to delta E4 is also analyzed. One of three specific complexes formed with a delta E4 probe appears to be T-cell specific.
Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy

Artemisinin and its derivatives are endoperoxide-containing compounds which represent a promising new class of antimalarial drugs. In the presence of intraparasitic iron, these drugs are converted into free radicals and other electrophilic intermediates which then alkylate specific malaria target proteins. Combinations of available derivatives and other antimalarial agents show promise both as first-line agents and in the treatment of severe disease.