gebhart/patrepeval huggingface dataset:
Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer (2013)

The microbiota is pivotal in the pathogenesis of inflammatory bowel disease (IBD)-associated inflammation-induced colorectal cancer (CRC), yet mechanisms for these effects remain poorly characterized. Here, we demonstrate that aberrant inflammasome-induced microbiota plays a critical role in CRC development, where mice deficient in the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome feature enhanced inflammation-induced CRC formation. Intriguingly, WT mice cohoused either with inflammasome-deficient mice or with mice lacking IL-18 feature exacerbated inflammation-induced CRC compared with singly housed WT mice. Enhanced tumorigenesis is dependent on microbiota-induced chemokine (C-C motif) ligand 5 (CCL5)-driven inflammation, which in turn promotes epithelial cell proliferation through local activation of the IL-6 pathway, leading to cancer formation. Altogether, our results mechanistically link the altered microbiota with the pathogenesis of inflammation-induced CRC and suggest that in some conditions, microbiota components may transfer CRC susceptibility between individuals.
Modulation of gene expression by antisense and antigene oligodeoxynucleotides and small interfering RNA (2005)

Antisense oligodeoxynucleotides, triplex-forming oligodeoxynucleotides and double-stranded small interfering RNAs have great potential for the treatment of many severe and debilitating diseases. Concerted efforts from both industry and academia have made significant progress in turning these nucleic acid drugs into therapeutics, and there is already one FDA-approved antisense drug in the clinic. Despite the success of one product and several other ongoing clinical trials, challenges still exist in their stability, cellular uptake, disposition, site-specific delivery and therapeutic efficacy. The principles, strategies and delivery consideration of these nucleic acids are reviewed. Furthermore, the ways to overcome the biological barriers are also discussed so that therapeutic concentrations at their target sites can be maintained for a desired period.
Relationship between Human Immunodeficiency Virus Type 1 Gag Multimerization and Membrane Binding (2000)

The human immunodeficiency virus type 1 (HIV-1) Gag precursor, Pr55(Gag), is necessary and sufficient for the assembly and release of viruslike particles. Binding of Gag to membrane and Gag multimerization are both essential steps in virus assembly, yet the domains responsible for these events have not been fully defined. In addition, the relationship between membrane binding and Gag-Gag interaction remains to be elucidated. To investigate these issues, we analyzed, in vivo, the membrane-binding and assembly properties of a series of C-terminally truncated Gag mutants. Pr55(Gag) was truncated at the C terminus of matrix (MAstop), between the N- and C-terminal domains of capsid (CA146stop), at the C terminus of capsid (p41stop), at the C terminus of p2 (p43stop), and after the N-terminal 35 amino acids of nucleocapsid (NC35stop). The ability of these truncated Gag molecules to assemble and release viruslike particles and their capacity to copackage into particles when coexpressed with full-length Gag were determined. We demonstrate that the amount of truncated Gag incorporated into particles is incrementally increased by extension from CA146 to NC35, suggesting that multiple sites in this region are involved in Gag multimerization. Using membrane flotation centrifugation, we observe that MA shows significantly reduced membrane binding relative to full-length Gag but that CA146 displays steady-state membrane-binding properties comparable to those of Pr55(Gag). The finding that the CA146 mutant, which contains only matrix and the N-terminal domain of capsid, exhibits levels of steady-state membrane binding equivalent to those of full-length Gag indicates that strong Gag-Gag interaction domains are not required for the efficient binding of HIV-1 Gag to membrane.
Identifying functional domains within terpene cyclases using a domain-swapping strategy. (1996)

Cyclic terpenes and terpenoids are found throughout nature. They comprise an especially important class of compounds from plants that mediate plant- environment interactions, and they serve as pharmaceutical agents with antimicrobial and anti-tumor activities. Molecular comparisons of several terpene cyclases, the key enzymes responsible for the multistep cyclization of C10, C15, and C20 allylic diphosphate substrates, have revealed a striking level of sequence similarity and conservation of exon position and size within the genes. Functional domains responsible for a terminal enzymatic step were identified by swapping regions approximating exons between a Nicotiana tabacum 5-epi-aristolochene synthase (TEAS) gene and a Hyoscyamus muticus vetispiradiene synthase (HVS) gene and by characterization of the resulting chimeric enzymes expressed in bacteria. While exon 4 of the TEAS gene conferred specificity for the predominant reaction products of the tobacco enzyme, exon 6 of the HVS gene conferred specificity for the predominant reaction products of the Hyoscyamus enzyme. Combining these two functional domains of the TEAS and HVS genes resulted in a novel enzyme capable of synthesizing reaction products reflective of both parent enzymes. The relative ratio of the TEAS and HVS reaction products was also influenced by the source of exon 5 present in the new chimeric enzymes. The association of catalytic activities with conserved but separate exonic domains suggests a general means for generating additional novel terpene cyclases.
A study of life and health conditions of inhabitants of Manabe Island (1982)

Characteristcs of environmental health conditions in Manabe island were surveyed from the standpoint of public health. The results obtained were as follows:1. Those employed in primary industries (fishing and farming) are greater in proportion in Manabe Island while those employed in secondary industries are higher in number in Kasaoka City excluding Manabe Island.2. The population of aged people and the dependence population index in Manabe Island were higher than those in Kasaoka City, a trend thought to be characteristic of isolated islands in the Inland Sea.3. The ratio of aged people and proportional mortality indicator (PMI) were higher in Manabe Island than that in Kasaoka City.4. Heart disease, injury of extremities, liver disease, and parasytosis showed a higher incidence in people who belonged to national health insurance in Manabe Island than those of Kasaoka City excluding Manabe Island.
The Escherichia coli serA-linked capsule locus and its flanking sequences are polymorphic, genetic evidence for the existence of more than two groups of capsule gene clusters (1993)

Two families of Escherichia coli capsules, termed groups I and II, have been defined previously on the basis of a number of biochemical and genetic criteria. Recently, a third group of capsules, termed I/II has been suggested on the basis of chemical structure and mode of expression. In this paper, we show that group I capsule-producing strains lack the serA-linked group II capsule genes. In addition, group I/II capsule-producing strains lack the group II capsule genes despite the former genes also mapping near to serA. Therefore, the genetic data presented in this paper support the existence of three groups of capsule gene clusters, two of which are linked to serA. Sequences flanking the K4 capsule genes were found in the chromosome of all E. coli strains examined and were sometimes present in multiple copies at different loci, indicating that this chromosomal region is highly polymorphic.
The Baculovirus Expression System: A Laboratory Guide (1993)

The baculoviruses - introduction the development of baculovirus expression vectors processing of foreign proteins synthesized using baculovirus vectors in insect cells construction of transfer vectors containing the foreign gene insect cell culture media and maintenance of insect cell lines propagation, titration and purification of AcMNPV in cell culture production and selelction of recombinant virus characterization of recombinant viruses scaling up the production of recombinant proteins in insect cells - laboratory bench level propagation of baculoviruses in insect larvae.
X-canceling MISR &#x2014; An X-tolerant methodology for compacting output responses with unknowns using a MISR (2007)

A new X-tolerant multiple-input signature register (MISR) compaction methodology is proposed which can compact output streams containing unknown (X) values. Unlike conventional X-masking approaches, it does not require any masking logic at the input of the MISR. Instead it uses symbolic simulation to express each bit of the MISR signature as a linear equation in terms of the X's. Linearly dependent combinations of the signature bits are identified with Gaussian elimination and XORed together using a programmable XOR to cancel out all X values thereby yielding deterministic values that are invariant of what the final values of the X's end up being during the test. These X-canceled values can be compacted in a separate MISR to generate a final X-free signature. Each intermediate signature for an m-bit MISR can tolerate k X's present anywhere in the output stream with error detection capability equivalent to using an m-k bit MISR with no unknowns. The tester storage requirement is a small constant times the total number of unknowns in the test set and thus does not depend on the scan architecture, the number of test vectors, or the distribution of X's which is a key advantage compared with other X-tolerant compaction schemes.
Towards a continuous dynamic kinetic resolution of 1-phenylethylamine using a membrane assisted, two vessel process (2007)

A continuous process with two separated reaction vessels provides a solution to the problems surrounding the combination of two catalysts in dynamic kinetic resolution reactions by retaining the biocatalyst in a lower temperature vessel with a microfiltration membrane and allowing the racemisation to occur efficiently in a higher temperature vessel.
Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse (1995)

Axonal navigation during development requires that cues present in the extracellular environment be capable of modifying the structure of the cone in a dynamic way. Protein kinase C (PKC) has long been suspected to be one of the multiple molecular relays present in the terminal structure of the developing axon and involved in the transduction of extracellular signals. The latter proposal is, however, based on the use of drugs or of protocols leading to pleiotropic and often nonspecific effects. In the present study, we have taken advantage of the discovery of a peptide capable of translocating across biological membranes and to accumulate in the cytoplasm and nucleus of cells in culture, to internalize a highly specific peptidic inhibitor of PKC. We demonstrate that linking the two peptides (vector and PKC inhibitor) allows the internalization of the latter in live cells, specifically inhibits PKC and provokes a rapid modification of growth cone morphology. This set of data thus establishes that a peptidic inhibitor of PKC activity, once internalized, provokes a change in growth cone morphology, reminiscent of the collapse phenotype. In addition, the present study describes a new efficient and harmless way to introduce pharmacologically active substances in neural cells in culture.
Prolonged cell‐free protein synthesis using dual energy sources: Combined use of creatine phosphate and glucose for the efficient supply of ATP and retarded accumulation of phosphate (2007)

The accumulation of inorganic phosphate inhibits protein synthesis in cell-free protein synthesis reactions that are energized by high-energy-phosphate-containing compounds. This study developed a new scheme for supplying energy using dual energy sources to enhance the regeneration of ATP and lower the rate of phosphate accumulation. In the proposed scheme, where creatine phosphate (CP) and glucose were simultaneously used as the energy sources, the phosphate released from the CP was subsequently used in the glycolytic pathway for the utilization of the glucose, which enhanced the ATP supply and reduced the rate of inorganic phosphate accumulation. When tested against different proteins, the developed method produced 2-3 times more protein than the conventional ATP regeneration methods using single energy sources.
<title>Automatic detection of pulmonary nodules in low-dose screening thoracic CT examinations</title> (1999)

Computed tomography of the chest can be used as a screening method for lung cancer in a high-risk population. However, the detection of lung nodules is a difficult and time-consuming task for radiologists. The developed technique should improve the sensitivity of the detection of lung nodules without showing too many false positive nodules. In a study, which should evaluate the feasibility of screening lung cancer, about 1400 thoracic studies were acquired. Scanning parameters were 120 kVp, 5 mm collimation pitch of 2, and a reconstruction index of 5 mm. This results in a data set of about 60 to 70 images per exam. In the images the detection technique first eliminates all air outside the patient, then soft tissue and bony structures are removed. In the remaining lung fields a three-dimensional region detection is performed and rule-based analysis is used to detect possible lung nodules. This technique was applied to a small subset (n equals 17) of above studies. Computation time is about 5 min on an O2 workstation. The use of low-dose exams proved not be a hindrance in the detection of lung nodules. All of the nodules (n equals 23), except one with a size of 3 mm, were detected. The false positive rate was less than 0.3 per image. We have developed a technique, which might help the radiologist in the detection of pulmonary nodules in CT exams of the chest.
Vaccines for fish in aquaculture (2005)

Vaccination plays an important role in large-scale commercial fish farming and has been a key reason for the success of salmon cultivation. In addition to salmon and trout, commercial vaccines are available for channel catfish, European seabass and seabream, Japanese amberjack and yellowtail, tilapia and Atlantic cod. In general, empirically developed vaccines based on inactivated bacterial pathogens have proven to be very efficacious in fish. Fewer commercially available viral vaccines and no parasite vaccines exist. Substantial efficacy data are available for new fish vaccines and advanced technology has been implemented. However, before such vaccines can be successfully commercialized, several hurdles have to be overcome regarding the production of cheap but effective antigens and adjuvants, while bearing in mind environmental and associated regulatory concerns (e.g., those that limit the use of live vaccines). Pharmaceutical companies have performed a considerable amount of research on fish vaccines, however, limited information is available in scientific publications. In addition, salmonids dominate both the literature and commercial focus, despite their relatively small contribution to the total volume of farmed fish in the world. This review provides an overview of the fish vaccines that are currently commercially available and some viewpoints on how the field is likely to evolve in the near future.
Misinterpreting the Therapeutic Effects of Small Interfering RNA Caused by Immune Stimulation (2008)

Activation of innate immunity has direct effects in modulating viral replication, tumor growth, angiogenesis, and inflammatory and other immunological processes. It is now established that unmodified siRNA can activate this innate immune response and therefore there is real potential for siRNA to elicit nonspecific therapeutic effects in a wide range of disease models. Here we demonstrate that in a murine model of influenza infection, the antiviral activity of siRNA is due primarily to immune stimulation elicited by the active siRNA duplexes and is not the result of therapeutic RNA interference (RNAi) as previously reported. We show that the misinterpretation stems from the use of a particular control green fluorescent protein (GFP) siRNA that we identify as having unusually low immunostimulatory activity compared with the active anti-influenza siRNA. Curiously, this GFP siRNA has served as a negative control for a surprising number of groups reporting therapeutic effects of siRNA. The inert immunologic profile of the GFP sequence was unique among a broad panel of published siRNAs, all of which could elicit significant interferon induction from primary immune cells. This panel included eight active siRNAs against viral, angiogenic, and oncologic targets, the reported therapeutic efficacy of which was based on comparison with the nonimmunostimulatory GFP siRNA. These results emphasize the need for researchers to anticipate, monitor, and adequately control for siRNA-mediated immune stimulation and calls into question the interpretation of numerous published reports of therapeutic RNAi in vivo. The use of chemically modified siRNA with minimal immunostimulatory capacity will help to delineate more accurately the mechanism of action underlying such studies.
Monoclonal Antibodies to Six-Transmembrane Epithelial Antigen of the Prostate-1 Inhibit Intercellular Communication In vitro and Growth of Human Tumor Xenografts In vivo (2007)

Six-transmembrane epithelial antigen of the prostate-1 (STEAP-1) is a novel cell surface protein highly expressed in primary prostate cancer, with restricted expression in normal tissues. In this report, we show STEAP-1 expression in prostate metastases to lymph node and bone and in the majority of human lung and bladder carcinomas. We identify STEAP-1 function in mediating the transfer of small molecules between adjacent cells in culture, indicating its potential role in tumor cell intercellular communication. The successful generation of two monoclonal antibodies (mAb) that bind to cell surface STEAP-1 epitopes provided the tools to study STEAP-1 susceptibility to naked antibody therapy. Both mAbs inhibited STEAP-1-induced intercellular communication in a dose-dependent manner. Furthermore, both mAbs significantly inhibited tumor growth in mouse models using patient-derived LAPC-9 prostate cancer xenografts and established UM-UC-3 bladder tumors. These studies validate STEAP-1 as an attractive target for antibody therapy in multiple solid tumors and provide a putative mechanism for mAb-induced tumor growth inhibition.
The unusual methanogenic seryl‐tRNA synthetase recognizes tRNASer species from all three kingdoms of life (2004)

The methanogenic archaea Methanococcus jannaschii and M. maripaludis contain an atypical seryl-tRNA synthetase (SerRS), which recognizes eukaryotic and bacterial tRNAsSer, in addition to the homologous tRNASer and tRNASec species. The relative flexibility in tRNA recognition displayed by methanogenic SerRSs, shown by aminoacylation and gel mobility shift assays, indicates the conservation of some serine determinants in all three domains. The complex of M. maripaludis SerRS with the homologues tRNASer was isolated by gel filtration chromatography. Complex formation strongly depends on the conformation of tRNA. Therefore, the renaturation conditions for in vitro transcribed tRNASer(GCU) isoacceptor were studied carefully. This tRNA, unlike many other tRNAs, is prone to dimerization, possibly due to several stretches of complementary oligonucleotides within its sequence. Dimerization is facilitated by increased tRNA concentration and can be diminished by fast renaturation in the presence of 5 mm magnesium chloride.
An Archaeal Immune System Can Detect Multiple Protospacer Adjacent Motifs (PAMs) to Target Invader DNA (2012)

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system provides adaptive and heritable immunity against foreign genetic elements in most archaea and many bacteria. Although this system is widespread and diverse with many subtypes, only a few species have been investigated to elucidate the precise mechanisms for the defense of viruses or plasmids. Approximately 90% of all sequenced archaea encode CRISPR/Cas systems, but their molecular details have so far only been examined in three archaeal species: Sulfolobus solfataricus, Sulfolobus islandicus, and Pyrococcus furiosus. Here, we analyzed the CRISPR/Cas system of Haloferax volcanii using a plasmid-based invader assay. Haloferax encodes a type I-B CRISPR/Cas system with eight Cas proteins and three CRISPR loci for which the identity of protospacer adjacent motifs (PAMs) was unknown until now. We identified six different PAM sequences that are required upstream of the protospacer to permit target DNA recognition. This is only the second archaeon for which PAM sequences have been determined, and the first CRISPR group with such a high number of PAM sequences. Cells could survive the plasmid challenge if their CRISPR/Cas system was altered or defective, e.g. by deletion of the cas gene cassette. Experimental PAM data were supplemented with bioinformatics data on Haloferax and Haloquadratum.
A new type of hemophore-dependent heme acquisition system of Serratia marcescens reconstituted in Escherichia coli (1997)

The utilization by Serratia marcescens of heme bound to hemoglobin requires HasA, an extracellular heme-binding protein. This unique heme acquisition system was studied in an Escherichia coli hemA mutant that was a heme auxotroph. We identified a 92-kDa iron-regulated S. marcescens outer membrane protein, HasR, which alone enabled the E. coli hemA mutant to grow on heme or hemoglobin as a porphyrin source. The concomitant secretion of HasA by the HasR-producing hemA mutant greatly facilitates the acquisition of heme from hemoglobin. This is the first report of a synergy between an outer membrane protein and an extracellular heme-binding protein, HasA, acting as a heme carrier, which we termed a hemophore.
Studies of Phosphorylation. III. Selective Phosphorylation of Unprotected Nucleosides (1969)

Abstract During an investigation of the factors affecting the reaction of 2′,3′-O-isopropylidene nucleosides with phosphoryl chloride, trialkyl phosphates were found to be powerful accelerators and useful solvents for the phosphorylation. The addition of a trialkyl phosphate to a large excess of phosphoryl chloride was markedly effective in promoting the phosphorylation; further, the lower alkyl phosphates, such as trimethyl and triethyl phosphates, were able to replace the excessive amount of phosphoryl chloride as solvents. When unprotected nucleosides were treated with phosphoryl chloride in trimethyl phosphate, the corresponding 5′-phosphates were mainly produced, together with a small amount of highly-phosphorylated products, in good yields. On the contrary, the treatment of 5′-O-acetyl nucleosides in a similar manner gave the corresponding 2′(or 3′)-nucleotides in low yields. The formation of the 2′(or 3′)-phosphate was strongly inhibited by the addition of a small amount of water to the reaction mixture. Thus, the selective phosphorylation of unprotected nucleosides to the 5′-nucleotides in a one-step procedure was accomplished.
Zinc-Mediated C−C Bond Sigmatropic Rearrangement:  A New and Efficient Methodology for the Synthesis of β-Diketones (2007)

A new and efficient methodology has been developed for the synthesis of β-diketones from aromatic α-bromo ketones in the presence of Furukawa reagent under mild conditions. The present transformation is proposed to proceed via a Reformatsky-type reaction of α-bromo ketones, followed by C−C bond sigmatropic rearrangement of the aldolate intermediate to give β-diketones in moderate to good isolated yields, while aliphatic α-bromomethyl ketones resulted in the formation of 2,4-disubstituted furans or cis-1,2-disubstituted cyclopropanols in moderate yields. The scope of this process was investigated, and a tentative mechanism was proposed.