gebhart/patrepeval huggingface dataset:
Processing bodies require RNA for assembly and contain nontranslating mRNAs (2005)

Recent experiments have defined cytoplasmic foci, referred to as processing bodies (P-bodies), wherein mRNA decay factors are concentrated and where mRNA decay can occur. However, the physical nature of P-bodies, their relationship to translation, and possible roles of P-bodies in cellular responses remain unclear. We describe four properties of yeast P-bodies that indicate that P-bodies are dynamic structures that contain nontranslating mRNAs and function during cellular responses to stress. First, in vivo and in vitro analysis indicates that P-bodies are dependent on RNA for their formation. Second, the number and size of P-bodies vary in response to glucose deprivation, osmotic stress, exposure to ultraviolet light, and the stage of cell growth. Third, P-bodies vary with the status of the cellular translation machinery. Inhibition of translation initiation by mutations, or cellular stress, results in increased P-bodies. In contrast, inhibition of translation elongation, thereby trapping the mRNA in polysomes, leads to dissociation of P-bodies. Fourth, multiple translation factors and ribosomal proteins are lacking from P-bodies. These results suggest additional biological roles of P-bodies in addition to being sites of mRNA degradation.
The clinical continuum of cryopyrinopathies: Novel CIAS1 mutations in North American patients and a new cryopyrin model (2007)

Our modeling provides insight into potential molecular mechanisms by which cryopyrin mutations can inappropriately activate an inflammatory response. A significant number of patients who are clinically diagnosed as having cryopyrinopathies do not have identifiable disease-associated mutations.
The cardiac safety of trastuzumab in the treatment of breast cancer (2010)

The majority of trastuzumab-related cardiac events observed have been asymptomatic declines in left ventricular ejection fraction. The incidence of severe congestive heart failure and cardiac death observed in the large adjuvant trastuzumab trials ranges from 0.6 to 4%. Both symptomatic and asymptomatic events are largely reversible and manageable; however, little is known about the significance of asymptomatic left ventricular ejection fraction decline and longer cardiac follow-up is needed. Close cardiac monitoring must be performed for all patients receiving anti-HER2 agents currently in the clinic or in development.
Three proteins define a class of human histone deacetylases related to yeast Hda1p (1999)

Gene expression is in part controlled by chromatin remodeling factors and the acetylation state of nucleosomal histones. The latter process is regulated by histone acetyltransferases and histone deacetylases (HDACs). Previously, three human and five yeast HDAC enzymes had been identified. These can be categorized into two classes: the first class represented by yeast Rpd3-like proteins and the second by yeast Hda1-like proteins. Human HDAC1, HDAC2, and HDAC3 proteins are members of the first class, whereas no class II human HDAC proteins had been identified. The amino acid sequence of Hda1p was used to search the GenBank/expressed sequence tag databases to identify partial sequences from three putative class II human HDAC proteins. The corresponding full-length cDNAs were cloned and defined as HDAC4, HDAC5, and HDAC6. These proteins possess certain features present in the conserved catalytic domains of class I human HDACs, but also contain additional sequence domains. Interestingly, HDAC6 contains an internal duplication of two catalytic domains, which appear to function independently of each other. These class II HDAC proteins have differential mRNA expression in human tissues and possess in vitro HDAC activity that is inhibited by trichostatin A. Coimmunoprecipitation experiments indicate that these HDAC proteins are not components of the previously identified HDAC1 and HDAC2 NRD and mSin3A complexes. However, HDAC4 and HDAC5 associate with HDAC3 in vivo. This finding suggests that the human class II HDAC enzymes may function in cellular processes distinct from those of HDAC1 and HDAC2.
SCF and Cullin/RING H2-Based Ubiquitin Ligases (1999)

Protein degradation is deployed to modulate the steady-state abundance of proteins and to switch cellular regulatory circuits from one state to another by abrupt elimination of control proteins. In eukaryotes, the bulk of the protein degradation that occurs in the cytoplasm and nucleus is carried out by the 26S proteasome. In turn, most proteins are thought to be targeted to the 26S proteasome by covalent attachment of a multiubiquitin chain. Ubiquitination of proteins requires a multienzyme system. A key component of ubiquitination pathways, the ubiquitin ligase, controls both the specificity and timing of substrate ubiquitination. This review is focused on a conserved ubiquitin ligase complex known as SCF that plays a key role in marking a variety of regulatory proteins for destruction by the 26S proteasome.
Gibberellin production and plant growth promotion from pure cultures of Cladosporium sp. MH-6 isolated from cucumber (Cucumis sativus L.) (2010)

Gibberellin (GA) production by soil fungi has received little attention, although substantial work has been carried out on other aspects of plant growth promoting fungi (PGPF). In our studies we investigated GA production and growth-promoting capacity of a novel fungal strain isolated from the roots of soil-grown cucumber. Pure cultures of 19 endophytic fungi were tested for shoot length promotion of Waito-C rice to identify the GA production capacity of these fungal isolates. Isolate MH-6 significantly increased shoot length (12.9 cm) of Waito-C, in comparison to control treatments. Bioassay with culture filtrate (CF) of MH-6 also significantly promoted growth attributes of cucumber plants. Analysis of MH-6 CF showed the presence of physiologically active (GA1, 1.97 ng/mL; GA3, 5.18 ng/mL; GA4, 13.35 ng/mL and GA7, 2.4 ng/ mL) in conjunction with physiologically inactive (GA9 [0.69 ng/mL], GA12 [0.24 ng/mL], GA15 [0.68 ng/ mL, GA19 [1.94 ng/mL and GA20 [0.78 ng/mL]) gibberellins. The CF of MH-6 produced greater amounts of GA3, GA4, GA7 and GA19 than wild type Fusarium fujikuroi, a fungus known for high production of GA. The fungal isolate MH-6 was identified as a new strain of Cladosporium sp. on the basis of sequence homology (99%) and phylogenetic analysis of 18S rDNA sequence.
Alternatives to antibiotics: bacteriocins, antimicrobial peptides and bacteriophages (2003)

Bacteriocins, antimicrobial peptides, and bacteriophage have attracted attention as potential substitutes for, or as additions to, currently used antimicrobial compounds. This publication will review research on the potential application of these alternative antimicrobial agents to poultry production and processing. Bacteriocins are proteinaceous compounds of bacterial origin that are lethal to bacteria other than the producing strain. It is assumed that some of the bacteria in the intestinal tract produce bacteriocins as a means to achieve a competitive advantage, and bacteriocin-producing bacteria might be a desirable part of competitive exclusion preparations. Purified or partially purified bacteriocins could be used as preservatives or for the reduction or elimination of certain pathogens. Currently only nisin, produced by certain strains of Lactococcus lactis subsp. lactis, has regulatory approval for use in certain foods, and its use for poultry products has been studied extensively. Exploration of the application of antimicrobial peptides from sources other than bacteria to poultry has not yet commenced to a significant extent. Evidence for the ability of chickens to produce such antimicrobial peptides has been provided, and it is likely that these peptides play an important role in the defense against various pathogens. Bacteriophages have received renewed attention as possible agents against infecting bacteria. Evidence from several trials indicates that phage therapy can be effective under certain circumstances. Numerous obstacles for the use of phage as antimicrobials for poultry or poultry products remain. Chiefly among them are the narrow host range of many phages, the issue of phage resistance, and the possibility of phage-mediated transfer of genetic material to bacterial hosts. Regulatory issues and the high cost of producing such alternative antimicrobial agents are also factors that might prevent application of these agents in the near future.
Electrostatic Interactions in Collagen-like Triple-Helical Peptides (1994)

Collagen-like peptides with potential for ion pair formation were studied to investigate the role of electrostatic interactions in the triple-helix conformation. Three peptides--(POG)10, the EK-containing peptide (POG)4EKG(POG)5, and T3-487, a peptide with 18 residues of type III collagen and a C-terminal (GPO)4 tail--all form stable triple helices in aqueous solution, with melting temperatures of 58, 46, and 26 degrees C, respectively, at neutral pH. The thermal stabilities of these peptides correlate with their imino acid content, which is 66%, 60%, and 41%, respectively. Variation of pH over the range of 1-13 led to 8-9 degrees C changes in the Tm of the EK-containing peptide and peptide T3-487, with the greatest stability seen at pH values where both acidic and basic residues are ionized. Equilibrium ultracentrifugation shows these peptides are largely trimeric at low temperature, with no hexamers or larger aggregates, indicating that the pH-dependent stability arises from intramolecular interaction. Computer modeling indicates both intrachain ion pairs and interchain ion pairs can form and stabilize the triple helix. Studies of the pH dependence of the thermal stability of (POG)10 and the N-terminal acetylated form of T3-487 indicate that repulsion of the three charged N-terminal or C-terminal ends has a destabilizing effect. Taking into account these end effects, the energy contribution of two oppositely charged residues in a triple helix which are sterically capable of participating in ion pairs and backbone hydrogen bonding is 0.5-1 kcal/mol ion pair. It is possible that the stabilizing influence of ion pairs arises indirectly, through elimination of like charge repulsion, formation of ion pairs in the single chain form, or solvent effects.
Transgenic Mouse Technology: Principles and Methods (2009)

Introduction of foreign DNA into the mouse germ line is considered a major technical advancement in the fields of developmental biology and genetics. This technology now referred to as transgenic mouse technology has revolutionized virtually all fields of biology and provided new genetic approaches to model many human diseases in a whole animal context. Several hundreds of transgenic lines with expression of foreign genes specifically targeted to desired organelles/cells/tissues have been characterized. Further, the ability to spatio-temporally inactivate or activate gene expression in vivo using the "Cre-lox" technology has recently emerged as a powerful approach to understand various developmental processes including those relevant to molecular endocrinology. In this chapter, we will discuss the principles of transgenic mouse technology, and describe detailed methodology standardized at our institute.
Three NF-kappa B binding sites in the human E-selectin gene required for maximal tumor necrosis factor alpha-induced expression. (1994)

Transcription of the gene encoding the endothelial cell-leukocyte adhesion molecule (ELAM-1; E-selectin) is induced in response to various cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1. A DNase I-hypersensitive site in the 5' proximal promoter region of the E-selectin gene is observed in human umbilical vein endothelial cells only following TNF-alpha treatment, suggesting the presence of a TNF-alpha-inducible element close to the transcriptional start site. Transient transfection studies in endothelial cells demonstrated that 170 bp of upstream sequences is sufficient to confer TNF-alpha inducibility. Systematic site-directed mutagenesis of this region revealed two regulatory elements (-129 to -110 and -99 to -80) that are essential for maximal promoter activity following cytokine treatment. Protein binding studies with crude nuclear extracts and recombinant proteins revealed that the two elements correspond to three NF-kappa B binding sites (site 1, -126; site 2, 116; and site 3, -94). All three sites can be bound by NF-kappa B when used as independent oligonucleotides in mobility shift assays. However, within the context of a larger promoter fragment, sites 2 and 3 are preferentially occupied over site 1. These data are consistent with results obtained in transfection studies demonstrating that mutations in sites 2 and 3 are more detrimental than mutations within site 1. Hence, inducibility of the E-selectin gene requires the interaction of NF-kappa B proteins bound to multiple regulatory elements.
The Therapeutic and Preventive Effect of RRR-α-Vitamin E Succinate on Prostate Cancer via Induction of Insulin-Like Growth Factor Binding Protein-3 (2007)

VES mediates its therapeutic and preventive effects against prostate cancer at least partially through up-regulating IGFBP-3, which inhibits cell proliferation and promotes cell apoptosis.
Inhibition of Urinary Bladder Carcinogenesis by Broccoli Sprouts (2008)

Isothiocyanates are a well-known class of cancer chemopreventive agents, and broccoli sprouts are a rich source of several isothiocyanates. We report herein that dietary administration to rats of a freeze-dried aqueous extract of broccoli sprouts significantly and dose-dependently inhibited bladder cancer development induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. The incidence, multiplicity, size, and progression of bladder cancer were all inhibited by the extract, while the extract itself caused no histologic changes in the bladder. Moreover, inhibition of bladder carcinogenesis by the extract was associated with significant induction of glutathione S-transferase and NAD(P)H:quinone oxidoreductase 1 in the bladder, enzymes that are important protectants against oxidants and carcinogens. Isothiocyanates are metabolized to dithiocarbamates in vivo, but dithiocarbamates readily dissociate to isothiocyanates. We found that >70% of the isothiocyanates present in the extract were excreted in the urine as isothiocyanate equivalents (isothiocyanates + dithiocarbamates) in 12 h after a single p.o. dose, indicating high bioavailability and rapid urinary excretion. In addition, the concentrations of isothiocyanate equivalents in the urine of extract-treated rats were 2 to 3 orders of magnitude higher than those in plasma, indicating that the bladder epithelium, the major site of bladder cancer development, is most exposed to p.o. dosed isothiocyanate. Indeed, tissue levels of isothiocyanate equivalents in the bladder were significantly higher than in the liver. In conclusion, broccoli sprout extract is a highly promising substance for bladder cancer prevention and the isothiocyanates in the extract are selectively delivered to the bladder epithelium through urinary excretion.
Theory of the optimally coupled Q-switched laser (1989)

The general equations describing Q-switched laser operation are transcendental in nature and require numerical solutions, which greatly complicates the optimization of real devices. Here, it is shown that, using the mathematical technique of Lagrange multipliers, one can derive simple analytic expressions for all of the key parameters of the optimally coupled laser, i.e. one which uses an optimum reflector to obtain maximum laser efficiency for a given pump level. These parameters can all be expressed as functions of a single dimensionless variable z, defined as the ratio of the unsaturated small-signal gain to the dissipative (nonuseful) optical loss, multiplied by a few simple constants. Laser design tradeoff studies and performance projections can be accomplished quickly with the help of several graphs and a simple hand calculator. Sample calculations for a high-grain Nd:YAG and a low-gain alexandrite laser are presented as illustrations of the technique.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease (2007)

Extensive chronic graft-versus-host disease (ecGVHD) is characterized by fibrosis similar to that of patients with systemic sclerosis (scleroderma). Since stimulatory autoantibodies against the platelet-derived growth factor (PDGF) receptor (PDGFR) have been found in patients with scleroderma and are responsible for the activation of skin fibroblasts, we tested the hypothesis that these autoantibodies are also present in patients affected by ecGVHD. Serum from 39 patients subjected to allogeneic stem cell transplantation for hematologic malignancies (22 with ecGVHD and 17 without cGVHD) and 20 healthy controls was assayed for the presence of stimulatory autoantibodies to the PDGFR by incubating purified IgG with mouse-embryo fibroblasts lacking PDGFR alpha or beta chains or with the same cells expressing PDGFR alpha. Stimulatory antibodies to the PDGFR were found selectively in all patients with ecGVHD but in none of the patients without cGVHD. Higher levels were detected in patients with generalized skin involvement and/or lung fibrosis. Antibodies recognized native PDGFR, induced tyrosine phosphorylation, accumulation of reactive oxygen species (ROS), and stimulated type 1 collagen gene expression through the Ha-Ras-ERK1/2-ROS signaling pathway. The biologic activity of these autoantibodies suggests a role in the development of fibrosis and argues for a common pathogenetic trait in ecGVDH and scleroderma phenotypes.
Inactivation of the cytochrome P450 gene CYP82E2 by degenerative mutations was a key event in the evolution of the alkaloid profile of modern tobacco (2007)

The alkaloid profile of cultivated tobacco (Nicotiana tabacum) is different from that of its two progenitors, Nicotiana sylvestris and Nicotiana tomentosiformis, in that tobacco accumulates nicotine as the most abundant alkaloid, while its ancestors convert nicotine to nornicotine in the senescing leaf. The nicotine-retaining phenotype of tobacco is thought to have evolved through the inactivation of the conversion loci inherited from its two progenitors. Here, the genetic changes associated with the inactivation of the conversion locus derived from N. sylvestris were investigated. Candidate genes were isolated from a N. sylvestris senescing leaf cDNA library and characterized by heterologous gene expression in yeast, site-directed mutagenesis and quantitative real-time polymerase chain reaction. A cytochrome P450 gene, designated NsylCYP82E2, was isolated from N. sylvestris. Located on the chromosomal fragment defined by the N. sylvestris conversion locus, NsylCYP82E2 confers high nicotine N-demethylase (NND) activity in the senescing leaves of N. sylvestris, but the gene is inactivated by two degenerative mutations in tobacco. Collectively with previously published data, these results show that inactivation of NND genes by degenerative mutations and/or transcriptional suppression played a key role in the evolution of the alkaloid profile of modern tobacco.
Alternative Intronic Polyadenylation Generates the Interleukin-6 Trans-signaling Inhibitor sgp130-E10 (2014)

Interleukin (IL)-6 signals via a receptor complex composed of the signal-transducing β-receptor gp130 and the non-signaling membrane-bound or soluble IL-6 receptor α (IL-6R, sIL-6R), which is referred to as classic and trans-signaling, respectively. IL-6 trans-signaling is functionally associated with the development of chronic inflammatory diseases and cancer. Soluble gp130 (sgp130) variants are natural inhibitors of trans-signaling. Differential splicing yields sgp130 isoforms. Here, we describe that alternative intronic polyadenylation in intron 10 of the gp130 transcript results in a novel mRNA coding for an sgp130 protein isoform (sgp130-E10) of 70-80 kDa. The sgp130-E10 protein was expressed in vivo in human peripheral blood mononuclear cells. To assess the biological activity of sgp130-E10, we expressed this variant as Fc-tagged fusion protein (sgp130-E10Fc). Recombinant sgp130-E10Fc binds to a complex of IL-6 and sIL-6R, but not to IL-6 alone, and specifically inhibits IL-6 trans-signaling. Thus, it might play an important role in the regulation of trans-signaling in vivo.
Microbiome in the Gut-Skin Axis in Atopic Dermatitis (2018)

The microbiome is vital for immune system development and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the skin and the gut have recently been linked to alterations in immune responses and to the development of skin diseases, such as atopic dermatitis (AD). In this review, we summarize the recent findings on the gut and skin microbiome, highlighting the roles of major commensals in modulating skin and systemic immunity in AD. Although our understanding of the gut-skin axis is only beginning, emerging evidence indicates that the gut and skin microbiome could be manipulated to treat AD.
Distributed strain and temperature sensing in plastic optical fiber using Rayleigh scatter (2009)

In recent years we have demonstrated the ability to analyze Rayleigh scatter in single- and multi-mode fused silica fibers to deduce strain and temperature shifts, yielding sensitivity and resolution similar to that obtained using Fiber Bragg Gratings. This technique employs scanning laser interferometry to obtain high spatial resolution Rayleigh scatter spectral information. One of the promising aspects of using Rayleigh scatter for distributed sensing is that the technique should work for any fiber that exhibits discernable Rayleigh scatter. We now demonstrate that distributed sensing with mm-range spatial resolution in off-the-shelf plastic multi-mode optical fiber is feasible. We report temperature and strain sensitivity, and comment on measurement range and hysteresis level. Distributed Rayleigh scatter sensing in plastic optical fiber may offer a valuable alternative to sensing in fused silica fibers because of plastic's low cost and differing mechanical and chemical properties.
Aliphatic Aldehyde Detection and Adsorption by Nonporous Adaptive Pillar[4]arene[1]quinone Crystals with Vapochromic Behavior (2018)

The detection and adsorption of volatile low-molecular-weight aliphatic aldehydes is of significance, owing to their physical volatility, chemical toxicity, and widespread applications in chemical industrial processes. Here, nonporous adaptive pillar[4]arene[1]quinone (EtP4Q1) crystals with vapochromic behavior are used for the volatile aliphatic aldehyde uptake and sensing. When desolvated EtP4Q1 crystals (EtP4Q1α) are exposed to aliphatic aldehydes with different carbon chain lengths, they quantitatively adsorb vapors of these aldehydes, accompanied by different color changes. Crystal structure analyses show that the structure of EtP4Q1 transforms from EtP4Q1α into the corresponding new structures after the adsorption of these aldehydes, which leads to different color changes. The selectivity of EtP4Q1α crystals, which function as both sensors and adsorbents upon exposure to mixed aldehyde vapors, is also explored. Finally, it is demonstrated that EtP4Q1α crystals can be recycled many times without loss of performance.
Synthesis and properties of DNA-PNA chimeric oligomers (1996)

Adenine, thymine and cytosine PNA monomers have been prepared using 3-amino-1,2-propanediol as a starting material. The benzoyl group was used to protect the exocyclic amines of the heterocyclic bases of A and C PNA monomers and the backbone primary amine was protected with the monomethoxytrityl group. The thymine and cytosine PNA monomers were used in conjunction with standard DNA synthesis monomers to produce chimeric PNA DNA (PDC) oligomers. Ultraviolet melting studies confirmed that these oligomers form stable hybrids with complementary DNA strands and that mismatches in the DNA but more so in the PNA sections lead to duplex destabilisation.