gebhart/patrepeval huggingface dataset:
Essential Role of Human Leukocyte Antigen-encoded Proteasome Subunits in NF-κB Activation and Prevention of Tumor Necrosis Factor-α-induced Apoptosis (2000)

The multisubunit proteasome complex is the principal mediator of nonlysosomal protein degradation. The proteasome subunit varies minimally between cells with the exception of LMP2, LMP7, and LMP10 subunits in rodent and human cells. LMP2 and LMP7 subunits are encoded by the human lymphocyte antigen region, and they optimize proteolytic mediated antigen presentation. The proteasome is also important for the function of transcription factor nuclear factor-kappaB (NF-kappaB). It is required for NF-kappaB subunits p50 and p52 generation and catalyzes degradation of phosphorylated IkappaBalpha. These proteasome-mediated reactions have now been shown to be defective in T2 cells, a human lymphocyte cell line that lacks both LMP2 and LMP7. Although T2 cells contain normal expression of p100 and p105, the abundance of p50 and p52 was greatly reduced. Tumor necrosis factor-alpha (TNF-alpha) induced normal phosphorylation of IkappaBalpha but failed to induce degradation of phosphorylated IkappaBalpha. Both DNA binding assays and luciferase assays revealed that TNF-alpha-induced NF-kappaB activation is defective in T2 cells. Unlike parental cells, T2 cells were susceptible to TNF-alpha-induced apoptosis. These data indicate human leukocyte antigen-linked proteasome subunits are essential for NF-kappaB activation and protection of cells from TNF-alpha-induced apoptosis.
Delivery of Therapeutic RNAi by Nanovehicles (2009)

Designer packaging: Nanovehicles created from cationic polymers and anionic oligonucleotides through electrostatic interaction play a most important role in nonviral siRNA delivery. The type and content of amine in the polymer determine the hydrophobicity, surface charge, and particle size of resulting nanovehicle. Targeted delivery may be achieved by modifying the nanovehicle by coupling moieties that bind specific cell surface receptors.
The Use of Benzylsulfonyl Chloride in Peptide Syntheses1,2 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Use of Benzylsulfonyl Chloride in Peptide Syntheses1,2H. Bayard Milne and Chi-Hsieh PengCite this: J. Am. Chem. Soc. 1957, 79, 3, 639–644Publication Date (Print):February 1, 1957Publication History Published online1 May 2002Published inissue 1 February 1957https://pubs.acs.org/doi/10.1021/ja01560a036https://doi.org/10.1021/ja01560a036research-articleACS PublicationsRequest reuse permissionsArticle Views357Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Efficacy of Sertraline in Preventing Relapse of Posttraumatic Stress Disorder: Results of a 28-Week Double-Blind, Placebo-Controlled Study (2001)

The results provide evidence for the ability of sertraline both to sustain improvement in PTSD symptoms and to provide prophylactic protection against relapse.
2-Deoxy-D-Glucose Feeding in Rats Mimics Physiologic Effects of Calorie Restriction (1998)

Calorie restriction (CR) extends the life span, slows the rate of aging, and delays the onset of many age-related diseases in short-lived laboratory species, primarily rodents. Although it is unknown if CR extends the life span in long-lived mammals, findings emerging from CR studies in rhesus monkeys agree with the extensive rodent literature that suggests this intervention can have beneficial effects in primates. Even if CR is shown to extend the life span in long-lived species, it is unlikely that the 30% to 40% reduction in intake used typically in this paradigm would become a widespread practice in humans. An alternative strategy may be to design interventions that "mimic" biologic effects of CR but do not significantly reduce food intake. The present study was designed to test the hypothesis that administration of a glucose analogue, 2-deoxy-D-glucose (2-DG) would mimic certain effects of CR. Specifically, we administered three doses (0.2%, 0.4%, and 0.6% w/w) of 2-DG in the diet to male Fischer-344 rats. Rats fed 0.4% 2-DG weighed slightly less than controls and exhibited significant reductions in body temperature and fasting serum insulin levels. Our findings suggest that it might be possible to design interventions to mimic certain metabolic effects, and perhaps other beneficial effects of CR such as life span extension and retardation of physiologic aging.
Randomized controlled trial design in rheumatoid arthritis: the past decade (2009)

Much progress has occurred over the past decade in rheumatoid arthritis trial design. Recognized challenges have led to the establishment of a clear regulatory pathway to demonstrate efficacy of a new therapeutic. The use of pure placebo beyond 12 to 16 weeks has been demonstrated to be unethical and thus background therapy and/or early rescue has become regular practice. Goals of remission and 'treating to targets' may prove more relevant to identify real-world use of new and existing therapeutics. Identification of rare adverse events associated with new therapies has resulted in intensive safety evaluation during randomized controlled trials and emphasis on postmarketing surveillance and use of registries.
KEGG for linking genomes to life and the environment (2007)

KEGG (http://www.genome.jp/kegg/) is a database of biological systems that integrates genomic, chemical and systemic functional information. KEGG provides a reference knowledge base for linking genomes to life through the process of PATHWAY mapping, which is to map, for example, a genomic or transcriptomic content of genes to KEGG reference pathways to infer systemic behaviors of the cell or the organism. In addition, KEGG provides a reference knowledge base for linking genomes to the environment, such as for the analysis of drug-target relationships, through the process of BRITE mapping. KEGG BRITE is an ontology database representing functional hierarchies of various biological objects, including molecules, cells, organisms, diseases and drugs, as well as relationships among them. KEGG PATHWAY is now supplemented with a new global map of metabolic pathways, which is essentially a combined map of about 120 existing pathway maps. In addition, smaller pathway modules are defined and stored in KEGG MODULE that also contains other functional units and complexes. The KEGG resource is being expanded to suit the needs for practical applications. KEGG DRUG contains all approved drugs in the US and Japan, and KEGG DISEASE is a new database linking disease genes, pathways, drugs and diagnostic markers.
Probing the Interaction between Feline Immunodeficiency Virus and CD134 by Using the Novel Monoclonal Antibody 7D6 and the CD134 (O×40) Ligand (2007)

The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T cells preferentially, inducing an AIDS-like immunodeficiency in its natural host species, the domestic cat. The primary receptor for FIV is CD134, a member of the tumor necrosis factor receptor superfamily, and all primary viral strains tested to date use CD134 for infection. We examined the expression of CD134 in the cat using a novel anti-feline CD134 monoclonal antibody (MAb), 7D6, and showed that as in rats and humans, CD134 expression is restricted tightly to CD4+, and not CD8+, T cells, consistent with the selective targeting of these cells by FIV. However, FIV is also macrophage tropic, and in chronic infection the viral tropism broadens to include B cells and CD8+ T cells. Using 7D6, we revealed CD134 expression on a B220-positive (B-cell) population and on cultured macrophages but not peripheral blood monocytes. Moreover, macrophage CD134 expression and FIV infection were enhanced by activation in response to bacterial lipopolysaccharide. Consistent with CD134 expression on human and murine T cells, feline CD134 was abundant on mitogen-stimulated CD4+ T cells, with weaker expression on CD8+ T cells, concordant with the expansion of FIV into CD8+ T cells with progression of the infection. The interaction between FIV and CD134 was probed using MAb 7D6 and soluble CD134 ligand (CD134L), revealing strain-specific differences in sensitivity to both 7D6 and CD134L. Infection with isolates such as PPR and B2542 was inhibited well by both 7D6 and CD134L, suggesting a lower affinity of interaction. In contrast, GL8, CPG, and NCSU were relatively refractory to inhibition by both 7D6 and CD134L and, accordingly, may have a higher-affinity interaction with CD134, permitting infection of cells where CD134 levels are limiting.
Differential Recognition of β-Lactam Antibiotics by Intestinal and Renal Peptide Transporters, PEPT 1 and PEPT 2 (1995)

This study was initiated to determine if there are differences in the recognition of beta -lactam antibiotics as substrates between intestinal and renal peptide transporters, PEPT 1 and PEPT 2. Reverse transcription-coupled polymerase chain reaction and/or Northern blot analysis have established that the human intestinal cell line Caco-2 expresses PEPT 1 but not PEPT 2, whereas the rat proximal tubule cell line SKPT expresses PEPT 2 but not PEPT 1. Detailed kinetic analysis has provided unequivocal evidence for participation of PEPT 2 in SKPT cells in the transport of the dipeptide glycylsarcosine and the aminocephalosporin cephalexin. The substrate recognition pattern of PEPT 1 and PEPT 2 was studied with cefadroxil (a cephalosporin) and cyclacillin (a penicillin) as model substrates for the peptide transporters constitutively expressed in Caco-2 cells (PEPT 1) and SKPT cells (PEPT 2). Cyclacillin was 9-fold more potent than cefadroxil in competing with glycylsacosine for uptake via PEPT 1. In contrast, cefadroxil was 13-fold more potent than cyclacillin in competing with the dipeptide for uptake via PEPT 2. The substrate recognition pattern of PEPT 1 and PEPT 2 was also investigated using cloned human peptide transporters functionally expressed in HeLa cells. Expression of PEPT 1 or PEPT 2 in HeLa cells was found to induce H(+)-coupled cephalexin uptake in these cells. As was the case with Caco-2 cells and SKPT cells, the uptake of glycylsarcosine induced in HeLa cells by PEPT 1 cDNA and PEPT 2 cDNA was inhibitable by cyclacillin and cefadroxil. Again, the PEPT 1 cDNA-induced dipeptide uptake was inhibited more potently by cyclacillin than by cefadroxil, and the PEPT 2 cDNA-induced dipeptide uptake was inhibited more potently by cefadroxil than by cyclacillin. It is concluded that there are marked differences between the intestinal and renal peptide transporters in the recognition of beta -lactam antibiotics as substrates.
Maturational Arrest of Fetal Muscle in Neonatal Myotonic Dystrophy (1976)

Skeletal muscles from four infants with a severe neonatal form of myotonic muscular dystrophy showed histopathologic features of immaturity. Three of the infants died in the neonatal period and were studied at autopsy; one of these and the still-living infant had a gastrocnemius muscle biopsy. The most severely involved muscles were those associated with arthrogrypotic joints regardless of function as flexors or extensors. Pharyngeal muscles and the diaphragm were also severely involved. Immature features included irregularly distributed small, round muscles fibers with large vesicular internal nuclei and sparse myofibrils. Histochemical differentiation was incomplete and fiber types often could not be distinguished. Muscle fiber degeneration and other features of myotonic dystrophy in adult muscle were lacking. Electron microscopy showed fine granular chromatin and convoluted nuclear membranes of centronuclear fibers, dialated transvers tubules that were aligned longitudinally as in fetal myotubes, poorly formed Z-bands, simple mitochondria, and many satellite cells. We suggest that these features represent an arrest in fetal muscle maturation due to unresponsiveness of an abnormal sarcolemma to trophic influences of normal innervation.
GABABReceptor Modulation of Voltage-Sensitive Calcium Channels in Spines and Dendrites (2011)

Although primarily studied at the cell body, GABA(B) receptors (GABA(B)Rs) are abundant at spines and dendrites of cortical pyramidal neurons, where they are positioned to influence both synaptic and dendritic function. Here, we examine how GABA(B)Rs modulate calcium (Ca) signals evoked by action potentials (APs) in spines and dendrites of layer 2/3 pyramidal neurons in mouse prefrontal cortex. We first use two-photon microscopy to show that GABA(B)Rs inhibit AP Ca signals throughout the entire dendritic arbor of these neurons. We then use local pharmacology and GABA uncaging to show that dendritic GABA(B)Rs also decrease the input resistance, shorten the AP afterdepolarization, and generate inhibitory postsynaptic potentials. However, we find that these electrophysiological effects recorded at the cell body do not correlate with the inhibition of AP Ca signals measured in spines and dendrites. Instead, we use voltage-clamp recordings to show that GABA(B)Rs directly inhibit several subtypes of voltage-sensitive calcium channels (VSCCs) in both spines and dendrites. Given the importance of VSCC-mediated Ca signals for neuronal function, our results have implications for the functional role of dendritic GABA(B)Rs in the prefrontal cortex and throughout the brain.
Role of monocytes in the expansion of human activated natural killer cells (1992)

Abstract We have studied the mechanisms underlying expansion of recombinant interleukin-2 (rIL-2)-stimulated natural killer (NK) cells in vitro. A population of NK cells expressing the CD56+/CD3-phenotype (98.9% +/- 0.42%) was obtained from normal human peripheral blood mononuclear cells (PBMNC) by fluorescence-activated cell sorting (FACS). Culture of NK cells in media containing rIL-2 (1,000 U/mL) for 18 days resulted in a population of activated NK cells (ANK) with significantly enhanced cytotoxicity, but only 2.6 +/- 0.56-fold expansion of cell number compared with the starting NK population. Culture of starting NK populations and autologous PBMNC in a Transwell system (Costar, Cambridge, MA), providing separation of the two cell populations by a 0.4-microns pore membrane, resulted in a dose-dependent increase in fold expansion of ANK (expansion = 19.9 +/- 4.0-fold; P &lt; .001; n = 22) significantly greater than that observed when NK were cultured alone. Further experiments using the Transwell system showed that the stimulatory effect of autologous PBMNC on ANK progenitor proliferation resides in the CD14+ monocyte fraction (maximal expansion = 14.5 +/- 1.5-fold; n = 17) and not in the CD5+ T-lymphocyte or CD19+ B- lymphocyte fractions. Direct coculture of purified NK and autologous monocytes in the same compartment, thus permitting cell-cell contact, resulted in significantly greater expansion of the ANK population (30.6 +/- 4.7-fold expansion, P &lt; .001; n = 10) than that observed when NK and monocytes were separated by the Transwell membrane. Finally, depletion of PBMNC of cells bearing CD5 and CD8 by panning on antibody- coated plastic flasks resulted in a starting cell population enriched for NK progenitors and for monocytes. Cultures of this resultant population for 18 days in the presence of rIL-2 yielded an ANK population similar to that obtained when CD56+/CD3- cells obtained by FACS were cocultured with autologous monocytes. These results suggest that proliferation of ANK requires autologous monocytes and is in part mediated by humoral factors, but is enhanced when NK and monocytes are in direct cell-cell contact. Depletion of cells bearing CD5 and CD8 from PBMNC is a single efficient method for obtaining a starting population capable of producing large numbers of ANK in culture that may lead to new therapeutic uses for the ANK population.
Filter Paper with Selective Absorption and Separation of Liquids that Differ in Surface Tension (2010)

Superhydrophobic and superoleophilic filter paper was successfully prepared by treating commercially available filter paper with a mixture of hydrophobic silica nanoparticles and polystyrene solution in toluene. Applications of the filter paper in separating liquids with low surface tensions such as oil and ethanol from water were investigated in detail. The oil uptake ability of the superhydrophobic filter paper was evaluated and the results show that the filter paper can selectively adsorb oil floating on a water surface or in aqueous emulsions. Furthermore, filtration of mixtures of oil and water through the paper can reduce the water content in the oil. Additionally, the filter paper can also extract ethanol from homogeneous aqueous solution.
Protein phosphatase inhibitors alter cellular microtubules and reduce carbachol-dependent protein secretion in lacrimal acini (2000)

Interference with normal cycles of protein phosphorylation and dephosphorylation in lacrimal acini impairs the stimulated secretory response. Although microtubules were clearly affected by protein phosphatase inhibition, changes in this array were not directly correlated with the reduced secretory response, suggesting that the inhibitory effects on secretion may proceed through microtubule-independent as well as microtubule-dependent mechanisms.
The effects of diphenyleneiodonium on mitochondrial reactions. Relation of binding of diphenylene[125I]iodonium to mitochondria to the extent of inhibition of oxygen uptake (1976)

1. Several ring-substituted derivatives of diphenyleneiodonium catalyse the exchange of Cl- and OH- ions across the inner membrane of rat liver mitochondria. They also inhibit state 3 and state 3u oxidations of glutamate plus malate in the presence of Cl- more than in its absence. Most have activities similar to diphenyleneiodonium, although 2,4-dichlorodiphenyleneiodonium is up to 50 times more active. 2. Diphenyleneiodonium inhibits soluble rat liver NADH dehydrogenase and NADH oxidation by rat liver sub-mitochondrial particles directly; 2,4-dichlorodiphenyleneiodonium is only about twice as inhibitory. 3. Liver mitochondria contain two classes of binding sites for diphenylene[125I]iodonium, namely high-affinity sites with an affinity constant of 3 X 10(5) M-1 (1--2 nmol/mg of protein), and low-affinity sites with an affinity constant of 1.3 X 10(3) M-1 (80 nmol/mg of protein). Both sites occur in hepatocytes with a relative enrichment of the low-affinity site. Nadh dehydrogenase preparations only apparently contain high-affinity binding sites. Only low-affinity sites occur in erythrocytes. 4. 2,4-Dichlorodiphenyleneiodonium competes with diphenylene[125I]iodonium for both low- and high-affinity sites, whereas tri-n-propyltin only competes for the low-affinity sites. 5. The high-affinity sites are apparently associated with NADH dehydrogenase and the low-affinity sites probably represent electrostatic binding of diphenylene[125I]iodonium to phospholipids. The high-affinity site does not appear to be associated with a rate-limiting stage of NADH oxidation.
Recombinant Glycoprotein Vaccine for the Prevention of Genital HSV-2 Infection (1999)

Efficient and sustained protection from sexual acquisition of HSV-2 infection will require more than high titers of specific neutralizing antibodies. Protection against sexually transmitted viruses involving exposure over a prolonged period will require a higher degree of vaccine efficacy than that achieved in this study.
Transgenic Animal Models of Neurodegenerative Diseases (2008)

Neurodegenerative diseases are complex disorders involving neuropathological and psychiatric alterations. Transgenic mice expressing mutant human Alzheimer precursor protein (βAPP), α-synuclein, and mutant huntingtin genes have been developed for Alzheimer’s, Parkinson’s, and Huntington’s disease (AD, PD, and HD), respectively. However, none of the existing mouse models completely represents the pathology of these diseases, including neuronal loss, cerebral atrophy, widespread neurofibrillary tangles, and neuropil threads in AD, formation of Lewy bodies and the extensive loss of dopaminergic neurons in PD, and neuronal loss and aggregate formation in HD. Although rat models have been shown to be superior to mouse models because of the brain size and the availability of more sophisticated behavioral testing, a common disadvantage in rodent models is the lack of neurodegeneration. Furthermore, rodents have relatively smaller brains and thus provide a limited behavioral repertoire for assessing transgene-associated structural and cognitive deficits. Nonhuman primates are ideally suited for modeling the neuropathology of neurodegenerative diseases because of their biological proximity to humans, size, and age-related development of lesions. Thus the development of a transgenic nonhuman primate model of neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Nevertheless, it is undeniable that rodent models contribute significantly to the understanding of neurodegenerative diseases and the development of cures. A transgenic nonhuman primate model will be able to mimic human conditions not only physiologically but also genetically. However, the development of transgenic rodent and nonhuman primate models of neurodegenerative diseases is equally important for unraveling the mystery of neurodegeneration and the development of early diagnosis and cures.
Specific suppression by prostaglandin E2 of activation-induced apoptosis of human CD4+CD8+ T lymphoblasts. (1995)

Receptors (Rs) for prostaglandin E2 (PGE2) of the EP2 subtype are expressed at high levels in rodent and human thymuses, with preferential localization on immature thymocytes. Human cultured lymphoblasts of the Tsup-1 line express CD4 and CD8 but only a low level of CD3, typical of immature thymocytes, and bear EP2-type Rs for PGE2 that were identified by binding of [3H]PGE2 and Ab to recombinant EP2Rs, and by cAMP responses to PGE2. PGE2 protected Tsup-1 cells from apoptosis initiated by diverse stimuli, including mitogenic lectins and anti-Fas or anti-CD3 plus anti-CD28 Abs, but not ionomycin, as assessed by suppression of both fragmentation of [3H]thymidine-labeled DNA and appearance of free 3'-OH ends of cleaved DNA. An EP2R-selective synthetic agonist also significantly suppressed lectin-induced apoptosis of Tsup-1 cells. Phosphodiesterase inhibition synergistically enhanced PGE2-induced increases in cAMP and decreases in apoptosis in parallel, which suggests that the EP2R-specific protective effect of PGE2 is mediated predominantly by cAMP suppression of apoptosis. Dibutyrylcyclic AMP alone protected Tsup-1 cells against lectin-induced apoptosis, but the maximal effect was less than that for PGE2. The thromboxane A2 mimetic U46619 initiated apoptosis of Tsup-1 cells that was suppressed significantly by PGE2. Immune negative selection of immature thymocytes thus may be regulated by opposing effects of endogenous eicosanoids that include destruction by thromboxane A2 and protection by PGE2.