gebhart/patrepeval huggingface dataset:
Identification, sequence analysis, and expression of a Corynebacterium glutamicum gene cluster encoding the three glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase, 3-phosphoglycerate kinase, and triosephosphate isomerase (1992)

To investigate a possible chromosomal clustering of glycolytic enzyme genes in Corynebacterium glutamicum, a 6.4-kb DNA fragment located 5' adjacent to the structural phosphoenolpyruvate carboxylase (PEPCx) gene ppc was isolated. Sequence analysis of the ppc-proximal part of this fragment identified a cluster of three glycolytic genes, namely, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene gap, the 3-phosphoglycerate kinase (PGK) gene pgk, and the triosephosphate isomerase (TPI) gene tpi. The four genes are organized in the order gap-pgk-tpi-ppc and are separated by 215 bp (gap and pgk), 78 bp (pgk and tpi), and 185 bp (tpi and ppc). The predicted gene product of gap consists of 336 amino acids (M(r) of 36,204), that of pgk consists of 403 amino acids (M(r) of 42,654), and that of tpi consists of 259 amino acids (M(r) of 27,198). The amino acid sequences of the three enzymes show up to 62% (GAPDH), 48% (PGK), and 44% (TPI) identity in comparison with respective enzymes from other organisms. The gap, pgk, tpi, and ppc genes were cloned into the C. glutamicum-Escherichia coli shuttle vector pEK0 and introduced into C. glutamicum. Relative to the wild type, the recombinant strains showed up to 20-fold-higher specific activities of the respective enzymes. On the basis of codon usage analysis of gap, pgk, tpi, and previously sequenced genes from C. glutamicum, a codon preference profile for this organism which differs significantly from those of E. coli and Bacillus subtilis is presented.
Proliferation Requirements of Cytomegalovirus-Specific, Effector-Type Human CD8+ T Cells (2002)

Two prototypic types of virus-specific CD8(+) T cells can be found in latently infected individuals: CD45R0(+)CD27(+)CCR7(-) effector-memory, and CD45RA(+)CD27(-)CCR7(-) effector-type cells. It has recently been implied that CD45RA(+)CD27(-)CCR7(-) T cells are terminally differentiated effector cells and as such have lost all proliferative capacity. We show in this study, however, that stimulation of CMV-specific CD45RA(+)CD27(-)CCR7(-) T cells with their cognate peptide in concert with either CD4(+) help or IL-2, IL-15, or IL-21 in fact induces massive clonal expansion. Concurrently, these stimulated effector T cells change cell surface phenotype from CD45RA to CD45R0 and regain CCR7, while effector functions are maintained. Our data imply that CD45RA(+)CD27(-)CCR7(-) effector-type T cells contribute to immunity not only by direct execution of effector functions, but also by yielding progeny in situations of viral reinfection or reactivation.
Longer Exposure Durations Increase Freeze Damage to Turf Bermudagrasses (2003)

Bermudagrasses, Cynodon sp, are susceptible to winter injury in the transition zone for warm- and cool-season turfgrasses. Our objectives were to determine relative freeze tolerance of recently released and standard cultivars using laboratory-based methodology, and to determine the effect of extended exposure duration on survival. Plants were clonally propagated, then established and acclimated in growth chambers before exposure to a range of temperatures in a freeze chamber. ‘Tifway’ and ‘TifSport’ (−7.9°C) were significantly hardier than ‘Princess’ (−6.9°C), but less freeze tolerant than ‘U-3’ (−8.9°C), ‘Patriot’ (−9.7°C), and ‘Midlawn’ (−10.3°C). Riviera (−8.3°C) was significantly hardier than Princess, but less freeze tolerant than Patriot and Midlawn. In a second set of experiments, acclimated plants were held at constant, subfreezing temperatures for various periods of time in a refrigerated bath. Survival of U-3 and Riviera decreased to 25% or less when exposed to −7.0°C for 2 or 5 d, compared with 100 and 83% survival, respectively, when plants were removed from the bath immediately after equilibrating at −7.0°C. Princess exhibited 89% survival when removed immediately after equilibrating at −5.4°C, but survival after 2, 24, and 72 h was 67, 30, and 11%, respectively. Although minimum exposure temperature is a primary determinant of survival, freeze damage to turf bermudagrasses increased as exposure duration increased.
Novel Guanosine Quartet Structure Binds to the HIV Envelope and Inhibits Envelope Mediated Cell Fusion (1995)

Abstract We have identified a phosphorothioate oligonucleotide T2G4T2, which is a potent inhibitor of HIV infection in vitro. The compound was identified by combinatorial screening of a library of all possible octanucleotide sequences. The oligonucleotide forms a parallel-stranded, tetrameric guanosine-quartet (G-quartet) structure which specifically binds to the HIV envelope glycoprotein (gp 120) and inhibits both cell-to-cell and virus-to-cell infection at submicromolar concentrations. In the current study we demonstrate that the tetramer inhibits the infection of laboratory-derived isolate of HIV-1 and HIV-2 in a variety of phenotypically distinct established human cell lines and a panel of biologically diverse clinical isolates in fresh human peripheral blood lymphocytes and macrophages. The compound was also active against all drug-resistant virus isolates tested. In combination with AZT, ISIS 5320 exhibits additive to slightly synergistic anti-HIV activity. Cell-based mechanism of action studies demonstrate that the compound inhibits the binding of infectious virus and virus-infected cells to uninfected target cells by binding to the cationic V3 loop of the envelope glycoprotein. The G-quartet structure is a potential candidate for use in anti-HIV chemotherapy.
The Combinatorial Library: A Multifunctional Resource (1996)

About 10 years ago Dr. Mario Geysen introduced a method for synthesizing a large number of peptides on solid supports simultaneously. This work has subsequently been generalized by many other research groups to develop technologies that allow from hundreds to thousands to millions of compounds to be synthesized in parallel. These large collections of compounds have been now termed combinatorial libraries. Much of the effort in this field has been directed to drug discovery. However, in recent years, these libraries have been shown to be very useful for finding compounds (such as inhibitors, binding agents, enzymes, and antibodies) that satisfy specific requirements. Thus these techniques represent a very excellent resource for the discovery of compounds for a variety of biotechnological process needs.
Structural Analysis of Semi-specific Oligosaccharide Recognition by a Cellulose-binding Protein of Thermotoga maritima Reveals Adaptations for Functional Diversification of the Oligopeptide Periplasmic Binding Protein Fold (2009)

Periplasmic binding proteins (PBPs) constitute a protein superfamily that binds a wide variety of ligands. In prokaryotes, PBPs function as receptors for ATP-binding cassette or tripartite ATP-independent transporters and chemotaxis systems. In many instances, PBPs bind their cognate ligands with exquisite specificity, distinguishing, for example, between sugar epimers or structurally similar anions. By contrast, oligopeptide-binding proteins bind their ligands through interactions with the peptide backbone but do not distinguish between different side chains. The extremophile Thermotoga maritima possesses a remarkable array of carbohydrate-processing metabolic systems, including the hydrolysis of cellulosic polymers. Here, we present the crystal structure of a T. maritima cellobiose-binding protein (tm0031) that is homologous to oligopeptide-binding proteins. T. maritima cellobiose-binding protein binds a variety of lengths of beta(1-->4)-linked glucose oligomers, ranging from two rings (cellobiose) to five (cellopentaose). The structure reveals that binding is semi-specific. The disaccharide at the nonreducing end binds specifically; the other rings are located in a large solvent-filled groove, where the reducing end makes several contacts with the protein, thereby imposing an upper limit of the oligosaccharides that are recognized. Semi-specific recognition, in which a molecular class rather than individual species is selected, provides an efficient solution for the uptake of complex mixtures.
Deleted in oral cancer‐1 ( doc‐l), a novel oral tumor suppressor gene (1995)

We have identified, isolated, and partially characterized doc-1, a novel cDNA sequence whose activity is consistent with a suppressor of hamster oral carcinogenesis. Doc-1 is an evolutionarily conserved gene exhibiting loss of heterozygosity and marked reduction in expression in malignant hamster oral keratinocytes. The full-length doc-1 cDNA encodes an 87 amino acid product that shows a significant homology to one of the seven novel genes induced in mouse fibroblasts by TNF-alpha. Transfection of the full-length doc-1 cDNA into malignant hamster oral keratinocytes alters the behavior of the recipients in terms of morphology, growth rate, and anchorage-independent growth, suggesting reversion of transformation phenotypes. We propose that doc-1 is a novel tumor suppressor gene in oral cancer development.
VIRAL PROTEINASES (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Coupled-channel Dalitz plot analysis of $D^+\to K^- π^+π^+$ decay (2016)

We demonstrate that partial wave amplitudes extracted from $D^+\to K^-π^+π^+$ Dalitz plot with a unitary coupled-channel model are significantly different from those obtained with an isobar model. The unitary coupled-channel model takes account of hadronic rescattering mechanisms involving all three mesons that have been missed in conventioanl isobar model analyses. The rescattering mechanisms contribute largely, and can triplicate the $D^+\to {K}^-π^+π^+$ decay width within our analysis. These findings deliver a warning that analysis results obtained with isobar models should be looked with a caution. The determination of the CKM angle $γ/ϕ_3$ is a highly relevant problem.
Preserved interfacial magnetism and giant antiferromagnetic exchange coupling in Co/Rh sandwiches (1997)

The interlayer coupling in Co/Rh/Co sandwiches prepared by UHV evaporation has been investigated by means of magnetization and transport experiments. We found that the antiferromagnetic coupling strength for thin Rh layers is the largest ever obtained in magnetic systems, reaching approximately 34 erg/cm2 for 5 Å thick Rh interlayer. This value is 7 to 8 times larger than the highest value previously observed in the Co/Ru system prepared under similar conditions. This unexpectedly large difference in the coupling strength between these two systems is mainly due to the magnetic nature of the interfaces. This is further supported by ab initio calculations of the magnetic moments in superlattices with mixed interfaces.
The Pathophysiologic Roles of Interleukin-6 in Human Disease (1998)

Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.
Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: Selective targeting to diseased versus healthy tissue (2015)

Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations.
A functionally split pathway for lysine synthesis in Corynebacterium glutamicium (1991)

Three different pathways of D,L-diaminopimelate and L-lysine synthesis are known in procaryotes. Determinations of the corresponding enzyme activities in Escherichia coli, Bacillus subtilis, and Bacillus sphaericus verified the fact that in each of these bacteria only one of the possible pathways operates. However, in Corynebacterium glutamicum activities are present which allow in principle the use of the dehydrogenase variant and succinylase variant of lysine synthesis together. Applying gene-directed mutagenesis, various C. glutamicum strains were constructed with interrupted ddh gene. These mutants have an inactive dehydrogenase pathway but are still prototrophic, which is proof that the succinylase pathway of D,L-diaminopimelate synthesis can be utilized. In strains with an increased flow of precursors to D,L-diaminopimelate, however, the inactivation of the dehydrogenase pathway resulted in a reduced formation of lysine, with concomitant accumulation of N-succinyl-diaminopimelate in the cytosol up to a concentration of 25 mM. These data show (i) that both pathways can operate in C. glutamicum for D,L-diaminopimelate and L-lysine synthesis, (ii) that the dehydrogenase pathway is not essential, and (iii) that the dehydrogenase pathway is a prerequisite for handling an increased flow of metabolites to D,L-diaminopimelate.
Choosing Targets for Gene Therapy (2011)

Gene therapy is often attempted in fatal diseases with no known cure, or after standard therapies have failed. Targeting gene defects includes addressing a single mutation, multiple mutations in several genes, or even addressing missing or extra copies in a particular disease. A defect in one specific gene may impair normal function of the corresponding expressed protein. For example, in X-linked severe combined immunodeficiency (X-SCID), there is a mutation in the IL2 receptor ┛ gene. Another classic example occurs in thalassemia propagated by a defect in the ┚-globulin gene. Some diseases are caused by multiple mutations in several genes. For example, some cardiovascular diseases may manifest due to mutations in different chromosomes which are a result of inherited or environmental factors. Before approaching a disease using gene therapy, the key protein(s) and pathways involved in the disease should first be identified. However, in some cases an abnormal gene is formed that results in disease; such is the case for the BcrAbl gene. The oncogenic Bcr-Abl protein is the causative agent of chronic myelogenous leukemia (CML) which could be blocked for CML treatment. Genomic sequencing information, microarrays, and biochemical assays can be used to determine upor downregulated proteins involved in disease, and will help determine the function of these proteins. In the case of some cancers, the signal transduction pathways for oncogenesis have been mapped out, allowing hub proteins to be identified. Hub proteins are essential proteins that interact with multiple other proteins in signaling cascades. If selected properly, adding back a tumor-suppressing hub protein (such as p53), or blocking an oncogenic hub protein (such as survivin) could halt cancer or alter disease progression. Gene mutations can result in mislocalization of these key proteins which can cause cancer; this mislocalization can be exploited with gene therapy approaches. Further, new types of gene therapy are being developed in our lab to direct proteins to other cellular compartments where their function is altered. This chapter will summarize these and other known targets and also focus on choosing newer targets for gene therapy.
Hyperparathyroidism. (1996)

Primary hyperparathyroidism is the most prevalent cause of hypercalcemia. Although renal stone disease and osteitis fibrosis were prominent complications of this disorder in the past, the advent of biochemical screening has resulted in earlier detection. This has changed the clinical presentation of primary hyperparathyroidism, so that as many as 80% of patients do not have any sign or symptom that can be attributed solely to the disease. Improvement in assays for PTH has allowed for accurate bio-chemical diagnosis in over 90% of cases. Neck exploration is the treatment of choice for any patient who presents with signs, symptoms, or complications of hypercalcemia or hyperparathyroidism. Medical therapy is indicated in patients who either cannot undergo surgery because of medical contraindication, failed prior neck surgery, unresectable parathyroid carcinoma or simply refuse surgery. Medical therapy is not optimal, although sex steroid replacement therapy in the postmenopausal woman has met with some success. Calcitonin, phosphate, and bisphosphonates may be used, but their long-term efficacy is not clear. Recent studies have suggested that a large proportion of patients with asymptomatic primary hyperparathyroidism do not demonstrate progression of disease in terms of renal dysfunction, bone disease, or biochemical changes in calcium or PTH. Guidelines have been established for medical follow-up of such patients. If any such patient develops signs or symptoms during medical follow-up, surgery is then indicated.
Modulation of prostate cancer growth in bone microenvironments (2003)

Bone remains one of the major sites, and most lethal host organs, for prostate cancer metastasis. Prostate cell spread and establishment in bone depends on multiple reciprocal modifications of bone stromal and epithelial cancer cell behaviors. This review focuses on recent advances in the characterization of cell-cell and cell-matrix interplay, effects on cell growth, adhesion and invasion, and several therapeutic possibilities for co-targeting prostate cancer cells and bone stroma. We address the topic from three main perspectives: (1) the normal and aging bone stromal environment, (2) the "reactive" bone stromal environment, and (3) the cancerous prostate epithelial cells themselves. First, normal, and especially aging, bones provide uniquely rich and "fertile soil" for roaming cancer cells. The interactions between prostate cancer cells and insoluble extracellular matrices, soluble growth factors, and/or sex steroid hormones trigger bone remodeling, through increased osteoclastogenesis and furthur matrix metalloproteinase activity. Second, after cancer cell arrival and establishment in the bone, host stromal cells respond, becoming "reactive" in a process again involving extracellular matrix remodeling, together with growth factor and steroid receptor signaling this process ultimately enhances cancer cell migration, stromal transdifferentiation, and invasion of the cancer tissues by stromal, inflammatory, and immune-responsive cells. Third, prostate cancer cells also respond to supportive bone microenvironments, where soluble and matrix-associated molecules affect cancer cell growth and gene expression, especially altering cancer cell surface receptor and integrin-mediated cell signaling. We discuss both integrin cell-matrix and gap junctional cell-cell communication between cancer cells and their microenvironments during prostate cancer progression.
Effect of supplementation with different doses of DHA on the levels of circulating DHA as non-esterified fatty acid in subjects of Asian Indian background (1998)

There is evidence to indicate that the high rates of coronary heart disease and myocardial infarction amongst Indians of Asian descent may be partly related to circulating nonesterified fatty acids (NEFA). As docosahexaenoic acid (DHA,22:6n-3) in NEFA form has been found to exhibit anti-platelet aggregatory and anti-arrhythmic potential in vitro, the effect of supplementary DHA was examined in healthy subjects of Asian Indian background. Furthermore, time- and dose-dependent changes in absolute levels of DHA as NEFA or phospholipid (PL) were compared. The subjects consumed 8 capsules daily of placebo (DHA-free) or low DHA (0.75 g/day)or high DHA (1.50 g/day) over 6 wks. Fasting blood samples were drawn at days 0, 21, and 42 for analysis of serum lipid/lipoprotein composition. No significant effect of DHA supplementation on the levels of serum lipid/lipoproteins (including Lp[a]) or blood pressure was found. However, the DHA level in serum phospholipid rose by 167% overall with low-dose supplementation (from 2.4-6.4 mol%) but only by an additional 23% upon doubling the dose from 0.75 g to 1.50 g/day. Furthermore, after 6 weeks of supplementation with 0.75 g or 1.5 g DHA/day, absolute concentrations of DHA as PL were not significantly different from the corresponding 3-week values. Interestingly, the absolute concentrations of serum DHA as NEFA showed a marked rise with low-dose supplementation (by 212% overall, from 2.4 to 7.5 microM) and a further 70% rise (to 12.7 microM) upon doubling the supplementation from 0.75 to 1.50 g/day. As well, the 6-week concentrations (DHA-NEFA) were significantly different than the corresponding 3-week values at both dose levels. Elevation of circulating DHA-NEFA levels via DHA supplementation, as shown herein, to concentrations that exhibit anti-thrombotic and anti-arrhythmic potential in vitro needs to be extended to trials where clinical end-points are determined.
Optimization of a self antigen for presentation of multiple epitopes in cancer immunity (2006)

T cells recognizing self antigens expressed by cancer cells are prevalent in the immune repertoire. However, activation of these autoreactive T cells is limited by weak signals that are incapable of fully priming naive T cells, creating a state of tolerance or ignorance. Even if T cell activation occurs, immunity can be further restricted by a dominant response directed at only a single epitope. Enhanced antigen presentation of multiple epitopes was investigated as a strategy to overcome these barriers. Specific point mutations that create altered peptide ligands were introduced into the gene encoding a nonimmunogenic tissue self antigen expressed by melanoma, tyrosinase-related protein-1 (Tyrp1). Deficient asparagine-linked glycosylation, which was caused by additional mutations, produced altered protein trafficking and fate that increased antigen processing. Immunization of mice with mutated Tyrp1 DNA elicited cross-reactive CD8(+) T cell responses against multiple nonmutated epitopes of syngeneic Tyrp1 and against melanoma cells. These multi-specific anti-Tyrp1 CD8(+) T cell responses led to rejection of poorly immunogenic melanoma and prolonged survival when immunization was started after tumor challenge. These studies demonstrate how rationally designed DNA vaccines directed against self antigens for enhanced antigen processing and presentation reveal novel self epitopes and elicit multi-specific T cell responses to nonimmunogenic, nonmutated self antigens, enhancing immunity against cancer self antigens.