gebhart/patrepeval huggingface dataset:
High-Affinity Androgen Binding and Androgenic Regulation of α1(I)-Procollagen and Transforming Growth Factor-β Steady State Messenger Ribonucleic Acid Levels in Human Osteoblast-Like Osteosarcoma Cells* (1991)

Clinical observations have demonstrated a positive effect of estrogens and androgens on the maintenance of structural bone integrity. This study examines the direct effects of androgenic hormones on the osteoblast-like human osteosarcoma cell line, HOS TE85. Employing radiolabeled dihydrotestosterone (DHT), 2800 saturable, high-affinity (dissociation constant = 0.66 nM) androgen binding sites were detected per HOS TE85 cell. Androgen binding was specific in that DHT and testosterone (T) displayed significantly greater competition than the progestins, progesterone and medroxyprogesterone. The expression of androgen receptors in HOS TE85 cells was further substantiated by Northern analysis. A human androgen receptor complementary DNA probe revealed a 9.5 kilobase transcript which corresponds to the predominant human androgen receptor transcript detected in human male reproductive tissues. Androgens were also found to elicit biological responses in HOS TE85 cells. Physiological concentrations of DHT and T decreased HOS TE85 cell proliferation as assessed by cell count. This finding suggests that DHT may also play a role in osteoblast differentiation. In support of this hypothesis, treatment with T (24 h, 10 nM) enhanced the abundance of both alpha 1(I)-procollagen messenger RNA (mRNA) (5-fold) and transforming growth factor-beta mRNA (2.2 fold). The nonaromatizable androgen DHT (24 h, 10 nM) elicited an increase in the steady state concentration of alpha 1(I)-procollagen mRNA similar to the increase observed with T treatment. Thus, in addition to the recent discovery of estradiol receptors and estrogenic regulation of HOS TE85 cells, it is now evident that these osteoblast-like osteosarcoma cells also express high affinity androgen binding sites and can respond biologically to androgens.
Properties of Tofus and Soy Milks Prepared from Soybeans Having Different Subunits of Glycinin (2000)

The contribution of soybean protein to the physical properties of tofu, a product manufactured by curdling soy milk with coagulants such as calcium or magnesium chloride, was studied by comparing the properties of soy milk prepared from soybeans with different subunits (I, IIa, and IIb) of glycinin with amino acid residues deleted. The breaking stress value of the tofu curds prepared from soybeans having group I was higher than those without group I. The soy milks having group I contained more protein particles and showed more sensitivity to calcium and magnesium ions than those without group I. The amounts of glycinin and protein particles were higher in the soy milks having group I than those in the soy milks without group I. To elucidate the influence of each group on the breaking stress, the glycinin content was adjusted to an identical level in soy milks having each group. Among the tofu curds from three groups, their order of hardness according to their breaking stress was IIa, IIb, and I. The order of particle content among these soy milks was also IIa, IIb, and I. Therefore, the results suggested that the breaking stress value of the tofu curd is dependent upon the number of protein particles in the soy milk and that the number of the particles is determined by the proportion and structure of glycinin in the soybean.
Alteration of substrate specificity for the endoribonucleolytic cleavage of RNA by the Tetrahymena ribozyme. (1989)

A shortened form of the intervening sequence of the self-splicing RNA from Tetrahymena thermophila catalyzes sequence-specific cleavage of RNA. Cleavage site selection involves a base-pairing interaction between the substrate RNA and a binding site within the intervening sequence. Single-base changes in this binding site were previously shown to alter substrate specificity in a predictable manner. To examine the generality with which substrate specificity can be altered, six variant catalytic RNAs (ribozymes) have been produced with two- or three-base changes in the active site. Each ribozyme cleaves its predicted substrate. The conditions required for good reactivity and for discrimination against cleavage at mismatched sites vary and were independently determined for each ribozyme.
Global Honey Bee Viral Landscape Altered by a Parasitic Mite (2012)

Emerging diseases are among the greatest threats to honey bees. Unfortunately, where and when an emerging disease will appear are almost impossible to predict. The arrival of the parasitic Varroa mite into the Hawaiian honey bee population allowed us to investigate changes in the prevalence, load, and strain diversity of honey bee viruses. The mite increased the prevalence of a single viral species, deformed wing virus (DWV), from ~10 to 100% within honey bee populations, which was accompanied by a millionfold increase in viral titer and a massive reduction in DWV diversity, leading to the predominance of a single DWV strain. Therefore, the global spread of Varroa has selected DWV variants that have emerged to allow it to become one of the most widely distributed and contagious insect viruses on the planet.
Construction of Transgenic Drosophila by Using the Site-Specific Integrase From Phage C31 (2004)

The phiC31 integrase functions efficiently in vitro and in Escherichia coli, yeast, and mammalian cells, mediating unidirectional site-specific recombination between its attB and attP recognition sites. Here we show that this site-specific integration system also functions efficiently in Drosophila melanogaster in cultured cells and in embryos. Intramolecular recombination in S2 cells on transfected plasmid DNA carrying the attB and attP recognition sites occurred at a frequency of 47%. In addition, several endogenous pseudo attP sites were identified in the fly genome that were recognized by the integrase and used as substrates for integration in S2 cells. Two lines of Drosophila were created by integrating an attP site into the genome with a P element. phiC31 integrase injected into embryos as mRNA functioned to promote integration of an attB-containing plasmid into the attP site, resulting in up to 55% of fertile adults producing transgenic offspring. A total of 100% of these progeny carried a precise integration event at the genomic attP site. These experiments demonstrate the potential for precise genetic engineering of the Drosophila genome with the phiC31 integrase system and will likely benefit research in Drosophila and other insects.
The SH3 Domain-containing Adaptor HIP-55 Mediates c-Jun N-terminal Kinase Activation in T Cell Receptor Signaling (2003)

HIP-55 (hematopoietic progenitor kinase 1 (HPK1)-interacting protein of 55 kDa, also called SH3P7 and mAbp1) is a novel SH3 domain-containing protein. HIP-55 binds to actin filaments both in vitro and in vivo. HIP-55 activates HPK1 and c-Jun N-terminal kinase (JNK), which are two important lymphocyte signaling molecules. Until now, the regulation and function of HIP-55 in T cell receptor (TCR) signaling were unknown. We found that HIP-55 was recruited to glycolipid-enriched microdomains upon TCR stimulation, which indicates that HIP-55 is regulated by TCR signaling. HIP-55 interacted with ZAP-70, a critical protein-tyrosine kinase in TCR signaling, and this interaction was induced by TCR signaling. ZAP-70 phosphorylated HIP-55 at Tyr-334 and Tyr-344 in vitro and in vivo, and the HIP-55 mutant (Y334F/Y344F) was not tyrosine-phosphorylated in stimulated T cells. To study its function in T cell activation, HIP-55-deficient Jurkat T cells were established using the RNA interference approach. In the HIP-55-deficient cells, TCR (but not UV)-stimulated JNK activation was decreased. Furthermore, the activation of HPK1, a known JNK upstream activator and HIP-55-interacting protein, was also decreased in the HIP-55-deficient cells. Our data reveal the regulation of HIP-55 during TCR signaling, and using a genetic approach, we demonstrate for the first time that HIP-55 plays a functional role in TCR signaling.
Partial purification of collagenase and gelatinase from human polymorphonuclear leucocytes. Analysis of their actions on soluble and insoluble collagens (1982)

The separation and further purification of human polymorphonuclear-leucocyte collagenase and gelatinase, using modifications of the method of Cawston & Tyler [(1979) Biochem J. 183, 647-656], are described. The final preparations yielded collagenase of specific activity 260 units/mg and gelatinase of specific activity 13 000 units/mg. Gelatinase was purified to apparent homogeneity in a latent form, and analysis of the activation of 125I-labelled latent enzyme by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and gel-filtration techniques suggested that no peptide material was lost on conversion into the active form. The purified natural inhibitors alpha 2-macroglobulin, tissue inhibitor of metalloproteinases ('TIMP') and amniotic-fluid inhibitor of metalloproteinases all inhibited the two polymorphonuclear-leucocyte metalloproteinases, but the last two inhibitors were slow to act and complete inhibition was difficult to attain. Collagenase degraded soluble types I and III collagen equally efficiently, but soluble type II collagen less well. Gelatinase alone had little activity on these substrates, although it enhanced the action of collagenase. Gelatinase was capable of degrading soluble types IV and V collagen at 25 degrees C, whereas collagenase was only active at higher temperatures when the collagens were susceptible to trypsin activity. By using tissue preparations of insoluble collagens (type I, II or IV) the activity of leucocyte collagenase was low and gelatinase activity was negligible, as measured by the solubilization of hydroxyproline-containing material. The two enzymes together were two or three times more effective in the degradation of these insoluble collagens.
ESEfinder: a web resource to identify exonic splicing enhancers (2003)

Point mutations frequently cause genetic diseases by disrupting the correct pattern of pre-mRNA splicing. The effect of a point mutation within a coding sequence is traditionally attributed to the deduced change in the corresponding amino acid. However, some point mutations can have much more severe effects on the structure of the encoded protein, for example when they inactivate an exonic splicing enhancer (ESE), thereby resulting in exon skipping. ESEs also appear to be especially important in exons that normally undergo alternative splicing. Different classes of ESE consensus motifs have been described, but they are not always easily identified. ESEfinder (http://exon.cshl.edu/ESE/) is a web-based resource that facilitates rapid analysis of exon sequences to identify putative ESEs responsive to the human SR proteins SF2/ASF, SC35, SRp40 and SRp55, and to predict whether exonic mutations disrupt such elements.
Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4 (2000)

Neutrophils recruited to the airways in chronic obstructive pulmonary disease (COPD) are thought to mediate tissue destruction. Neutrophil recruitment is increased during bacterial exacerbations. The inflammatory process was studied in patients with an acute exacerbation of COPD in order to ascertain the role of leukotriene B4 (LTB4). The sputum of eight subjects with a bacterial exacerbation of COPD was analysed for neutrophil products (myeloperoxidase, elastase) and chemoattractants (interleukin-8 (IL-8) and LTB4). The contribution of LTB4 to the chemotactic activity of the sputum sol phase was determined using the LTB4 receptor antagonist LY293111. The concentrations of the serum acute phase proteins alpha1-proteinase inhibitor, alpha1-antichymotrypsin and C-reactive protein were measured. All patients received appropriate broad-spectrum antibiotic treatment for 7-14 days. Initially, the sputum myeloperoxidase activity was high, indicating neutrophil influx; this was associated with high levels of IL-8 and LTB4. All these concentrations fell with treatment (p<0.01). The chemotactic activity of the sputum was raised on presentation and fell with treatment (p<0.01). LTB4 contributed approximately 30% of the total chemotactic activity on presentation; this diminished with therapy. All acute phase proteins were raised on presentation and fell with therapy (p<0.01). These findings suggest that leukotriene B4 contributes to neutrophil influx into the airway in chronic obstructive pulmonary disease and may influence disease progression.
Hematologic Response to Three Alternative Dosing Schedules of Azacitidine in Patients With Myelodysplastic Syndromes (2009)

All three alternative dosing regimens produced HI, RBC transfusion independence, and safety responses consistent with the currently approved AZA regimen. These results support AZA benefits in transfusion-dependent lower-risk MDS patients.
Perspectives in Pancreatic and Islet Cell Transplantation for the Therapy of IDDM (1997)

Endocrine pancreas transplantation could provide an ideal solution to the problem posed by IDDM. Although preliminary clinical success achieved over the past few years has been considerably higher with whole pancreatic transplant than with isolated islet grafts, both approaches remain experimental. Islet grafts might gain, over time, increasing credibility and might eventually provide an easier alternative in terms of grafting procedures and patient management, as compared with the more "traumatizing" whole-pancreas transplantation, but only if the pending technical problems are fully surmounted. Combined pancreas/kidney (either simultaneous pancreas/kidney [SPK] or pancreas after kidney [PAK]) transplantation, under general immunosuppression, in IDDM patients also suffering from end-stage renal disease (ESRD) is a procedure that may be worth pursuing in selected cases. However, there are still quite serious reservations about the scaled-up applicability of pancreas transplant alone (PTA) in patients with "brittle" IDDM; major restrictions are not only the necessity of pharmacological immunosuppression, but also the lower functional performance of PTA, especially as compared with SPK grafting. In terms of islets, as problems of human islet yield and purity are gradually being overcome, the problem of islet graft-directed immune destruction hampers the success of ongoing clinical trials in IDDM patients. The invariable requirement of general immunosuppression affects pancreatic as much as islet grafts, although a number of alternative, yet experimental, immunoprotection strategies in progress might suit islets better than they would whole organs. Another issue concerns the relative inadequacy of cadaveric donor organ availability, the requirements of which are more stringent for islets because of the persistent variability of islet cell yield per organ. Tremendous experimental efforts are in progress to create xenogeneic porcine/bovine islets and, perhaps over a longer period of time, human/nonhuman engineered insulin-producing cells suitable for graft within special immunoisolation barrier membranes.
Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases. (1991)

Two epidermal growth factor-stimulated protein kinases that correspond to ERK1 and ERK2 have been purified from human epidermoid carcinoma cells (Northwood, I. C., Gonzalez, F. A., Wartmann, M., Raden, D. L., and Davis, R. J. (1991) J. Biol. Chem. 266, 15266-15276). A consensus primary sequence for substrates of ERK1 has been identified as -Pro-Leu-Ser/Thr-Pro- (Alvarez, E., Northwood, I. C., Gonzalez, F. A., Latour, D. A., Seth, A., Abate, C., Curran, T., and Davis, R. J. (1991) J. Biol. Chem. 266, 15277-15285). However, the structural determinants for substrate recognition are not understood. We performed a systematic analysis of the effect of point mutations in the primary sequence of peptide substrates on the rate of phosphorylation by ERK1 and ERK2. The results of this investigation demonstrate that the substrate specificities of the ERK1 and ERK2 protein kinases are very similar. We propose that the primary sequence of substrates for ERK1 and ERK2 protein kinases can be generalized as -Pro-Xaan-Ser/Thr-Pro- (where Xaa is a neutral or basic amino acid and n = 1 or 2).
Inhibiting phosphoinositide 3-kinases (2005)

Commentary to:PWT-458, A Novel Pegylated-17-Hydroxywortmannin, Inhibits Phosphatidylinositol 3-Kinase Signaling and Suppresses Growth of Solid TumorsK. Yu, J. Lucas, T. Zhu, A. Zask, C. Gaydos, L. Toral-Barza, J. Gu, F. Li, I. Chaudhary, P. Cai, J. Lotvin, R. Petersen, M. Ruppen, M. Fawzi, S. Ayral-Kaloustian, J. Skotnicki, T. Mansour, P. Frost and J. Gibbons
THE SYMPATHETIC NERVOUS SYSTEM AND LONG‐TERM REGULATION OF ARTERIAL PRESSURE: WHAT ARE THE CRITICAL QUESTIONS? (1997)

1. The role of the sympathetic nervous system in long-term control of arterial pressure remains unclear despite decades of intense research. 2. Previous studies have shown that denervation of arterial baroreceptors does not chronically increase arterial pressure. As baroreceptors are thought to provide the primary 'error signal' to the autonomic nervous system, this has been interpreted as evidence against neural control of arterial pressure over long periods of time. 3. The possibility that other 'error signals' are important in the long-term control of sympathetic activity (and arterial pressure) is introduced. 4. The following 'Critical Questions' are presented for subsequent discussion: (i) is the sympathetic nervous system a 'major player' in the long-term control of arterial pressure; (ii) why doesn't arterial pressure remain at hypertensive levels after arterial baroreceptor denervation; and (iii) which 'error signals' are most important in the long-term control of sympathetic outflow?
High-level diterpene production by transient expression in Nicotiana benthamiana (2013)

With this optimized method for diterpene synthase expression and product analysis, a single infiltrated leaf of N. benthamiana would be sufficient to produce quantities required for the structure elucidation of unknown diterpenes. The method will also be of general use for gene function discovery, pathway reconstitution and metabolic engineering of diterpenoid biosynthesis in plants.
Metabolic targeting of hypoxia and HIF1 in solid tumors can enhance cytotoxic chemotherapy (2007)

Solid tumors frequently contain large regions with low oxygen concentrations (hypoxia). The hypoxic microenvironment induces adaptive changes to tumor cell metabolism, and this alteration can further distort the local microenvironment. The net result of these tumor-specific changes is a microenvironment that inhibits many standard cytotoxic anticancer therapies and predicts for a poor clinical outcome. Pharmacologic targeting of the unique metabolism of solid tumors could alter the tumor microenvironment to provide more favorable conditions for anti-tumor therapy. Here, we describe a strategy in which the mitochondrial metabolism of tumor cells is increased by pharmacologic inhibition of hypoxia-inducible factor 1 (HIF1) or its target gene pyruvate dehydrogenase kinase 1 (PDK1). This acute increase in oxygen consumption leads to a corresponding decrease in tumor oxygenation. Whereas decreased oxygenation could reduce the effectiveness of some traditional therapies, we show that it dramatically increases the effectiveness of a hypoxia-specific cytotoxin. This treatment strategy should provide a high degree of tumor specificity for increasing the effectiveness of hypoxic cytotoxins, as it depends on the activation of HIF1 and the presence of hypoxia, conditions that are present only in the tumor, and not the normal tissue.
A New Type of Artificial Oxygen Carrier: Soluble Hyperpolymeric Haemoglobin with Negligible Oncotic Pressure—Production of Thermally Stable Hyperpolymers from Human Blood with Glutaraldehyde as Cross-Linker (1992)

(1992). A New Type of Artificial Oxygen Carrier: Soluble Hyperpolymeric Haemoglobin with Negligible Oncotic Pressure—Production of Thermally Stable Hyperpolymers from Human Blood with Glutaraldehyde as Cross-Linker. Biomaterials, Artificial Cells and Immobilization Biotechnology: Vol. 20, No. 2-4, pp. 287-291.
Prognostic and predictive significance of immune cells infiltrating cutaneous melanoma (2015)

The tumor microenvironment is shaped by interactions between malignant cells and host cells representing an integral component of solid tumors. Host cells, including elements of the innate and adaptive immune system, can exert both positive and negative effects on the outcome of the disease. In melanoma, studies on the prognostic impact of the lymphoid infiltrate in general, and that of T cells, yielded controversial results. According to our studies and data in the literature, a high peritumoral density of activated T cells, increased amount of B lymphocytes and mature dendritic cells (DCs) predicted longer survival, while intense infiltration by plasmacytoid DCs or neutrophil granulocytes could be associated with poor prognosis. Besides its prognostic value, evaluation of the components of immune infiltrate could provide biomarkers for predicting the efficacy of the treatment and disease outcome in patients treated with immunotherapy or other, non-immune-based modalities as chemo-, radio-, or targeted therapy.
Improving the Fidelity of Thermus Thermophilus DNA Ligase (1996)

The DNA ligase from Thermus thermophilus (Tth DNA ligase) seals single-strand breaks (nicks) in DNA duplex substrates. The specificity and thermostability of this enzyme are exploited in the ligase chain reaction (LCR) and ligase detection reaction (LDR) to distinguish single base mutations associated with genetic diseases. Herein, we describe a quantitative assay using fluorescently labeled substrates to study the fidelity of Tth DNA ligase. The enzyme exhibits significantly greater discrimination against all single base mismatches on the 3-side of the nick in comparison with those on the 5-side of the nick. Among all 12 possible single base pair mismatches on the 3-side of the nick, only T-G and G-T mismatches generated a quantifiable level of ligation products after 23 h incubation. The high fidelity of Tth DNA ligase can be improved further by introducing a mismatched base or a universal nucleoside analog at the third position of the discriminating oligonucleotide. Finally, two mutant Tth DNA ligases, K294R and K294P, were found to have increased fidelity using this assay.
Organolanthanide-Catalyzed Hydroamination (2004)

Organolanthanides are highly efficient catalysts for inter- and intramolecular hydroamination of various C-C unsaturations such as alkenes, alkynes, allenes, and dienes. Attractive features of organolanthanide catalysts include very high turnover frequencies and excellent stereoselectivities, rendering this methodology applicable to concise synthesis of naturally occurring alkaloids and other polycyclic azacycles. The general hydroamination mechanism involves turnover-limiting C-C multiple bond insertion into the Ln-N bond, followed by rapid protonolysis by other amine substrates. Sterically less encumbered ligand designs have been developed to improve reaction rates, and metallocene and nonmetallocene chiral lanthanide complexes have been synthesized for enantioselective hydroamination.