gebhart/patrepeval huggingface dataset:
GTP cyclohydrolase I gene transfer reverses tetrahydrobiopterin deficiency and increases nitric oxide synthesis in endothelial cells and isolated vessels from diabetic rats (2004)

Nitric oxide (NO) synthesis in endothelial cells is impaired in diabetes. We previously showed that impaired NO synthesis in the spontaneously diabetic BB (BBd) rat is due to decreased levels of tetrahydrobiopterin (BH4), secondary to decreased expression of GTP cyclohydrolase I (GTPCH). The aim of this study was to utilize adenoviral GTPCH gene transfer to reverse BH4 deficiency and repair the ability of endothelial cells to produce NO. GTPCH gene transfer increased BH4 levels in BBd endothelial cells from 0.17 +/- 0.02 (mean +/-SE) to 73.37 +/- 14.42 pmol/million cells and NO production from 0.77 +/- 0.07 to 18.74 +/- 5.52 nmol/24 h/million cells. To demonstrate a functional effect of increasing BH4 concentrations in tissues, we transferred GTPCH into aortic rings from BBd and Zucker diabetic fatty (ZDF) rats, models of human type I and type II diabetes, respectively. GTPCH gene transfer led to a dose-dependent increase in acetylcholine-induced vasorelaxation, preventable by inhibiting NO synthase. Maximal relaxation of virus-treated rings (10(10) virus particles/ml) to acetylcholine was significantly higher than sham-treated rings (BBd 64% vs. 37%, P<0.005; ZDF 80% vs. 44%, P<0.05). This study demonstrates that GTPCH gene transfer can reverse BH4 deficiency in both type I and type II diabetes and provides an experimental basis for using gene therapy to treat cardiovascular complications in diabetic patients.
The effect of various concentrations of human recombinant epidermal growth factor on split‐thickness skin wounds (2006)

Epidermal growth factor (EGF) is a potent stimulant of epithelialisation. However, topical application of EGF to achieve facilitated re-epithelialisation in partial thickness wounds has been controversial. A total of 10 pigs, each with eight 4 x 4 cm partial thickness wounds, were treated twice a day for 10 days to observe the effect of human recombinant EGF in concentrations of 0.1, 1, 5, 10, 25 ug/g, vehicle only and two controls. The control and the vehicle-only wounds each demonstrated 100% healing time (HT100) of 9.31 +/- 1.34 and 8.5 +/- 1.12 while the wounds treated with EGF ointment with concentrations of 0.1 (HT100 = 6.4 +/- 0.71), 1 (HT100 = 5.2 +/- 0.63), 5 (HT100 = 5.8 +/- 0.85), 10 (HT100 = 7.1 +/- 1.45) and 25 ug/g (HT100 = 7.4 + 0.57) demonstrated significant reduction in time to achieve re-epithelialisation. Among the EGF-treated wounds, the wounds treated with EGF concentrations of 1 and 5 ug/g achieved the fastest re-epithelialisation with evidence of substantial increase in basal keratinocyte activity observed through Ki-67 activity. In conclusion, this article demonstrates the efficacy of human recombinant EGF in facilitating re-epithelialisation of partial thickness wounds with the most efficient healing found in EGF concentrations of 1 and 5 ug/g.
Retinoic acid-induced CD38 antigen as a target for immunotoxin-mediated killing of leukemia cells (2004)

A major obstacle in the successful delivery of antibody-based therapeutics to tumor cells is the heterogeneity of target antigen expression. We reported previously that retinoic acid (RA) is a potent and selective inducer of the cell-surface antigen CD38 in myeloid leukemia cells. The purpose of this study was to determine whether the RA-induced CD38 antigen could be a target for an anti-CD38-based immunotoxin to induce selective killing of leukemia cells. The combination of RA and the anti-CD38 gelonin immunotoxin induced a synergistic killing of leukemia cells. Thus, coculture of myeloid leukemia cells and cell lines with as little as 1 nM RA in the presence of immunotoxin induced substantial killing (>90%) of leukemia cell clones. More importantly, the blasts of myeloid leukemia patients, irrespective of their morphological and phenotypic features, also responded to the RA and immunotoxin combination when cultured ex vivo. A similar synergistic effect between RA and immunotoxin was observed against a multidrug-resistant variant subline of HL-60 cells. However, another variant of HL-60 cells, HL-60R, in which the retinoid receptor function has been abrogated by a trans-dominant-negative mutation, exhibited complete resistance to the immunotoxin-induced killing effect in the presence or absence of RA. Our results suggest that RA combined with anti-CD38-based therapeutic agent may offer exciting opportunities for the treatment of myeloid leukemias despite their multiplicity of genetic and clinical varieties.
Characterization and nucleotide sequence of the cryptic cel operon of Escherichia coli K12. (1990)

Wild-type Escherichia coli are not able to utilize beta-glucoside sugars because the genes for utilization of these sugars are cryptic. Spontaneous mutations in the cel operon allow its expression and enable the organism to ferment cellobiose, arbutin and salicin. In this report we describe the structure and nucleotide sequence of the cel operon. The cel operon consists of five genes: celA, whose function is unknown; celB and celC which encode phosphoenolpyruvate-dependent phosphotransferase system enzyme IIcel and enzyme IIIcel, respectively, for the transport and phosphorylation of beta-glucoside sugars; celD, which encodes a negative regulatory protein; and celF, which encodes a phospho-beta-glucosidase that acts on phosphorylated cellobiose, arbutin and salicin. The mutationally activated cel operon is induced in the presence of its substrates, and is repressed in their absence. A comparison of proteins encoded by the cel operon with functionally equivalent proteins of the bgl operon, another cryptic E. coli gene system responsible for the catabolism of beta-glucoside sugars, revealed no significant homology between these two systems despite common functional characteristics. The celD and celF encoded repressor and phospho-beta-glucosidase proteins are homologous to the melibiose regulatory protein and to the melA encoded alpha-galactosidase of E. coli, respectively. Furthermore, the celC encoded PEP-dependent phosphotransferase system enzyme IIIcel is strikingly homologous to an enzyme IIIlac of the Gram-positive organism Staphylococcus aureus. We conclude that the genes for these two enzyme IIIs diverged much more recently than did their hosts, indicating that E. coli and S. aureus have undergone relatively recent exchange of chromosomal genes.
Pituitary-dependent and -independent secretion of CS caused by bacterial endotoxin in rats (1986)

Injection of bacterial endotoxin [lipopolysaccharide (LPS)] or immobilization stress increased serum levels of ACTH with a concomitant increase in the levels or corticosterone (CS) of rats. LPS also caused a significant increase in the serum CS levels of hypophysectomized rats. In contrast, immobilization stress-induced CS release was abolished completely in these rats. Injection of histamine, a possible mediator of LPS-induced CS secretion, provoked a significant increase in the serum CS levels of hypophysectomized rats. Neither histamine nor LPS had any appreciable effect on production or release of CS by cultured adrenal cells. These results suggest that LPS-induced CS secretion is largely dependent on hypophysial ACTH release but it also depends, in part, on an extrapituitary mechanism and that the LPS-induced pituitary-independent secretion of CS is mediated by histamine produced in the peripheral tissues. On the other hand, stress-provoked CS secretion is absolutely dependent on the pituitary-adrenocortical system.
Zbtb20-Induced CA1 Pyramidal Neuron Development and Area Enlargement in the Cerebral Midline Cortex of Mice (2009)

Expression of the transcriptional repressor Zbtb20 is confined to the hippocampal primordium of the developing dorsal midline cortex in mice. Here, we show that misexpression of Zbtb20 converts projection neurons of the subiculum and postsubiculum (dorsal presubiculum) to CA1 pyramidal neurons that are innervated by Schaffer collateral projections in ectopic strata oriens and radiatum. The Zbtb20-transformed neurons express Bcl11B, Satb2, and Calbindin-D28k, which are markers of adult CA1 pyramidal neurons. Downregulation of Zbtb20 expression by RNA interference impairs the normal maturation of CA1 pyramidal neurons resulting in deficiencies in Calbindin-D28k expression and in reduced apical dendritic arborizations in stratum lacunosum moleculare. Overall, the results show that Zbtb20 is required for various aspects of CA1 pyramidal neuron development such as the postnatal extension of apical dendritic arbors in the distal target zone and the subtype differentiation of Calbindin-D28k-positive subsets. They further suggest that Zbtb20 plays a role in arealization of the midline cortex.
Prenylated Flavonoids from the Roots ofSophora flavescens withTyrosinase Inhibitory Activity (2003)

Prenylated flavonoids containing the resorcinol moiety were isolated as tyrosinase inhibitors from the roots of Sophora flavescens by activity-guided fractionation. Among the 12 compounds isolated, kuraridin, kurarinone and norkurarinol showed stronger inhibitory potencies (IC 50 = 1.1, 1.3 and 2.1 microM, respectively) than that of kojic acid (IC 50 = 11.3 microM), a well known tyrosinase inhibitor. Substitution of a lavandulyl or hydroxylavandulyl group at the C-8 position and a methoxy or hydroxy group at the C-5 position are essential for the inhibitory effect.
Alveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice (2017)

The aim of candidate universal influenza vaccines is to provide broad protection against influenza A and B viruses. Studies have demonstrated that broadly reactive antibodies require Fc-Fc gamma receptor interactions for optimal protection; however, the innate effector cells responsible for mediating this protection remain largely unknown. Here, we examine the roles of alveolar macrophages, natural killer cells, and neutrophils in antibody-mediated protection. We demonstrate that alveolar macrophages play a dominant role in conferring protection provided by both broadly neutralizing and non-neutralizing antibodies in mice. Our data also reveal the potential mechanisms by which alveolar macrophages mediate protection in vivo, namely antibody-induced inflammation and antibody-dependent cellular phagocytosis. This study highlights the importance of innate effector cells in establishing a broad-spectrum antiviral state, as well as providing a better understanding of how multiple arms of the immune system cooperate to achieve an optimal antiviral response following influenza virus infection or immunization.Broadly reactive antibodies that recognize influenza A virus HA can be protective, but the mechanism is not completely understood. Here, He et al. show that the inflammatory response and phagocytosis mediated by the interaction between protective antibodies and macrophages are essential for protection.
Effect of nicotine on rectal mucus and mucosal eicosanoids. (1994)

Because ulcerative colitis is largely a disease of non-smokers and nicotine may have a beneficial effect on the disease, the effect of nicotine on rectal mucosa in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 microns) was significantly reduced by low dose (22 microns, p = 0.0011), and increased by high dose nicotine (48 microns, p = 0.035). Incorporation of radioactive glucosamine into papain resistant glycoconjugates was unchanged, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secretion in the rectum and large bowel.
A Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Transdermal Dihydrotestosterone Gel on Muscular Strength, Mobility, and Quality of Life in Older Men with Partial Androgen Deficiency (2001)

The efficacy and safety of androgen supplementation in older men remains controversial. Despite biochemical evidence of partial androgen deficiency in older men, controlled studies using T demonstrate equivocal benefits. Furthermore, the importance of aromatization and 5alpha reduction in androgen actions among older men remains unclear. Dihydrotestosterone is the highest potency natural androgen with the additional features that it is neither aromatizable nor susceptible to potency amplification by 5alpha reduction. Therefore, the effects of dihydrotestosterone may differ from those of T in older men. This study evaluated the efficacy and safety of 3 months treatment with transdermal dihydrotestosterone gel on muscle strength, mobility, and quality of life in ambulant, community-dwelling men aged 60 yr or older. Eligible men (plasma T < or =15 nmol/liter) were randomized to undergo daily dermal application of 70 mg dihydrotestosterone gel (n = 18) or vehicle (n = 19) and were studied before, monthly during, and 1 month after treatment. Among 33 (17 dihydrotestosterone, 16 placebo) men completing the study with a high degree of compliance, dihydrotestosterone had significant effects on circulating hormones (increased dihydrotestosterone; decreased total and free testosterone, LH, and FSH; unchanged SHBG and estradiol), lipid profiles (decreased total and low-density lipoprotein cholesterols; unchanged high-density lipoprotein cholesterol and triglycerides), hematopoiesis (increased hemoglobin, hematocrit, and red cell counts), and body composition (decreased skinfold thickness and fat mass; unchanged lean mass and waist to hip ratio). Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee but not in knee extension or shoulder contraction, nor was there any significant change in gait, balance, or mobility tests, in cognitive function, or in quality of life scales. Dihydrotestosterone treatment had no adverse effects on prostate (unchanged prostate volumes and prostate-specific antigen) and cardiovascular (no adverse change in vascular reactivity or lipids) safety markers. We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstrates expected androgenic effects, short-term safety, and limited improvement in lower limb muscle strength but no change in physical functioning or cognitive function.
In Vivo Endoscopic Tissue Identification by Rapid Evaporative Ionization Mass Spectrometry (REIMS) (2015)

Gastrointestinal cancers are a leading cause of mortality, accounting for 23 % of cancer-related deaths worldwide. In order to improve outcomes from these cancers, novel tissue characterization methods are needed to facilitate accurate diagnosis. Rapid evaporative ionization mass spectrometry (REIMS) is a technique developed for the in vivo classification of human tissue through mass spectrometric analysis of aerosols released during electrosurgical dissection. This ionization technique was further developed by utilizing surface induced dissociation and was integrated with an endoscopic polypectomy snare to allow in vivo analysis of the gastrointestinal tract. We tested the classification performance of this novel endoscopic REIMS method in vivo. It was shown to be capable of differentiating between healthy layers of the intestinal wall, cancer, and adenomatous polyps based on the REIMS fingerprint of each tissue type in vivo.
Solid-Supported Combinatorial Synthesis of Structurally Diverse β-Lactams (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSolid-Supported Combinatorial Synthesis of Structurally Diverse β-LactamsBeatrice Ruhland, Ashok Bhandari, Eric M. Gordon, and Mark A. GallopView Author Information Affymax Research Institute, 4001 Miranda Avenue Palo Alto, California 94304 Cite this: J. Am. Chem. Soc. 1996, 118, 1, 253–254Publication Date (Web):January 10, 1996Publication History Received29 September 1995Published online10 January 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja953322phttps://doi.org/10.1021/ja953322prapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views869Altmetric-Citations142LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Addition reactions,Anions,Monomers,Organic polymers,Peptides and proteins Get e-Alerts
Identification of Endothelial Cell Binding Sites on the Laminin γ1 Chain (1999)

The laminins belong to a family of trimeric basement membrane glycoproteins with multiple domains, structures, and functions. Endothelial cells bind laminin-1 and form capillary-like structures when plated on a laminin-1-rich basement membrane matrix, Matrigel. Laminin-1 is composed of 3 chains, alpha1, beta1, and gamma1. Because laminin-1 is known to contain multiple biologically active sites, we have screened 156 synthetic overlapping peptides spanning the entire laminin gamma1 chain for potential angiogenic sequences. Only 7 of these peptides, designated as C16, C25, C30, C38, C64, C75, and C102, disrupted the formation of capillary-like structures by human umbilical vein endothelial cells on Matrigel. Dose-response experiments in the presence of 50 to 200 microg/mL showed that tube formation was prevented by most peptides at 150 and 200 microg/mL, except for C16, which showed strong activity at all concentrations. Active peptides promoted vessel sprouting from aorta rings and angiogenesis in the chick chorioallantoic membrane assay. In addition, the active peptides also promoted endothelial cell adhesion to dishes coated with 0.1 microg of peptide and inhibited attachment to laminin-1 but not to plastic or fibronectin. Four of the active peptides, C25, C38, C75, and C102, may have cell-type specificity with endothelial cells, since they did not promote PC12 neurite outgrowth or adhesion of B16-F10 melanoma and human submandibular gland cells. These results suggest that specific laminin gamma1-chain peptides have angiogenic activity with potential therapeutic applications.
An Energy-Efficient Micropower Neural Recording Amplifier (2007)

This paper describes an ultralow-power neural recording amplifier. The amplifier appears to be the lowest power and most energy-efficient neural recording amplifier reported to date. We describe low-noise design techniques that help the neural amplifier achieve input-referred noise that is near the theoretical limit of any amplifier using a differential pair as an input stage. Since neural amplifiers must include differential input pairs in practice to allow robust rejection of common-mode and power supply noise, our design appears to be near the optimum allowed by theory. The bandwidth of the amplifier can be adjusted for recording either neural spikes or local field potentials (LFPs). When configured for recording neural spikes, the amplifier yielded a midband gain of 40.8 dB and a -3-dB bandwidth from 45 Hz to 5.32 kHz; the amplifier's input-referred noise was measured to be 3.06 muVrms while consuming 7.56 muW of power from a 2.8-V supply corresponding to a noise efficiency factor (NEF) of 2.67 with the theoretical limit being 2.02. When configured for recording LFPs, the amplifier achieved a midband gain of 40.9 dB and a -3-dB bandwidth from 392 mHz to 295 Hz; the input-referred noise was 1.66 muVrms while consuming 2.08 muW from a 2.8-V supply corresponding to an NEF of 3.21. The amplifier was fabricated in AMI's 0.5-mum CMOS process and occupies 0.16 mm(2) of chip area. We obtained successful recordings of action potentials from the robust nucleus of the arcopallium (RA) of an anesthesized zebra finch brain with the amplifier. Our experimental measurements of the amplifier's performance including its noise were in good accord with theory and circuit simulations.
Current Blockades of Proteins inside Nanopores for Real-Time Metabolome Analysis (2020)

Biological nanopores are emerging as powerful and low-cost sensors for real-time analysis of biological samples. Proteins can be incorporated inside the nanopore, and ligand binding to the protein adaptor yields changes in nanopore conductance. In order to understand the origin of these conductance changes and develop sensors for detecting metabolites, we tested the signal originating from 13 different protein adaptors. We found that the quality of the protein signal depended on both the size and charge of the protein. The engineering of a dipole within the surface of the adaptor reduced the current noise by slowing the protein dynamics within the nanopore. Further, the charge of the ligand and the induced conformational changes of the adaptor defined the conductance changes upon metabolite binding, suggesting that the protein resides in an electrokinetic minimum within the nanopore, the position of which is altered by the ligand. These results represent an important step toward understanding the dynamics of the electrophoretic trapping of proteins inside nanopores and will allow developing next-generation sensors for metabolome analysis.