gebhart/patrepeval huggingface dataset:
Regulation of plasminogen activation: a role for melanotransferrin (p97) in cell migration (2003)

We recently reported that human recombinant melanotransferrin (p97) presents a high transport rate across the blood-brain barrier that might involve the low-density lipoprotein receptor-related protein (LRP). We now report new interactions between p97 and another LRP ligand, the urokinase plasminogen activator (uPA) complex. By using biospecific interaction analysis, both pro-uPA and plasminogen are shown to interact with immobilized p97. Moreover, the activation of plasminogen by pro-uPA is increased by soluble p97. Because the uPA system plays a crucial role in cell migration, both in cancer and in angiogenesis, we also measured the impact of both endogenous membrane-bound and exogenous p97 on cell migration. The monoclonal antibody L235 (which recognizes a conformational epitope on p97) inhibited the migration of human microvascular endothelial cells (HMECs-1) and of human melanoma SK-MEL-28 cells, indicating that endogenous membrane-bound p97 could be associated with this process. In addition, low concentrations of exogenous p97 (10 and 100 nM) inhibited HMEC-1 and SK-MEL28 cell migration by more than 50%. These results indicate that membrane-bound and soluble p97 affect the migration capacity of endothelial and melanoma cells and suggest that p97 could be involved in the regulation of plasminogen activation by interacting with pro-uPA and plasminogen.
Synthetic Biomimetic Hydrogels Incorporated with Ephrin-A1 for Therapeutic Angiogenesis (2006)

Eph receptors and ephrin ligands are essential for vascular development and angiogenic remodeling. In this work, we developed biomimetic poly(ethylene glycol)-diacrylate hydrogels incorporated with ephrin-A1 and examined their angiogenic properties. Ephrin-A1 was covalently immobilized on the surface of hydrogels by chemical modification and photopolymerization. Ephrin-A1 immobilized on hydrogels was found to retain its capacity to stimulate endothelial cell adhesion in a dose-dependent manner as similar findings were observed on polystyrene culture wells pre-adsorbed with ephrin-A1. Cell adhesion stimulated by ephrin-A1 was abolished by treatment with soluble RGDS and anti-alpha(v)beta3 integrin but not anti-alpha(v)beta5 integrin antibodies, suggesting that ephrin-A1 activates cell adhesion through alpha(v)beta3 integrins. Also, surface immobilized ephrin-A1 was found to induce endothelial tubule formation with luminal diameters ranging 5-30 microm on hydrogels. The results of these studies demonstrate that pro-angiogenic properties of ephrin-A1 are preserved in hydrogels and suggest potential applications of this hydrogel system in regenerative medicine and tissue engineering.
Development of liver tumors in transforming growth factor alpha transgenic mice. (1992)

We studied the development of liver tumors in male transforming growth factor alpha (TGF-alpha) transgenic mice of the CD1 strain and examined the expression of the transgene by immunohistochemistry and in situ hybridization. Livers of 4-5-week-old transgenic mice contained areas of centribobular hypertrophy with low glucose-6-phosphatase activity. These areas progressively expanded, and hypertrophy and dysplasia became generalized in livers of mice at 10-12 months of age. The expression of the transgene, determined by either immunohistochemistry or in situ hybridization, was uneven in animals that were 10 weeks old or older. The positive hepatocytes formed patches with a predominant centrilobular distribution. We studied a total of 23 liver tumors (7 hepatocellular carcinomas and 16 adenomas) obtained from 11 mice at 13-15 months of age and from one 7-month-old animal which received zinc sulfate to induce the transgene. The carcinomas were well differentiated tumors, without glucose-6-phosphatase or gamma-glutamyltranspeptidase activity, that developed from the dysplastic parenchyma and occasionally within an adenoma. In all carcinomas and in 56% of the adenomas there was overexpression of the transgene in relationship to the surrounding tissue. The majority of the tumors that overexpressed TGF-alpha were alpha-fetoprotein positive, while alpha-fetoprotein staining was not detected in tumors (all adenomas) that did not show excessive transgene expression. We conclude that TGF-alpha functions as a promoter of liver carcinogenesis through its effect as an autocrine inducer of hepatocyte proliferation. Further, the data indicate that TGF-alpha overexpression may favor tumor progression.
Therapeutic Potential of HPMPC (Cidofovir), PMEA (Adefovir) and Related Acyclic Nucleoside Phosphonate Analogues as Broad-Spectrum Anttviral Agents (1997)

Abstract This article reviews the antiviral features of the acyclic nucleoside phosphonate (ANP) analogues, with a special focus on the most recent findings concerning the biochemistry and clinical efficacy of HPMPC [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine; cidofovir; Vistide®] and PMEA [9-(2-phosphonyl-methoxyethyl)adenine; adefovir].
Therapeutic Targeting of CD6 in Autoimmune Diseases: A Review of Cuban Clinical Studies with the Antibodies IOR-T1 and Itolizumab (2016)

The CD6 molecule is a pan T cell marker involved in T cell regulation. Although CD6 expression has been correlated with human autoimmune diseases, only a few therapeutic approaches are exploring this molecule as target in the clinic. The biological functions and mechanisms of actions of CD6 have not been definitively established. It is probable that this molecule plays a dual role as a modulator of intracellular signaling. Itolizumab is a humanized monoclonal antibody specific for human CD6, developed at the Center of Molecular Immunology in Havana, Cuba. Its parent murine antibody, the IOR-T1 mAb, had been obtained in the 80's at the Institute of Oncology and Radiology, also in Havana. This article provides an overview of the clinical data obtained in Cuban patients with autoimmune diseases who have been treated with IOR-T1 mAb or itolizumab. Furthermore, we discuss the possible mechanism of action of itolizumab basing the analysis on recent site mutagenesis and structural data, which, contrary to previous interpretations, points to a steric blocking of the CD6-CD166 interaction in the cellular context. Overall, the conducted clinical studies have demonstrated that itolizumab has favorable clinical effects and a safety profile when used as monotherapy in patients with rheumatoid arthritis and psoriasis. So far, in vitro and in vivo evidences indicate that itolizumab has immunomodulatory and anti-inflammatory effects. Hence, itolizumab represents a new therapeutic option for autoimmune diseases such as rheumatoid arthritis and psoriasis.
Activity screening of environmental metagenomic libraries reveals novel carboxylesterase families (2017)

Abstract Metagenomics has made accessible an enormous reserve of global biochemical diversity. To tap into this vast resource of novel enzymes, we have screened over one million clones from metagenome DNA libraries derived from sixteen different environments for carboxylesterase activity and identified 714 positive hits. We have validated the esterase activity of 80 selected genes, which belong to 17 different protein families including unknown and cyclase-like proteins. Three metagenomic enzymes exhibited lipase activity, and seven proteins showed polyester depolymerization activity against polylactic acid and polycaprolactone. Detailed biochemical characterization of four new enzymes revealed their substrate preference, whereas their catalytic residues were identified using site-directed mutagenesis. The crystal structure of the metal-ion dependent esterase MGS0169 from the amidohydrolase superfamily revealed a novel active site with a bound unknown ligand. Thus, activity-centered metagenomics has revealed diverse enzymes and novel families of microbial carboxylesterases, whose activity could not have been predicted using bioinformatics tools.
Metabolically Programmed Polyamine Analogue Antidiarrheals (1996)

The design, synthesis, and testing of a novel class of antidiarrheal drugs based on a tetraamine pharmacophore are reported. While N1,N14-diethylhomospermine (DEHSPM) (5 mg/kg) completely prevents diarrhea in rodents, tissue distribution studies demonstrated that the principal metabolite of DEHSPM, homospermine (HSPM), accumulates and persists in tissues for a protracted period of time. This accumulation accounts for a large part of the chronic toxicity of DEHSPM. Thus a major objective was to develop a metabolically labile analogue of DEHSPM which retained the desirable biological properties of the parent drug. Hydroxyl groups, sites vulnerable to further metabolic transformation, were introduced into the external aminobutyl segments providing N1,N14-diethyl-(3R),(12R)-dihydroxyhomospermine [(HO)2-DEHSPM]. The design concept was assisted by molecular modeling, which predicted that (HO)2DEHSPM would have a Ki for polyamine transport essentially identical with that of DEHSPM. The experimentally measured Ki and also the observed values of other biological properties of (HO)2DEHSPM were in fact identical with those of DEHSPM, including IC50 against L1210 cells, impact on the NMDA receptor, and impact on L1210 native polyamine pools. Most significantly, however, there was no accumulation of the dideethylated metabolite in tissues from mice treated chronically with (HO)2DEHSPM, and (HO)2DEHSPM was 3-fold less toxic than DEHSPM. Finally, (HO)2DEHSPM completely prevented diarrhea in the castor oil-treated rat model at a dose of 5 mg/kg, just as did DEHSPM.
The FTIR spectrum of prostate cancer cells allows the classification of anticancer drugs according to their mode of action (2011)

The number of anticancer agents that fail in the clinic far outweighs those considered effective, suggesting that the selection procedure for progression of drug molecules into the clinic requires improvement. Traditionally, new drugs are evaluated for their potential to kill cancer cell lines. This approach is obviously not sufficient, and molecules with new modes of action are required. We suggest here that the infrared spectrum of cells exposed to anticancer drugs could offer an opportunity to obtain a fingerprint of the metabolic changes induced by the drugs. Because the infrared spectrum of cells yields a precise image of all the chemical bonds present in the sample, different drug targets are likely to yield different infrared fingerprints characteristic of the 'mode of action' of the therapeutic agent under investigation. In turn, drug-induced metabolic disorders should be amenable to classification in the same way that bacteria gender, species, and strains can be classified. We examined here a human prostate cancer PC-3 cell line exposed to 7 well described antimitotics. In a first step the IC(50) values were determined. For FTIR imaging, PC-3 cells were exposed to the IC(50) concentration of each drug for 48 h. About one hundred images of 4096 IR spectra at 8 cm(-1) spectral resolution were acquired. We show with a Student t-test that the different molecules tested induced different infrared spectral modifications. Furthermore, drugs known to induce similar types of metabolic disturbances appear to cluster when spectrum shapes are analyzed. Finally, supervised statistical methods allowed the building of an efficient and discriminant model. When the discriminant model was applied to a full infrared image a good sorting was generally obtained and misclassified spectra generally belonged to a small number of specific cells. Taken all together these data suggest that FTIR could be used for the classification of drug action.
DNA double-strand breaks induced by high NaCl occur predominantly in gene deserts (2011)

High concentration of NaCl increases DNA breaks both in cell culture and in vivo. The breaks remain elevated as long as NaCl concentration remains high and are rapidly repaired when the concentration is lowered. The exact nature of the breaks, and their location, has not been entirely clear, and it has not been evident how cells survive, replicate, and maintain genome integrity in environments like the renal inner medulla in which cells are constantly exposed to high NaCl concentration. Repair of the breaks after NaCl is reduced is accompanied by formation of foci containing phosphorylated H2AX (γH2AX), which occurs around DNA double-strand breaks and contributes to their repair. Here, we confirm by specific comet assay and pulsed-field electrophoresis that cells adapted to high NaCl have increased levels of double-strand breaks. Importantly, γH2AX foci that occur during repair of the breaks are nonrandomly distributed in the mouse genome. By chromatin immunoprecipitation using anti-γH2AX antibody, followed by massive parallel sequencing (ChIP-Seq), we find that during repair of double-strand breaks induced by high NaCl, γH2AX is predominantly localized to regions of the genome devoid of genes ("gene deserts"), indicating that the high NaCl-induced double-strand breaks are located there. Localization to gene deserts helps explain why the DNA breaks are less harmful than are the random breaks induced by genotoxic agents such as UV radiation, ionizing radiation, and oxidants. We propose that the universal presence of NaCl around animal cells has directly influenced the evolution of the structure of their genomes.
Chemically Derived, Ultrasmooth Graphene Nanoribbon Semiconductors (2008)

We developed a chemical route to produce graphene nanoribbons (GNR) with width below 10 nanometers, as well as single ribbons with varying widths along their lengths or containing lattice-defined graphene junctions for potential molecular electronics. The GNRs were solution-phase-derived, stably suspended in solvents with noncovalent polymer functionalization, and exhibited ultrasmooth edges with possibly well-defined zigzag or armchair-edge structures. Electrical transport experiments showed that, unlike single-walled carbon nanotubes, all of the sub-10-nanometer GNRs produced were semiconductors and afforded graphene field effect transistors with on-off ratios of about 10(7) at room temperature.
Viral Genes and Methylation (2003)

Epigenetics represents a new frontier in cancer research. Methylation is the best studied of the epigenetic mechanisms that regulate gene expression. Regulation of gene expression by means of methylation has been reported for tumor suppressor genes, oncogenes, viral promoters, and age-related genes. In this review, the regulation of viral gene expression by methylation is discussed, with particular emphasis on: (1) the virus-specific factors that bind to promoter regions; (2) the implications of this knowledge for designing viral vectors that can be used to deliver genes for the purpose of gene therapy; and (3) the use of this knowledge for the early detection and prevention of cancer. Since methylation can be reversed by a variety of exogenous agents, great potential exists to develop interventions that target cancer-associated aberrant methylation in an effort to reverse or prevent carcinogenesis.
Left Ventricular Mass in Diabetes-Hypertension (1992)

The data suggest that DM accelerates the development of LVH in patients with essential hypertension independent of arterial pressure and, therefore, may contribute to the increased cardiovascular morbidity and mortality in patients with hypertension.
Claudin-5 is involved in breast cancer cell motility through the N-WASP and ROCK signalling pathways (2012)

This study portrays a very new and interesting role for Claudin-5 in cell motility involving the N-WASP signalling cascade indicating a possible role for Claudin-5 in the metastasis of human breast cancer.
Treatment of venous malformations with an intense pulsed light source (IPLS) technology: A retrospective study (1999)

Background and Objective The intense pulsed light source (IPLS) technology provides an innovative concept in the treatment of vascular lesions. We investigated the effectiveness of IPLS in the treatment of venous malformations. Study Design/Materials and Methods A retrospective study of 11 patients with venous malformations (VMA) treated with IPLS was initiated. Clinical VMA characteristics recorded were size and location. Data collected included treatment parameters (filters, pulse duration, fluence, and pulse sequencing), % clearance, and side effects (e.g., swelling, blisters, crusting, pain, altered pigmentation, and scarring). Results Good and very good (70–100%) clearance was achieved in 8 malformations smaller than 100 cm2. Especially small lesions needed only 2–3 treatments. Three VMA larger than 100 cm2 could be cleared well in an average of 18 sessions. The most frequently used parameters were the 590 nm filter in long pulse mode, triple pulses, and fluences at an average of 80.4 J/cm2. Side effects included prolonged erythema in 23.6, swelling in 17.9%, crusting in 4.7%. Bleeding, hypo-, hyperpigmentation, and scarring were rare (0.9% respectively). Conclusion IPLS presents an effective method for treating VMA, especially small malformations, with a justifiable rate of side effects when optimal parameters are chosen. Lasers Surg. Med. 25:170–177, 1999. © 1999 Wiley-Liss, Inc.
Psychosocial Aspects of Youth Disability Sport (2006)

Psychosocial aspects of participation in youth disability sport were examined using social-cognitive theory and the sport commitment model. An international sample of athletes with disabilities ( N = 112) reported high levels of sport commitment and sport enjoyment, perceived physical ability, and sport friendship quality. They perceived their parents to provide moderately strong levels of encouragement of their sport participation. Correlational analyses indicated moderate to strong relationships among sport commitment, sport enjoyment, and perceived physical ability. Sport commitment, parental encouragement, and sport friendship quality were only somewhat related. Regression analyses indicated that enjoyment was a significant predictor (i.e., 43% of the variance) of sport commitment. The sport experience was a positive one for these athletes and enjoyment is likely a critical motivational factor in promoting a continued desire to remain in sport.
Wide Varieties of Cationic Nanoparticles Induce Defects in Supported Lipid Bilayers (2008)

Nanoparticles with widely varying physical properties and origins (spherical versus irregular, synthetic versus biological, organic versus inorganic, flexible versus rigid, small versus large) have been previously noted to translocate across the cell plasma membrane. We have employed atomic force microscopy to determine if the physical disruption of lipid membranes, formation of holes and/or thinned regions, is a common mechanism of interaction between these nanoparticles and lipids. It was found that a wide variety of nanoparticles, including a cell penetrating peptide (MSI-78), a protein (TAT), polycationic polymers (PAMAM dendrimers, pentanol-core PAMAM dendrons, polyethyleneimine, and diethylaminoethyl-dextran), and two inorganic particles (Au-NH2, SiO2-NH2), can induce disruption, including the formation of holes, membrane thinning, and/or membrane erosion, in supported lipid bilayers.
Comparison of Scaling of In-Plane and Perpendicular Spin Transfer Switching Technologies by Micromagnetic Simulation (2010)

Spin transfer torque switching-basis of operation of innovative memory technology-STT-RAM (spin transfer torque memory) has been actively studied in the recent years with two prevalent technologies emerging at fast pace: in-plane and perpendicular. The crucial question for future development is which technology provides better scaling to smaller sizes. The present work provides evaluation of scalability of these two approaches based on micromagnetic modeling.
Investigation of the Configurational Stabilities of Chiral Isocyanoacetates in Multicomponent Reactions (2011)

Isocyanoacetates are uniquely reactive compounds characterized by an ambivalent isocyano functional group and an enolizable α-carbon. It is widely believed that chiral α-substituted isocyanoacetates are configurationally unstable in some synthetically useful isocyanide-based multicomponent reactions. Herein, we demonstrate that chiral isocyanoacetates can be used with minimal to negligible epimerization in a variety of canonical Ugi four-component condensations as well as Joullié-Ugi three-component condensations, reactions that are particularly useful for constructing complex peptide structures in a single synthetic operation.
Molecular characterization of a prokaryotic polypeptide sequence that catalyzes Au crystal formation (2004)

The gold crystal-forming E. coli polypeptide sequence, MHGKTQATSGTIQS, is one of several polypeptide sequences that interacts with gold interfaces and catalyzes the formation of Au crystals in solution, with nucleated Au crystals preferentially featuring the (111) interface. To date, there have been no experimental studies which explore the structure of E. coli-expressed gold binding proteins or the binding of Au(III) ions by these polypeptides. In this present report, multidisciplinary approaches were applied to the 42-AA gold binding protein-1 (GBP-1/42) and to a model polypeptide representing the 14-AA integral repeat of this protein (GBP-1/14). CD and NMR spectroscopy indicate that neither the integral repeat nor the GBP-1 protein adopt folded structures in the apo form or in the presence of Au(III) ions; the integral repeat adopts a random coil-extended structure conformation [i.e., (MHGKTQA)random coil–(TSGTIQS)extended] and the GBP-1 protein appears to be similarly structured. These features are inconsistent with a templating structure. Mass spectrometry experiments indicate that the integral repeat binds up to two Au(III) ions per polypeptide molecule, and 1H NMR ROESY experiments pinpoint the interaction of Au(III) within two sites: the -QAT- region of the integral repeat MHGKTQATSGTIQS sequence, and, at the negatively charged C-terminus of this sequence. Collectively, our findings support the hypothesis that GBP-1 does not catalyze Au crystal formation via a templating mechanism; rather, the open, unfolded structure of this protein, combined with the presence of accessible proton donor/acceptor amino acids (Ser, Thr, Lys, Gln, His) most likely play a role in Au crystal formation in solution and may also explain the interactive nature of this polypeptide with Au interfaces.