gebhart/patrepeval huggingface dataset:
Inhibitory effects of phenolic compounds on benzo(a)pyrene-induced neoplasia. (1980)

The inhibitory effects of 18 synthetic phenolic compounds added to the diet on benzo(a)pyrene-induced neoplasia of the forestomach of female ICR/Ha mice have been determined. Seven of the compounds showed suppression of neoplasia. The most potent inhibitors were p-methoxyphenol, 2-tert-butyl-4-hydroxyanisole [the minor isomer of 2(3)-tert-butyl-4-hydroxyanisole] and 3,5-di-tert-butylcatechol. A second group of compounds with a weaker inhibitory activity consisted of 3,5-di-tert-butylphenol, 3-tert-butyl-4-hydroxyanisole [the major isomer of 2(3)-tert-butyl-4-hydroxyanisole], 2-tert-butylhydroquinone, and 2-tert-butylphenol. In additional experiments, three naturally occurring phenolic derivatives of cinnamic acid, i.e., o-hydroxycinnamic acid, 3,4-dihydroxycinnamic acid (caffeic acid), and 4-hydroxy-3-methyoxycinnamic acid (ferulic acid), were investigated. All three suppressed benzo(a)pyrene-induced neoplasia of the forestomach. Humans ingest a variety of phenols. Data as to the inhibitory capacities of members of this group of compounds are of importance for evaluating the role that they play in determining the reaction to exposure to chemical carcinogens.
Effect of Lidocaine on Reducing Injury in a Rat Electrical Burn Model (2012)

Electrical injuries induce progressive tissue loss. We evaluated the effect of lidocaine on tissue necrosis after electrical burn injuries. Forty-two male Wistar albino rats (250-300 g) were divided into 3 groups [Group A (n=6), control group without an electrical burn injury; and Groups B (n=18) and C (n=18), electrical burn injury groups without and with lidocaine therapy, respectively]. Three separate analyses were performed at different time points on 6 of 18 rats from Groups B and C at each time point. Electrical burns were induced by applying 220 V AC between the left upper and right lower extremities for 10 seconds. Myeloperoxidase and malondialdehyde levels were measured in skin and muscle biopsy specimens after the first hour, fresh and dry weight differences in the amputated extremities were calculated after 24 hours, and live and necrotic tissue areas were measured at 7 days after burn injury. We found that lidocaine reduced edema, the number of neutrophils, and neutrophil damage in tissues. We conclude that lidocaine decreased the amount of necrotic tissue caused by electric injury.
Comparative genomic hybridization using oligonucleotide microarrays and total genomic DNA (2004)

Array-based comparative genomic hybridization (CGH) measures copy-number variations at multiple loci simultaneously, providing an important tool for studying cancer and developmental disorders and for developing diagnostic and therapeutic targets. Arrays for CGH based on PCR products representing assemblies of BAC or cDNA clones typically require maintenance, propagation, replication, and verification of large clone sets. Furthermore, it is difficult to control the specificity of the hybridization to the complex sequences that are present in each feature of such arrays. To develop a more robust and flexible platform, we created probe-design methods and assay protocols that make oligonucleotide microarrays synthesized in situ by inkjet technology compatible with array-based comparative genomic hybridization applications employing samples of total genomic DNA. Hybridization of a series of cell lines with variable numbers of X chromosomes to arrays designed for CGH measurements gave median ratios for X-chromosome probes within 6% of the theoretical values (0.5 for XY/XX, 1.0 for XX/XX, 1.4 for XXX/XX, 2.1 for XXXX/XX, and 2.6 for XXXXX/XX). Furthermore, these arrays detected and mapped regions of single-copy losses, homozygous deletions, and amplicons of various sizes in different model systems, including diploid cells with a chromosomal breakpoint that has been mapped and sequenced to a precise nucleotide and tumor cell lines with highly variable regions of gains and losses. Our results demonstrate that oligonucleotide arrays designed for CGH provide a robust and precise platform for detecting chromosomal alterations throughout a genome with high sensitivity even when using full-complexity genomic samples.
Evidence for functional and physical association between Caenorhabditis elegans SEL-10, a Cdc4p-related protein, and SEL-12 presenilin (1998)

Mutations in either of two human presenilin genes (PS1 and PS2) cause Alzheimer's disease. Here we describe genetic and physical interactions between Caenorhabditis elegans SEL-10, a member of the Cdc4p family of proteins, and SEL-12, a C. elegans presenilin. We show that loss of sel-10 activity can suppress the egg-laying defective phenotype associated with reducing sel-12 activity, and that SEL-10 can physically complex with SEL-12. Proteins of the Cdc4p family have been shown to target proteins for ubiquitin-mediated turnover. The functional and physical interaction between sel-10 and sel-12 therefore offers an approach to understanding how presenilin levels are normally regulated.
Magnetic Separation in Bioprocessing Beyond the Analytical Scale: From Biotechnology to the Food Industry (2019)

Downstream processing needs more innovative ideas to advance and overcome current bioprocessing challenges. Chromatography is by far the most prevalent technique used by a conservative industrial sector. Chromatography has many advantages but also often represents the most expensive step in a pharmaceutical production process. Therefore, alternative methods as well as further processing strategies are urgently needed. One promising candidate for new developments on a large scale is magnetic separation, which enables the fast and direct capture of target molecules in fermentation broths. There has been a small revolution in this area in the last 10-20 years and a few papers dealing with the use of magnetic separation in bioprocessing examples beyond the analytical scale have been published. Since each target material is purified with a different magnetic separation approach, the comparison of processes is not trivial but would help to understand and improve magnetic separation and thus making it attractive for the technical scale. To address this issue, we report on the latest achievements in magnetic separation technology and offer an overview of the progress of the capture and separation of biomolecules derived from biotechnology and food technology. Magnetic separation has great potential for high-throughput downstream processing in applied life sciences. At the same time, two major challenges need to be overcome: (1) the development of a platform for suitable and flexible separation devices and (2) additional investigations of advantageous processing conditions, especially during recovery. Concentration and purification factors need to be improved to pave the way for the broader use of magnetic applications. The innovative combination of magnetic gradients and multipurpose separations will set new magnetic-based trends for large scale downstream processing.
An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: Role in tumor cell glycolysis and the Warburg effect (1999)

Cancer cells maintain a high glycolytic rate even in the presence of oxygen, a phenomenon first described over 70 years ago and known historically as the Warburg effect. Fructose 2,6-bisphosphate is a powerful allosteric regulator of glycolysis that acts to stimulate the activity of 6-phosphofructo-1-kinase (PFK-1), the most important control point in mammalian glycolysis. The steady state concentration of fructose 2,6-bisphosphate in turn depends on the activity of the enzyme 6-phosphofructo-2-kinase (PFK-2)/fructose-2, 6-bisphosphatase, which is expressed in several tissue-specific isoforms. We report herein the identification of a gene product for this enzyme that is induced by proinflammatory stimuli and which is distinguished by the presence of multiple copies of the AUUUA mRNA instability motif in its 3'-untranslated end. This inducible gene for PFK-2 is expressed constitutively in several human cancer cell lines and was found to be required for tumor cell growth in vitro and in vivo. Inhibition of inducible PFK-2 protein expression decreased the intracellular level of 5-phosphoribosyl-1-pyrophosphate, a product of the pentose phosphate pathway and an important precursor for nucleic acid biosynthesis. These studies identify a regulatory isoenzyme that may be essential for tumor growth and provide an explanation for long-standing observations concerning the apparent coupling of enhanced glycolysis and cell proliferation.
Cellular distribution of type I and type II receptors for transforming growth factor-beta. (1986)

Affinity labeling of target cells for transforming growth factor-beta (TGF beta) by cross-linking with 125I-TGF beta via disuccinimidyl suberate or by the photoreactive analogue 4-azidobenzoyl-125I-TGF beta has revealed the presence of multiple TGF beta receptor forms. Two distinct types of TGF beta receptors can be distinguished based on structural analysis of the 125I-TGF beta-labeled species by peptide mapping. Type I TGF beta receptors include the 280-kilodalton labeled receptor form previously found to be the subunit of a disulfide-linked TGF beta receptor complex. (Massagué, J. (1985) J. Biol. Chem. 260, 7059-7066), as well as a 65-kDa labeled receptor form present in all cell lines examined, and a 130-140-kDa labeled receptor form detected only in 3T3-L1 cells. The 280-kDa form is the major TGF beta receptor species in most cell lines examined, but is apparently absent in rat skeletal muscle myoblasts. Type I TGF beta receptors bind TGF beta with an apparent Kd of 50-500 pM. Type II TGF beta receptors include an 85-kDa labeled receptor form present in all mammalian cells examined and a 110-kDa labeled receptor form present in chick embryo fibroblasts. Type II TGF beta receptors bind TGF beta with an apparent Kd of about 50 pM. Except for the 280-kDa type I TGF beta receptor form, none of the TGF beta receptor forms described here is found as part of a disulfide-linked receptor complex. All the TGF beta receptor forms described here behave as intrinsic membrane proteins exposed on the surface of intact cells.
Antibody Targeted siRNA Delivery (2011)

It is very clear that RNA interference (RNAi) is a potent and versatile tool for gene silencing. One of the hurdles to making siRNA/miRNA a human therapeutic includes effective in vivo delivery and being able to deliver drugs to target cells only. The commercial success of in vivo applications of RNAi hinges on the development of new delivery methods. Our strategy involves the use of antibody-based delivery agents to target and deliver siRNA into specific cell types. We have developed antibody-based agents for directed delivery into cultured cells and animal disease models. Using antibodies against various cell surface receptors, modified siRNAs are attached to antibody complexes using RNA carrier proteins. The complex can then be intravenously administered to in vivo models and taken up by specific cells via receptor-mediated endocytosis. The labile structure of the linking agents enables release of siRNA molecules post internalization. Using this targeting strategy, we have developed a method that allows any commercially available or recombinant antibody to be conjugated to siRNA for delivery purposes.
The roles of tyrosines 24, 31, and 60 in the high affinity binding of insulin-like growth factor-I to the type 1 insulin-like growth factor receptor. (1990)

A series of insulin-like growth factor I (IGF-I) structural analogs in which one or more of the three tyrosine residues were replaced with nonaromatic residues were produced and their binding properties characterized. The single point mutations, [Leu24]IGF-I, [Ala31]IGF-I, and [Leu60]IGF-I result in an 18-, 6-, or 20-fold loss in affinity, respectively, for the type 1 IGF receptor. Multiple mutations, [Ala31,Leu60]IGF-I, [Leu24, Ala31]IGF-I, [Leu24, Leu60]IGF-I, or [Leu24, Ala31, Leu60]IGF-I result in a 520-, 240-, 1200-, or greater than 1200-fold loss in affinity, respectively, at the type 1 IGF receptor. In contrast, none of the analogs display greater than a 2-fold loss in affinity for the acid-stable human serum binding proteins. At the insulin receptor, [Ala31]IGF-I and [Leu24]IGF-I are equipotent to and 5-fold less potent than IGF-I, whereas [Leu60]IGF-I and the multiple mutation analogs are inactive up to 10 microM. Analogs [Leu24]IGF-I, [Ala31]IGF-I, and [Leu24, Ala31]IGF-I are equipotent to IGF-I at the type 2 IGF receptor, whereas all analogs containing Leu60 demonstrate little measurable affinity at this receptor. Thus, Tyr24, Tyr31, and Tyr60 are involved in the high affinity binding of IGF-I to the type 1 IGF receptor, while Tyr60 is important for maintaining binding to the type 2 IGF receptor.
Purification and properties of alpha-D-mannose:beta-1,2-N-acetylglucosaminyl-transferases and alpha-D-mannosidases from human adenocarcinoma. (1984)

Two specific N-acetylglucosaminyltransferases, alpha-1,3-mannoside:beta-2-N-acetylglucosaminyltransferase (transferase I) and alpha-1,6-mannoside:beta-2-N-acetylglucosaminyltransferase (transferase II), which catalyze the transfer of N-acetylglucosamine (GlcNAc) from uridine diphospho-GlcNAc to terminal branched alpha-mannosyl (Man) residues, were purified from liver metastases of human colon adenocarcinoma. Transferase I was assayed with Man alpha 1,6(Man alpha 1,3)Man alpha 1,6(Man alpha 1,3)Man beta 1,4GlcNAc beta 1, 4GlcNAc-Asn (Km 0.35 mM), and transferase II was assayed with Man alpha 1,6(GlcNAc beta 1,2Man alpha 1,3)Man beta 1,4GlcNAc beta 1,4-Glc-NAc-Asn (Km 1.0 mM), in which Asn is asparagine. The Km of transferase I for Man alpha 1,6(Man alpha 1,3)Man beta 1,4GlcNAc-beta 1,4)-(Fuc alpha 1,6)GlcNAc-Asn was 1 mM. The specificity of the interaction of transferase I with ovalbumin, ovomucoid, the modified heavy chain of porcine immunoglobulin G and glycopeptides prepared from these glycoproteins was examined by kinetic and structural analysis. The best macromolecular substrates for transferase I were ovalbumin devoid of terminal GlcNAc and some mannose, a solubilized preparation of the heavy chain of porcine immunoglobulin G, devoid of sialic acid, galactose, and terminal GlcNAc, and untreated ovomucoid. The apparent KmS were 45, 19, and 390 microM for ovalbumin, the modified heavy chain of immunoglobulin G, and untreated ovomucoid, respectively. The apparent Km of the enzyme for uridine diphospho-GlcNAc was not significantly influenced by the nature of the glycoprotein acceptor, and it varied between 14 and 20 microM for the different glycoproteins. The structures of the oligosaccharide chains in these glycoproteins which acted as acceptors for the purified enzyme were determined. A major glycopeptide product with the structure Man alpha 1,3(Man alpha 1,6)Man alpha 1,6(14C-GlcNAc beta 1,2Man-alpha 1,3)Man beta 1,4GlcNAc-beta 1,4-GlcNAc-Asn was isolated from both ovalbumin and ovomucoid following incubation with transferase I. The specificity of the enzyme for terminal branched mannosyl residues attached to a beta-linked mannose unit greatly restricts the action of this transferase to this juncture in the synthesis of complex-type oligosaccharide chains of N-asparagine-linked glycoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)
Murine Monocyte Chemoattractant Protein (MCP)-5: A Novel CC Chemokine That Is a Structural and Functional Homologue of Human MCP-1 (1997)

The chemokines are a large family of cytokines that control the recruitment of leukocytes in immune and inflammatory responses. We describe the isolation of a novel murine CC chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC chemokine cluster on mouse chromosome 11 and was most closely related to human MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein was a potent chemoattractant for peripheral blood monocytes, was only weakly active on eosinophils at high doses, and was inactive on neutrophils. MCP-5 induced a calcium flux in peripheral blood mononuclear cells, but not in purified murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5. Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes, and its expression was markedly induced in macrophages activated in vitro and in vivo. Moreover, MCP-5 expression was up-regulated in the lungs of mice following aerosolized antigen challenge of sensitized mice, and during the host response to infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.
Stemming heart failure with cardiac‐ or reprogrammed‐stem cells (2008)

Despite extensive efforts to control myocyte growth by genetic targeting of the cell cycle machinery and small molecules for cardiac repair, adult myocytes themselves appeared to divide a limited number of times in response to a variety of cardiac muscle stresses. Rare tissue-resident stem cells are thought to exist in many adult organs that are capable of self-renewal and differentiation and possess a range of actions that are potentially therapeutic. Recent studies suggest that a population of cardiac stem cells (CSCs) is maintained after cardiac development in the adult heart in mammals including human beings; however, homeostatic cardiomyocyte replacement might be stem cell-dependent, and functional myocardial regeneration after cardiac muscle damage is not yet considered as sufficient to fully maintain or reconstitute the cardiovascular system and function. Although it is clear that adult CSCs have limitations in their capabilities to proliferate extensively and differentiate in response to injury in vivo for replenishing mature car-diomyocytes and potentially function as resident stem cells. Transplantation of CSCs expanded ex vivo seems to require an integrated strategy of cell growth-enhancing factor(s) and tissue engineering technologies to support the donor cell survival and subsequent proliferation and differentiation in the host microenvironment. There has been substantial interest regarding the evidence that mammalian fibroblasts can be genetically reprogrammed to induced pluripotent stem (iPS) cells, which closely resemble embryonic stem (ES) cell properties capable of differentiating into functional cardiomyocytes, and these cells may provide an alternative cell source for generating patient-specific CSCs for therapeutic applications.
Diffraction phase microscopy for quantifying cell structure and dynamics (2006)

We have developed diffraction phase microscopy as a new technique for quantitative phase imaging of biological structures. The method combines the principles of common path interferometry and single-shot phase imaging and is characterized by subnanometer path-length stability and millisecond-scale acquisition time. The potential of the technique for quantifying nanoscale motions in live cells is demonstrated by experiments on red blood cells.
Clear cell renal cell carcinoma associated microRNA expression signatures identified by an integrated bioinformatics analysis (2013)

Abstract Background Clear cell renal cell carcinoma (ccRCC) represents the most invasive and common adult kidney neoplasm. Mounting evidence suggests that microRNAs (miRNAs) are important regulators of gene expression. But their function in tumourigenesis in this tumour type remains elusive. With the development of high throughput technologies such as microarrays and NGS, aberrant miRNA expression has been widely observed in ccRCC. Systematic and integrative analysis of multiple microRNA expression datasets may reveal potential mechanisms by which microRNAs contribute to ccRCC pathogenesis. Methods We collected 5 public microRNA expression datasets in ccRCC versus non-matching normal renal tissues from GEO database and published literatures. We analyzed these data sets with an integrated bioinformatics framework to identify expression signatures. The framework incorporates a novel statistic method for abnormal gene expression detection and an in-house developed predictor to assess the regulatory activity of microRNAs. We then mapped target genes of DE-miRNAs to different databases, such as GO, KEGG, GeneGo etc, for functional enrichment analysis. Results Using this framework we identified a consistent panel of eleven deregulated miRNAs shared by five independent datasets that can distinguish normal kidney tissues from ccRCC. After comparison with 3 RNA-seq based microRNA profiling studies, we found that our data correlated well with the results of next generation sequencing. We also discovered 14 novel molecular pathways that are likely to play a role in the tumourigenesis of ccRCC. Conclusions The integrative framework described in this paper greatly improves the inter-dataset consistency of microRNA expression signatures. Consensus expression profile should be identified at pathway or network level to address the heterogeneity of cancer. The DE-miRNA signature and novel pathways identified herein could provide potential biomarkers for ccRCC that await further validation.
Substrate modification combined with pulmonary vein isolation improves outcome of catheter ablation in patients with persistent atrial fibrillation: a prospective randomized comparison (2006)

PVI alone is insufficient in the treatment of persistent AF. However, additional left linear lesions increase the success rate significantly. Early AF-relapses are associated with a negative outcome after PVI alone but not following additional SM.
Probiotic Lactobacillus reuteri Attenuates the Stressor-Enhanced Severity of Citrobacter rodentium Infection (2013)

Stressor exposure has been shown to enhance host susceptibility and the severity of a plethora of illnesses, including gastrointestinal disease. In mice, susceptibility to Citrobacter rodentium has been shown to be dependent on host genetics as well as the composition of the intestinal microbiota, but the effects of stressor exposure on this gastrointestinal pathogen have not been elucidated fully. Previously, our lab showed that exposure to the prolonged-restraint stressor prior to a challenge with C. rodentium alters the intestinal microbiota community structure, including a reduction of beneficial genera such as Lactobacillus, which may contribute to stressor-enhanced C. rodentium-induced infectious colitis. To test the effects of stressor exposure on C. rodentium infection, we exposed resistant mice to a prolonged-restraint stressor concurrent with pathogen challenge. Exposure to prolonged restraint significantly enhanced C. rodentium-induced infectious colitis in resistant mice, as measured by increases in colonic histopathology, colonic inflammatory mediator gene production, and pathogen translocation from the colon to the spleen. It was further tested if the beneficial bacterium Lactobacillus reuteri could reduce the stressor-enhanced susceptibility to C. rodentium-enhanced infectious colitis. While L. reuteri treatment did not reduce all aspects of stressor-enhanced infectious colitis, it did significantly reduce pathogen translocation from the colon to the spleen. Taken together, these data demonstrate the deleterious effects that prolonged stressor exposure can have at the onset of a gastrointestinal infection by its ability to render a resistant mouse highly susceptible to C. rodentium. Probiotic treatment ameliorated the systemic manifestations of stress on colonic infection.