gebhart/patrepeval huggingface dataset:
Recent Advances in CRISPR Base Editing: From A to RNA (2018)

ADVERTISEMENT RETURN TO ISSUEPREVViewpointNEXTRecent Advances in CRISPR Base Editing: From A to RNAJennifer N. Bjerke†, Patrick C. Beardslee†, and Brian R. McNaughton*†‡View Author Information† Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States‡ Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, Colorado 80523, United States*E-mail: [email protected]Cite this: Biochemistry 2018, 57, 6, 886–887Publication Date (Web):January 26, 2018Publication History Received19 December 2017Published online26 January 2018Published inissue 13 February 2018https://pubs.acs.org/doi/10.1021/acs.biochem.7b01276https://doi.org/10.1021/acs.biochem.7b01276editorialACS PublicationsCopyright © 2018 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views3594Altmetric-Citations2LEARN 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 PDF (347 KB) Get e-AlertscloseSUBJECTS:Adenine,Genetics,Nucleic acids,Peptides and proteins,Protein engineering Get e-Alerts
Like an intuitive and courteous butler: a proactive personal agent for task management (2009)

The ability to proactively offer assistance promises to make personal agents more helpful to their users. We characterize the properties desired of proactive behaviour by a personal assistant agent in the realm of task management, and present an extended agent cognition model that features a meta-level layer charged with identifying potentially helpful actions and determining when it is appropriate to perform them. The reasoning that answers these questions draws on a theory of proactivity that describes user desires and a model of helpfulness. Operationally, assistance patterns represent a compiled form of this knowledge, instantiating meta-cognition over the agent's beliefs about its user's activities as well as over world state. We have implemented the resulting generic framework for proactive goal generation and deliberation as part of a personal assistant agent in the desktop domain.
Microfluidics for flow cytometric analysis of cells and particles (2005)

This review describes recent developments in microfabricated flow cytometers and related microfluidic devices that can detect, analyze, and sort cells or particles. The high-speed analytical capabilities of flow cytometry depend on the cooperative use of microfluidics, optics and electronics. Along with the improvement of other components, replacement of conventional glass capillary-based fluidics with microfluidic sample handling systems operating in microfabricated structures enables volume- and power-efficient, inexpensive and flexible analysis of particulate samples. In this review, we present various efforts that take advantage of novel microscale flow phenomena and microfabrication techniques to build microfluidic cell analysis systems.
Developmental expression of NOS isoforms in fetal rat lung: implications for transitional circulation and pulmonary angiogenesis (1996)

To better understand the role of nitric oxide (NO) in fetal lung development, specifically in the transition of the fetal circulation at birth, we studied the timing of cell-specific expression of NO synthase (NOS) isoforms from formation of lung buds (13th day of gestation) to 7 days postnatal. Expression of NOS was studied using immunohistochemical labeling with antibodies against the three known NOS isoforms and the NADPH diaphorase technique (NADPH-d). Endothelial NOS (eNOS) immunoreactivity was found in the cells of the 14-day fetal lung. As gestation proceeded, the quantity of these immunopositive cells increased, and they coalesced to form an inner (endothelial) layer of pulmonary vessels. This process of angiogenesis marked by eNOS-positive cells was seen from 15 days of gestation to at least 7 days postnatal. A majority of the eNOS immunoreactivity appeared densely in one focal spot in the cytoplasm, indicating that during development the eNOS may be primarily located in a cytoplasmic organelle. Epithelial cells of the rat airway from the same developmental period were positively stained with both brain NOS antibody (bNOS) and NADPH-d at the beginning of 13 days of gestation. Then the intensity of stainings began to decrease and reached the lowest level in the 16-day fetal lung. However, the NOS stainings of the epithelium, especially in small canalicular structures of the airways, began to increase at 18 days of gestation and was dramatically elevated at 20 days of gestation (term is 22 days). Postnatally, NOS in epithelium was decreased in distal airways in conjunction with the formation of alveolar structure. Inducible NOS (iNOS) immunoreactivity was also found in the epithelium of rat lung airways after 16 days of gestation. Unlike the bNOS staining, iNOS immunoreactivity exhibited a pattern of a small dot-like staining within epithelial cytoplasm during gestation and the first day postnatal, then changed to a pattern of diffuse cytoplasmic staining by the 7th postnatal day. This study concludes that 1) expression of three isoforms of NOS is present and regulated during lung development; 2) markedly increased NOS in epithelium near term supports a role for NO in mediating the pulmonary transition from fetal to neonatal life; and 3) eNOS immunohistochemistry serves as an effective marker to follow the process of pulmonary angiogenesis and suggests the concept of in situ formation of endothelial vesicles in developing mesenchyme.
Purification of nuclear proteins that bind to cisplatin-damaged DNA. Identity with high mobility group proteins 1 and 2. (1992)

The biochemical processes responsible for the recognition and repair of cisplatin-damaged DNA in human cells are not well understood. We have developed a damaged DNA affinity precipitation technique that allows the direct visualization and characterization of cellular proteins that bind to cisplatin-damaged DNA. The method separates damaged DNA-binding proteins from complex radiolabeled cell mixtures and further resolves them into individual polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This technique is complementary to gel retardation and Southwestern blotting analyses that have been previously used to identify cellular components that specifically bind to cisplatin-damaged DNA. Using this technique, we have characterized a set of HeLaS3 nuclear proteins of 26.5, 28, 90, and 97 kDa that specifically bind to cisplatin-DNA adducts. Competition studies with soluble cisplatin-damaged DNA confirmed these findings. The major cisplatin-damaged DNA-binding proteins of 26.5 and 28 kDa recognized adducts of DNA modified with cisplatin but not with its trans-isomer or with UV radiation. These proteins were purified 450-fold to near homogeneity by ion-exchange and cisplatin-damaged DNA affinity chromatography. Amino-terminal sequence analysis showed that the 26.5- and 28-kDa proteins were identical to high mobility group (HMG) proteins HMG-2 and HMG-1, respectively.
Serum levels of soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) in endometrial cancer. (1996)

The pretreatment serum levels of the soluble receptors for tumor necrosis factor (p55 and p75 sTNFr) were retrospectively measured in 38 patients with endometrial cancer and 55 patients with benign uterine diseases as controls. Serum p55 and p75 sTNFr levels were significantly higher in patients with endometrial cancer (median = 2.4 ng/ml, range = 1.4-6.8 ng/ml, and median = 7.1 ng/ml, range = 2.5-19.5 ng/ml, respectively) than in controls (median = 1.7 ng/ml, range = 0.5-4.0 ng/ml, p < 0.0001, and median = 5.2 ng/ml, range = 2.6-21.9 ng/ml, p = 0.03, respectively). In the former, serum p55 and p75 sTNFr values correlated with the extent of disease (stage III-IV versus I-II: p = 0.04 and p = 0.03, respectively). Among the 23 patients with stage I endometrial cancer who underwent initial surgery, the preoperative serum levels of both receptors correlated with the histologic grade and myometrial invasion but not with the clinical outcome. In conclusion, a stage-dependent release of the soluble receptors for TNF into the bloodstream occurs in patients with endometrial cancer.
Cyclic AMP-dependent protein kinase in mitochondria and cytosol from different-sized follicles and corpora lutea of porcine ovaries. (1981)

cAMP-dependent protein kinase was examined in mitochondria and cytosol prepared from different-sized antral follicles and corpora lutea of porcine ovaries. In all ovarian tissues examined except small follicles, protein kinase-specific activity was significantly higher in mitochondria than in cytosol, with the highest to lowest activities being found in medium (4-6 mm) follicles, large (7-12 mm) follicles, corpora lutea, and small (1-3 mm) follicles, respectively. Using the photoaffinity analogue [32P]8-N3cAMP, two major cAMP binding proteins with Mr = 47,000 (the apparent regulatory subunit of protein kinase Type I) and 54,000-56,000 (Type II) were found in all ovarian preparations. Type II was predominant in the cytosol of all ovarian samples, with the cytosolic Type I to Type II ratio increasing from approximately 0.05 in small and medium follicles top approximately 0.20 in large follicles and corpora lutea. In contrast, ovarian mitochondrial preparations contained relatively more Type I than did cytosol, with the mitochondrial Type I to Type II ratio increasing from approximately 0.50 in small and medium follicles to 0.88 in large follicles and 2.96 in corpora lutea. Also, mitochondrial [4-14C]cholesterol conversion and 3 beta-hydroxysteroid dehydrogenase/isomerase activities increased with follicle size and luteinization. These results suggest that Type I may play a role in the regulation of ovarian mitochondrial steroidogenesis.
Chimeragenesis of the Fatty Acid Binding Site of Cytochrome P450BM3. Replacement of Residues 73−84 with the Homologous Residues from the Insect Cytochrome P450 CYP4C7 (2004)

A protein fragment of P450BM3 (residues 73-84) which participates in palmitoleate binding was subjected to scanning chimeragenesis. Amino acids 73-84, 73-78, 75-80, and 78-82 were replaced with the homologous fragments of the insect terpenoid hydroxylase CYP4C7. The four chimeric proteins, C(73-84), C(73-78), C(75-80), and C(78-82), were expressed, purified, and characterized. All the chimeric proteins contained all the cofactors and catalyzed monooxygenation of palmitate and of the sesquiterpene farnesol. Chimeragenesis altered substrate binding as shown by the changes in the amplitude of the palmitate-induced type I spectral shift. C(78-82) had monooxygenase activities close to those of P450BM3, while the rest of the chimeric proteins had monooxygenase activities that were inhibited relative to that of wild-type P450BM3. The extent of inhibition of the chimeric proteins varied depending on the substrate, and in the case of C(73-84), farnesol and palmitate oxidation was inhibited by 1 and 4 orders of magnitude, respectively. (1)H NMR spectroscopy and GC-MS were used to identify products of farnesol and palmitate oxidation. Wild-type P450BM3 and all chimeric proteins catalyzed oxidation of farnesol with formation of 9-hydroxyfarnesol and farnesol 10,11- and 2,3-epoxides. Three of the four chimeric proteins also formed a new compound, 5-hydroxyfarnesol, which was the major product in the case of C(73-78). In addition to hydroxylation of the C13-C15 atoms, the chimeric enzymes catalyze significant hydroxylation of the C10-C12 atoms of palmitate. In the case of C(78-82), the rates of formation of 11- and 12-hydroxypalmitates increased 7-fold compared to that of wild-type P450BM3 to 106 and 212 min(-)(1), respectively, while the rate of 10-hydroxypalmitate synthesis increased from zero to 106 min(-)(1). Thus, chimeragenesis of the region of residues 73-84 of the substrate binding site shifted the regiospecificity of substrate oxidation toward the center of the farnesol and palmitate molecules.
Coronary Side-Effect Potential of Current and Prospective Antimigraine Drugs (1998)

All current and prospective antimigraine drugs contract the human coronary artery in vitro, but in view of low efficacy, these drugs are unlikely to cause myocardial ischemia at therapeutic plasma concentrations in healthy subjects. In patients with coronary artery disease, however, these drugs must remain contraindicated. The sustained contraction by ergotamine and dihydroergotamine seems to be an important disadvantage compared with sumatriptan-like drugs.
Isolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action. (1989)

Inhibitory insulin-like growth factor binding protein (In-IGF-BP) has been purified to homogeneity from medium conditioned by TE89 human osteosarcoma cells by two different methods using Sephadex G-100 gel filtration, FPLC Mono Q ion-exchange, HPLC C4 reverse-phase, HPLC CN reverse-phase, and affinity chromatographies. In-IGF-BP thus purified appeared to be homogeneous and unique by the following criteria. (i) N-terminal sequence analysis yielded a unique sequence (Asp-Glu-Ala-Ile-His-Cys-Pro-Pro-Glu-Ser-Glu-Ala-Lys-Leu-Ala). (ii) Amino acid composition of In-IGF-BP revealed marked differences with the amino acid compositions of other known BPs. (iii) In-IGF-BP exhibited a single band with a molecular mass of 25 kDa under reducing conditions on sodium dodecyl sulfate/polyacrylamide gels. IGF-I and IGF-II but not insulin displaced the binding of 125I-labeled IGF-I or 125I-labeled IGF-II binding to In-IGF-BP. In-IGF-BP inhibited basal, IGF-stimulated bone cell proliferation and serum-stimulated bone cell proliferation. Forskolin increased synthesis of In-IGF-BP in TE85 human osteosarcoma cells in a dose-dependent manner. Based on these findings, we conclude that In-IGF-BP is a protein that has a unique sequence and significant biological actions on bone cells.
Pancreatic carcinomas deposit laminin-5, preferably adhere to laminin-5, and migrate on the newly deposited basement membrane. (1997)

We studied the adhesion mechanism of pancreatic carcinoma using in vitro adhesion and migration assays of stable cell lines and tumors grown from these cell lines in nude mice. We also compared the results with the expression profiles of laminins and their receptors in pancreatic carcinomas to evaluate the relevance of these mechanisms in vivo. All of the cell lines preferably adhered to laminin-5, irrespective of their capability to synthesize laminin-5. Cell migration was studied in the presence of hepatocyte growth factor, as it increased the speed of migration manyfold. Herbimycin A treatment and antibodies against the beta 1 and alpha 3 integrin subunits and laminin alpha 3 chain almost entirely blocked cell migration of the BxPC-3 cell line, whereas migration was nearly unaffected by RGD peptide and only moderately inhibited by antibody against the alpha 6 integrin subunit. Indirect immunofluorescence microscopy of wounded BxPC-3 cells suggested a rapid endocytosis of alpha 3 integrin subunit in the cells at the margin of the wound and a rapid, polarized rearrangement of the alpha 6 beta 4 integrin. Especially HGF-treated cultures showed a prominent cytoplasmic reaction for laminin-5 at the margin of the wound. Xenografted cells formed tumors that produced and deposited the same laminin chains as the in vitro cultures. Frozen sections of human pancreatic carcinomas showed reactivity for laminin chains suggestive for expression of laminin-1 and laminin-5. Both xenografted tumors and human pancreatic carcinomas also showed stromal reactivity for laminin-5. Electron microscopy of the human tumors suggested that this was due to an abundant reduplication the basement-membrane-like material around the nests of malignant cells. Our results suggest that pancreatic carcinomas synthesize and deposit laminin-5 in the basement membrane in an abnormal manner. Invading cells adhere to this newly produced basement membrane and migrate on it by using the alpha 3 beta 1 integrin receptor recognizing laminin-5.
Nematode Chondroitin Polymerizing Factor Showing Cell-/Organ-specific Expression Is Indispensable for Chondroitin Synthesis and Embryonic Cell Division (2004)

Chondroitin polymerization was first demonstrated in vitro when human chondroitin synthase (ChSy) was coexpressed with human chondroitin polymerizing factor (ChPF), which is homologous to ChSy but has little glycosyltransferase activity. To analyze the biological function of chondroitin, the Caenorhabditis elegans ortholog of human ChSy (sqv-5) was recently cloned, and the expression of its product was depleted by RNA-mediated interference (RNAi) and deletion mutagenesis. Blocking of chondroitin synthesis resulted in defects of cytokinesis in early embryogenesis, and eventually, cell division stopped. Here, we cloned the ortholog of human ChPF in C. elegans, PAR2.4. Despite little glycosyltransferase activity of the gene product, chondroitin polymerization was demonstrated as in the case of mammals when PAR2.4 was coexpressed with cChSy in vitro. The worm phenotypes including the reversion of cytokinesis, observed after the depletion of PAR2.4 by RNAi, were very similar to the cChSy (sqv-5)-RNAi phenotypes. Thus, PAR2.4 in addition to cChSy is indispensable for the biosynthesis of chondroitin in C. elegans, and the two cooperate to synthesize chondroitin in vivo. The expression of the PAR2.4 protein was observed in seam cells, which can act as neural stem cells in early embryonic lineages. The expression was also detected in vulva and distal tip cells of the growing gonad arms from L3 through to the young adult stage. These findings are consistent with the notion that chondroitin is involved in the organogenesis of the vulva and maturation of the gonad and also indicative of an involvement in distal tip cell migration and neural development.
Human immunodeficiency virus-infected T cells and monocytes are killed by monoclonal human anti-gp41 antibodies coupled to ricin A chain. (1989)

Two human monoclonal antibodies specific for the envelope glycoprotein (gp), gp41, of the human immunodeficiency virus were conjugated to deglycosylated ricin A chain. These immunotoxins killed human immunodeficiency virus-infected H9 (T cell) and U937 (monocyte) cell lines but were nontoxic to the uninfected cell lines or to class II-positive Daudi cells. Specific killing of infected H9 cells could be completely blocked by recombinant gp160 and partially blocked by unconjugated anti-gp41 antibody but was not blocked by recombinant gp120 or human IgG demonstrating specificity for gp41. The specific toxicity of the immunotoxins for infected U937 cells was markedly potentiated by chloroquine.
Western diet and Western diseases: Some hormonal and biochemical mechanisms and associations (1990)

Breast cancer, prostate cancer, coronary heart disease and colon cancer belong to the so-called Western diseases and a general opinion is that diet is a significant or even the main factor increasing incidence and mortality of these diseases in the Western world. This review describes studies carried out in this department for about 10 years, many in collaboration with scientists abroad, and with the aim to clarify some of the connections between the diet and sex hormone, lipid and bile acid metabolism. A Western-type diet elevates plasma levels of sex hormones and decreases the sex hormone binding globulin concentration, increasing the bioavailability of these steroids. The same diet results in low formation of mammalian lignans and isoflavonic phytoestrogens. These diphenolic compounds seem to affect hormone metabolism and production and cancer cell growth by many different mechanisms making them candidates for a role as cancer protective substances. The precursors of these diphenols are to be found in fiber-rich unrefined grain products, various seeds, beans and probably also in pulses, peas and berries. Some types of fiber seem to influence sex hormone and bile acid metabolism mainly by partial interruption of the enterohepatic circulation, by alteration of intestinal metabolism and by increasing fecal excretion of these compounds. The sex hormone pattern found in connection with a Western-type diet is prevailing in the breast cancer patients, but is only partly a result of the diet.
Genetic and Environmental Regulation of Dauer Larva Development (1997)

I. INTRODUCTION Dauer larvae were first identified as a special larval stage of insect-parasitic nematodes. These larvae, which differed structurally from all other stages of the same species, were termed “dauerlarven” by Fuchs (1915). The dauer (enduring) stage of Caenorhabditis elegans is formed when environmental conditions are inadequate for successful reproduction. In abundant food, the animal develops continuously through the four larval stages (L1–L4) to the adult. Coincident with increased population density and limited food supply, development is arrested at the second molt, and the third-stage larva that is formed is structurally and behaviorally specialized for dispersal and long-term survival (Cassada and Russell 1975). Dauer larvae do not feed, but they can survive at least four to eight times the normal 2-week life span of C. elegans (Klass and Hirsh 1976). When favorable conditions are encountered, the dauer larva begins to feed and resumes development to the adult. Both entry into and exit from the dauer stage are developmental responses to specific chemosensory cues. These cues inform the larva whether there will be sufficient food available to support its reproduction. The environmental cues are first assessed and integrated throughout the L1 stage (Golden and Riddle 1984b). The primary cue is a Caenorhabditis-specific pheromone constitutively released by the nematodes (Golden and Riddle 1984c). The pheromone is very stable and hydrophobic and has chromatographic properties similar to those of hydroxylated fatty acids and bile acids. The concentration of pheromone reflects nematode population density. Temperature and food modulate the response to pheromone...
Future strategies for the treatment of diastolic heart failure (2006)

It is estimated that 30% to 50% of heart failure patients have preserved systolic left ventricular (LV) function, often referred to as diastolic heart failure (DHF). Mortality is high in this patient population, and morbidity and rate of hospitalization are similar to those of patients with systolic heart failure. The management of patients with diastolic heart failure is essentially empirical, limited, and disappointing. New drugs, devices, and gene therapy based treatment options are currently under investigation. In this review, future strategies for the treatment of diastolic heart failure are discussed.