gebhart/patrepeval huggingface dataset:
Lung epithelial stem cells (2002)

This review concentrates on recent evidence about lung stem cell origins and plasticity. The range of potential cells which can repopulate the injured lung, classically the basal and mucous secretory cells of the trachea, the Clara cells of the bronchiole, and the type II pneumocyte of the alveolus, has been extended to include the mucus-gland duct cells of the trachea and bronchus. Some evidence suggests that there are variant Clara cells that lack cytochrome P-450 and so are spared toxic activation of xenobiotics, and may aid bronchiolar repopulation after injury, such as with naphthalene. There may even be involvement of the neuroepithelial bodies or cells in this, though the evidence is not yet conclusive. The search for a resident pulmonary multipotent cell for repopulating any lung epithelium has not yet been successful. The picture remains similar to earlier conclusions, in that the local stem or precursor cell is the most likely to contribute to local needs in times of tissue damage. There remains a major challenge for lung cancer treatment, where high-dose chemo- or radio-therapy may be hoped to promote the seeding and repair of lung parenchyma by circulating bone marrow stem cells, as seen in liver models. Patient survival rates do not yet suggest that this occurs to any great extent, but this remains to be shown formally. The effects of prior fibrosis and tumour necrosis are probably confounding factors in this lack of rescue.
The effects on neonatal piglet behaviour and tissue composition of feeding sows a diet containing a high level of docosahexaenoic acid (DHA) in late gestation and lactation (1997)

Neonatal mortality is a major source of economic loss to the pig industry. Polyunsaturated fatty acids (PUFAs), especially DHA, have been implicated in brain development in man and other species and a pre-natal supply of PUFAs may have a role in influencing post-natal survival. The purpose of this study was to investigate the effect of feeding increased amounts of DHA during gestation and early lactation, on piglet viability and tissue composition.
808. Monitoring of Transgene Expression in Cancer Patients with Positron Emission Tomography (PET) (2005)

Bruno Sangro,1 Ivan Penuelas,2 Guillermo Mazzolini,1 Jose F. Boan,2 Josep M. Marti-Climent,2 Maria Ruiz,1 Cheng Qian,1 Nagichettiar Satyamurthy,3 Jorge R. Barrio,3 Michael E. Phelps,3 Jose A. Richter,2 Sam Gambhir,4 Jesus Prieto,1
Studies of Amyloid β‐Protein Precursor Expression in Alzheimer's Disease (1991)

The generation of the beta/A4 peptide and its accumulation into insoluble amyloid deposits represent key events in the neuropathologic process of Alzheimer's disease (AD). This posit has gained further support from recent reports that beta/A4 is directly responsible for the death of neurons. Potential therapies for AD aimed at abating the production of beta/A4 will require the basic knowledge of where it comes from. The 4.2-kD peptide is derived from a much larger amyloid precursor protein (APP) encoded by a gene that produces multiple transcripts. Employing in situ hybridization with biotinylated oligonucleotide probes, we set out to define which forms of the precursor are synthesized in affected regions of AD brain (e.g., hippocampal formation) and to determine the cell populations responsible for their manufacture.
TAA Polyepitope DNA-Based Vaccines: A Potential Tool for Cancer Therapy (2010)

DNA-based cancer vaccines represent an attractive strategy for inducing immunity to tumor associated antigens (TAAs) in cancer patients. The demonstration that the delivery of a recombinant plasmid encoding epitopes can lead to epitope production, processing, and presentation to CD8+ T-lymphocytes, and the advantage of using a single DNA construct encoding multiple epitopes of one or more TAAs to elicit a broad spectrum of cytotoxic T-lymphocytes has encouraged the development of a variety of strategies aimed at increasing immunogenicity of TAA polyepitope DNA-based vaccines. The polyepitope DNA-based cancer vaccine approach can (a) circumvent the variability of peptide presentation by tumor cells, (b) allow the introduction in the plasmid construct of multiple immunogenic epitopes including heteroclitic epitope versions, and (c) permit to enroll patients with different major histocompatibility complex (MHC) haplotypes. This review will discuss the rationale for using the TAA polyepitope DNA-based vaccination strategy and recent results corroborating the usefulness of DNA encoding polyepitope vaccines as a potential tool for cancer therapy.
Isomerization of Alkylphosphites. III. The Synthesis of n-Alkylphosphonic Acids (1945)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsomerization of Alkylphosphites. III. The Synthesis of n-Alkylphosphonic AcidsGennady M. KosolapoffCite this: J. Am. Chem. Soc. 1945, 67, 7, 1180–1182Publication Date (Print):July 1, 1945Publication History Published online1 May 2002Published inissue 1 July 1945https://pubs.acs.org/doi/10.1021/ja01223a045https://doi.org/10.1021/ja01223a045research-articleACS PublicationsRequest reuse permissionsArticle Views647Altmetric-Citations85LEARN 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-Alertsclose Get e-Alerts
ChemInform Abstract: Chemotherapeutic Agents. Part 20. Antileishmanial and Immunoadjuvant Activities of Rationally Designed Thiopyrimidines. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Increased neostriatal dopamine activity after intraperitoneal or intranasal administration of L-DOPA: On the role of benserazide pretreatment (1997)

L-DOPA provides the most potent medication to treat Parkinson's disease, and such systemic treatment is usually combined with a peripheral amino acid decarboxylase inhibitor to amplify its central effectiveness. Since L-DOPA can lose its efficacy or can lead to adverse effects with prolonged application, current pharmacokinetic and dynamic research is aimed at improving the drug's applicability. In a previous study, performed with in vivo microdialysis in the anesthetized rat, we have shown that intranasal L-DOPA administration (without prior decarboxylase inhibition) can increase extracellular dopamine levels in the neostriatum. Using similar experimental conditions in the present experiment, we tested the neurochemical effects of L-DOPA treatment in combination with the peripheral amino acid decarboxylase inhibitor benserazide. In accordance with other data, it was found that the combination of i.p. benserazide and i.p. L-DOPA led to pronounced increases of extracellular levels of dopamine, dihydroxyplenylacetic acid and homovanillic acid in the neostriatum, whereas i.p. L-DOPA alone only moderately increased dopamine, but strongly increased the metabolite levels. Furthermore, increased dopamine levels, and weaker increases of dihydroxyplenylacetic acid and homovanillic acid were observed after i.p. benserazide followed by intranasal L-DOPA. Finally, we found that i.p. benserazide alone can lead to pronounced increases in neostriatal dopamine and moderate increases of dihydroxyplenylacetic acid levels, whereas it did not affect homovanillic acid. Thus, not only the combination of L-DOPA (i.p. or intranasal) with the presumed peripheral L-DOPA decarboxylase inhibitor benserazide, but also each component alone can affect dopamine activity in the brain. Especially the findings with benserazide treatment might be of relevance for understanding the mechanisms of current L-DOPA therapy, since they indicate that part of the treatment's actions may possibly be determined by central dopaminergic effects of the accompanying amino acid decarboxylase inhibitor.
No Association Between EGF Gene Polymorphism and Gastric Cancer (2005)

The etiology of gastric cancer is not well-understood. Epidermal growth factor (EGF) transduces growth signals to mitogen-activated protein kinase via RAS and BRAF, and EGF/EGF receptor interaction is important for tumor growth and progression. Previous studies have reported that the EGF +61 (A/G) single nucleotide polymorphism in the 5'-untranslated region of the EGF gene is functional, and is associated with gastric cancer and various malignancy. Individuals with the EGF A/A genotype produce less EGF than individuals with G/G or G/A. We investigated a single nucleotide polymorphism at exon 1 of EGF, named rs4444903 in NCI dbSNP, in 454 Japanese subjects undergoing a health checkup and 202 patients with gastric cancer. Genotype was determined by PCR with confronting two-pair primers. Results showed that EGF polymorphism was not associated with gastric cancer but that the EGF A/A genotype showed a protective effect (odds ratios, 0.58; 95% confidence interval, 0.29-1.17 relative to G/G). Furthermore, when we divided cases into two groups, a differentiated type and an undifferentiated type, the A/A and G/A combined was found to be lower frequency in the latter type than in the former type without significance (OR, 0.81; 95% confidence interval, 0.44-1.49 relative to G/G). As is the case with any malignancy, other factors are involved, including environmental and host factors. The present results show that although EGF is necessary for cancer, it is not sufficient. We also found ethnic heterogeneity in the functional EGF polymorphism. Because the relationship between EGF polymorphism and malignancy remains inconsistent, confirmation of the role of EGF polymorphism in gastric cancer requires a much larger study.
Characterization of the adsorption of conjugated and unconjugated bile acids to insoluble, amorphous calcium phosphate. (1994)

Recently we showed that supplemental dietary calcium stimulates the intestinal formation of insoluble calcium phosphate and decreases the ratio of dihydroxy to trihydroxy bile acids in human duodenal bile. Because previous in vitro studies indicated that these effects could be due to differential adsorption of bile acids to amorphous calcium phosphate, we characterized the binding of bile acids to calcium phosphate. Freshly formed, amorphous, calcium phosphate bound and thus precipitated glycine-conjugated and unconjugated bile acids, whereas taurine-conjugated bile acids showed little binding. Glycochenodeoxycholic acid hardly adsorbed to other insoluble calcium phosphates, including hydroxyapatite. Adsorption studies using increasing amounts of glycine-conjugated and unconjugated bile acids showed that binding occurred above a bile acid-specific critical minimum concentration, dependent on bile acid hydrophobicity. The simultaneous use of a fluorescent hydrophobic probe indicated that this binding was due to ionic adsorption of monomers of bile acids, followed by their hydrophobic aggregation on the calcium phosphate surface, probably in the form of a bilayer. Finally, using human duodenal bile we found that amorphous calcium phosphate, but not Ca2+, preferentially bound and thus precipitated dihydroxy bile acids. We conclude that freshly formed, amorphous, calcium phosphate is a prerequisite for adsorption of bile acids and that monomers of glycine-conjugated and unconjugated dihydroxy bile acids have a high binding affinity for amorphous calcium phosphate.
Collagen deposition in HIV-1 infected lymphatic tissues and T cell homeostasis (2002)

Lymphatic tissues (LTs) are structurally organized to promote interaction between antigens, chemokines, growth factors, and lymphocytes to generate an immunologic response and maintain normal-sized populations of CD4(+) and CD8(+) T cells. Inflammation and tissue remodeling that accompany local innate and adaptive immune responses to HIV-1 replication cause damage to the LT architecture. As a result, normal populations of CD4(+) and CD8(+) T cells cannot be supported and antigen-lymphocyte interactions are impaired. This conclusion is supported herein following LT sampling before and during anti-HIV therapy in persons with acute, chronic, and late-stage HIV-1 infection. Among seven individuals treated with anti-retroviral therapy (ART) and four individuals deferring therapy we found evidence of significant paracortical T cell zone damage associated with deposition of collagen, the extent of which was inversely correlated with both the size of the LT CD4(+) T cell population and the change in peripheral CD4(+) T cell count with anti-HIV therapy. The HIV-1-associated inflammatory changes and scarring in LT both limit the ability of the tissue to support and reestablish normal-sized populations of CD4(+) T cells and suggest a novel mechanism of T cell depletion that may explain the failure of ART to significantly increase CD4(+) T cell populations in some HIV-1-infected persons.
A General Synthetic Route to Defined, Biologically Active Multivalent Arrays (1999)

A new, general strategy for the synthesis of biologically active multivalent arrays displaying diverse functionality has been developed. This method exploits the ability of ring-opening metathesis polymerizations to produce polymers of defined lengths. By incorporating N-hydroxysuccinimide esters into the polymers, recognition epitopes bearing nucleophilic functional groups, in this case an α-mannose derivative, can be attached. The synthesis, characterization, and biological evaluation of mannose-bearing polymers demonstrated the utility of this new methodology. This strategy will facilitate the creation of diverse multivalent libraries and the large-scale production of multidentate ligands.
Proteases and proteolytic cleavage of storage proteins in developing and germinating dicotyledonous seeds (1996)

Proteolytic cleavage plays an important role in storage protein deposition and reactivation in seeds. Precursor polypeptides are processed by limited proteolysis to mature subunits of reserve proteins in storage tissue cells of developing seeds. Steps of proteolytic processing are closely related to steps in intracellular protein transfer through the endomembrane system and to the deposition in the storage vacuole. In germinating seeds special endopeptidases trigger storage protein breakdown by limited proteolysis. The induced conformation changes of storage proteins open them to attack by additional endo- and exopeptidases which degrade the protein reserves completely. Proteases that catalyse limited cleavage or complete degradation are synthesized as precursors which also undergo stepwise limited proteolysis when they are formed in cotyledons of developing or germinating seeds. In general, this processing transforms enzymatically inactive proenzymes into active proteases. Different compartments participate in the processing steps. Many of the proteases are encoded by small multigene families. Different members of the corresponding protease families seem to act during seed development and germination. Proteolytic processes that contribute to the molecular maturation and to the reactivation of storage proteins in dicotyledonous seeds seem to be controlled by (1) differential expression of members of the protease-encoding gene families; (2) stepwise processing and activation of protease precursor polypeptides; (3) transient differential compartmentation of precursors and mature polypeptides of proteases and storage proteins, respectively; and (4) interacting changes in storage protein structure and protease action. The present knowledge on these processes is reviewed.
The WASp-like protein Scar regulates macropinocytosis, phagocytosis and endosomal membrane flow inDictyostelium (2001)

Scar, a member of the WASp protein family, was discovered in Dictyostelium discoideum during a genetic screen for second-site mutations that suppressed a developmental defect. Disruption of the scar gene reduced the levels of cellular F-actin by 50%. To investigate the role of Scar in endocytosis, phagocytosis and endocytic membrane trafficking, processes that depend on actin polymerization, we have analyzed a Dictyostelium cell line that is genetically null for Scar. Rates of fluid phase macropinocytosis and phagocytosis are significantly reduced in the scar- cell-line. In addition, exocytosis of fluid phase is delayed in these cells and movement of fluid phase from lysosomes to post-lysosomes is also delayed. Inhibition of actin polymerization with cytochalasin A resulted in similar phenotypes, suggesting that Scar-mediated polymerization of the actin cytoskeleton was important in the regulation of these processes. Supporting this conclusion, fluorescence microscopy revealed that some endo-lysosomes were ringed with F-actin in control cells but no F-actin was detected associated with endo-lysosomes in Scar null cells. Disruption of the two genes encoding the actin monomer sequestering protein profilin in wild-type cells causes defects in the rate of pinocytosis and fluid phase efflux. Consistent with a predicted physical interaction between Scar and profilin, disrupting the scar gene in the profilin null background results in greater decreases in the rate of fluid phase internalization and fluid phase release compared to either mutant alone. Taken together, these data support a model in which Scar and profilin functionally interact to regulate internalization of fluid and particles and later steps in the endosomal pathway, probably through regulation of actin cytoskeleton polymerization.
Evidence for a novel regulatory pathway activated by (carba)prostacyclin in preadipose and adipose cells (1996)

Prostacyclin, one of the major prostanoids generated in adipose tissue, has been previously described as an autocrine/paracrine adipogenic effector, acting, in preadipose cells, by means of cAMP and free Ca2+ as cell surface receptor-mediated messengers. The present study presents evidence for the first time that its stable analogue, carbaprostacyclin, is unique among prostanoids in regulating the expression of two differentiation-dependent genes in preadipose and adipose cells in a way distinct from that elicited by its cell surface receptor. This regulation is likely mediated by some member(s) of the peroxisome proliferator-activated receptor family and suggests that prostacyclin behaves as an intracrine effector of adipose cell differentiation.
Foldamers with Heterogeneous Backbones (2008)

The functions performed by proteins and nucleic acids provide the foundation for life. Chemists have recently begun to ask whether it is possible to design synthetic oligomers that approach the structural and functional complexities of these biopolymers. The study of foldamers, non-natural oligomers displaying discrete folding propensities, has demonstrated that there are several synthetic backbones that exhibit biopolymer-like conformational behavior. Early work in this area focused on oligomers comprised of a single type of monomer subunit, but recent efforts have highlighted the potential of mixed or "heterogeneous" backbones to expand the structural and functional repertoire of foldamers. In this Account, we illustrate the promise of heterogeneous backbone foldamers by focusing on examples containing both alpha- and beta-amino acid residues. Some beta-residues bear protein-like side chains, while others have cyclic structures that confer conformational rigidity. The study of heterogeneous backbone foldamers has several advantages over that of their homogeneous backbone counterparts, including access to many new molecular shapes based on variations in the stoichiometries and patterns of the subunit combinations and improved prospects for side chain diversification. Recent efforts to develop alpha/beta-peptide foldamers can be divided into two conceptually distinct classes. The first includes entities prepared using a "block" strategy, in which alpha-peptide segments and beta-peptide segments are combined to form a hybrid oligomer. The second class encompasses designs in which alpha- and beta-amino acid monomers are interspersed in a regular pattern throughout an oligomer sequence. One alpha/beta-peptide helical secondary structure, containing C=O(i)...H-N(i+4) H-bonds analogous to those in the alpha-helix, has been shown via crystallography to form helix bundle quaternary structures. Desirable biological functions have been elicited from alpha/beta-peptide foldamers. Efforts to mimic naturally occurring host-defense alpha-peptides have yielded new antimicrobial agents and have led to a reexamination of the long-held views regarding structure-activity relationships among these alpha-peptides and their analogues. Foldamers offer new platforms for mimicry of the molecular surfaces involved in specific protein-protein recognition events; recent achievements in the preparation of alpha/beta-peptide inhibitors of the protein-protein interactions involved in apoptotic signaling (e.g., between Bcl-xL and pro-apoptotic partners) have revealed the benefits of employing heterogeneous backbones relative to homogeneous backbones for foldamer-based designs. These initial successes in the development of alpha/beta-peptides exhibiting specific biological activities highlight the potential of heterogeneous backbone foldamers for use in biomedical applications and provide guidelines for future studies into new target functions.