gebhart/patrepeval huggingface dataset:
The role of glycogen synthase kinase 3 in the early stages of Alzheimers’ disease (2008)

There are two different types of Alzheimers' disease, familiar Alzheimers' disease (FAD) and Sporadic Alzheimers' disease (SAD), and the origin of the disease could be different in both familial and sporadic cases. In terms of FAD, mutations in three different genes are likely to promote the onset of the disease whereas for SAD, different risk factors might be involved. Nevertheless, downstream of the initial causes of the disease some common factors may be involved. In this review, rather than the differences, we have focused on some of the common features shared by Alzheimers' patients, irrespective of the origin of their disorder. Among these common features, at the molecular level, the activation of the protein kinase GSK3 may be relevant.
Role of the Gastric Pacesetter Potential Defined by Electrical Pacing (1972)

This experiment substantiates the hypothesis that the gastric pacesetter potential sets the pace of gastric contractions. By pacing the gastric pacesetter potential with electrical stimuli during periods of spontaneous and pentagastrin-induced contractile activity, we also paced gastric contractions.
Use of esters of N-hydroxysuccinimide in the synthesis of N-acylamino acids (1967)

Several crystalline N-hydroxysuccinimide esters of short- and long-chain fatty acids have been synthesized. These compounds react with free amino acids to form preferentially N-acylamino acids. The reaction of the N-hydroxysuccinimide esters with hydroxylamine and the behavior of the N-acylamino acids on thin-layer chromatography are described.
Molecular Understanding and Design of Zwitterionic Materials (2014)

Zwitterionic materials have moieties possessing cationic and anionic groups. This molecular structure leads to unique properties that can be the solutions of various application problems. A typical example is that zwitterionic carboxybetaine (CB) and sulfobetaine (SB) materials resist nonspecific protein adsorption in complex media. Considering the vast number of cationic and anionic groups in the current chemical inventory, there are many possible structural variations of zwitterionic materials. The diversified structures provide the possibility to achieve many desired properties and urge a better understanding of zwitterionic materials to provide design principles. Molecular simulations and modeling are a versatile tool to understand the structure-property relationships of materials at the molecular level. This progress report summarizes recent simulation and modeling studies addressing two fundamental questions regarding zwitterionic materials and their applications as biomaterials. First, what are the differences between zwitterionic and nonionic materials? Second, what are the differences among zwitterionic materials? This report also demonstrates a molecular design of new protein-resistant zwitterionic moieties beyond conventional CB and SB based on design principles developed from these simulation studies.
Activation of the hypoxia‐inducible factor pathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors (2003)

Hypoxia-inducible transcription factors (HIF) mediate complex adaptations to reduced oxygen supply, including neoangiogenesis. Regulation of HIF occurs mainly through oxygen-dependent destruction of its alpha subunit. In the presence of oxygen, two HIFalpha prolyl residues undergo enzymatic hydroxylation, which is required for its proteasomal degradation. We therefore tested whether pharmacological activation of HIFalpha by hydroxylase inhibitors may provide a novel therapeutic strategy for the treatment of ischemic diseases. Three distinct prolyl 4-hydroxylase inhibitors-l-mimosine (L-Mim), ethyl 3,4-dihydroxybenzoate (3,4-DHB), and 6-chlor-3-hydroxychinolin-2-carbonic acid-N-carboxymethylamid (S956711)-demonstrated similar effects to hypoxia (0.5% O2) by inducing HIFalpha protein in human and rodent cells. L-Mim, S956711, and, less effectively, 3,4-DHB also induced HIF target genes in cultured cells, including glucose transporter 1 and vascular endothelial growth factor, as well as HIF-dependent reporter gene expression. Systemic administration of L-Mim and S956711 in rats led to HIFalpha induction in the kidney. In a sponge model for angiogenesis, repeated local injection of the inhibitors strongly increased invasion of highly vascularized tissue into the sponge centers. In conclusion, structurally distinct inhibitors of prolyl hydroxylation are capable of inducing HIFalpha and HIF target genes in vitro and in vivo and induce adaptive responses to hypoxia, including angiogenesis.
Influence of DMBA-induced mammary cancer on the liver CPT I, mit HMG-CoA synthase and PPARα mRNA expression in rats fed a low or high corn oil diet (2004)

Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I) and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) enzymes play a key role in regulation of fatty acid oxidation and in ketogenic pathways, respectively. Their expression are regulated by fatty acids mainly by the peroxisome proliferator-activated receptor alpha (PPARalpha). To investigate possible mechanisms through which cancer alters the lipid metabolism, we analyzed by Northern blot, the mRNA relative abundance of these proteins in liver from healthy and DMBA-induced mammary tumor-bearing rats fed a low or high corn oil diet. Serum levels of lipids, body weight and mass were also determined. Whereas mRNA steady-state levels of CPT I and mit HMG-CoA synthase were unaffected by the presence of the extra-hepatic tumor, the cancer state seemed to modify the regulation of the expression of these genes by high fat diet. We hypothesize that putative changes in PPARalpha mRNA levels could have contributed to such alterations. These results, together with changes in serum lipid profiles, body weight and mass, indicate fat mobilization and non-enhanced oxidation rates despite a high-fat feeding. This effect of the cancer state could be related to tumor aggressiveness and suggest a preferential redirection of long-chain fatty acids into energetic and specific pathways of the cancer cells.
Reproducible establishment of hemopoietic supportive stromal cell lines from murine bone marrow. (1989)

Stromal cell lines, designated MS-1, -2, -3, -4, -5, -6, and -7 were established by irradiating the adherent cells in long-term bone marrow cultures with 900-rad x-rays. Two of the cell lines, MS-1 and MS-5, have the capacity to support the growth of hemopoietic stem cells (spleen colony-forming cells and granulocyte-macrophage colony-forming cells) for greater than 2 months in vitro. These two cell lines were alkaline phosphatase-, peroxidase-, and factor VIII-negative and positive for periodic acid-Schiff and nonspecific esterase. Extracellular matrix proteins such as fibronectin, laminin, and collagen type I were produced by these two cell lines. Neither MS-1 cell- nor MS-5 cell-conditioned medium supported the growth of hemopoietic stem cells, and hemopoietic stem cells were found preferentially to be under and on MS-1 and MS-5 layers rather than in suspension. Close contact with the MS-1 cell layer or the MS-5 cell layer appears to be essential in maintaining hemopoiesis in vitro. Conditioned media from MS-1 cells and MS-5 cells stimulated granulocyte colony formation from murine bone marrow cells in semisolid culture.
Protective anti-reovirus monoclonal antibodies and their effects on viral pathogenesis (1993)

We used a recently isolated and characterized panel of monoclonal antibodies (MAbs) specific for cross-reactive determinants on reovirus outer capsid proteins to define mechanisms of antibody-mediated protection in vivo. We studied the capacities of MAbs to protect against lethal infection with reoviruses which differ in site of primary replication, route of spread, and central nervous system tropism. We found the following. (i) MAbs specific for each of the viral outer capsid proteins (sigma 1, sigma 3, and mu 1) and the core spike protein (lambda 2) were protective under certain circumstances. (ii) In vitro properties of MAbs, including isotype, neutralization of viral infectivity, inhibition of virus-induced hemagglutination, and avidity of binding, were poorly predictive of the capacities of MAbs to protect in vivo. (iii) MAbs did not act at a single stage during pathogenesis to mediate protection; instead, protective MAbs were capable of altering a variety of stages in reovirus pathogenesis. (iv) MAbs protective against one reovirus also protected against other reoviruses that utilized different pathogenetic strategies, suggesting that the viral epitope bound by an antibody rather than the pathogenetic strategy employed by the virus is a critical determinant of antibody-mediated protection in vivo. (v) A prominent mechanism of protective MAb action is inhibition of viral spread through nerves from a site of primary replication (e.g., the intestine or muscle tissue) to the central nervous system.
Symptomatische Therapie der Alzheimer-Demenz (2002)

No causal treatment or highly effective preventive strategies are available for Alzheimer's disease to date. Symptomatic measures are still essential to improve cognitive and behavioural deficits. Acetylcholinesterase inhibitors, the NMDA-antagonist memantine and the phytopharmaco ginkgo biloba are currently the substances most extensively studied and most widely used to improve cognition and activities of daily living. Behavioural disturbances oftentimes respond to antidementia drugs, but may demand specific treatment with neuroleptics, antidepressants, stabilizers and other substances.
An Escherichia coli host strain useful for efficient overproduction of cloned gene products with NaCl as the inducer (1997)

Salt-induced overexpression of genes cloned downstream of the phage T7 phi10 promoter was demonstrated in an Escherichia coli strain (GJ1158) which carries a single chromosomally integrated copy of the gene for phage T7 RNA polymerase under transcriptional control of the cis-regulatory elements of the osmoresponsive proU operon. Plasmids that have been constructed to obtain overproduction of individual target gene products in strain BL21(DE3) (by addition of isopropyl-beta-D-thiogalactopyranoside as an inducer) can directly be transformed into GJ1158. The NaCl induction regimen was also shown to be associated with a decreased propensity for sequestration of overexpressed target proteins within insoluble inclusion bodies.
Analysis of the Noncoding Regions of Measles Virus Strains in the Edmonston Vaccine Lineage (2001)

The noncoding sequence of five Edmonston vaccine viruses (AIK-C, Moraten, Rubeovax, Schwarz, and Zagreb) and those of a low-passage Edmonston wild-type (wt) measles virus have been determined and compared. Twenty-one nucleotide positions were identified at which Edmonston wt and one or more vaccine strains differed. The location of some of these nucleotide substitutions suggests that they may influence the efficiency of mRNA synthesis, processing, and translation, as well as genome replication and encapsidation. Five nucleotide substitutions were conserved in all of the vaccine strains. Two of these were in the genomic 3'-terminal transcriptional control region and could affect RNA synthesis or encapsidation. Three were found within the 5'-untranslated region of the F mRNA, potentially altering translation control sequences. The remaining vaccine virus base changes were found in one to four vaccine strains. Their genomic localization suggests that some may modify cis-acting regulatory domains, including the Kozak consensus element of the P and M genes, the F gene-end signal, and the F mRNA 5'-untranslated sequence.
Fast implementations of reconstruction-based scatter compensation in fully 3D SPECT image reconstruction (1998)

Accurate scatter compensation in SPECT can be performed by modelling the scatter response function during the reconstruction process. This method is called reconstruction-based scatter compensation (RBSC). It has been shown that RBSC has a number of advantages over other methods of compensating for scatter, but using RBSC for fully 3D compensation has resulted in prohibitively long reconstruction times. In this work we propose two new methods that can be used in conjunction with existing methods to achieve marked reductions in RBSC reconstruction times. The first method, coarse-grid scatter modelling, significantly accelerates the scatter model by exploiting the fact that scatter is dominated by low-frequency information. The second method, intermittent RBSC, further accelerates the reconstruction process by limiting the number of iterations during which scatter is modelled. The fast implementations were evaluated using a Monte Carlo simulated experiment of the 3D MCAT phantom with 99mTc tracer, and also using experimentally acquired data with 201Tl tracer. Results indicated that these fast methods can reconstruct, with fully 3D compensation, images very similar to those obtained using standard RBSC methods, and in reconstruction times that are an order of magnitude shorter. Using these methods, fully 3D iterative reconstruction with RBSC can be performed well within the realm of clinically realistic times (under 10 minutes for 64 x 64 x 24 image reconstruction).
High Field Magnetic Resonance Imaging Evaluation of Superparamagnetic Iron Oxide Nanoparticles in a Permanent Rat Myocardial Infarction (2003)

Nanoparticle injection made it possible to discriminate normal from infarcted myocardium on T2-weighted images. However, the high magnetic field prevented the visualization of the T1 effect of SPIO nanoparticles.
The Neurofibromatosis Type 2 Gene Product, merlin, Reverses the F-Actin Cytoskeletal Defects in Primary Human Schwannoma Cells (2002)

Schwannoma tumors, which occur sporadically and in patients with neurofibromatosis, account for 8% of intracranial tumors and can only be treated by surgical removal. Most schwannomas have biallelic mutations in the NF2 tumor suppressor gene. We previously showed that schwannoma-derived Schwann cells exhibit membrane ruffling and aberrant cell spreading when plated onto laminin, indicative of fundamental F-actin cytoskeletal defects. Here we expand these observations to a large group of sporadic and NF2-related tumors and extend them to schwannomatosis-derived tumors. Mutation at NF2 correlated with F-actin abnormalities, but the extent of morphological change did not correlate with the type of NF2 mutation. We used a recently described molecular strategy, TAT-mediated protein transfer, to acutely introduce the NF2 protein, merlin, into primary human schwannoma cells in an attempt to reverse the cytoskeletal phenotype. Abnormal ruffling and cell spreading by cells with identified NF2 mutations were rapidly reversed by introduction of TAT-merlin. The effect is specific to TAT-merlin isoform 1, the growth-suppressive isoform of merlin. TAT-merlin isoform 2, a TAT-merlin mutant (L64P), and merlin lacking TAT were ineffective in reversing the cytoskeletal phenotype. Results show that merlin isoform 1 is sufficient to restore normal actin organization in NF2-deficient human tumor cells, demonstrating a key role for merlin in the NF2 phenotype. These results lay the foundation for epigenetic complementation studies in NF2 mouse models and possibly for experiments to evaluate the utility of merlin transduction into patients as protein therapy.
Degradation of xenobiotic compounds by lignin-degrading white-rot fungi: enzymology and mechanisms involved. (2005)

White-rot fungi (WRF) are ubiquitous in nature with their natural ability to compete and survive. WRF are the only organisms known to have the ability to degrade and mineralize recalcitrant plant polymer lignin. Their potential to degrade second most abundant carbon reserve material lignin on the earth make them important link in global carbon cycle. WRF degrade lignin by its unique ligninolytic enzymatic machinery including lignin peroxidase, manganese peroxidase, laccase, cellobiose dehydrogenase, H2O2-generating enzymes, etc. The ligninolytic enzymes system is non-specific, extracellular and free radical based that allows them to degrade structurally diverse range of xenobiotic compounds. Lignin peroxidase and manganese peroxidase carry out direct and indirect oxidation as well as reduction of xenobiotic compounds. Indirect reactions involved redox mediators such as veratryl alcohol and Mn2+. Reduction reactions are carried out by carboxyl, superoxide and semiquinone radicals, etc. Methylation is used as detoxification mechanism by WRF. Highly oxidized chemicals are reduced by transmembrane redox potential. Degradation of a number of environmental pollutants by ligninolytic system of white rot fungi is described in the present review.
Targeted Single-Wall Carbon Nanotube-Mediated Pt(IV) Prodrug Delivery Using Folate as a Homing Device (2008)

Most low-molecular-weight platinum anticancer drugs have short blood circulation times that are reflected in their reduced tumor uptake and intracellular DNA binding. A platinum(IV) complex of the formula c, c, t-[Pt(NH 3) 2Cl 2(O 2CCH 2CH 2CO 2H)(O 2CCH 2CH 2CONH-PEG-FA)] ( 1), containing a folate derivative (FA) at an axial position, was prepared and characterized. Folic acid offers a means of targeting human cells that highly overexpress the folate receptor (FR). Compound 1 was attached to the surface of an amine-functionalized single-walled carbon nanotube (SWNT-PL-PEG-NH 2) through multiple amide linkages to use the SWNTs as a "longboat delivery system" for the platinum warhead, carrying it to the tumor cell and releasing cisplatin upon intracellular reduction of Pt(IV) to Pt(II). The ability of SWNT tethered 1 to destroy selectively FR(+) vs FR(-) cells demonstrated its ability to target tumor cells that overexpress the FR on their surface. That the SWNTs deliver the folate-bearing Pt(IV) cargos into FR(+) cancer cells by endocytosis was demonstrated by the localization of fluorophore-labeled SWNTs using fluorescence microscopy. Once inside the cell, cisplatin, formed upon reductive release from the longboat oars, enters the nucleus and reacts with its target nuclear DNA, as determined by platinum atomic absorption spectroscopy of cell extracts. Formation of the major cisplatin 1,2-intrastrand d(GpG) cross-links on the nuclear DNA was demonstrated by use of a monoclonal antibody specific for this adduct. The SWNT-tethered compound 1 is the first construct in which both the targeting and delivery moieties have been incorporated into the same molecule; it is also the first demonstration that intracellular reduction of a Pt(IV) prodrug leads to the cis-{Pt((NH 3) 2} 1,2-intrastrand d(GpG) cross-link in nuclear DNA.
Hydrogen gas sensor using Pd nanowires electro-deposited into anodized alumina template (2006)

This paper demonstrates a new kind of hydrogen sensor using palladium (Pd) nanowires. Hydrogen sensors using Pd metal have usually been utilizing the incremental change in electrical resistance of Pd upon hydrogen incorporation. Unlike the conventional Pd hydrogen sensors, however, the electrical resistance of the present Pd nanowire sensor decreases when hydrogen is incorporated into Pd nanowires. It is considered to be due to swelling of the nanowires as the result of hydrogen incorporation and subsequent narrowing of gaps between the nanowires, even though each nanowire should have had the higher resistance inherently. Because of extraordinarily high surface area of nanowires, the performance of sensing the hydrogen concentration was found to superior by far to the conventional Pd sensors. The response and recovery times are quite fast to be about 0.7 and 20 s, respectively and the sensing range of 0.2 ~ 1% 1% hydrogen concentration is suitable for the hydrogen safety sensors. The sensor introduced in this paper is unique with regard to both the sensing mechanism and performance
Essential Role of Gab1 for Signaling by the C-Met Receptor in Vivo (2000)

The docking protein Gab1 binds phosphorylated c-Met receptor tyrosine kinase directly and mediates signals of c-Met in cell culture. Gab1 is phosphorylated by c-Met and by other receptor and nonreceptor tyrosine kinases. Here, we report the functional analysis of Gab1 by targeted mutagenesis in the mouse, and compare the phenotypes of the Gab1 and c-Met mutations. Gab1 is essential for several steps in development: migration of myogenic precursor cells into the limb anlage is impaired in Gab1-/- embryos. As a consequence, extensor muscle groups of the forelimbs are virtually absent, and the flexor muscles reach less far. Fewer hindlimb muscles exist, which are smaller and disorganized. Muscles in the diaphragm, which also originate from migratory precursors, are missing. Moreover, Gab1-/- embryos die in a broad time window between E13.5 and E18.5, and display reduced liver size and placental defects. The labyrinth layer, but not the spongiotrophoblast layer, of the placenta is severely reduced, resulting in impaired communication between maternal and fetal circulation. Thus, extensive similarities between the phenotypes of c-Met and HGF/SF mutant mice exist, and the muscle migration phenotype is even more pronounced in Gab1-/-:c-Met+/- embryos. This is genetic evidence that Gab1 is essential for c-Met signaling in vivo. Analogy exists to signal transmission by insulin receptors, which require IRS1 and IRS2 as specific docking proteins.
Nucleotide sequence of the repressor gene of the RA1 tetracycline resistance determinant: structural and functional comparison with three related Tet repressor genes (1984)

The tetracycline resistance determinant of RA1 was cloned. It consists of at least two genes oriented with opposite polarity, tetA for resistance and tetR for regulation. The transcriptional control sequence was identified and analyzed. It consists of overlapping promotors with divergent orientation and a tandem arrangement of operators. Nucleotide sequencing revealed two open reading frames. One codes for a protein which was identified as a Tet repressor by comparing its primary structure with those of other Tet repressors. The RA1 tetR gene codes for 218 amino acids with a calculated molecular weight of 24.4 kDa. In the primary sequence of the RA1-, pSC101-, Tn10-, and RP1/Tn1721-encoded Tet repressors, 36% of the amino acids are identical. This homology is clustered within the first 150 amino acids, 49% of which are identical among all four proteins. These results are discussed with respect to their structure and function in comparison to other DNA binding proteins.
Subdivision of Large Introns in Drosophila by Recursive Splicing at Nonexonic Elements (2005)

Many genes with important roles in development and disease contain exceptionally long introns, but special mechanisms for their expression have not been investigated. We present bioinformatic, phylogenetic, and experimental evidence in Drosophila for a mechanism that subdivides many large introns by recursive splicing at nonexonic elements and alternative exons. Recursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns >20 kb, but they are found only at the expected frequency on the antisense strands, and they are underrepresented within introns <10 kb. The predicted sites in long introns are highly conserved between Drosophila melanogaster and Drosophila pseudoobscura, despite extensive divergence of other sequences within the same introns. These patterns of enrichment and conservation indicate that recursive splice sites are advantageous in the context of long introns. Experimental analyses of in vivo processing intermediates and lariat products from four large introns in the unrelated genes kuzbanian, outspread, and Ultrabithorax confirmed that these introns are removed by a series of recursive splicing steps using the predicted nonexonic sites. Mutation of nonexonic site RP3 within Ultrabithorax also confirmed that recursive splicing is the predominant processing pathway even with a shortened version of the intron. We discuss currently known and potential roles for recursive splicing.