gebhart/patrepeval huggingface dataset:
Single gene substitution rotavirus reassortants containing the major neutralization protein (VP7) of human rotavirus serotype 4 (1986)

A series of reassortants was isolated from coinfection of cell cultures with wild-type bovine rotavirus (UK strain [serotype 6]) or rhesus rotavirus (strain MMU18006 [serotype 3]) and a tissue culture-adapted human rotavirus strain, ST3 (serotype 4). Monospecific antiserum or a set of monoclonal antibodies to the major outer capsid neutralization glycoprotein, VP7, of the animal rotavirus parent was used to select for reassortants with human rotavirus serotype 4 neutralization specificity. The majority of reassortants contained only gene 9 of the human rotavirus parent, ST3, whereas the remaining genes were derived from the animal rotavirus parent. These single human rotavirus gene substitution reassortants were neutralized to high titer by hyperimmune serum directed at ST3, thus demonstrating that gene 9 of ST3 codes for the major neutralization protein of this strain. Moreover, these single gene substitution, reassortants were also neutralized to low titer by antiserum directed at their animal rotavirus parent, probably because they derived gene 4, which codes for another outer capsid protein, VP3, from their animal rotavirus parent. None of the reassortants derived gene 4, which had previously been shown to be responsible for host range restriction of human rotaviruses in tissue culture, from ST3, despite the fact that the ST3 strain used for gene reassortment had been tissue culture adapted.
Genomic and proteomic microglial profiling: pathways for neuroprotective inflammatory responses following nerve fragment clearance and activation (2007)

Microglia, a primary immune effector cell of the central nervous system (CNS) affects homeostatic, neuroprotective, regenerative and degenerative outcomes in health and disease. Despite these broad neuroimmune activities linked to specific environmental cues, a precise cellular genetic profile for microglia in the context of disease and repair has not been elucidated. To this end we used nucleic acid microarrays, proteomics, immunochemical and histochemical tests to profile microglia in neuroprotective immune responses. Optic and sciatic nerve (ON and SN) fragments were used to stimulate microglia in order to reflect immune consequences of nervous system injury. Lipopolysaccharide and latex beads-induced microglial activation served as positive controls. Cytosolic and secreted proteins were profiled by surface enhanced laser desorption ionization-time of flight (SELDI-TOF) ProteinChip, 1D and 2D difference gel electrophoresis. Proteins were identified by peptide sequencing with tandem mass spectrometry, ELISA and western blot tests. Temporal expression of pro-inflammatory cytokines, antioxidants, neurotrophins, and lysosomal enzyme expression provided, for the first time, a unique profile of secreted microglia proteins with neuroregulatory functions. Most importantly, this molecular and biochemical signature supports a broad range of microglial functions for debris clearance and promotion of neural repair after injury.
Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. (1988)

A detailed study of the qualitative and quantitative composition of bile acids in human fetal gallbladder bile is described. Bile was collected during early gestation (weeks 16-19) and analyzed by gas chromatography and mass spectrometry, fast atom bombardment ionization mass spectrometry, and high performance liquid chromatography. Bile acids were separated into different conjugate groups by chromatography on the lipophilic anion exchange gel, diethylaminohydroxypropyl Sephadex LH-20. Quantitatively more than 80% of the bile acids were secreted into bile conjugated to taurine. Unconjugated bile acids and glycine conjugates accounted for 5-10% of the total biliary bile acids. Bile acid sulfates were present only in trace amounts indicating that quantitatively sulfation is not an important pathway in bile acid metabolism during development. Total biliary bile acid concentrations were low (0.1-0.4 mM) when compared to reported values for adult bile (greater than 10 mM). Chenodeoxycholic acid was the major biliary bile acid and exceeded cholic acid concentrations by 1.43-fold indicating either a relative immaturity in 12 alpha-hydroxylase activity during early life or a dominance of alternative pathways for chenodeoxycholic acid synthesis. A relatively large proportion of the biliary bile acids comprised metabolites not found in adult bile. The presence of relatively high proportions of hyocholic acid (often greater than cholic acid) and several 1 beta-hydroxycholanoic acid isomers indicates that C-1 and C-6 hydroxylation are important pathways in bile acid synthesis during development. We describe, for the first time, evidence for the existence of a C-4 hydroxylation pathway in the metabolism of bile acids, which may be unique to early human development. Mass spectrometry was used to confirm the identification of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic and 3 alpha,4 beta-dihydroxy-5 beta-cholanoic acids. Quantitatively, these C-4 hydroxylated bile acids accounted for 5-15% of the total biliary bile acids of the fetus, suggesting that C-4 hydroxylation is quantitatively an important pathway in the bile acid metabolism during early life.
Creation of a Superhydrophobic Surface from an Amphiphilic Polymer (2003)

Poly(vinyl alcohol), an inherently amphiphilic material, can act as a superhydrophobic surface when deposited as nanofibers on an aluminum oxide membrane (see picture). The arrangement of the hydrophobic and hydrophilic functional groups, both in the surface and within the interior of the material, has a marked effect on surface activity. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2003/z19807_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Lipid Rafts Mediate Ultraviolet Light‐induced Fas Aggregation in M624 Melanoma Cells (2006)

Ultraviolet light (UV) induces aggregation of Fas-receptor through a Fas-ligand-independent pathway. However, the mechanism of ultraviolet light-induced Fas-receptor aggregation is not known. In this report, we show that lipid rafts mediate ultraviolet light-induced aggregation of Fas. Our data show that UV induces a redistribution of Fas-receptor in a 25-5% Optiprep continuous gradient. The amount of Fas-receptorS is significantly increased in a gradient fraction that contain lipid rafts and is associated with an increase of FADD and caspase-8. Our data also show that the active dimeric form of caspase-8 (p44/p41) is increased in the lipid raft fraction. In addition, our data show that cholesterol, a major component of lipid rafts, is significantly reduced in only the lipid raft fractions after UV-irradiation. However, ceramide, another major lipid raft component, is increased evenly in all gradient fractions after UV-irradiation. These results suggest that UV alters the composition of major lipid raft components, which leads to the recruitment of Fas-receptor and FADD, with subsequent activation of caspase-8. Based on our results, we propose a novel mechanism by which UV induces apoptosis through a membrane lipid raft-mediated signaling pathway.
Expression in Escherichia coli of rat neurotensin receptor fused to membrane proteins from the membrane-containing bacteriophage PRD1. (1994)

Bacteriophage PRD1 is a membrane-containing phage which could be used for expression of foreign membrane proteins such as neurotensin receptor (NTR), a seven-helix G-protein coupled receptor. To ensure recognition of NTR by the phage system six different fusion genes were constructed, each encoding a different phage integral membrane protein fused to the N-terminus of NTR, and expression of the fusion proteins in Escherichia coli was analysed. Here we report the identification of two fusion constructs that retained the function of NTR in E. coli. This provides the basis to develop the phage system as a heterologous expression system for seven-helix receptors.
Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. (1994)

Apolipoprotein E3-Leiden (APOE*3-Leiden) transgenic mice have been used to study the effect of different cholesterol-containing diets on the remnant lipoprotein levels and composition and on the possible concurrent development of atherosclerotic plaques. On high fat/cholesterol (HFC) diet, the high expressing lines 2 and 181 developed severe hypercholesterolemia (up to 40 and 60 mmol/liter, respectively), whereas triglyceride levels remained almost normal when compared with regular mouse diet. The addition of cholate increased the hypercholesterolemic effect of this diet. In lines 2 and 181, serum levels of apo E3-Leiden also increased dramatically upon cholesterol feeding (up to 107 and 300 mg/dl, respectively). In these high expressing APOE*3-Leiden transgenic mice, the increase in both serum cholesterol and apo E3-Leiden occurred mainly in the VLDL/LDL-sized fractions, whereas a considerable increase in large, apo E-rich HDL particles also occurred. In contrast to the high expressing lines, the low expressing line 195 reacted only mildly upon HFC diet. On HFC diets, the high expresser APOE*3-Leiden mice developed atherosclerotic lesions in the aortic arch, the descending aorta, and the carotid arteries, varying from fatty streaks containing foam cells to severe atherosclerotic plaques containing cholesterol crystals, fibrosis, and necrotic calcified tissue. Quantitative evaluation revealed that the atherogenesis is positively correlated with the serum level of cholesterol-rich VLDL/LDL particles. In conclusion, with APOE*3-Leiden transgenic mice, factors can be studied that influence the metabolism of remnant VLDL and the development of atherosclerosis.
157. Synthetic antimalarials. Part XXVII. Some derivatives of phthalazine, quinoxaline, and isoquinoline (1948)

R. D. Haworth and S. Robinson, J. Chem. Soc., 1948, 777 DOI: 10.1039/JR9480000777
A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET. (2004)

18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.
Isolation and characterization of ftsZ alleles that affect septal morphology (1992)

The ftsZ gene encodes an essential cell division protein that specifically localizes to the septum of dividing cells. In this study we characterized the effects of the ftsZ2(Rsa) mutation on cell physiology. We found that this mutation caused an altered cell morphology that included minicell formation and an increased average cell length. In addition, this mutation caused a temperature-dependent effect on cell lysis. During this investigation we fortuitously isolated a novel temperature-sensitive ftsZ mutation that consisted of a 6-codon insertion near the 5' end of the gene. This mutation, designated ftsZ26(Ts), caused an altered polar morphology at the permissive temperature and blocked cell division at the nonpermissive temperature. The altered polar morphology resulted from cell division and correlated with an altered geometry of the FtsZ ring. An intragenic cold-sensitive suppressor of ftsZ26(Ts) that caused cell lysis at the nonpermissive temperature was isolated. These results support the hypothesis that the FtsZ ring determines the division site and interacts with the septal biosynthetic machinery.
A Tutorial on Parametric Image Registration (2007)

A tutorial, with all the details related to the parametric image registration task, has been presented. Also two new methods (Method 1 and Method 3) are presented besides the classical method to compute derivatives of images. Method 1 computes the image derivatives faster than the other two methods, but it does not give accurate estimations. Methods 2 and 3 take more time because they compute derivatives of the transformed image (at each iteration) while method 1 computes derivatives of the input image only once. Method 3 is an improved version of method 2 because it takes into account the exact derivatives needed. However the classical method 2, reported in the literature is the same as the method 3 under translations. Experiments confirm the poor estimation computed by method 2 when rotations, scaling, or an affine transformation are involved. In general, derivatives of images with big values are recommended when the right transformation is far away from identity, in other words, when big translations, rotations, scaling, etc., are involved. In contrast, small values of are recommended to get more accurate results. In fact, we mixed both strategies, big values at first and then small values.
Binding of aflatoxin B1 to DNA inhibited by ajoene and diallyl sulfide. (1992)

Components of garlic have been shown to inhibit a variety of tumors induced by chemical carcinogens. In this study we determined the effects of ajoene and diallyl sulfide (DAS), two organosulfur compounds of garlic, on the metabolism and DNA binding of aflatoxin B1 (AFB1) using rat liver 9000Xg supernatant as the metabolic activation system. Organosoluble and water-soluble metabolites of [3H]AFB1 were isolated by reverse-phase high performance liquid chromatography (HPLC). The effects of ajoene and DAS on glutathione-S-transferase (GST) were determined using 1-chloro-2,4-dinitrobenzene as the substrate. Ajoene and DAS at 100 mg/ml inhibited [3H]AFB1 binding to calf thymus DNA and adduct formation. They decreased the formation of both organosoluble and water-soluble metabolites of [3H]AFB1. Neither compound significantly affected GST activity. These results indicate that ajoene and DAS affected AFB1 metabolism and DNA binding by inhibiting phase I enzymes and may therefore be considered as potential cancer chemopreventive agents.
Definition of a sequence, RYVVLPR, within laminin peptide F-9 that mediates metastatic fibrosarcoma cell adhesion and spreading. (1990)

A synthetic peptide from the inner globule of the B1 chain of laminin, termed peptide F-9 (RYVVLPRPVCFEKGMNYTVR; residues 641-660), has been shown to have heparin-binding and cell adhesion-promoting activities for diverse cell types (Charonis et al., J. Cell. Biol., 107: 1253-1260, 1988). In this study, the metastatic murine fibrosarcoma cell line, UV-2237-MM, adhered and spread on surfaces coated with laminin and peptide F-9 in a concentration- and time-dependent fashion. Cells migrated toward laminin in Boyden microchemotaxis chambers but not toward peptide F-9. However, exogenous soluble peptide F-9 inhibited both the adhesion and migration of cells toward laminin. Polyclonal antibodies raised against peptide F-9 were capable of inhibiting laminin-mediated cell adhesion and migration. Peptide F-9 is located 265 residues from CDPGYIGSR, another sequence on the B1 chain of laminin which has been reported by others to promote cell adhesion (Graft et al., Cell, 48: 989-996, 1987). In contrast to peptide F-9, various control peptides including CDPGYIGSR did not promote the adhesion, spreading, or migration of the UV-2237-MM fibrosarcoma cells. In addition, neither exogenous peptide CDPGYIGSR nor antibodies raised against peptide CDPGYIGSR were capable of inhibiting laminin-mediated cell adhesion or migration. These results indicate that peptide F-9, but not peptide CDPGYIGSR, represents a major fibrosarcoma cell adhesion-promoting domain on intact laminin. A series of overlapping peptides were synthesized which contained various portions of the parent peptide F-9. The use of these peptides in cell adhesion assays demonstrated that the sequence RYVVLPR from the amino terminus of peptide F-9 was essential for cell adhesion-promoting activity.
Coupled alteration of transcription and splicing by a single oncogene: Boosting the effect on cyclin D1 activity (2008)

In cancer cells, gene expression is altered at the levels of transcription and mRNA maturation, with many splice variants being associated with cancer. Splicing is tightly connected to transcription and can be affected by transcription elongation dynamics. Moreover, various transcriptional coregulators that are altered in cancer, such as the proto-oncogene EWS, are thought to play a role in splicing. A recent study shows that an alteration of EWS in Ewing sarcoma alters the dynamics of RNA polymerase II over the CCND1 proto-oncogene encoding cyclin D1, leading to an increase in its transcription and to an alteration of splicing that results in high levels of the oncogenic cyclin D1b splice isoform. The cyclin D1b isoform is highly expressed in Ewing sarcoma cells and tumors and stimulates Ewing sarcoma cell growth. Thus, alterations of transcriptional regulators in disease may lead to splicing alterations. We review these data and discuss how this concept may apply to various factors that are altered in cancer.
Overproduction of the yeast STE12 protein leads to constitutive transcriptional induction. (1990)

Haploid a and alpha cells of the yeast Saccharomyces cerevisiae respond to the pheromones alpha- and a-factor, respectively, by increasing transcription of inducible genes, arresting cell division, and forming cell-surface projections. These responses are dependent on the activity of several genes, including STE12, whose product binds to the pheromone response element located within the regulatory DNA sequences of inducible genes. We assayed the effects of overproducing the STE12 protein in both STE+ cells, as well as ste2, ste7, and ste11 mutant cells. We find that overproduction leads to increased transcription of pheromone-inducible genes and is able to suppress the mating defect of the ste mutants. These results suggest that one effect of pheromone treatment may be to increase the ability of the STE12 protein to activate transcription. In addition, we observed that cells cannot tolerate very high levels of the STE12 protein, and many arrest in G1 with a large size and morphological changes. Thus, constitutively high-level transcription of pheromone-inducible genes causes cells to display some features similar to treatment with pheromone.
src homology 2 domain–containing tyrosine phosphatase SHP-1 controls the development of allergic airway inflammation (2003)

Th2 cells are generated from naive CD4 T cells upon T cell receptor (TCR) recognition of antigen and IL-4 stimulation and play crucial roles in humoral immunity against infectious microorganisms and the pathogenesis of allergic and autoimmune diseases. A tyrosine phosphatase, SHP-1, that contains src homology 2 (SH2) domains is recognized as a negative regulator for various intracellular signaling molecules, including those downstream of the TCR and the IL-4 receptor. Here we assessed the role of SHP-1 in Th1/Th2 cell differentiation and in the development of Th2-dependent allergic airway inflammation by using a natural SHP-1 mutant, the motheaten mouse. CD4 T cells appear to develop normally in the heterozygous motheaten (me/+) thymus even though they express decreased amounts of SHP-1 (about one-third the level of wild-type thymus). The me/+ naive splenic CD4 T cells showed enhanced activation by IL-4 receptor-mediated signaling but only marginal enhancement of TCR-mediated signaling. Interestingly, the generation of Th2 cells was increased and specific cytokine production of mast cells was enhanced in me/+ mice. In an OVA-induced allergic airway inflammation model, eosinophilic inflammation, mucus hyperproduction, and airway hyperresponsiveness were enhanced in me/+ mice. Thus, SHP-1 may have a role as a negative regulator in the development of allergic responses, such as allergic asthma.
Attachment site recognition and regulation of directionality by the serine integrases (2013)

Serine integrases catalyze the integration of bacteriophage DNA into a host genome by site-specific recombination between 'attachment sites' in the phage (attP) and the host (attB). The reaction is highly directional; the reverse excision reaction between the product attL and attR sites does not occur in the absence of a phage-encoded factor, nor does recombination occur between other pairings of attachment sites. A mechanistic understanding of how these enzymes achieve site-selectivity and directionality has been limited by a lack of structural models. Here, we report the structure of the C-terminal domains of a serine integrase bound to an attP DNA half-site. The structure leads directly to models for understanding how the integrase-bound attP and attB sites differ, why these enzymes preferentially form attP × attB synaptic complexes to initiate recombination, and how attL × attR recombination is prevented. In these models, different domain organizations on attP vs. attB half-sites allow attachment-site specific interactions to form between integrase subunits via an unusual protruding coiled-coil motif. These interactions are used to preferentially synapse integrase-bound attP and attB and inhibit synapsis of integrase-bound attL and attR. The results provide a structural framework for understanding, testing and engineering serine integrase function.
Expression of Human nPTB Is Limited by Extreme Suboptimal Codon Content (2008)

Our results provide a striking illustration of the importance of mRNA codon content in determining levels of protein expression, even within cells of the natural host species.
An improved method for localizing electric brain dipoles (1990)

Methods for localizing electrical dipolar sources in the brain differ from one another by the models they use to represent the head, the specific formulas used in the calculation of the scalp potentials, the way that the reference electrode is treated, and by the algorithm employed to find the least-squares fit between the measured and calculated EEG potentials. The model presented here is based on some of the most advanced features found in other models, and on some improvements. The head is represented by a three-layer spherical model. The potential on any point on the scalp due to any source is found by a closed formula, which is not based on matrix rotations. The formulas will accept any surface electrode as the reference electrode. The least-squares procedure is based on optimal dipoles, reducing the number of unknowns in the iterations from six to three. The new method was evaluated by localizing five implanted dipolar sources in human sensorimotor cortex. The distances between the locations of the sources as calculated by the method, and the actual locations were between 0.4 and 2.0 cm. The sensitivity of the method to uncertainties encountered whenever a real head has to be modeled by a three-layer model has also been assessed.
Intracochlear drug delivery systems (2011)

Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases.