gebhart/patrepeval huggingface dataset:
Structural diversity in twin-arginine signal peptide-binding proteins (2007)

The twin-arginine transport (Tat) system is dedicated to the translocation of folded proteins across the bacterial cytoplasmic membrane. Proteins are targeted to the Tat system by signal peptides containing a twin-arginine motif. In Escherichia coli, many Tat substrates bind redox-active cofactors in the cytoplasm before transport. Coordination of cofactor insertion with protein export involves a "Tat proofreading" process in which chaperones bind twin-arginine signal peptides, thus preventing premature export. The initial Tat signal-binding proteins described belonged to the TorD family, which are required for assembly of N- and S-oxide reductases. Here, we report that E. coli NapD is a Tat signal peptide-binding chaperone involved in biosynthesis of the Tat-dependent nitrate reductase NapA. NapD binds tightly and specifically to the NapA twin-arginine signal peptide and suppresses signal peptide translocation activity such that transport via the Tat pathway is retarded. High-resolution, heteronuclear, multidimensional NMR spectroscopy reveals the 3D solution structure of NapD. The chaperone adopts a ferredoxin-type fold, which is completely distinct from the TorD family. Thus, NapD represents a new family of twin-arginine signal-peptide-binding proteins.
623. The synthesis of amino-sugars from glycopyranosiduloses (1965)

P. M. Collins and W. G. Overend, J. Chem. Soc., 1965, 3448 DOI: 10.1039/JR9650003448
Interaction between human albumin polymers and the envelope polypeptide of hepatitis B virus (P31) containing the translation product of the pre-S2 region. (1987)

Two preparations of human serum albumin (Cohn fraction V), when subjected to high-performance liquid chromatography, were found to contain albumin polymers with molecular sizes of 35 X 10(4) daltons or greater (breakthrough fraction), as well as tetramers, trimers and dimers. They bound to the envelope polypeptide of hepatitis B virus composed of translation products of the pre-S2 region and the S gene (P31), carrying the receptor for polymerized human serum albumin, with an activity increasing in parallel with the degree polymerization.
Wide Distribution of a High-Virulence Borrelia burgdorferi Clone in Europe and North America (2008)

The A and B clones of Borrelia burgdorferi sensu stricto, distinguished by outer surface protein C (ospC) gene sequences, are commonly associated with disseminated Lyme disease. To resolve phylogenetic relationships among isolates, we sequenced 68 isolates from Europe and North America at 1 chromosomal locus (16S-23S ribosomal RNA spacer) and 3 plasmid loci (ospC,dbpA, and BBD14). The ospC-A clone appeared to be highly prevalent on both continents, and isolates of this clone were uniform in DNA sequences, which suggests a recent trans-oceanic migration. The genetic homogeneity of ospC-A isolates was confirmed by sequences at 6 additional chromosomal housekeeping loci (gap, alr, glpA, xylB, ackA, and tgt). In contrast, the ospC-B group consists of genotypes distinct to each continent, indicating geographic isolation. We conclude that the ospC-A clone has dispersed rapidly and widely in the recent past. The spread of the ospC-A clone may have contributed, and likely continues to contribute, to the rise of Lyme disease incidence.
Circulating Adhesion Molecules VCAM-1, ICAM-1, and E-selectin in Carotid Atherosclerosis and Incident Coronary Heart Disease Cases (1997)

These data indicate that plasma levels of ICAM-1 and E-selectin may serve as molecular markers for atherosclerosis and the development of CHD.
Pattern Formation in a Complex Reaction System by Chemomechanical Coupling (2003)

In an experimental study of the polyacrylamide-methylene blue-sulfide-oxygen (PA-MBO) sytem a variety of concentration patterns have been observed. Initially, stripes or hexagons form. The latter transform to chevrons or white-eye patterns. Honeycombs are a third type of structure that develops from either white-eye or hexagonal patterns. For hexagons, the pattern wavelength shows a nearly proportional dependence on the height of the reaction layer. The motion of small tracer particles serve to monitor physical changes within the medium. There are three distinct phases of particle movement. The first one is caused by hydrodynamic flows in the pre-gel solution, whereas the third, and possibly the second, phase arises from localized volume changes within the gel.
Hemiparetic Gait Parameters in Overground Versus Treadmill Walking (2001)

Collectively, these results demonstrate that the TM induces an immediate alteration toward a more consistent and symmetric gait pattern. Further investigation is needed to determine whether TM training leads to motor relearning and neuroplasticity in chronic hemiparetic subjects.
Contribution of Antigen-Primed CD8+ T Cells to the Development of Airway Hyperresponsiveness and Inflammation Is Associated with IL-13 (2004)

The role of Th2/CD4 T cells, which secrete IL-4, IL-5, and IL-13, in allergic disease is well established; however, the role of CD8(+) T cells (allergen-induced airway hyperresponsiveness (AHR) and inflammation) is less clear. This study was conducted to define the role of Ag-primed CD8(+) T cells in the development of these allergen-induced responses. CD8-deficient (CD8(-/-)) mice and wild-type mice were sensitized to OVA by i.p. injection and then challenged with OVA via the airways. Compared with wild-type mice, CD8(-/-) mice developed significantly lower airway responsiveness to inhaled methacholine and lung eosinophilia, and exhibited decreased IL-13 production both in vivo, in the bronchoalveolar lavage (BAL) fluid, and in vitro, following Ag stimulation of peribronchial lymph node (PBLN) cells in culture. Reconstitution of sensitized and challenged CD8(-/-) mice with allergen-sensitized CD8(+) T cells fully restored the development of AHR, BAL eosinophilia, and IL-13 levels in BAL and in culture supernatants from PBLN cells. In contrast, transfer of naive CD8(+) T cells or allergen-sensitized CD8(+) T cells from IL-13-deficient donor mice failed to do so. Intracellular cytokine staining of lung as well as PBLN T cells revealed that CD8(+) T cells were a source of IL-13. These data suggest that Ag-primed CD8(+) T cells are required for the full development of AHR and airway inflammation, which appears to be associated with IL-13 production from these primed T cells.
Probing Specific Sequences on Single DNA Molecules with Bioconjugated Fluorescent Nanoparticles (2000)

Nanometer-sized fluorescent particles (latex nanobeads) have been covalently linked to DNA binding proteins to probe specific sequences on stretched single DNA molecules. In comparison with single organic fluorophores, these nanoparticle probes are brighter, are more stable against photobleaching, and do not suffer from intermittent on/off light emission (blinking). Specifically, we demonstrate that the site-specific restriction enzyme EcoRI can be conjugated to 20-nm fluorescent nanoparticles and that the resulting nanoconjugates display DNA binding and cleavage activities of the native enzyme. In the absence of cofactor magnesium ions, the EcoRI conjugates bind to specific sequences on double-stranded DNA but do not initiate enzymatic cutting. For single DNA molecules that are stretched and immobilized on a solid surface, nanoparticles bound at specific sites can be directly visualized by multicolor fluorescence microscopy. Direct observation of site-specific probes on single DNA molecules opens new possibilities in optical gene mapping and in the fundamental study of DNA-protein interactions.
Immune Complex and Fc Receptor-Mediated Augmentation of Antigen Presentation for in Vivo Th Cell Responses (2000)

It has recently been established that FcRs are involved in the triggering of type II and III inflammatory responses. Although FcR is not believed to be involved in the regulation of T cell function, the in vivo contribution of FcRs to T cell function still remains unclear. We analyzed in vivo responses of delayed-type hypersensitivity and proliferation of CD4+ T cells to Ags in FcRgamma-/- mice lacking the expression and function of FcgammaRI, FcgammaRIII, and FcepsilonRI. We found that the delayed-type hypersensitivity response in FcRgamma-/- mice is significantly decreased compared with that in wild-type mice. Moreover, the secondary responses of proliferation and cytokine production as well as the Ab formation by CD4+ T cells from FcRgamma-/- mice to Ag and normal APCs were also reduced. In contrast, in vitro primary T cell proliferative responses upon stimulation with anti-TCR Ab or MLR as well as in vivo primary response against staphylococcus enterotoxin B administration were not different between T cells from FcRgamma-/- and wild-type mice. In addition, the Ag presentation function of APCs from unimmunized FcRgamma-/- mice was normal. On the other hand, Ab-deficient mice also revealed impaired T cell responses. These results demonstrate that the defective T cell responses in FcRgamma-/- mice were due to impaired Ag presentation during in vivo priming not to a defect in T cells. Therefore, they suggest that the FcRs on APCs mediate efficient priming of Th cell responses in vivo in an immune complex-dependent manner.
Successful treatment of severe complicated measles with non-specific transfer factor. (1995)

Severe complicated measles has a high mortality rate and no specific treatment. Ten patients with complicated measles - 9 infants with respiratory failure and a 15 year old boy with encephalitis - received immunotherapy with Non-specific Transfer Factor (NTF). The patients had variable degrees of undernourishment and were severely ill when immunotherapy was started. 8/9 cases with respiratory failure were cured. One died of bronchoaspiration while recovering from the measles. The case with encephalitis showed no neurological sequelae two weeks after receiving the last dose of NTF. Treatment of complicated measles with NTF in these patients seemed very effective and deserves further trial.
The electrochemical actuator using electrochemically-deposited poly-aniline film (1995)

Electrochemomechanical polymer actuators were fabricated by using the electro-deposited poly-aniline film. Using LASER displacement meter, we can easily get the in-situ observation of the displacement and the cyclic voltammogram[1]. At the redox reaction from leuco-emeraldine salt to emeraldine salt(ES), PANI film showed large deformation. On the other hand, at the redox reaction from ES to pernigraniline salt, PANI film showed the slight contraction.
Rapamycin Enhances Adenovirus-Mediated Cancer Imaging and Therapy in Pre-Immunized Murine Hosts (2013)

Tumor-specific adenoviral vectors comprise a fruitful gene-based diagnostic imaging and therapy research area for advanced stage of cancer, including metastatic disease. However, clinical translation of viral vectors has encountered considerable obstacles, largely due to host immune responses against the virus. Here, we explored the utilization of an immunosuppressant, rapamycin, to circumvent the anti-adenovirus immunity in immunocompetent murine prostate cancer models. Rapamycin diminished adenoviral-induced acute immune response by inhibiting NF-κB activation; it also reduced the scale and delayed the onset of inflammatory cytokine secretion. Further, we found that rapamycin abrogated anti-adenovirus antibody production and retarded the function of myeloid cells and lymphocytes that were activated upon viral administration in pre-immunized hosts. Thus, the co-administration of rapamycin prolonged and enhanced adenovirus-delivered transgene expression in vivo, and thereby augmented the imaging capability of adenoviral vectors in both bioluminescent and positron emission tomography modalities. Furthermore, we showed that despite an excellent response of cancer cells to a cytotoxic gene therapeutic vector in vitro, only minimal therapeutic effects were observed in vivo in pre-immunized mice. However, when we combined gene therapy with transient immunosuppression, complete tumor growth arrest was achieved. Overall, transient immunosuppression by rapamycin was able to boost the diagnostic utility and therapeutic potentials of adenoviral vectors.
Iodine, Thyroid Autoimmunity and Cancer (2015)

This review focuses on two different topics: (a) iodine and autoimmune thyroid disease (AITD) and (b) AITD and papillary thyroid carcinoma (PTC). Iodine intake modifies the expression of thyroid diseases and has been associated with induction of AITD. Thyroglobulin (Tg) is an important target in iodine-induced autoimmune response due to post-translational modifications of iodinated Tg, as suggested in animal models. We have shown that the unmasking of a cryptic epitope on Tg contributes to iodine-induced thyroid autoimmunity in humans. The relationship between AITD and PTC has been suggested in many studies. The presence of two different mechanisms has been hypothesized, one typical of AITD and the other of an immune reaction to PTC. We have shown that in AITD, the pattern of Tg recognition by anti-Tg antibodies (TgAb) is 'restricted' to the immunodominant regions of Tg, while in patients with non-AITD, such as nodular goiter and PTC devoid of thyroid lymphocytic infiltration at histology, TgAb show a less restricted epitopic pattern and bind also to other regions of Tg. Thyroid function may also affect the frequency of PTC, the risk of cancer increasing with serum TSH levels. We have shown that this mechanism, rather than thyroiditis per se, plays a major role in the association of PTC with Hashimoto's thyroiditis, as a consequence of the autoimmune process leading to a progressive increase of serum TSH in these patients.
HDAC4 Represses Matrix Metalloproteinase-13 Transcription in Osteoblastic Cells, and Parathyroid Hormone Controls This Repression (2010)

Parathyroid hormone (PTH) is a hormone regulating bone remodeling through its actions on both bone formation and bone resorption. Previously we reported that PTH induces matrix metalloproteinase-13 (MMP-13) transcription in osteoblastic cells. Here, we show that histone deacetylase 4 (HDAC4) interacts with Runx2, binds the MMP-13 promoter, and suppresses MMP-13 gene transcription in the rat osteoblastic cell line, UMR 106-01. PTH induces the rapid cAMP-dependent protein kinase-dependent release of HDAC4 from the MMP-13 promoter and subsequent transcription of MMP-13. Knock-out of HDAC4 either by siRNA in vitro or by gene deletion in vivo leads to an increase in MMP-13 expression, and overexpression of HDAC4 decreases the PTH induction of MMP-13. All of these observations indicate that HDAC4 represses MMP-13 gene transcription in bone. Moreover, PTH stimulates HDAC4 gene expression and enzymatic activity at times corresponding to the reassociation of HDAC4 with the MMP-13 promoter and a decline in its transcription. Thus, HDAC4 is a basal repressor of MMP-13 transcription, and PTH regulates HDAC4 to control MMP-13 promoter activity. These data identify a novel and discrete mechanism of regulating HDAC4 levels and, subsequently, gene expression.
Structural diversity of sequentially identical subsequences of proteins: Identical octapeptides can have different conformations (1998)

One of the most important questions in the protein folding problem is whether secondary structures are formed entirely by local interactions. One way to answer this question is to compare identical subsequences of proteins to see if they have identical structures. Such an exercise would also reveal a lower limit on the number of amino acids needed to form unique secondary structures. In this context, we have searched the April 1996 release of the Protein Data Bank for sequentially identical subsequences of proteins and compared their structures. We find that identical octamers can have different conformations. In addition, there are several examples of identical heptamers with different conformations, and the number of identical hexamers with different conformations has increased since the previous PDB releases. These observations imply that secondary structure can be formed entirely by non-local interactions and that an identical match of up to eight amino acids may not imply structural similarity. In addition to the larger context of the protein folding problem, these observations have implications for protein structure prediction methods. Proteins 30:228–231, 1998. © 1998 Wiley-Liss, Inc.
ANALYSIS OF PLEIOTROPISM AT THE DOMINANT WHITE-SPOTTING (W) LOCUS OF THE HOUSE MOUSE: A DESCRIPTION OF TEN NEW W ALLELES (1981)

Characterization of the pleiotropic effects of ten new putative W locus mutations, nine co-isogenic and one highly congenic with the C57BL/6J strain, reveals a wide variety of influences upon pigmentation, blood formation and gametogenesis. None of the putative alleles, each of which is closely linked to Ph, a gene 0.1 cM from W, gave evidence of complementation with W39, a new allele previously shown to be allelic to Wv. All W/W39 genotypes resulted in black-eyed-white anemics with reduced gametogenic activity. Homozygotes for seven of these mutations are lethal during perinatal life; anemic embryos have been identified in litters produced by intercross matings involving each of these alleles.--Phenotypes of mice of several mutant genotypes provide exceptions to the frequent observation that a double dose of dominant W alleles (e.g., W/Wv or W/W) results in defects of corresponding severity in each of the three affected tissues. One viable homozygote has little or no defect in blood formation, and another appears to have normal fertility. The phenotypes of these homozygotes support the conclusion that the three tissue defects are not dependent on each other for their appearance and probably do not result from a single physiological disturbance during the development of the embryo.--Although homozygosity for members of this series results in a wide range of phenotypes, the absence of complementation of any allele with W39, the close proximity of each mutant to Ph, and the fact that all alleles produce detectable (though sometimes marginal) defects in the same tissues affected by W and Wv, support the hypothesis that each new mutant gene is a W allele.
The Functional Gastrointestinal Disorders: Diagnosis, Pathophysiology, and Treatment : A Multinational Consensus (1994)

Functional gastrointestinal disorders comprise many unexplained afflictions for which no organic cause can be identified. These disturbances occur worldwide and make up half the gastroenterology cases in the Western world. Diagnosis and management is complicated by the fact that no-one can decide whether the disorders have an emotional or a psychological basis. This book presents a single source of standardized definitions, diagnostic criteria and treatment recommendations for these common conditions. Physicians should no longer need to make a diagnosis of exclusion; this book should provide a consensus document of management and treatment.
Effect of vitamin B2 deficiency on rat liver dihydropyrimidine dehydrogenase activity. (1991)

Effect of vitamin B2 deficiency on rat liver dihydropyrimidine dehydrogenase was investigated. It was found that the purified enzyme contains 2 mol flavin per molecule, which consists of equal proportions of flavin-adenine dinucleotide (FAD) and riboflavin 5'-phosphate (FMN). When rats were fed on a vitamin B2-deficient diet for 5 weeks, dihydropyrimidine dehydrogenase activity in the liver was diminished, followed by a decrease in enzyme concentration. Moreover, the addition of exogenous FAD or FMN did not restore the activity. Thus endogenous flavin may regulate the enzyme half-life or synthesis. Lowering of dihydropyrimidine dehydrogenase activity in the livers of rats fed on a vitamin B2-deficient diet did not affect the uridine, uracil and sigma UMP (the sum of acid soluble uracil 5'-nucleotides) pool in liver.
Bone acidic glycoprotein-75 is a major synthetic product of osteoblastic cells and localized as 75- and/or 50-kDa forms in mineralized phases of bone and growth plate and in serum. (1990)

Anti-peptide and anti-protein antisera were produced which both recognize bone acidic glycoprotein-75 (Mr = 75,000) and an apparent fragment or biosynthetic intermediate (Mr = 50,000) in calcified tissues and/or serum. A fragment-precursor relationship is suggested from the fact that closely spaced doublet polypeptides of Mr = 50,000 could be produced by proteolysis of the purified protein upon long term storage. No reactivity was detected with osteopontin, bone sialoprotein, or small bone proteoglycans. Bone acidic glycoprotein-75 represents 0.5-1% of the total radiolabeled proteins synthesized by explant cultures of neonatal calvaria or growth plate, by calvarial outgrowth cultures, and by rat osteosarcoma cells. Amounts produced by explant cultures and calvarial outgrowth cultures were similar to that for osteopontin, a major product of osteoblasts. In osteosarcoma cultures, 80% of labeled antigens were associated with the cell layer fraction wherein specific immunoprecipitation pelleted Mr = 50,000 and 75,000 sized antigens. Bone acidic glycoprotein-75 (Mr = 75,000) is enriched in 4 M guanidine HCl/0.5 EDTA extracts of neonatal rat bone and growth plate tissues, whereas largely absent from heart, lung, spleen, liver, brain, and kidney. Explant cultures of these noncalcifying tissues also synthesized bone acidic glycoprotein-75 antigen, but the quantities produced were only 5% or less that obtained with calvaria. By immunohistochemistry, antigenicity is associated with the bony shaft and calcified cartilage of long bones, but is absent from associated soft tissues. These finding demonstrate that bone acidic glycoprotein-75 is antigenically distinct, predominantly localized to calcified tissues, represents a major product of normal osteoblastic cells and may undergo a characteristic fragmentation in vivo and in vitro.
Prostaglandin (PG) F2αReceptor Expression and Signaling in Human Endometrium: Role of PGF2αin Epithelial Cell Proliferation (2003)

Prostaglandin (PG) F(2alpha), a member of the prostanoid bioactive lipid family, is secreted by human endometrium throughout the menstrual cycle and is present in both menstrual fluid and medium of endometrial explants in culture. PGF(2alpha) mediates its effects through a seven-transmembrane G-protein-coupled receptor (FP). The aim of this study was to examine the temporal expression, signaling, and role of FP receptor in the human endometrium. Quantitative RT-PCR analysis demonstrated highest expression of FP receptor in the mid- to late-proliferative phase, compared with early-proliferative and secretory phase endometrium. In situ hybridization studies localized FP receptor mRNA expression to the epithelial cell compartment during the mid- to late-proliferative phase. Moreover, treatment of endometrial tissue with 1-100 nM PGF(2alpha) induced a concentration-dependent increase in inositol phosphate mobilization, indicating functional FP receptor expression. The Ishikawa human endometrial epithelial cell line was used to investigate further the signaling and role of PGF(2alpha) in endometrial epithelial cells. Ishikawa cells endogenously express the FP receptor, and treatment with 1-100 nM PGF(2alpha) elicits a concentration-dependent increase in inositol phosphate release. Moreover, treatment of Ishikawa cells with 100 nM PGF(2alpha) induced phosphorylation of ERK1/2 that was abolished when cells were cotreated with 50 micro M PD98059 (MAPK kinase inhibitor) or 10 micro M U73122 [phospholipase C (PLC) inhibitor]. Treatment of Ishikawa cells with PGF(2alpha) for 24 h induced a significant concentration-dependent increase in Ishikawa cell proliferation. Coincubation of the cells with 50 micro M PD98059 or 2 micro M U73122 demonstrated that PLC inhibition significantly reduced PGF(2alpha)-induced proliferation, whereas MAPK kinase inhibition had no effect. In summary, these studies demonstrate increased FP receptor expression in endometrial epithelial cells during the proliferative phase of the menstrual cycle and identify a role for PGF(2alpha) in epithelial cell proliferation via a PLC-dependent pathway.