gebhart/patrepeval huggingface dataset:
Cloning and sequencing of the genes coding for the 10- and 60-kDa heat shock proteins from Pseudomonas aeruginosa and mapping of a species-specific epitope (1991)

A genomic library of Pseudomonas aeruginosa DNA was screened with a monoclonal antibody (MAb 2528) specific for the P. aeruginosa 60-kDa heat shock protein. A positive clone, pAS-1, was isolated. The gene coding for P. aeruginosa chaperonin (hsp60) was localized to a 2-kb EcoRI fragment subcloned in pAS-2. A sequence analysis of pAS-2 and parts of pAS-1 identified two open reading frames that encoded proteins with calculated molecular masses of 10 and 57 kDa. In amino acid sequence comparison studies the sequences of these proteins, which were designated GroES and GroEL, exhibited up to 78% homology with known prokaryotic sequences of 10- and 60-kDa heat shock proteins (hsp10 and hsp60). In order to map the epitope recognized by MAb 2528, a series of GroEL nested carboxy-terminal deletion clones were tested with MAb 2528. We identified the clone with the shortest insertion that was still recognized by MAb 2528 and the clone with the largest insertion that was not recognized by MAb 2528. The 3' ends of the insertions were determined by sequencing and were found to delimit a region that encoded 25 amino acid residues. Synthetic oligonucleotides that coded for peptides possibly resembling the epitope within this region were ligated into expression vector pGEX-3X, and fusion proteins expressed by these clones were tested for reactivity with MAb 2528. By using this method we determined that the decapeptide QADIEARVLQ (positions 339 to 348 on GroEL) was responsible for the binding of P. aeruginosa-specific MAb 2528.
The role of myostatin and bone morphogenetic proteins in muscular disorders (2006)

Skeletal muscle is the largest organ in the human body, and plays an important role in body movement and metabolism. Skeletal muscle mass is lost in genetic disorders such as muscular dystrophy, muscle wasting and ageing. Chemicals and proteins that restore muscle mass and function are potential drugs that can improve human health and could be used in the clinic. Myostatin is a muscle-specific member of the transforming growth factor (TGF)-beta superfamily that plays an essential role in the negative regulation of muscle growth. Inhibition of myostatin activity is a promising therapeutic method for restoring muscle mass and strength. Potential inhibitors of myostatin include follistatin domain-containing proteins, myostatin propeptide, myostatin antibodies and chemical compounds. These inhibitors could be beneficial for the development of clinical drugs for the treatment of muscular disorders. Bone morphogenetic protein (BMP) plays a significant role in the development of neuromuscular architecture and its proper functions. Modulation of BMP activity could be beneficial for muscle function in muscular disorders. This review will describe the current progress in therapy for muscular disorders, emphasising the importance of myostatin as a drug target.
Androgen Maintenance of Erectile Function in the Rat Penis1 (1992)

Previous research has shown that the frequency and duration of penile erection is diminished after castration and that replacement with testosterone will restore the process. Using rats, the present study was designed to confirm that erection is androgen-dependent and to determine whether castration and androgen replacement affect the penile vascular smooth muscle responsiveness to vasoactive drugs. Blood pressure in the corpus cavernosum was measured directly during erections induced by electrical stimulation of the autonomic innervation of the penis. Maximal cavernosal pressure was markedly reduced after castration but was returned to normal levels if the castrated animals were treated with testosterone. Infusion of nitroglycerin (vasodilator) or phenylephrine (vasoconstrictor) resulted in a decline in cavernosal pressure in androgen-treated animals but not in castrated animals, even though the mean arterial blood pressure was strongly affected in all treatment groups by these drugs. When an inhibitor of nitric oxide synthesis was infused, cavernosal pressure was decreased in all groups, indicating that this substance is involved in penile erection. Taken together, these results show that androgens maintain the erectile process and may act specifically to support the responsiveness of the vascular smooth muscle to vasoactive drugs.
Unravelling the functional significance of PCSK9 (2007)

Mutations of PCSK9 are associated either with hypercholesterolemia or with hypocholesterolemia. In the latter case, the incidence of coronary heart disease is reduced, thereby demonstrating that low LDL cholesterol levels from birth are highly beneficial. PCSK9 promotes the degradation of the LDL receptor in hepatocytes apparently both intracellularly and by being a secreted protein that can bind the LDL receptor and be internalized. By virtue of its role as a major inhibitor of the LDL receptor, PCSK9 is a promising therapeutic target. Specific PCSK9 pharmacological inhibitors may prove to be useful in amplifying the well documented benefits of statins.
Monaural sound localization revisited (1997)

Research reported during the past few decades has revealed the importance for human sound localization of the so-called "monaural spectral cues." These cues are the result of the direction-dependent filtering of incoming sound waves accomplished by the pinnae. One point of view about how these cues are extracted places great emphasis on the spectrum of the received sound at each ear individually. This leads to the suggestion that an effective way of studying the influence of these cues is to measure the ability of listeners to localize sounds when one of their ears is plugged. Numerous studies have appeared using this monaural localization paradigm. Three experiments are described here which are intended to clarify the results of the previous monaural localization studies and provide new data on how monaural spectral cues might be processed. Virtual sound sources are used in the experiments in order to manipulate and control the stimuli independently at the two ears. Two of the experiments deal with the consequences of the incomplete monauralization that may have contaminated previous work. The results suggest that even very low sound levels in the occluded ear provide access to interaural localization cues. The presence of these cues complicates the interpretation of the results of nominally monaural localization studies. The third experiment concerns the role of prior knowledge of the source spectrum, which is required if monaural cues are to be useful. The results of this last experiment demonstrate that extraction of monaural spectral cues can be severely disrupted by trial-to-trial fluctuations in the source spectrum. The general conclusion of the experiments is that, while monaural spectral cues are important, the monaural localization paradigm may not be the most appropriate way to study their role.
Triazoles. Part IX. 1,2,4-Triazolyl ketones (1968)

3-Benzoyl-1,2,4-triazole and 1- and 5-substituted 1,2,4-triazol-3-yl aryl ketones have been prepared by the oxidation of the corresponding 3-benzyl-1,2,4-triazoles. The Beckmann rearrangement of the oximes of 1-phenyl-3-benzoyl-1,2,4-triazole was studied. Unusual i.r. bands of 3-aroyl-5-pyridyl-1,2,4-triazoles are ascribed to proton tunnellng.
Mycobacterial protein antigens: a compilation (1992)

In response to recommendations from the Steering Committees responsible for co-ordination of World Health Organization programmes for research on the immunology of leprosy (IMMLEP) and tuberculosis (IMMTUB), a list was prepared summarizing the properties of mycobacterial proteins currently under investigation with respect to their immunological activities. After consultation with more than 40 laboratories world-wide this list was extended to form the compilation shown below and is intended to provide a comprehensive and convenient reference for future studies in this field.
Studies on Anti-MRSA Parenteral Cephalosporins. I. Synthesis and Antibacterial Activity of 7.BETA.-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2(Z)-hydroxyiminoacetamido]-3-(substituted imidazo [1,2-b]-pyridazinium-1-yl)methyl-3-cephem-4-carboxylates and Related Compounds. (2000)

In order to improve the antibacterial activity of cefozopran (CZOP) against methicillin-resistant Staphylococcus aureus (MRSA), we initiated chemical modification to introduce a 2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-hydroxyimino acetyl group at the C-7 position and a 3- or 6-substituted imidazo[1,2-b]pyridazinium or 5-substituted imidazo[1,2-a]pyridinium group at the C-3' position. Although this approach successfully enhanced the anti-MRSA activity of CZOP two to eight times, a slight decrease in the activity against Gram-negative bacteria including Pseudomonas aeruginosa was involved. Among the novel derivatives, 3-(6-aminoimidazo[1,2-b]pyridazinium-1-yl)methyl-7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)hydroxyiminoacetamido]-3-cephem-4-carboxylate (44a) showed an excellent balance of activity against MRSA and Gram-negative bacteria.
Structural Biology of Shared Cytokine Receptors (2007)

Recent structural information for complexes of cytokine receptor ectodomains bound to their ligands has significantly expanded our understanding of the macromolecular topology and ligand recognition mechanisms used by our three principal shared cytokine signaling receptors-gp130, gamma(c), and beta(c). The gp130 family receptors intricately coordinate three structurally unique cytokine-binding sites on their four-helix bundle cytokine ligands to assemble multimeric signaling complexes. These organizing principles serve as topological blueprints for the entire gp130 family of cytokines. Novel structures of gamma(c) and beta(c) complexes show us new twists, such as the use of a nonstandard sushi-type alpha receptors for IL-2 and IL-15 in assembling quaternary gamma(c) signaling complexes and an antiparallel interlocked dimer in the GM-CSF signaling complex with beta(c). Unlike gp130, which appears to recognize vastly different cytokine surfaces in chemically unique fashions for each ligand, the gamma(c)-dependent cytokines appear to seek out some semblance of a knobs-in-holes shape recognition code in order to engage gamma(c) in related fashions. We discuss the structural similarities and differences between these three shared cytokine receptors, as well as the implications for transmembrane signaling.
A new tubulin polymerization inhibitor, auristatin PE, induces tumor regression in a human Waldenstrom's macroglobulinemia xenograft model. (1999)

Waldenstrom's macroglobulinemia (WM) is an uncommon lymphoproliferative disease which remains incurable with current treatment protocols. We have previously established a permanent WM cell line, WSU-WM, which grows as a xenograft in severe combined immune deficient (SCID) mice. In this study, we investigated the anti-tumor effects of auristatin PE (a structural modification of the marine, shell-less mollusk peptide constituent dolastatin 10). WSU-WM cells were cultured in RPMI-1640 at a concentration of 2x10(5) cells/ml using 24-well plates. Auristatin PE or dolastatin 10 were added to triplicate wells and cell count and viability were assessed after 24, 48 and 72 h. Results showed that both agents were active against WSU-WM, and were able to induce complete growth inhibition at 100 pg/ml. The efficacy of these agents in vivo was evaluated using the WSU-WM SCID mouse xenograft model. Auristatin PE and dolastatin 10 were given i.v. via tail vein at 2.0 mg/kg and 0.2 mg/kg, respectively. The agents were given every second day for three injections which represent the maximum tolerated doses. Tumor growth inhibition (T/C), tumor growth delay (T-C), and log10 kill for auristatin PE and dolastatin 10 were 0%, 18 days, 2.83 and 67%, 2 days, 0.06, respectively. Based on these animal results, dolastatin 10 was inactive while auristatin PE was highly active. We therefore focused further investigation on auristatin PE to understand some of its mechanisms of action. Using two flow cytometry assays, propidium iodide for cell cycle analysis and 7-amino actinomycin D (7AAD) to detect apoptosis, we were able to demonstrate that auristatin PE at 10 pg/ml after 24 h arrested 50% of WSU-MW cells in G2M. Concomitantly, 31% of auristatin PE-treated cells entered apoptosis. By 72 h, greater than 75% of the cells became apoptotic. The activity of auristatin PE should be evaluated in other tumor types and in clinical trials.
Immunochemical analysis of Lyme disease spirochetes. (1985)

Sera from patients with Lyme disease (LD) originating in the United States and Europe were examined by western blot analysis for antibodies to LD spirochete components. Whereas some components reacted with antibodies from the majority of patients, other components, notably an abundant cellular protein with an apparent molecular weight of 34,000 were less commonly bound. This latter proteinaceous component was in a region of the polyacrylamide gel electrophoresis profile which demonstrated variability between different LD spirochete isolates. Thus, there may be more than one serotype of LD spirochete, and the 34,000-range proteins may be a basis for such a distinction.
The Mechanism Underlying Cystic Fibrosis Transmembrane Conductance Regulator Transport from the Endoplasmic Reticulum to the Proteasome Includes Sec61β and a Cytosolic, Deglycosylated Intermediary (1998)

Endoplasmic reticulum (ER) degradation pathways can selectively route proteins away from folding and maturation. Both soluble and integral membrane proteins can be targeted from the ER to proteasomal degradation in this fashion. The cystic fibrosis transmembrane conductance regulator (CFTR) is an integral, multidomain membrane protein localized to the apical surface of epithelial cells that functions to facilitate Cl- transport. CFTR was among the first membrane proteins for which a role of the proteasome in ER-related degradation was described. However, the signals that route CFTR to ubiquitination and subsequent degradation are not known. Moreover, limited information is available concerning the subcellular localization of polyubiquitinated CFTR or mechanisms underlying retrograde dislocation of CFTR from the ER membrane to the proteasome either before or after ubiquitination. In the present study, we show that proteasome inhibition with clasto-lactacystin beta-lactone (4 microM, 1 h) stabilizes the presence of a deglycosylated CFTR intermediate for up to 5 h without increasing the core glycosylated (band B) form of CFTR. Deglycosylated CFTR is present under the same conditions that result in accumulation of polyubiquitinated CFTR. Moreover, the deglycosylated form of both wild type and DeltaF508 CFTR can be found in the cytosolic fraction. Both the level and stability of cytosolic, deglycosylated CFTR are increased by proteasome blockade. During retrograde translocation from the ER to the cytosol, CFTR associates with the Sec61 trimeric complex. Sec61 is the key component of the mammalian co-translational protein translocation system and has been proposed to function as a two way channel that transports proteins both into the ER and back to the cytosol for degradation. We show that the level of the Sec61.CFTR complexes are highest when CFTR degradation proceeds at the greatest rate (approximately 90 min after pulse labeling). Quantities of Sec61.CFTR complexes are also increased by inhibition of the proteasome. Based on these results, we propose a model in which complex membrane proteins such as CFTR are transported through the Sec61 trimeric complex back to the cytosol, escorted by the beta subunit of Sec61, and degraded by the proteasome or by other proteolytic systems.
Genome-wide open chromatin regions and their effects on the regulation of silk protein genes in Bombyx mori (2017)

Nucleosome-depleted open chromatin regions (OCRs) often harbor transcription factor (TF) binding sites that are associated with active DNA regulatory elements. To investigate the regulation of silk-protein genes, DNA molecules isolated from the silk glands of third-day fifth-instar silkworm larvae and embryo-derived (BmE) cells were subjected to formal dehyde-assisted isolation of regulatory elements (FAIRE) and high-throughput sequencing. In total, 68,000 OCRs were identified, and a number of TF-binding motifs were predicted. In particular, OCRs located near silk-protein genes contained potential binding sites for functional TFs. Moreover, many TFs were found to bind to clusters of OCRs upstream of silk-protein genes, and to regulate the expression of these genes. The expression of silk protein genes may be related not only to regulating TFs (such as fkh, Bmdimm, and Bmsage), but also to developmental and hormone-induced TFs (such as zen, eve, Br, and eip74ef). Elucidation of genome-wide OCRs and their regulatory motifs in silk protein genes will provide valuable data and clues for characterizing the mechanisms of transcriptional control of silk protein genes.
Effect of Water on the Activation Thermodynamics of Deep Eutectic Solvents Based on Carboxybetaine and Choline (2018)

Thermodynamic characteristics as well as peculiarities of hydrogen bonding in aqueous solutions of new deep eutectic solvents (DES) based on synthetic carboxybetaine have been studied. Cheap starting reagents (acrylic acid and 2-dimethylaminoethanol), simple preparation, and high yields are the advantages of the proposed betaine. Analyses of the calculated stabilization energies and natural bond orbital delocalization energies revealed the absence of preferential association in aqueous reline solutions tested for the comparative purpose. On the other hand, it was demonstrated that water preferentially associates with betaine molecules as this type of interaction was proved to possess the highest stabilization energy among the considered complexes. These data were used to discuss the anomalous behavior of the experimentally determined enthalpy and entropy factor of a viscous flow. Thus, sharp increase in the values of TΔ S<sub>A</sub> and Δ H<sub>A</sub> was demonstrated for the betaine-based solutions with 30-40 wt % water. The observed thermodynamic peculiarities were explained in terms of structurization of the betaine-based DES caused by strong H-bonding between betaine and water molecules and were supported with experimental IR spectroscopy measurements.
Mycobacterial heat‐shock proteins as carrier molecules. II: The use of the 70‐kDa mycobacterial heat‐shock protein as carrier for conjugated vaccinescan circumvent the need for adjuvants and Bacillus Calmette Guérin priming) (1992)

In a recent work, we have shown that mycobacterial heat-shock proteins (hsp) of 65-kDa (GroEL-type) and 70-kDa (DnaK-type) acted as carrier molecules in mice, previously primed with Mycobacterium tuberculosis var. bovis (bacillus Calmette-Guérin, BCG), for the induction of high and long-lasting titers of IgG against the repetitive malaria synthetic peptide (NANP)40. Anti-peptide antibodies were induced when the malaria peptide, conjugated to the mycobacterial hsp, was given in the absence of any adjuvants (Lussow et al., Eur. J. Immunol. 1991. 87:2960). In this report, we show that mice immunized with peptides or oligosaccharides conjugated to the 70-kDa hsp produced high titers of IgG antibodies in the absence of any previous priming with BCG. The anti-peptide antibody response persisted for at least 1 year. This adjuvant-free carrier effect of the 70-kDa hsp was T cell dependent, since no anti-peptide nor anti-70-kDa IgG antibodies were induced in athymic nu/nu mice. Previous immunization of mice with the 65-kDa or 70-kDa hsp did not have any negative effect on the induction of anti-peptide IgG antibodies after immunization with hsp-peptide conjugates in the absence of adjuvants. Furthermore, preimmunization with the 65-kDa hsp could substitute for BCG in providing an effective priming for the induction of anti-(NANP) antibodies. Finally, both the 65-kDa and 70-kDa hsp acted as carrier molecules for the induction of IgG antibodies to group C meningococcal oligosaccharides, in the absence of adjuvants. These findings strongly suggest that the use of hsp as carriers in conjugated constructs for the induction of anti-peptide and anti-oligosaccharide antibodies could be of value in the design of new vaccines for eventual use in humans.
Characterization of bile acid methyl ester acetate derivatives using gas-liquid chromatography, electron impact, and chemical ionization mass spectrometry (1976)

The gas-liquid chromatographic retention times on 0.5% SP-525 for 48 bile acids and related compounds as their methyl ester acetate derivatives are given. Ion tables for electron impact spectra have been compiled that permit direct access to ion structures for any given ion mass. Chemical ionization yields highly simplified mass spectra with two or three ions predominating for each compound. When the relative retention times of bile acids as their methyl ester acetates are combined with selective ion monitoring techniques in chemical ionization mass spectrometry, the retention time and ion mass number form a coordinate system which can be a powerful tool in the characterization of bile acid mixtures.
Tyrosol is a quorum-sensing molecule in Candida albicans (2004)

The human fungal pathogen Candida albicans shows a significant lag in growth when diluted into fresh minimal medium. This lag is abolished by the addition of conditioned medium from a high-density culture. The active component of conditioned medium is tyrosol, which is released into the medium continuously during growth. Under conditions permissive for germ-tube formation, tyrosol stimulates the formation of these filamentous protrusions. Because germ-tube formation is inhibited by farnesol, another quorum-sensing molecule, this process must be under complex positive and negative control by environmental conditions. The identification of tyrosol as an autoregulatory molecule has important implications on the dynamics of growth and morphogenesis in Candida.