gebhart/patrepeval huggingface dataset:
Combined Approaches to the Synthesis and Study of Glycoproteins (2009)

Carbohydrates are the basis for many therapeutic and diagnostic strategies, yet the full potential of glycans in medicine has not been realized. The study of the precise role of different carbohydrates, bound to either proteins or lipids, is hampered by difficulties in accessing pure, well-defined glycoconjugates. This Review highlights recent advances in glycobiology with a particular emphasis on oligosaccharide synthesis and conjugation techniques for the construction of homogeneous glycoconjugates. New methods for the study of protein-glycan interactions such as carbohydrate arrays and in vivo visualization of glycosylation pattern changes will also be addressed. The development of glycotherapeutics is just beginning, and much remains to be understood about the relationship between glycoconjugate structure and function. The emergence of novel tools will certainly facilitate and expand the use of carbohydrates in therapeutics and diagnostics.
Coenzyme A transferase from Clostridium acetobutylicum ATCC 824 and its role in the uptake of acids (1989)

Coenzyme A (CoA) transferase from Clostridium acetobutylicum ATCC 824 was purified 81-fold to homogeneity. This enzyme was stable in the presence of 0.5 M ammonium sulfate and 20% (vol/vol) glycerol, whereas activity was rapidly lost in the absence of these stabilizers. The kinetic binding mechanism was Ping Pong Bi Bi, and the Km values at pH 7.5 and 30 degrees C for acetate, propionate, and butyrate were, respectively, 1,200, 1,000, and 660 mM, while the Km value for acetoacetyl-CoA ranged from about 7 to 56 microM, depending on the acid substrate. The Km values for butyrate and acetate were high relative to the intracellular concentrations of these species; consequently, in vivo enzyme activity is expected to be sensitive to changes in those concentrations. In addition to the carboxylic acids listed above, this CoA transferase was able to convert valerate, isobutyrate, and crotonate; however, the conversion of formate, n-caproate, and isovalerate was not detected. The acetate and butyrate conversion reactions in vitro were inhibited by physiological levels of acetone and butanol, and this may be another factor in the in vivo regulation of enzyme activity. The optimum pH of acetate conversion was broad, with at least 80% of maximal activity from pH 5.9 to greater than 7.8. The purified enzyme was a heterotetramer with subunit molecular weights of about 23,000 and 25,000.
Optical and Redox Properties of a Series of 3,4-Ethylenedioxythiophene Oligomers (2002)

The optical and redox properties of a series of 3,4-ethylenedioxythiophene oligomers (EDOTn, n=1-4) and their beta,beta'-unsubstituted analogues (Tn, n=1-4) are described. Both series are end capped with phenyl groups to prevent irreversible alpha-coupling reactions during oxidative doping. Absorption and fluorescence spectra of both series reveal a significantly higher degree of intrachain conformational order in the EDOTn oligomers. Oxidation potentials (E(PA1) and E(PA2)) determined by cyclic voltammetry reveal that those of EDOTn are significantly lower than the corresponding Tn oligomers as a consequence of the electron-donating 3,4-ethylenedioxy substitution. Linear fits of E(PA1) and E(PA2) versus the reciprocal number of double bonds reveal significantly steeper slopes for the EDOTn than for the Tn oligomers. This could indicate a more effective conjugation for the EDOTn series, confirmed by the fact that coalescence of E(PA1) and E(PA2) is reached already at relatively short chain lengths ( approximately 5 EDOT units) in contrast to the Tn series (>10 thiophene units). The stepwise chemical oxidation of the EDOTn and Tn oligomers in solution was carried out to obtain radical cations and dications. The energies of the optical transitions of the radical cations and dications as determined by UV/Vis/NIR spectroscopy were similar for the two series. These spectroscopic observations are consistent with quantum-chemical calculations performed on the singly charged molecules. Cooling solutions containing T2.+, T3.+, EDOT2.+, and EDOT3.+ revealed the reversible formation of dimers, albeit with a somewhat different tendency, expressed in the values for the dimerization enthalpy.
Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression (2004)

The hormonal form of vitamin D(3), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is an immune system modulator and induces expression of the TLR coreceptor CD14. 1,25(OH)(2)D(3) signals through the vitamin D receptor, a ligand-stimulated transcription factor that recognizes specific DNA sequences called vitamin D response elements. In this study, we show that 1,25(OH)(2)D(3) is a direct regulator of antimicrobial innate immune responses. The promoters of the human cathelicidin antimicrobial peptide (camp) and defensin beta2 (defB2) genes contain consensus vitamin D response elements that mediate 1,25(OH)(2)D(3)-dependent gene expression. 1,25(OH)(2)D(3) induces antimicrobial peptide gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines, and 1,25(OH)(2)D(3) along with LPS synergistically induce camp expression in neutrophils. Moreover, 1,25(OH)(2)D(3) induces corresponding increases in antimicrobial proteins and secretion of antimicrobial activity against pathogens including Pseudomonas aeruginosa. 1,25(OH)(2)D(3) thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections.
Regional localisation of left ventricular sheet structure: integration with current models of cardiac fibre, sheet and band structure (2007)

The architecture of the heart remains controversial despite extensive effort and recent advances in imaging techniques. Several opposing and non-mutually compatible models have been proposed to explain cardiac structure, and these models, although limited, have advanced the study and understanding of heart structure, function and development. We describe key areas of similarity and difference, highlight areas of contention and point to the important limitations of these models. Recent research in animal models on the nature, geometry and interaction of cardiac sheet structure allows unification of some seemingly conflicting features of the structural models. Intriguingly, evidence points to significant inter-individual structural variability (within constrained limits) in the canine, leading to the concept of a continuum (or distribution) of cardiac structures. This variability in heart structure partly explains the ongoing debate on myocardial architecture. These developments are used to construct an integrated description of cardiac structure unifying features of fibre, sheet and band architecture that provides a basis for (i) explaining cardiac electromechanics, (ii) computational simulations of cardiac physiology and (iii) designing interventions.
Vasculogenic female sexual dysfunction: vaginal engorgement and clitoral erectile insufficiency syndromes. (1998)

The first phase of the female sexual response, associated with neurotransmitter-mediated vascular smooth muscle relaxation, results in increased vaginal lubrication, wall engorgement and luminal diameter as well as increased clitoral length and diameter. Specific physiologic impairments of vasculogenic female sexual dysfunction include vaginal engorgement and clitoral erectile insufficiency syndromes. These syndromes exist when during sexual stimulation abnormal arterial circulation into the vagina or clitoris, usually from atherosclerotic vascular disease, interferes with normal vascular physiologic processes. Clinical symptoms may include delayed vaginal engorgement, diminished vaginal lubrication, pain or discomfort with intercourse, diminished vaginal sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished clitoral orgasm. An animal model of this syndrome, with significant physiologic responses between the control and the atherosclerotic pelvic nerve stimulated hemodynamic responses, is discussed. Non-atherosclerotic, traumatic vascular disease of the ilio-hypogastric-pudendal arterial bed from pelvic fractures or blunt perineal trauma may also result in diminished vaginal/clitoral arterial blood flow following sexual stimulation. Diagnostic studies assessing the hemodynamic integrity of the ilio-hypogastric-pudendal arterial bed to the vagina and clitoris and new oral/topical pharmacologic strategies for enhancing vaginal/clitoral blood flow in patients with vasculogenic female sexual dysfunction are discussed. There is a growing body of evidence that women with sexual dysfunction will commonly have physiologic abnormalities, such as vasculogenic female sexual dysfunction, contributing to their overall sexual health problems.
Novel Neuroleptics Improve Attentional Functioning in Schizophrenic Patients: Ziprasidone and Aripiprazole (1997)

Abstract Past research has established that traditional neuroleptic treatment improves attentional functioning in schizophrenic (SZ) patients. The present investigation expands on this finding by examining attentional improvement in nine acute SZ patients treated with either the novel neuroleptic ziprasidone or aripiprazole over a 4-week inpatient period. Twelve SZ in patients receiving typical neuroleptic treatment over the same time period served as controls. The results revealed that while all patients showed marked attentional improvement from medication-free baseline to week 4 of treatment, the SZ patients who received novel antipsychotics showed significant improvement on immediate recall and reaction time measures. These results suggest that novel neuroleptic treatment, perhaps through preferential activation of the prefrontal cortical pathways, improves SZ patients' information processing speed and efficiency.
Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches (2017)

These patients are in a desperate and vulnerable situation, and illicit psychoactive substances are often considered a last resort. There appeared to be little or no interest in psychoactive effects per se as these were rather tolerated or avoided by using sub-psychoactive doses. Primarily, psilocybin, lysergic acid diethylamide, and related psychedelic tryptamines were reportedly effective for both prophylactic and acute treatment of cluster headache and migraines. Treatment results with cannabis were more unpredictable. No severe adverse events were reported, but it was observed how desperation sometimes spurred risky behavior when obtaining and testing various treatment alternatives. The forum discourse mainly revolved around maximizing treatment results and minimizing potential harms.
Characterization of Hepatitis G Virus (GB-C Virus) Particles: Evidence for a Nucleocapsid and Expression of Sequences Upstream of the E1 Protein (1998)

Hepatitis G virus (HGV or GB-C virus) is a newly described virus that is closely related to hepatitis C virus (HCV). Based on sequence analysis and by evaluation of translational initiation codon preferences utilized during in vitro translation, HGV appears to have a truncated or absent core protein at the amino terminus of the HGV polyprotein. Consequently, the biophysical properties of HGV may be very different from those of HCV. To characterize HGV particle types, we evaluated plasma from chronically infected individuals with and without concomitant HCV infection by using sucrose gradient centrifugation, isopycnic banding in cesium chloride, and saline density flotation centrifugation. Similar to HCV, HGV particles included an extremely-low-density virion particle (1.07 to 1.09 g/ml) and a nucleocapsid of approximately 1.18 g/ml. One major difference between the particle types was that HGV was consistently more stable in cesium chloride than HCV. Plasma samples from chronically HGV-infected individuals and controls were assessed by a synthetic peptide-based immunoassay to determine if they contained HGV antibody specific for a conserved region in the coding region upstream of the E1 protein. Chronically HGV-infected individuals contained antibody to the HGV core protein peptide, whereas no binding to a hepatitis A virus peptide control was observed. Competitive inhibition of binding to the HGV peptide confirmed the specificity of the assay. These data indicate that HGV has a nucleocapsid and that at least part of the putative core region of HGV is expressed in vivo.
The Escherichia coli K-12 "wild types" W3110 and MG1655 have an rph frameshift mutation that leads to pyrimidine starvation due to low pyrE expression levels (1993)

The widely used and closely related Escherichia coli "wild types" W3110 and MG1655, as well as their common ancestor W1485, starve for pyrimidine in minimal medium because of a suboptimal content of orotate phosphoribosyltransferase, which is encoded by the pyrE gene. This conclusion was based on the findings that (i) the strains grew 10 to 15% more slowly in pyrimidine-free medium than in medium containing uracil; (ii) their levels of aspartate transcarbamylase were highly derepressed, as is characteristic for pyrimidine starvation conditions; and (iii) their levels of orotate phosphoribosyltransferase were low. After introduction of a plasmid carrying the rph-pyrE operon from strain HfrH, the growth rates were no longer stimulated by uracil and the levels of aspartate transcarbamylase were low and similar to the levels observed for other strains of E. coli K-12, E. coli B, and Salmonella typhimurium. To identify the mutation responsible for these phenotypes, the rph-pyrE operon of W3110 was cloned in pBR322 from Kohara bacteriophage lambda 2A6. DNA sequencing revealed that a GC base pair was missing near the end of the rph gene of W3110. This one-base-pair deletion results in a frame shift of translation over the last 15 codons and reduces the size of the rph gene product by 10 amino acid residues relative to the size of RNase PH of other E. coli strains, as confirmed by analysis of protein synthesis in minicells. The truncated protein lacks RNase PH activity, and the premature translation stop in the rph cistron explains the low levels of orotate phosphoribosyltransferase in W3110, since close coupling between transcription and translation is needed to support optimal levels of transcription past the intercistronic pyrE attenuator.
Creation of transgenic sugar beet lines expressing insect pest resistance genes cry1C and cry2A (2014)

Impact of insect pests makes a significant limitation of the sugar beet crop yield. Integration of cry-genes of Bacillus thuringiensis into plant genome is one of the promising strategies to ensure plant resistance. The aim of this work was to obtain sugar beet lines (based on the MM 1/2 line) transformed with cry2A and cry1Cgenes. We have optimized transformation protocol and direct plant let regeneration protocol from leaf explants using 1 mg/l benzylaminopurine as well as 0,25 mg/l benzylaminopurine and 0,1 mg/l indole-butyric acid. Consequently, transgenic sugar beet lines transformed with vector constructs pRD400-cry1C and pRD400-cry2A have been obtained. PCR analysis revealed integration of cry2A and cry1C into genome of transgenic lines and expression of these genes in leaf tissues was shown by reverse transcription PCR.
A systematic study of microdosing psychedelics (2019)

The phenomenon of 'microdosing', that is, regular ingestion of very small quantities of psychedelic substances, has seen a rapid explosion of popularity in recent years. Individuals who microdose report minimal acute effects from these substances yet claim a range of long-term general health and wellbeing benefits. There have been no published empirical studies of microdosing and the current legal and bureaucratic climate makes direct empirical investigation of the effects of psychedelics difficult. In Study One we conducted a systematic, observational investigation of individuals who microdose. We tracked the experiences of 98 microdosing participants, who provided daily ratings of psychological functioning over a six week period. 63 of these additionally completed a battery of psychometric measures tapping mood, attention, wellbeing, mystical experiences, personality, creativity, and sense of agency, at baseline and at completion of the study. Analyses of daily ratings revealed a general increase in reported psychological functioning across all measures on dosing days but limited evidence of residual effects on following days. Analyses of pre and post study measures revealed reductions in reported levels of depression and stress; lower levels of distractibility; increased absorption; and increased neuroticism. To better understand these findings, in Study Two we investigated pre-existing beliefs and expectations about the effects of microdosing in a sample of 263 nave and experienced microdosers, so as to gauge expectancy bias. All participants believed that microdosing would have large and wide-ranging benefits in contrast to the limited outcomes reported by actual microdosers. Notably, the effects believed most likely to change were unrelated to the observed pattern of reported outcomes. The current results suggest that dose controlled empirical research on the impacts of microdosing on mental health and attentional capabilities are needed.
Dramatic regulation of heparanase activity and angiogenesis gene expression in synovium from patients with rheumatoid arthritis (2008)

These findings are novel and contribute to our understanding of joint destruction in RA, suggesting that heparanase may be a reliable prognostic factor for RA progression and an attractive target for the treatment of RA.
An azidomethyl protective group in the synthesis of oligoribonucleotides by the phosphotriester method (2009)

A rapid and effective method of an automatic oligoribonucleotide synthesis alternative to the phosphoroamidite one was developed based on the phosphotriester approach of internucleotide bond formation under intramolecular O-nucleophilic catalysis and the use of an azidomethyl group for protection of a nucleotide 2'-hydroxyl function.
Transmission of Hepatitis C by Intrahepatic Inoculation with Transcribed RNA (1997)

More than 1% of the world's population is chronically infected with hepatitis C virus (HCV). HCV infection can result in acute hepatitis, chronic hepatitis, and cirrhosis, which is strongly associated with development of hepatocellular carcinoma. Genetic studies of HCV replication have been hampered by lack of a bona fide infectious molecular clone. Full-length functional clones of HCV complementary DNA were constructed. RNA transcripts from the clones were found to be infectious and to cause disease in chimpanzees after direct intrahepatic inoculation. This work defines the structure of a functional HCV genome RNA and proves that HCV alone is sufficient to cause disease.
NBQX Blocks Acute and Late Epileptogenic Effects of Perinatal Hypoxia (1995)

Clinically, and in experimental models, perinatal hypoxic encephalopathy is commonly associated with seizures. We previously described a rat model in which hypoxia induces seizures and permanently increases in seizure susceptibility in immature rats [postnatal day (P) 10-12] but not in older rats. In the present study, we compared the effect of pretreatment with the excitatory amino acid antagonists MK-801 and NBQX versus lorazepam in our rat model of perinatal hypoxia. Animals exposed to hypoxia at P10 without treatment have frequent seizures during hypoxia and subsequently exhibit increased seizure susceptibility to flurothyl. Treatment with 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX 20 mg/kg) effectively suppressed hypoxia-induced seizures in immature rats and also protected against permanent changes in flurothyl threshold in adulthood, whereas treatment with MK-801 (1 mg/kg) or lorazepam (LZP 1 mg/kg) did not prevent these hypoxia-related epileptogenic effects. These results suggest that activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA) receptors may partly mediate the age-dependent epileptogenic effect of hypoxia in the perinatal period.
AAED1 modulates proliferation and glycolysis in gastric cancer (2018)

Gastric cancer is one of the most common and lethal malignancies globally, especially in East Asia. Although significant progress has been made in the diagnosis and treatment of the disease, the overall survival rate remains unchanged at 20‑25%. Thus, there is an urgent need for a better understanding of the disease. Recent years have witnessed the critical roles of aberrant cancer cell metabolism in the maintenance of malignant properties of cancer cells, and targeting cancer cell metabolism has been regarded as a novel aspect in the development of treatments against cancer. In the present study, we identified a novel gene, AAED1 (AhpC/TSA antioxidant enzyme domain containing 1), which is upregulated in gastric cancer cells. By using lentivirus mediated transfection method, we silenced AAED1 expression and silencing of AAED1 inhibited cancer cell proliferation in vitro in gastric cancer cell lines, as demonstrated by cell viability and colony formation assay. Furthermore, we uncovered novel functions of AAED1 in regulating hypoxia inducible factor 1α (HIF1α) and the resultant aerobic glycolysis, which was measured by extracellular flux analysis. Collectively, the results of the present study uncovered novel markers that could identify the possible molecular mechanisms involved in gastric cancer.