gebhart/patrepeval huggingface dataset:
The MC4 receptor and control of appetite (2006)

Mutations in the human melanocortin (MC)4 receptor have been associated with obesity, which underscores the relevance of this receptor as a drug target to treat obesity. Infusion of MC4R agonists decreases food intake, whereas inhibition of MC receptor activity by infusion of an MC receptor antagonist or with the inverse agonist AgRP results in increased food intake. This review addresses the role of the MC system in different aspects of feeding behaviour. MC4R activity affects meal size and meal choice, but not meal frequency, and the type of diet affects the efficacy of MC4R agonists to reduce food intake. The central sites involved in the different aspects of feeding behaviour that are affected by MC4R signalling are being unravelled. The paraventricular nucleus plays an important role in food intake per se, whereas MC signalling in the lateral hypothalamus is associated with the response to a high fat diet. MC4R signalling in the brainstem has been shown to affect meal size. Further genetic, behavioural and brain-region specific studies need to clarify how the MC4R agonists affect feeding behaviour in order to determine which obese individuals would benefit most from treatment with these drugs. Application of MCR agonists in humans has already revealed side effects, such as penile erections, which may complicate introduction of these drugs in the treatment of obesity.
Spreading Cerebral Oligemia in Classical‐ and Normal Cerebral Blood Flow in Common Migraine (1982)

SYNOPSIS Regional cerebral blood flow was studied with intra‐arterial 133 Xenon technique in 254 areas of a hemisphere during the development of classical migraine attacks in seven patients. We describe a gradual spread of reduced cerebral blood flow starting at the posterior pole of the hemisphere and advancing in a mode quite similar to the spreading depression phenomenon of Leao. In three patients the oligemia was preceeded by focal or perifocal hyperemia. Functional activation by speech etc. was usually impaired or abolished during prodromes or accompaniments. Headache was found concommitantly with cerebral blood flow reduction and cannot be caused by reactive hyperemia in these patients. Similar findings were made in two patients studied with tomographic 133 Xenon technique. During induced common migraine attacks repeated cerebral blood flow studies with stationary detectors (N =3) and with tomographic technique (N =4) revealed no alterations of global or cerebral blood flow. Also tomographic determination of spontaneous common migraine attacks in four patients was normal. It is concluded that the two forms of migraine are different with respect to cerebral blood flow abnormalities and that they should be studied separately in the future. Greater interest should be directed towards the phenomenon of spreading depression as a possible model of the classical migraine attack.
Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus. (1993)

Colony-stimulating factor-1 (CSF-1) is a member of the immediate early gene family, which is expressed in mitogen-stimulated quiescent fibroblasts. The biological effects of CSF-1 are multifaceted and include stimulation of the proliferation and differentiation of myeloid progenitors and activity of circulating monocytes and tissue-specific macrophages. Ablation of circulating levels of biologically active CSF-1 in mice leads to osteopetrosis and sterility, thus implicating a role for CSF-1 in bone remodeling and implantation. Identification of regulatory elements and cognate transcription factors that bind the csf-1 promoter and mediate such diverse expression patterns is of great interest. We identified a sequence element at -273 to -265 (relative to the transcription initiation site) in the murine csf-1 promoter, which contains overlapping consensus sequences for the Wilms' tumor protein (WT1), EGR-1, SP1, and SP3 proteins. WT1 and EGR-1 proteins produced in vitro bound to this sequence, and co-transfection of wt1 with a csf-1-cat reporter plasmid resulted in repression of promoter activity. Interestingly, nuclear extracts prepared from serum-stimulated C3H10T1/2 cells contained predominantly SP1 and SP3 binding activities, which recognized the -273 to -265 site. Thus repression of the csf-1 promoter by WT1 at this site may involve competition between SP1 family transcriptional activators and the WT1 repressor. Colony-stimulating factor-1 may be a physiologically relevant target gene for regulation by the WT1 transcription factor.
Modulated expression of human peripheral blood microRNAs from infancy to adulthood and its role in aging (2014)

Accumulating evidence suggests a role for microRNAs (miRNAs) in regulating various processes of mammalian postnatal development and aging. To investigate the changes in blood-based miRNA expression from preterm infants to adulthood, we compared 365 miRNA expression profiles in a screening set of preterm infants and adults. Approximately one-third of the miRNAs were constantly expressed from postnatal development to adulthood, another one-third were differentially expressed between preterm infants and adults, and the remaining one-third were not detectable in these two groups. Based on their expression in infants and adults, the miRNAs were categorized into five classes, and six of the seven miRNAs chosen from each class except one with age-constant expression were confirmed in a validation set containing infants, children, and adults. Comparing the chromosomal locations of the different miRNA classes revealed two hot spots: the miRNA cluster on 14q32.31 exhibited age-constant expression, and the one on 9q22.21 exhibited up-regulation in adults. Furthermore, six miRNAs detectable in adults were down-regulated in older adults, and four chosen for individual quantification were verified in the validation set. Analysis of the network functions revealed that differentially regulated miRNAs between infants and adults and miRNAs that decreased during aging shared two network functions: inflammatory disease and inflammatory response. Four expression patterns existed in the 11 miRNAs from infancy to adulthood, with a significant transition in ages 9-20 years. Our results provide an overview on the regulation pattern of blood miRNAs throughout life and the possible biological functions performed by different classes of miRNAs.
Norepinephrine Enhances Fibrosis Mediated by TGF-β in Cardiac Fibroblasts (2002)

Cardiac fibrosis results from proliferation of interstitial fibroblasts and concomitant increased biosynthesis of extracellular matrix (ECM) components and is often complicated by cardiac hypertrophy. This study was conducted to investigate whether norepinephrine (NE) potentiates transforming growth factor-beta (TGF-beta)-induced cardiac fibrosis. The expression of the cardiac ECM proteins, plasminogen activator inhibitor-1 (PAI-1), fibronectin, and collagen type I, was examined by Western blotting using extracts from neonatal rat primary cardiac fibroblasts. In cardiac fibroblasts, treatment with a combination of NE and TGF-beta1 increased cell proliferation and ECM expression. Luciferase assays were conducted to clarify the effect of NE on TGF-beta signaling. TGF-beta1 (1 ng/mL) increased the specific signaling activity 2-fold, whereas the combination of NE (10 micro mol/L) and TGF-beta1 (1 ng/mL) resulted in an approximate 10-fold increase in specific signaling activity. We confirmed that treatment with NE markedly enhances TGF-beta-induced phosphorylation of activating transcription factor 2 (ATF-2). These results indicated that NE has a synergistic effect on TGF-beta signaling. To determine whether this activation by NE was mediated by the TGF-beta1 receptor, we used a dominant negative vector of the TGF-beta1 type II receptor, and the synergistic effects were inhibited. Furthermore, this synergistic effect was attenuated by a specific inhibitor of p38, SB203680. These data indicate that NE enhances cardiac fibrosis through TGF-beta1 post-receptor signaling, predominantly via the p38 MAP kinase pathway.
Probable precursors of [Leu]enkephalin and [Met]enkephalin in adrenal medulla: peptides of 3-5 kilodaltons. (1980)

Adrenal chromaffin granules contain at least 10 peptides, ranging in size from 3 to 5 kilodaltons, that yield, upon digestion with trypsin, peptides that show specific binding to opiate receptors. All are distinctly different from beta-endorphin. Two of these peptides have been purified to homogeneity and subjected to chemical analysis. One is apparently a [Met]enkephalin precursor containing two copies of the [Met]enkephalin sequence. The other peptide contains both [Leu]enkephalin and [Met]enkephalin sequences and is presumably a common precursor of the two forms of enkephalin.
Lipid-lowering effects of anti-angiopoietin-like 4 antibody recapitulate the lipid phenotype found in angiopoietin-like 4 knockout mice (2007)

We used gene knockout mice to explore the role of Angiopoietin-like-4 (Angptl4) in lipid metabolism as well as to generate anti-Angptl4 mAbs with pharmacological activity. Angptl4 -/- mice had lower triglyceride (TG) levels resulting both from increased very low-density lipoprotein (VLDL) clearance and decreased VLDL production and had modestly lower cholesterol levels. Also, both Angptl4 -/- suckling mice and adult mice fed a high-fat diet showed reduced viability associated with lipogranulomatous lesions of the intestines and their draining lymphatics and mesenteric lymph nodes. Treating C57BL/6J, ApoE -/-, LDLr -/-, and db/db mice with the anti-Angptl4 mAb 14D12 recapitulated the lipid and histopathologic phenotypes noted in Angptl4 -/- mice. This demonstrates that the knockout phenotype reflects not only the physiologic function of the Angptl4 gene but also predicts the pharmacologic consequences of Angptl4 protein inhibition with a neutralizing antibody in relevant models of human disease.
DOPA Decarboxylase Activity in Attention Deficit Hyperactivity Disorder Adults. A [Fluorine-18]Fluorodopa Positron Emission Tomographic Study (1998)

Converging evidence implicates the dopaminergic system and the prefrontal and nigrostriatal regions in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Using positron emission tomography (PET) with [fluorine-18]fluorodopa (F18-DOPA), we compared the integrity of the presynaptic dopaminergic function between 17 ADHD adults and 23 healthy controls. The ratio of the isotope concentration of specific regions to that of nonspecific regions reflects DOPA decarboxylase activity and dopamine storage processes. Of three composite regions (prefrontal cortex, striatum, and midbrain), only the prefrontal cortex showed significantly different F18-DOPA ratios in ADHD as compared with control adults (p < 0.01). The medial and left prefrontal areas were the most altered (lower F18-DOPA ratios by 52 and 51% in ADHD as compared with controls). Similarly, the interaction [sex x diagnosis] was significant only in the prefrontal cortex (p < 0.02): lower ratios in men than in women in ADHD and vice versa in controls. These findings suggest that a prefrontal dopaminergic dysfunction mediates ADHD symptoms in adults and that gender influences this abnormality. On the basis of previous neuroimaging findings in ADHD showing discrepant findings in adults and adolescents and on evidence for midbrain dopaminergic defect in adolescents, we hypothesize that the prefrontal dopaminergic abnormality in ADHD adults is secondary and results from an interaction of the primary subcortical dopaminergic deficit with processes of neural maturation and neural adaptation.
A Novel Epimerase That Converts GlcNAc-P-P-undecaprenol to GalNAc-P-P-undecaprenol in Escherichia coli O157 (2009)

Escherichia coli strain O157 produces an O-antigen with the repeating tetrasaccharide unit alpha-D-PerNAc-alpha-l-Fuc-beta-D-Glc-alpha-D-GalNAc, preassembled on undecaprenyl pyrophosphate (Und-P-P). These studies were conducted to determine whether the biosynthesis of the lipid-linked repeating tetrasaccharide was initiated by the formation of GalNAc-P-P-Und by WecA. When membrane fractions from E. coli strains K12, O157, and PR4019, a WecA-overexpressing strain, were incubated with UDP-[3H]GalNAc, neither the enzymatic synthesis of [3H]GlcNAc-P-P-Und nor [3H]GalNAc-P-P-Und was detected. However, when membrane fractions from strain O157 were incubated with UDP-[3H]GlcNAc, two enzymatically labeled products were observed with the chemical and chromatographic properties of [3H]GlcNAc-P-P-Und and [3H]GalNAc-P-P-Und, suggesting that strain O157 contained an epimerase capable of interconverting GlcNAc-P-P-Und and GalNAc-P-P-Und. The presence of a novel epimerase was demonstrated by showing that exogenous [3H]GlcNAc-P-P-Und was converted to [3H]GalNAc-P-P-Und when incubated with membranes from strain O157. When strain O157 was metabolically labeled with [3H]GlcNAc, both [3H]GlcNAc-P-P-Und and [3H]GalNAc-P-P-Und were detected. Transformation of E. coli strain 21546 with the Z3206 gene enabled these cells to synthesize GalNAc-P-P-Und in vivo and in vitro. The reversibility of the epimerase reaction was demonstrated by showing that [3H]GlcNAc-P-P-Und was reformed when membranes from strain O157 were incubated with exogenous [3H]GalNAc-P-P-Und. The inability of Z3206 to complement the loss of the gne gene in the expression of the Campylobacter jejuni N-glycosylation system in E. coli indicated that it does not function as a UDP-GlcNAc/UDP-GalNAc epimerase. Based on these results, GalNAc-P-P-Und is synthesized reversibly by a novel GlcNAc-P-P-Und epimerase after the formation of GlcNAc-P-P-Und by WecA in E. coli O157.
Synthesis and Antimalarial Activity of Some New Quinazoline Derivatives (1984)

Department of Chemical Engineering and Technology, Panjab University, Chandigarh-160 014 <em>Manuscript received 8 April 1982, revised 18 April 1984, accepted 21 July 1984</em> Dialkylaminoalkylamino and dialkylaminomethylarylamino derivatives of quinazoline have been synthesised for their antimalarial activity.
Identification of Sweetpotato Cultivars Using Isozyme Analysis (1991)

The enzymes alcohol dehydrogenase, diaphorase, esterase, glutamate dehydrogenase, glucosephosphate isomerase, isocitrate dehydrogenase, malate dehydrogenase, malic enzyme, 6-phosphogluconate dehydrogenase, phosphoglucomutase, shikimate dehydrogenase, and xanthine dehydrogenase were analyzed by starch gel electrophoresis of leaf tissue from nine sweetpotato [Ipomoea batatas (L.) Lam.] cultivars. Bands of most enzymes were well-defined. Polymorphisms were found in nine enzymes, and cultivars were identified by comparing polymorphisms.
Prediction of ligand‐binding sites of proteins by molecular docking calculation for a random ligand library (2010)

A new approach to predicting the ligand-binding sites of proteins was developed, using protein-ligand docking computation. In this method, many compounds in a random library are docked onto the whole protein surface. We assumed that the true ligand-binding site would exhibit stronger affinity to the compounds in the random library than the other sites, even if the random library did not include the ligand corresponding to the true binding site. We also assumed that the affinity of the true ligand-binding site would be correlated to the docking scores of the compounds in the random library, if the ligand-binding site was correctly predicted. We call this method the molecular-docking binding-site finding (MolSite) method. The MolSite method was applied to 89 known protein-ligand complex structures extracted from the Protein Data Bank, and it predicted the correct binding sites with about 80-99% accuracy, when only the single top-ranked site was adopted. In addition, the average docking score was weakly correlated to the experimental protein-ligand binding free energy, with a correlation coefficient of 0.44.
Degassing the “Killer Lakes” Nyos and Monoun, Cameroon (2004)

A unique humanitarian, scientific, and technical experiment is currently taking place in a forgotten mountainous region of West Africa. The experiment is on the verge of reaching its operational stage, which consists of the eradication of a “new” natural hazard; one that is potentially devastating, but which has been known for only 20 years. The Lake Nyos catastrophe, which claimed 1800 victims in August 1986, was not unprecedented. Indeed, 2 years previously a lethal gas burst, originating from nearby Lake Monoun in the same remote area of Cameroon, killed 37 people—an odd and tragic episode that went almost unnoticed. One had never before heard of Mother Nature asphyxiating human beings and most higher animals on such a scale in a single and brief non‐volcanic event.
Functional analysis of the herpes simplex virus UL42 protein (1993)

The herpes simplex virus UL42 gene encodes a multifunctional polypeptide (UL42) that is essential for virus DNA replication. To further understand the relationship between the structure of UL42 and the role that it plays during virus replication, we analyzed an extensive set of mutant UL42 proteins for the ability to perform the three major biochemical functions ascribed to the protein:binding to DNA, stably associating with the virus DNA polymerase (Pol), and acting to increase the length of DNA chains synthesized by Pol. Selected mutants were also assayed for their ability to complement the replication of a UL42 null virus. The results indicated that the N-terminal 340 amino acids of UL42 were sufficient for all three biochemical activities and could also support virus replication. Progressive C-terminal truncation resulted in the loss of detectable DNA-binding activity before Pol binding, while several mutations near the N terminus of the polypeptide resulted in an altered interaction with DNA but had no apparent affect on Pol binding. More dramatically, an insertion mutation at residue 160 destroyed the ability to bind Pol but had no effect on DNA binding. This altered polypeptide also failed to increase the length of DNA product synthesized by Pol, and the mutant gene could not complement the growth of a UL42 null virus, indicating that the specific interaction between Pol and UL42 is necessary for full Pol function and for virus replication. This study confirms the validity of the Pol-UL42 interaction as a target for the design of novel therapeutic agents.
ISOMER COMPOSITION and SPECTRA OF THE DARK and LIGHT ADAPTED FORMS OF ARTIFICIAL BACTERIORHODOPSINS* (1991)

Abstract– The isomer composition and spectral properties of 15 artificial bacteriorhodopsin (bR) pigments, based on a series of retinal analogs with polyene residue modified below C 9 are determined for both dark‐adapted (DA) and light‐adapted (LA) forms. Similarly to native bR, in all cases only two isomers, C 13 =C 14 cis (13‐cis) and M‐trans , are observed. However, the artificial DA pigments have a lower 13‐d.s content than native DA bR (˜ 66%) while the corresponding LA pigments have a much higher 13‐ cis content (11‐69%) than native LA bR (&lt;2%). Thus, in variance with the native pigment, in all of the artificial systems light also induced the reversed all ‐trans 13‐cis process. The data are accounted for in terms of specific steric interactions between the polyene and the protein binding site which allow a (C 15 ‐anti)( C ls ‐syn ) isomerization during the photocycle of the artificial pigments, but not in the case of native bR. This accounts for the high proton pumping efficiency of the natural pigment. The nature of a highly red shifted light‐adapted form of two of the artificial pigments is investigated and discussed. It is also shown that, in variance with native bR, several artificial pigments exhibit identical absorption spectra for their 13‐ cis and all ‐trans isomers. It is concluded that the spectral data for the above species of artificial pigments do not lead to a clear molecular model for the origin of the spectral shift between 13‐ cis and all ‐trans bR.
Factors Influencing [F-18] 2-Fluoro-2-Deoxy-d-Glucose (F-18 FDG) Uptake in Melanoma Cells: The Role of Proliferation Rate, Viability, Glucose Transporter Expression and Hexokinase Activity (2005)

Using human (SK-MEL 23, SK-MEL 24 and G361) and murine (B16) melanoma cell lines, the coregulatory potential of the uptake of the positron emission tomography (PET) tracer, [Fluorine-18] 2-fluoro-2-deoxy-D-glucose (F-18 FDG) has been investigated in relationship to tumor characteristics. Comparative studies among the four melanoma cell lines demonstrated that the lowest FDG uptake in SK-MEL 24 corresponded strongly to the data for DT (population doubling time) and MTT (tetrazolium salt) cell viability as well as hexokinase (HK) activity, but was not related to the glucose transporter 1 (GLUT 1) expression level. Furthermore, the FDG uptake in each melanoma cell line measured by cell cycle kinetics was significantly positively correlated to both the proliferation index (PI=S/G2M phase fractions) and the cell viability, though with one exception relating to the PI of the lowest FDG uptake cell line, SK-MEL 24. No positive correlation was found between the expression of GLUT 1 and FDG uptake in any individual cell line. However, the HK activities in SK-MEL 23 and 24 showed considerable positive relationships with FDG uptake. Our present study suggests that both the proliferation rate and the cell viability of melanoma cells may be key factors for FDG uptake and that HK activity, rather than GLUT 1 expression, seems to be a major factor.
Escherichia coli Virulence Factors and Serotypes in Acute Bacterial Prostatitis (1997)

The predominance of O serotypes in female urinary tract infections and a high percentage of multiple VFs among the prostatitis isolates suggested that VFs play important roles in the pathogenesis of acute bacterial prostatitis.