julilili42/papers huggingface dataset:
Gating of inward‐rectifier K+ channels by intracellular pH
2000-10-01

Inward rectifier K + channels of the K ir 1.1 (ROMK) and K ir 4.1 subtype are predominantly expressed in epithelial cells where they are responsible for K + transport across the plasma membrane. Uniquely among the members of the K ir family, these channels are gated by intracellular pH in the physiological range. pH‐gating involves structural rearrangements in cytoplasmic domains and the P‐loop of the K ir protein. The energy for the gating transition is delivered by protonation of a lysine residue that is located prior to the first transmembrane segment and serves as a ‘pH sensor’. The anomalous titration required for lysine operating in the neutral pH range results from its close interaction with two positively charged arginines from the distant N‐ and C‐termini termed the R/K/R triad. Disturbance of this triad as results from a number of point mutations found in patients with hyperprostaglandin E syndrome (HPS) increases the p K a of the pH sensor and results in channels being permanently inactivated under physiological conditions. This article will focus on the mechanism of pH‐gating, its implications for the tertiary structure of K ir proteins and on its significance for the pathogenesis of HPS.
Learning effects on event-related brain potentials
2000-10-01

This study investigates whether learning can manifest itself in EEG changes without explicit awareness of the acquired knowledge and without any motor requirement (to rule out acquisition of motor skills). Subjects passively heard particular stimulus combinations interspersed with random combinations. Immediately after this, stimulus combinations were presented which contained violations of the previously learned regular sequences. These violations elicited two frontally distributed negative waves peaked at about 250 ms and 500 ms, respectively. None of the participants could detect any regularity of the stimulation. No significant difference between regular vs random stimulus combinations was found during acquisition. These findings indicate that learning without explicit knowledge does not require motor activity (i.e. is independent of learning response sequences) and does not depend on stimulus probabilities.
The PPARγ2 Polymorphism Pro12Ala is Associated with Better Insulin Sensitivity in the Offspring of Type 2 Diabetic Patients
2000-10-01

Recently, a highly prevalent polymorphism of the PPARgamma2-receptor (Pro12Ala) was described and found to be associated with reduced transcriptional activity. Both human and animal studies suggested that this polymorphism may be associated with increased insulin sensitivity. However, an effect independent of other factors known to influence insulin sensitivity has yet to be demonstrated. Therefore, we compared insulin sensitivity using the hyperinsulinemic-euglycemic clamp technique in 37 subjects heterozygous for the PPARgamma2-Pro12Ala mutation and 37 control subjects negative for the PPARgamma2-Pro12Ala. The control group was selected from 190 subjects by pair-matching for sex, BMI, fat distribution and body composition. In the group heterozygous for the polymorphism steady-state plasma insulin during the clamp was significantly lower (63.3 microU/ml +/- 2.8) than in the control group (74.9 microU/ml +/- 4.0, p = 0.02). While MCR of glucose was similar in the PPARgamma2-Pro12Ala group (8.1 ml/kg x min x 100 +/- 0.5) and the control group (7.6 ml/kg x min x 100 +/- 3.0, p = 0.7), the insulin sensitivity index was significantly higher in the PPARgamma2-Pro12Ala group (12.5 mg/kg x min x microU/ml +/- 0.9 vs. 9.7 mg/kg x min x microU/ml +/- 0.8, p = 0.039). In addition, an arbitrary lipolysis index (decrease in FFA divided by increase in insulin) was also found to be marginally higher in the PPARgamma2-Pro12Ala group (8.0 +/- 0.9) compared to the control group (6.1 +/- 0.7, p = 0.097). In conclusion, these data suggest that the PPARgamma2-Pro12Ala mutation is associated with better insulin sensitivity of glucose disposal and possibly, also of antilipolysis.
G protein modulation of recombinant P/Q‐type calcium channels by regulators of G protein signalling proteins
2000-10-01

1. Fast synaptic transmission is triggered by the activation of presynaptic Ca(2+) channels which can be inhibited by Gβγ subunits via G protein-coupled receptors (GPCR). Regulators of G protein signalling (RGS) proteins are GTPase-accelerating proteins (GAPs), which are responsible for &gt;100-fold increases in the GTPase activity of G proteins and might be involved in the regulation of presynaptic Ca(2+) channels. In this study we investigated the effects of RGS2 on G protein modulation of recombinant P/Q-type channels expressed in a human embryonic kidney (HEK293) cell line using whole-cell recordings. 2. RGS2 markedly accelerates transmitter-mediated inhibition and recovery from inhibition of Ba(2+) currents (I(Ba)) through P/Q-type channels heterologously expressed with the muscarinic acetylcholine receptor M2 (mAChR M2). 3. Both RGS2 and RGS4 modulate the prepulse facilitation properties of P/Q-type Ca(2+) channels. G protein reinhibition is accelerated, while release from inhibition is slowed. These kinetics depend on the availability of G protein α and βγ subunits which is altered by RGS proteins. 4. RGS proteins unmask the Ca(2+) channel β subunit modulation of Ca(2+) channel G protein inhibition. In the presence of RGS2, P/Q-type channels containing the β(2a) and β(3) subunits reveal significantly altered kinetics of G protein modulation and increased facilitation compared to Ca(2+) channels coexpressed with the β(1b) or β(4) subunit.
The dopamine D2 receptor (DRD2) gene–a genetic risk factor in heavy smoking?
2000-10-01

Abstract Indications of a genetic predisposition to nicotine dependence have been derived from numerous epidemiological data and from individual genetic studies suggesting the involvement of the dopaminergic D2 receptor. Previous association studies defined the TaqlA polymorphism as a risk factor for addiction, in particular for alcoholism and tobacco dependence. Results of investigations into this polymorphism in 110 severely addicted smokers and a control group of 60 population‐matched German non‐smokers did not support these findings. However, our results indicate an association between the DRD2‐Fokl‐1 allele and the onset and intensity of smoking.
Effect of Norethisterone Acetate on Estrogen Metabolism in Postmenopausal Women
2000-10-01

Dominance of estradiol metabolism at the D-ring over the A-ring metabolism may play a role in the pathophysiology of human breast carcinogenesis. Currently, the influence of progestins on breast cancer risk is debated when added to postmenopausal estradiol replacement therapy. However, nothing is known about the action of progestins on estradiol metabolism. Therefore, the effect of oral and transdermal estradiol/norethisterone acetate (NETA) was investigated on the ratio of the main D-ring metabolite 16alpha-hydroxyestrone (16-OHE1) to the main Aring metabolite 2-hydroxyestrone (2-OHE1). The ratio of 16-OHE1 to 2-OHE1 after transdermal hormone replacement therapy (HRT) was 0.43 before treatment, 0.35 after estradiol and 0.52 after estradiol + NETA. The ratio after oral HRTwas 0.94 before treatment, 0.86 after estradiol and 2.30 after estradiol + NETA. Because of the high variations, no statistical significance could be calculated. Since there was a tendency to an increase after oral estradiol + NETA treatment, the individual patient profiles were examined. Here, three patients in the oral treatment group showed a significant increase of the ratio after the estradiol/NETA phase. In conclusion, transdermal NETA in HRT did not elicit any change in estrogen metabolism after 2 weeks' treatment. However, oral NETA may in some cases have an impact on estradiol metabolism which should be further evaluated.
Normalization of elevated CD4/CD8 (double‐negative) T cells after thymectomy parallels clinical remission in myasthenia gravis associated with thymic hyperplasia but not thymoma
2000-10-01

T-cell–dependent B-cell help is likely to be of major importance in the pathogenesis of myasthenia gravis, but mechanisms provoking a pathological anti–acetylcholine receptor (AChR) response are poorly understood. We report on the dysregulation of recently identified CD4−/CD8− (double-negative) T cells (DN T cells), which have been shown to participate in immunoregulation and antibody augmentation. Compared with healthy controls, significantly increased frequencies of DN T cells were found in the blood of myasthenia gravis patients with lymphofollicular hyperplasia. After thymectomy, however, normalization in the number of these cells was seen in parallel with clinical improvement and reduction in anti-AChR antibody titers. The effect of thymectomy was observed irrespective of adjuvant treatment and held true for up to 4 years of follow-up. In marked contrast, frequencies similar to control values were found in myasthenia gravis patients with thymoma, with thymectomy having no further reducing effect. These data indicate that CD4−/CD8− T cells not only participate in the pathogenesis of myasthenia gravis but also correlate with disease activity and histological findings. Ann Neurol 2000;48:603–608
A Practical Evaluation of Popular Volume Rendering Algorithms
2000-10-01

This paper evaluates and compares four volume rendering algorithms that have become rather popular for rendering datasets described on uniform rectilinear grids: raycasting, splatting, shear-warp, and hardware-assisted 3D texture-mapping. In order to assess both the strengths and the weaknesses of these algorithms in a wide variety of scenarios, a set of real-life benchmark datasets with different characteristics was carefully selected. In the rendering, all algorithm-independent image synthesis parameters, such as viewing matrix, transfer functions, and optical model, were kept constant to enable a fair comparison of the rendering results. Both image quality and computational complexity were evaluated and compared, with the aim of providing both researchers and practitioners with guidelines on which algorithm is most suited in which scenario. Our analysis also indicates the current weakness in each algorithm's pipeline, and possible solutions to these as well as pointers for future research are offered.
Speed Perception is Affected by the Ebbinghaus–Titchener Illusion
2000-10-01

We examined whether the apparent extent of motion affects speed perception. On the first presentation of each trial, a light dot travelled horizontally across a central circle of one of the Ebbinghaus configurations (with either small or large inducing elements). On the second presentation, observers adjusted the speed of a dot moving within the central circle alone so as to match the speed perceived in the first presentation. For all stimulus speeds (1.3, 2.1, and 5.5 deg s −1 ), the matched speed with small inducing circles was systematically less than that with large inducing circles. The findings indicate that the perceived speed depends on the apparent extent of motion: the larger the apparent size of a frame, the slower the apparent speed. These results are consistent with the predictions of transposition effects in visual motion.
NON-STATIONARY DRYING KINETICS IN A BATCH PHARMACEUTICAL FLUIDIZED BED COATING PROCESS
2000-10-01

ABSTRACT In this paper a physically based mathematical model for the description of particle wetting, temperature and humidity characteristics during a non-stationary fluidized bed spray-drying of granules or during a non-stationary fluidized bed coating in a Hüttlin®-Kugelcoater HKC 05-TJ is introduced. Using this model it is possible to calculate the humidity and temperature of the air, the degree of particle wetting, the temperatures of both the liquid layer and the particles under consideration and the influence of the wall of the apparatus and its surroundings. The effects of start-up and shut-down processes on the results as well as the time dependence of the discontinuous process with varying process parameters such as the amount of liquid sprayed in and its temperature, the amount of fluidising air and its temperature are simulated and the results were compared with those obtained experimentally using a Hüttlin -Kugelcoater HKC 05-TJ. Furthermore, the growth of the bed and the increase of particle masses during a discontinuous coating and granulation processes were taken into account in a simplified manner. Key Words and Phrases: Dynamic simulationGranulationParticle formationMathematical model
Synthese und Kristallstruktur von (Ph3PAu)4[AuMn(CO)5]2 und (Ph3PAu)3Re(CO)4/ Synthesis and Crystal Structure of (Ph3PAu)4 [AuMn(CO)5]2 and (Ph3PAu)3Re(CO)4
2000-10-01

Abstract The reaction of [Mn(CO) 5 ] - with the cluster cation [(Ph 3 PAu) 8 ] 2+ in thf yields the heterometallic cluster [(Ph 3 PAu) 4 [AuMn(CO) 5 ] 2 (1) as the main product besides small amounts of (Ph 3 PAu) 3 Mn(CO) 4 . The former crystallizes as 1-thf in form of red blocks in the triclinic space group P1 with a = 1391,0( 1), b = 1426.7( 1), c = 2308.3(2) pm, α = 92.87(1), β = 97.54( 1), γ = 96.43(1)° and Z = 2. The inner Au 6 skeleton of the almost centrosymmetrical cluster consists of two Au 4 tetrahedra sharing one edge. Two gold atoms bind a Mn(CO) 5 fragment, whereas to the other four gold atoms phosphine ligands are coordinated. The Au-Au distances range from 263.2(1) to 281.9(1) pm, and the Au-Mn distances are 256.6(3) and 256.9(2) pm. By the reaction of [(Ph 3 PAu) 8 ] 2+ with [Re 2 (CO) 9 ] 2- the cluster (Ph 3 PAu) 3 Re(CO) 4 (2) is obtained in low yield besides the homometallic cluster [(AuPPh 3 ) 7 ] + as the main product. 2 crystallizes from toluene as 2 C 7 H 8 in the form of yellow blocks with the orthorhombic space group Pna2 1 , and a = 1758.7(3), b = 1648.7(5), c = 2049.3(5) pm. The four metal atoms form a planar lozenge with the Re atom in equatorial position. The Re-Au distances range from 271.2(1) to 273.7(1) pm, and the Au-Au distances are 278.2(1) and 278.4(1) pm
N -Methoxyalkyl-Funktionalisierte α-Diketodiimide/ N -Methoxyalkyl Functionalized α-Diketodiimides
2000-10-01

Abstract The α-diketodiimides C 10 H 20 N 2 O 2 (2a) and C 12 H 24 N 2 O 2 (2b) are prepared by reacting butane- 2,3-dione with the corresponding α,π-amino- (methoxy)alkanes (1); the X-ray structure of 2a is reported
Comparative Study of the Use of a Suturing System and Titanium Clips.
2000-10-01

There is a need for secure and easy methods for suturing in laparoscopic surgery, no matter whether vessels are to be ligated, two structures sutured together, or the cystic duct is to be occluded in cholecystectomy. Laparoscopic suturing can be done with a suture, using automatic sewing devices or clips. Improper ligation of a vessel for example can result in bleeding, which is more difficult to treat in a laparoscopic procedure than in an open procedure. By using a Roeder knot in laparoscopic suturing, tying of the knot requires some expertise and makes the procedure more complicated and time-consuming.
Determinants for cap trimethylation of the U2 small nuclear RNA are not conserved between Trypanosoma brucei and higher eukaryotic organisms
2000-10-01

In most eukaryotic organisms the U2 small nuclear RNA (snRNA) gene is transcribed by RNA polymerase II to generate a primary transcript with a 5' terminal 7-methylguanosine cap structure. Following nuclear export, the U2 snRNA is assembled into a core ribonucleoprotein particle (RNP). This involves binding a set of proteins that are shared by spliceosomal snRNPs to the highly conserved Sm site. Prior to nuclear import, the snRNA-(guanosine-N:2)-methyltransferase appears to interact with the core RNP and hypermethylates the cap structure to 2,2, 7-trimethylguanosine (m(3)G). In the protist parasite Trypanosoma brucei, U-snRNAs are complexed with a set of common proteins that are analogous to eukaryotic Sm antigens but do not have a highly conserved Sm sequence motif, and most U-snRNAs are synthesised by RNA polymerase III. Here, we examined the determinants for m(3)G cap formation in T.brucei by expressing mutant U2 snRNAs in vivo and assaying trimethylation and RNP assembly by immunoprecipitation. Surprisingly, these studies revealed that the Sm-analogous region is not required either for binding of the common proteins or for cap trimethylation. Furthermore, except for the first 24 nt which are part of the U2 promoter, the U2 coding region could be substituted or deleted without affecting cap trimethylation.
Potent stimulation and inhibition of the CFTR Cl− current by phloxine B
2000-10-01

The effects of the fluoresceine derivative, phloxine B, on the Cl − current through the cystic fibrosis transmembrane conductance regulator (CFTR) were examined in Xenopus oocytes expressing human CFTR. In whole oocytes, the CFTR Cl − current (I CFTR ) was activated by superfusion with isobutylmethylxanthine and forskolin. I CFTR was stable during activation and deactivated rapidly upon washout of the activation solution. Phloxine B slowed deactivation and, at high concentrations, inhibited I CFTR weakly. In excised inside‐out macropatches, I CFTR was activated by the catalytic subunit of protein kinase A (cPKA) and MgATP. Phloxine B (0.01–3 μ M ), applied after activation, increased I CFTR within 30 s followed by a slow decrease which became dominant at high concentrations. Slowing of deactivation of the CFTR was observed at all concentrations. The effect of phloxine B after 30 s had a bell‐shaped concentration‐dependence with midpoints at 45 and 1600 n M for the stimulatory and the inhibitory limb, respectively; maximum stimulation was about 1.8 times. The slow inhibitory component, measured after 6 min, occurred with an IC 50 value of ∼1 μ M . In the absence of cPKA, phloxine B did not stimulate I CFTR . In the presence of cPKA and MgATP, the effects of phloxine B were more prominent at low (0.02 m M ) than at high ATP (2 m M ). The data show that phloxine B modulates I CFTR by increasing channel activity and slowing channel deactivation; at high concentrations inhibition dominates. The effects may be mediated by direct interactions with CFTR from the inside of the cell. British Journal of Pharmacology (2000) 131 , 433–440; doi: 10.1038/sj.bjp.0703600
Superoxide Production by Phagocytes in Myeloid Graffi Tumor-Bearing Hamsters
2000-10-01

Abstract A progressive suppression of the phagocytic ability of peritoneal macrophages and polymorphonuclears (PMNs) in hamsters with transplanted myeloid tumors was previously established. The i.p. application of Cu/Zn SOD, isolated from the fungal strain Humicola lutea (HLSOD) (2 injections before and 5 injections after tumor transplantation) induced the mean survival time of the animals as well as a temporally stimulating action on the macrophage and PMNs phagocyting indices. In the present work, the superoxide production of peritoneal macrophages and PMNs during 30 days of tumor progression was followed. Effects of the application of HLSOD in an optimal protective dose on the superoxide production in peritoneal macrophages and blood PMNs were examined. The spontaneous and phorbolmyristate acetate (PMA)-inducible O 2 - production in both types of phagocytes was 4-5- fold increased in tumor-bearing hamsters (TBH), as compared to the controls, at day 14 after tumor transplantation (the day of tumor appearance in transplanted animals). Furthermore, O 2 - production was also similar to the control values for the following days of observation.HLSOD treatment of TBH induced a normalization of superoxide production in macrophages and PMNs. Therefore, the established decrease of superoxide anions in phagocyting cells of TBH indicates possible effects of HLSOD on the host antioxidant defense.
Inward rectifier potassium channels and a multitude of intracellular gating molecules
2000-10-01

Inward rectifier potassium channels were first described in 1949 by Bernhard Katz, who reported an ‘anomalous’ rectifying potassium conductance in muscle tissue. This potassium conductance was considered anomalous because it increased with hyperpolarization and decreased with depolarization in contrast to the classical potassium conductance. The fact that these channels conduct larger inward currents than outward currents gave rise to the name inward rectifier potassium (Kir) channel. The molecular nature of Kir channels has been known since 1993, when the first two members were cloned. Subsequent work identified a large number of Kir channels that form a superfamily of eukaryotic proteins expressed in many tissues and responsible for import physiological processes including cell excitability, insulin secretion, K+ homeostasis, vascular tone and regulation of the heart rate. In contrast to the complexity of regulatory functions mediated by Kir channels, their molecular architecture is very simple. They are assembled from four subunits consisting of two transmembrane segments with cytoplasmic N- and C-terminal domains and a connecting loop which makes up the pore’s selectivity filter. Although, their structural plan is simple, their gating is very complex. In fact Kir channels display the perhaps most versatile gating behaviour of any ion channel class. Gating molecules comprise a multitude of intracellular factors including polyamines, nucleotides, pH, G-proteins and phospholipids. These molecules interact with different regions of the Kir channel, inducing either opening or closing of the channel’s pore. Thus, Kir channels can be considered as versatile ligand-gated ion channels with the ability to accept a multitude of different intracellular ligands. However, not every Kir channel is sensitive to all ligands. Rather, the members of the different Kir channel subfamilies are gated by a distinct set of molecules. These gating mechanisms are not only of biophysical interest but central for the diverse functions of Kir channels in physiology. The main objective of the following four review articles is to present the current understanding of the molecular mechanisms that underlie the gating of Kir channels by intracellular factors. The first review by Oliver et al. is an introduction to the Kir channel family and discusses the mechanism of inward rectification mediated by polyamines that is common to all Kir channels. Each of the following reviews will then focus on a different Kir channel subfamily, discussing the intracellular factors and mechanisms that regulate the subfamily members as well as their importance for physiology and pathophysiology.
Theology in the Conflict of Interpretations—Before the Text
2000-10-01

The aim of this essay is to reflect on the character of theology in general, understood as a hermeneutic theology, by way of reference to the work of Paul Ricoeur. The author endeavours to delineate a distinctively contemporary Lutheran hermeneutics, employing Ricoeur as his main partner in dialogue.
Book Review: Anticipating Total War: The German and American Experiences, 1871-1914
2000-10-01

Journal Article Book Review: Anticipating Total War: The German and American Experiences, 1871–1914 Get access Aribert Reimann Aribert Reimann University of Tübingen Search for other works by this author on: Oxford Academic Google Scholar German History, Volume 18, Issue 4, October 2000, Pages 528–530, https://doi.org/10.1177/026635540001800420 Published: 01 October 2000