bluuebunny/crossref_metadata_2025 huggingface dataset:
Dialysis Dose Parameters. How Much We Can Improve Them in Our Clinical Practice? Role of Online Conductivity Monitor
Authors: Cigarrán S. , Coronel F. , Torrente J. , Sevilla M. , Baylón J.C.D.
Published: December 2004

The mortality and morbidity of hemodialysis patients is, to a large extent, determined by demographics and by existing comorbidities, but it is obvious that variations in dialysis dose have substantial effects. Using eKt/V, 1.2 monthly comparisons are recommended by European guidelines, but they assume that dose is maintained during all monthly sessions. Because of dialysis‐related problems like hypotension, reduction of blood flow, dialysis time, microclotting of the dialyzer, and vascular access problems, the delivered dose may vary from session to session. New developed devices based on online conductivity clearance reflect the electrolyte clearance and, thus, clearance of urea. The aim of this prospective study was to show the variability of dialysis dose. 24 anuric patients were studied during 3 months: 20.8% were diabetics, mean age 64.7 ± 18.2 years; 16% females. Access blood were AVFi and the effective dialyzed blood flow was set at 350 mL/min, with recirculation <5%. BMI was 25.4 ± 3.8 kg/m2 and body weight was 69.7 ± 12 kg. All patients were dialyzed thrice weekly (245 ± 21 min) with dialysis machine 4008H (Fresenius Medical Care) equipped with online conductivity monitor (OCM) and the hollow fiber high‐flux polysulfone membrane (HF‐80 1.8 m2) and helixone (Fx‐60, 1.6 m2). OCM was validated for our population and reported in other abstracts (r2 = 0.96, p < 0.001). Dialysate flow was maintained at 500 mL/min, with standard dialysate liquid. Each patient was subjected to OCM on regular sessions during 3 months, and blood Kt/V samples were taken on midweek day, once a month. Data were processed and statistically analyzed with SPSS 11.0 software package. Kt/V OCM relation with other baseline characteristics was assessed by using contingency tables, t‐tests, analysis of variance, and linear regression, as appropriate. All the tests were performed for a 0.05 significance level. The conductivity‐based OCM provides an accurate tool to monitor the dose and control of each hemodialysis session and adds to the efficiency of current dialysis adequacy monitoring. OCM device requires little maintenance, and no extra effort is needed. Monthly Kt/V does not reflect the variability of each session. Further studies are necessary to evaluate its influence on morbidity and mortality.

  Descriptives  

Variables
Minimum
Maximum
Mean
SD

Age (year)
31
86
64.75
18.243

Membrane surface
1.6
1.8
 1.675
0.0989

Interdialysis weight gain
500
4200
2266.67
1016.673

BMI
18.22
31.03
25.4155
3.83630

Time on dialysis (min)
210
320
245.21
21.340

OCM
0.990
1.880
1.29921
0.201072

dPVV/Kt/V (Daugirdas)
1.00
2.09
1.4067
0.21924

Watson volume (L)
25.8
49.3
36.833
6.3095
Hurricane‐induced nitrous oxide fluxes from a wet tropical forest
Authors: Erickson Heather E. , Ayala Gaddiel
Published: December 2004

Hurricane activity is predicted to increase over the mid‐Atlantic as global temperatures rise. Nitrous oxide (N2O), a greenhouse gas with a substantial source from tropical soils, may increase after hurricanes yet this effect has been insufficiently documented. On September 21, 1998, Hurricane Georges crossed Puerto Rico causing extensive defoliation. We used a before–after design to assess the effect of Georges on N2O emissions, and factors likely influencing N2O fluxes including soil inorganic nitrogen pools and soil water content in a humid tropical forest at El Verde, Puerto Rico. Emissions of N2O up to 7 months post‐Georges ranged from 5.92 to 4.26 ng cm−2 h−1 and averaged five times greater than fluxes previously measured at the site. N2O emissions 27 months after the hurricane remained over two times greater than previously measured fluxes. Soil ammonium pools decreased after Georges and remained low. The first year after the hurricane, nitrate pools increased, but not significantly when compared against a single measurement made before the hurricane. Soil moisture and temperature did not differ significantly in the two sampling periods. These results suggest that hurricanes increase N2O fluxes in these forests by altering soil N transformations and the relative availabilities of inorganic nitrogen.
Short‐ and long‐term greenhouse gas and radiative forcing impacts of changing water management in Asian rice paddies
Authors: Frolking Steve , Li Changsheng , Braswell Rob , Fuglestvedt Jan
Published: December 2004

Fertilized rice paddy soils emit methane while flooded, emit nitrous oxide during flooding and draining transitions, and can be a source or sink of carbon dioxide. Changing water management of rice paddies can affect net emissions of all three of these greenhouse gases. We used denitrification–decomposition (DNDC), a process‐based biogeochemistry model, to evaluate the annual emissions of CH4, N2O, and CO2 for continuously flooded, single‐, double‐, and triple‐cropped rice (three baseline scenarios), and in further simulations, the change in emissions with changing water management to midseason draining of the paddies, and to alternating crops of midseason drained rice and upland crops (two alternatives for each baseline scenario). We used a set of first‐order atmospheric models to track the atmospheric burden of each gas over 500 years. We evaluated the dynamics of the radiative forcing due to the changes in emissions of CH4, N2O, and CO2 (alternative minus baseline), and compared these with standard calculations of CO2‐equivalent emissions using global warming potentials (GWPs). All alternative scenarios had lower CH4 emissions and higher N2O emissions than their corresponding baseline cases, and all but one sequestered carbon in the soil more slowly. Because of differences in emissions, in radiative forcing per molecule, and in atmospheric time constants (lifetimes), the relative radiative impacts of CH4, N2O, and CO2 varied over the 500‐year simulations. In three of the six cases, the initial change in radiative forcing was dominated by reduced CH4 emissions (i.e. a cooling for the first few decades); in five of the six cases, the long‐term radiative forcing was dominated by increased N2O emissions (i.e. a warming over several centuries). The overall complexity of the radiative forcing response to changing water management could not easily be captured with conventional GWP calculations.
The effect of intracellular acidification on the relationship between cell volume and membrane potential in amphibian skeletal muscle
Authors: Fraser James A. , Middlebrook Claire E. , Usher‐Smith Juliet A. , Schwiening Christof J. , Huang Christopher L.‐H.
Published: December 2004

The relationship between cell volume (Vc) and membrane potential (Em) in Rana temporaria striated muscle fibres was investigated under different conditions of intracellular acidification. Confocal microscope xz‐scanning monitored the changes in Vc, whilst conventional KCl and pH‐sensitive microelectrodes measured Em and intracellular pH (pHi), respectively. Applications of Ringer solutions with added NH4Cl induced rapid reductions in Vc that rapidly reversed upon their withdrawal. These could be directly attributed to the related alterations in extracellular tonicity. However: (1) a slower and persistent decrease in Vc followed the NH4Cl withdrawal, leaving Vc up to 10% below its resting value; (2) similar sustained decreases in resting Vc were produced by the addition and subsequent withdrawal of extracellular solutions in which NaCl was isosmotically replaced with NH4Cl; (3) the same manoeuvres also produced a marked intracellular acidification, that depended upon the duration of the preceding exposure to NH4Cl, of up to 0.53 ± 0.10 pH units; and (4) the corresponding reductions in Vc similarly increased with this exposure time. These reductions in Vc persisted and became more rapid with Cl− deprivation, thus excluding mechanisms involving either direct or indirect actions of pHi upon Cl−‐dependent membrane transport. However they were abolished by the Na+,K+‐ATPase inhibitor ouabain. The Em changes that accompanied the addition and withdrawal of NH4+ conformed to a Nernst equation modified to include realistic NH4+ permeability terms, and thus the withdrawal of NH4+ restored Em to close to control values despite a persistent change in Vc. Finally these Em changes persisted and assumed faster kinetics with Cl− deprivation. The relative changes in Vc, Em and pHi were compared to predictions from the recent model of Fraser and Huang published in 2004 that related steady‐state values of Vc and Em to the mean charge valency (zx) of intracellular membrane‐impermeant anions, X−i. By assuming accepted values of intracellular buffering capacity (βi), intracellular acidification was shown to produce quantitatively predictable decreases in Vc. These findings thus provide experimental evidence that titration of the anionic zx by increased intracellular [H+] causes cellular volume decrease in the presence of normal Na+,K+‐ ATPase activity, with Cl−‐dependent membrane fluxes only influencing the kinetics of such changes.
Activation of ferret erythrocyte Na+–K+–2Cl− cotransport by deoxygenation
Authors: Flatman Peter W.
Published: December 2004

Deoxygenation of ferret erythrocytes stimulates Na+–K+–2Cl− cotransport by 111% (s.d., 46) compared to controls in air. Half‐maximal activation occurs at a PO2 of 24 mmHg (s.d., 2) indicating that physiological changes in oxygen tension can influence cotransport function. Approximately 25–35% of this stimulation can be attributed to the rise of intracellular free magnesium concentration that occurs on deoxygenation (from 0.82 (s.d., 0.07) to 1.40 mm (s.d., 0.17)). Most of the stimulation is probably caused by activation of a kinase which can be prevented or reversed by treating cells with the kinase inhibitors PP1 or staurosporine, or by reducing cell magnesium content to submicromolar levels. Stimulation by deoxygenation is comparable with that caused by calyculin A or sodium arsenite, compounds that cause a 2‐ to 3‐fold increase in threonine phosphorylation of the cotransporter which can be detected with phospho‐specific antibodies. However, the same approach failed to detect significant changes in threonine phosphorylation following deoxygenation. The results suggest that deoxygenation causes activation of a kinase that either phosphorylates the transporter, but probably not on threonine, or phosphorylates another protein that in turn influences cotransporter behaviour. They also indicate that more than one kinase and phosphatase are involved in cotransporter phosphorylation.
α‐Adrenoceptor constrictor responses and their modulation in slow‐twitch and fast‐twitch mouse skeletal muscle
Authors: Lambert David G. , Thomas Gail D.
Published: December 2004

Vasoconstrictor responses to sympathetic nerve stimulation and their sensitivity to metabolic modulation reportedly differ in fast‐twitch and slow‐twitch muscles, but the underlying mechanisms are not known. Both α1‐ and α2‐adrenoceptors mediate these vascular responses in fast‐twitch muscle, while their roles in slow‐twitch muscle are less well defined. In this study, the phosphorylation of smooth muscle myosin regulatory light chain (smRLC) was measured as an index of vasoconstriction in slow‐twitch soleus muscles and fast‐twitch extensor digitorum longus (EDL) muscles isolated from C57BL/6J mice. In soleus muscles, incubation with phenylephrine (PE) or UK 14,304 to selectively activate α1‐ or α2‐adrenoceptors resulted in concentration‐dependent increases in smRLC phosphorylation. To evaluate metabolic modulation of these responses, vasodilator pathways previously implicated in such modulation in fast‐twitch muscle were activated in soleus muscles by treatment with the nitric oxide (NO) donor nitroprusside or the ATP‐sensitive potassium (KATP) channel opener cromakalim. Both drugs inhibited responses to UK 14,304, but not to PE. The effect of nitroprusside to antagonize UK 14,304 responses was prevented by inhibition of guanylyl cyclase or by blockade of KATP channels, but not by blockade of other potassium channels. Results were similar in EDL muscles. These data provide the first evidence for α2‐adrenoceptor‐mediated constriction in slow‐twitch muscle, and show that it is sensitive to modulation by NO via a cGMP‐dependent mechanism that requires KATP channel activation. Based on the similar findings in soleus and EDL muscles, fibre type does not appear to determine the innate vascular response to α1‐ or α2‐adrenoceptor activation.
The Search for Biomarkers of Aging: Next Stop
INK4a/ARF
Locus
Authors: Dimri Goberdhan P.
Published: December 2004

Although several biomarkers of aging have been described in the literature, it is only recently that gerontologists have started to search for molecular biomarkers of aging. A gene or a set of genes that are expressed in a wide range of tissues and exhibit an age-dependent, easily quantifiable increase in their expression represent a possible molecular biomarker of aging. Because the physiology of an organism is profoundly affected by the pattern of gene expression, it is hoped that molecular biomarkers of aging will more accurately predict the physiological age of an organism than the chronological age. A recent report from Sharpless's laboratory examines the possibility that the tumor suppressors p16 and ARF (encoded by the
INK4a/ARF
locus) represent molecular biomarkers of aging in rodent models.
Temperatures, Winds, and Composition in the Saturnian System
Authors: Flasar F. M. , Achterberg R. K. , Conrath B. J. , Pearl J. C. , Bjoraker G. L. , Jennings D. E. , Romani P. N. , Simon-Miller A. A. , Kunde V. G. , Nixon C. A. , Bézard B. , Orton G. S. , Spilker L. J. , Spencer J. R. , Irwin P. G. J. , Teanby N. A. , Owen T. C. , Brasunas J. , Segura M. E. , Carlson R. C. , Mamoutkine A. , Gierasch P. J. , Schinder P. J. , Showalter M. R. , Ferrari C. , Barucci A. , Courtin R. , Coustenis A. , Fouchet T. , Gautier D. , Lellouch E. , Marten A. , Prangé R. , Strobel D. F. , Calcutt S. B. , Read P. L. , Taylor F. W. , Bowles N. , Samuelson R. E. , Abbas M. M. , Raulin F. , Ade P. , Edgington S. , Pilorz S. , Wallis B. , Wishnow E. H.
Published: December 2004

Stratospheric temperatures on Saturn imply a strong decay of the equatorial winds with altitude. If the decrease in winds reported from recent Hubble Space Telescope images is not a temporal change, then the features tracked must have been at least 130 kilometers higher than in earlier studies. Saturn's south polar stratosphere is warmer than predicted from simple radiative models. The C/H ratio on Saturn is seven times solar, twice Jupiter's. Saturn's ring temperatures have radial variations down to the smallest scale resolved (100 kilometers). Diurnal surface temperature variations on Phoebe suggest a more porous regolith than on the jovian satellites.
AMPA Receptor Cycling in the Synapse
Authors: Contractor Anis , Heinemann Stephen F.
Published: December 2004

Ionotropic glutamate receptors (GluRs) are involved in mediating signaling in response to synaptic activity. In addition to converting the chemical signal released from the presynaptic terminal to an electrical response in the postsynaptic neuron, these receptors are critically involved in activity-dependent, long-term changes in synaptic strength and, therefore, are central to processes thought to underlie learning and memory. The animation provides an interactive illustration of how activity-dependent changes in the glutamate receptor composition and numbers at the synapse may contribute to synaptic plasticity.
Dynamic Control of Nuclear Receptor Transcription
Authors: Fowler Amy M. , Alarid Elaine T.
Published: December 2004

This Perspective highlights experiments that probe the complexity and regulation underlying cyclical association of nuclear receptor transcriptional complexes with DNA. Using advanced in vivo and in vitro techniques, these studies emphasize the importance of chromatin remodeling and histone modification in defining the timing and nature of the cycles. In addition, they reveal the multiplicity of receptor-coregulator complexes that reside on a single promoter. These conceptual and technical achievements integrate kinetic and combinatorial regulation into a new dynamic model of nuclear receptor–mediated transcription.
Spectral Analysis of Calcium Oscillations
Authors: Uhlén Per
Published: December 2004

Calcium (Ca
2+
) oscillations are universal signals exploited by cells to regulate a vast number of cellular processes. Frequency and amplitude, the key features of oscillating waves, can yield information that can be decoded by intracellular processes. Analysis and quantification of Ca
2+
oscillations are crucial for understanding the general concept of Ca
2+
signaling. This protocol presents a method for performing spectral analysis of Ca
2+
oscillations using MATLAB software.
The Jak-STAT Pathway Stimulated by Interleukin 6
Authors: Horvath Curt M.
Published: December 2004

Signal transducer and activator of transcription 3 (STAT3) is widely expressed and activated by a variety of growth-regulating signals as well as diverse cytokines that use gp130 signaling receptors. STAT3 is critical for embryonic development and stem cell biology, as well as inflammation, growth regulation, and multiple immune regulatory and homeostatic functions. The animation shows activation of STAT3 in response to interleukin 6 (IL6), a cytokine involved in triggering inflammation.
Phosphorelay Signaling in Yeast in Response to Changes in Osmolarity
Authors: Santos Jennifer L. , Shiozaki Kazuhiro
Published: December 2004

In the yeast,
Saccharomyces cerevesiae
, phosphorelay signaling systems that involve a three-step His-Asp-His-Asp phosphotransfer are involved in transmitting signals in response to cellular stress. The animation shows one example of such a phosphorelay system involved in yeast responses to changes in osmolarity. Under conditions of low osmolarity, a histidine-aspartate phosphorelay pathway transmits information that deactivates one signaling pathway and activates gene expression through another pathway. In response to high osmolarity, the Sln1 kinase that initiates the phosphorelay is inhibited and the Hog1 mitogen-activated protein kinase cascade is active.
Plant G Proteins, Phytohormones, and Plasticity: Three Questions and a Speculation
Authors: Assmann Sarah M.
Published: December 2004

Heterotrimeric guanine nucleotide-binding proteins (G proteins) composed of Gα, Gβ, and Gγ subunits are important transducers of hormonal signals in organisms as evolutionarily distant as plants and humans. The genomes of diploid angiosperms, such as that of the model species
Arabidopsis thaliana
, encode only single canonical Gα and Gβ subunits, only two identified Gγ subunits, and just one regulator of G protein signaling (RGS) protein. However, a wide range of processes—including seed germination, shoot and root growth, and stomatal regulation—are altered in
Arabidopsis
and rice plants with mutations in G protein components. Such mutants exhibit altered responsiveness to a number of plant hormones, including gibberellins, brassinosteroids, abscisic acid, and auxin. This review describes possible mechanisms by which such pleiotropic effects are generated and considers possible explanations for why G protein component mutations in plants fail to be lethal. A possible role of G protein signaling in the control of phenotypic plasticity, a hallmark of plant growth, is also discussed.
MIRROR MATTER ADMIXTURES IN KL→γγ
Authors: SÁNCHEZ-COLÓN G. , GARCÍA A.
Published: December 2004

Based on possible, albeit tiny, admixtures of mirror matter in ordinary mesons we study the KL→γγ transition. We find that this process can be described with a small SU (3) symmetry breaking of only 3%. We also determine the η–η' mixing angle and the pseudoscalar decay constants. The results for these parameters are consistent with those obtained in the literature. They favor three recent determinations; the first is based on two analytical constraints, the second one based on next-to-leading order power corrections, and the third one on a phenomenological determination of the mixing parameters in the framework of the quark-flavor mixing scheme.
Direct ANP inhibition of hypoxia-induced inflammatory pathways in pulmonary microvascular and macrovascular endothelial monolayers
Authors: Irwin D. C. , Tissot van Patot M. C. , Tucker A. , Bowen R.
Published: December 2004

Atrial natriuretic peptide (ANP) has been shown to reduce hypoxia-induced pulmonary vascular leak in vivo, but no explanation of a mechanism has been offered other than its vasodilatory and natriuretic actions. Recently, data have shown that ANP can protect endothelial barrier functions in TNF-α-stimulated human umbilical vein endothelial cells. Therefore, we hypothesized that ANP actions would inhibit pulmonary vascular leak by inhibition of TNF-α secretion and F-actin formation. Bovine pulmonary microvascular (MVEC) and macrovascular endothelial cell (LEC) monolayers were stimulated with hypoxia, TNF-α, or bacterial endotoxin (LPS) in the presence or absence of ANP, and albumin flux, NF-κB activation, TNF-α secretion, p38 mitogen-activated protein kinase (MAPK), and F-actin (stress fiber) formation were assessed. In Transwell cultures, ANP reduced hypoxia-induced permeability in MVEC and TNF-α-induced permeability in MVEC and LEC. ANP inhibited hypoxia and LPS increased NF-κB activation and TNF-α synthesis in MVEC and LEC. Hypoxia decreased activation of p38 MAPK in MVEC but increased activation of p38 MAPK and stress fiber formation in LEC; TNF-α had the opposite effect. ANP inhibited an activation of p38 MAPK in MVEC or LEC. These data indicate that in endothelial cell monolayers, hypoxia activates a signal cascade analogous to that initiated by inflammatory agents, and ANP has a direct cytoprotective effect on the pulmonary endothelium other than its vasodilatory and natriuretic properties. Furthermore, our data show that MVEC and LEC respond differently to hypoxia, TNF-α-stimulation, and ANP treatment.
Strain-dependent differences in responses to exercise training in inbred and hybrid mice
Authors: Massett Michael P. , Berk Bradford C.
Published: December 2004

The aim of this study was to characterize the response to exercise training in several mouse strains and estimate the genetic contribution to phenotypic variation in the responses to exercise training. Male mice from three inbred strains [C57Bl/6J (BL6), FVB/NJ (FVB), and Balb/cJ (Balb/c)] and three hybrid F1strains [CB6F1/J (CB6 = female Balb/c × male BL6), B6F F1(female BL6 × male FVB), and FB6 F1(female FVB × male BL6)] completed an exercise performance test before and after a 4-wk treadmill running program. Distance was used as the primary estimate of endurance exercise performance. FVB mice showed the greatest response to training, with five- to sevenfold greater increases in distance run compared with BL6 and Balb/c strains. Specifically, BL6, FVB, and Balb/c strains increased distance by 33, 172, and 23%, respectively. A similar pattern of changes across strains was observed for run time (17, 87, and 11%) and work (99, 287, and 57%). As a group, F1hybrid mice derived from BL6 and FVB strains showed an intermediate response to training (61%). However, further analysis indicated that training responses in FB6 F1mice (80%) were ∼2.5-fold greater than responses in B6F F1mice (33%, P = 0.08). A similar pattern of changes between FB6 and B6F F1mice was observed for run time (44.5 and 17%) and work (141 and 59%). These data demonstrate that there are large strain-dependent differences in training responses among inbred mouse strains, suggesting that genetic background contributes significantly to adaptation to exercise. Furthermore, the contrasting responses in B6F and FB6 F1strains show that a maternal component strongly influences strain-dependent differences in training responses.
NO and NO-independent mechanisms mediate ETBreceptor buffering of ET-1-induced renal vasoconstriction in the rat
Authors: Just Armin , Olson Andrea J. M. , Falck John R. , Arendshorst William J.
Published: December 2004

Vascular endothelin (ET) type B (ETB) receptors exert dilator and constrictor actions in a complex interaction with ETAreceptors. We aimed to clarify the presence and relative importance of nitric oxide (NO) and other mechanisms underlying the dilator effects of ETBreceptors in rat kidneys. Complete inhibition of NO production with Nω-nitro-l-arginine methyl ester (l-NAME, 25 mg/kg iv) enhanced the renal vasoconstriction elicited by ET-1 injected into the renal artery from −15 to −30%. Additional infusion of the NO donor nitroprusside (NP) into the renal artery did not reverse this effect (−29%) but effectively buffered ANG II-mediated vasoconstriction. Similarly, ET-1 responses were enhanced after a smaller intrarenal dose of l-NAME (−22 vs. −15%) and were unaffected by subsequent NP infusion (−21%). These results indicate that the responsiveness to ET-1 is buffered by ETBreceptor-stimulated phasic release of NO, rather than its static mean level. Infusion of the ETBreceptor antagonist BQ-788 into the renal artery further enhanced the ET-1 constrictor response to NP + l-NAME (−92 vs. −49%), revealing an NO-independent dilator component. In controls, vasoconstriction to ET-1 was unaffected by vehicle (−27 vs. −20%) and markedly enhanced by BQ-788 (−70%). The same pattern was observed when indomethacin (Indo) was used to inhibit cyclooxygenase (−20% for control, −22% with Indo, and −56% with ETBantagonist) or methylsulfonyl-6-(2-propargyloxyphenyl)-hexanamide (MS-PPOH) or miconazole + Indo was used to inhibit epoxygenase alone (−10% for control, −11% with MS-PPOH, and −35% with ETBantagonist) or in combination (−14% for control, −20% with Indo + miconazole, and −43% with ETBantagonist). We conclude that phasic release of NO, but not its static level, mediates part of the dilator effect of ETBreceptors and that an NO-independent mechanism, distinct from prostanoids and epoxyeicosatetraenoic acids, perhaps ETBreceptor clearance of ET-1, plays a major buffering role.
Regulation of Human ApoA-I by Gemfibrozil and Fenofibrate Through Selective Peroxisome Proliferator-Activated Receptor α Modulation
Authors: Duez Hélène , Lefebvre Bruno , Poulain Philippe , Torra Inés Pineda , Percevault Frédéric , Luc Gérald , Peters Jeffrey M. , Gonzalez Frank J. , Gineste Romain , Helleboid Stéphane , Dzavik Vladimir , Fruchart Jean-Charles , Fiévet Catherine , Lefebvre Philippe , Staels Bart
Published: December 2004

Objective—

The objective of this trial was to study the effects of fenofibrate (FF) and gemfibrozil (GF), the most commonly used fibrates, on high-density lipoprotein (HDL) and apolipoprotein (apo) A-I.

Methods and Results—

In a head-to-head double-blind clinical trial, both FF and GF decreased triglycerides and increased HDL cholesterol levels to a similar extent, whereas plasma apoA-I only increased after FF but not GF. Results in human (h) apoA-Itransgenic (hA-ITg) peroxisome proliferator-activated receptor (PPAR) α−/− mice demonstrated that PPARα mediates the effects of FF and GF on HDL in vivo. Although plasma and hepatic mRNA levels of hapoA-I increased more pronouncedly after FF than GF in hA-ITgPPARα+/+ mice, both fibrates induced acylCoAoxidase mRNA similarly. FF and GF transactivated PPARα with similar activity and affinity on a DR-1 PPAR response element, but maximal activation on the hapoA-I DR-2 PPAR response element was significantly lower for GF than for FF. Moreover, GF induced recruitment of the coactivator DRIP205 on the DR-2 site less efficiently than did FF.

Conclusion—

Both GF and FF exert their effects on HDL through PPARα. Whereas FF behaves as a full agonist, GF appears to act as a partial agonist due to a differential recruitment of coactivators to the promoter. These observations provide an explanation for the differences in the activity of these fibrates on apoA-I.
Epicardial Fiber Organization in Swine Right Ventricle and Its Impact on Propagation
Authors: Vetter Frederick J. , Simons Stephen B. , Mironov Sergey , Hyatt Christopher J. , Pertsov Arkady M.
Published: December 2004

Fiber organization is important for myocardial excitation and contraction. It can be a major factor in arrhythmogenesis and current distribution during defibrillation shocks. In this study, we report the discovery of a previously undetected thin epicardial layer in swine right ventricle (RV) with distinctly different fiber orientation, which significantly affects epicardial propagation. Experiments were conducted in isolated coronary-perfused right ventricular free wall preparations (n=8) stained with the voltage-sensitive dye di-4-ANEPPS. Optical signals were recorded from the epicardium with a CCD video camera at 800 fps. Preparations were sectioned parallel to the epicardial surface with a resolution of 50 μm or better. To link the histological data with the observed activation patterns, resulting fiber angles were introduced into a 3D computer model to simulate the electrical activation and voltage-dependent optical signals. In all preparations, we detected a thin epicardial layer with almost no depth-dependent fiber rotation. The thickness of this layer (
z
0
) varied from 110 to 930 μm. At the boundary of this layer, we observed an abrupt change in fiber angle by 64±13° followed by a gradual fiber rotation in the underlying layers. In preparations with
z
0
<700 μm, optical mapping during epicardial stimulation revealed unusual diamond- and rectangular-shaped activation fronts with two axes of fast conduction. Computer simulations accurately predicted the features of the experimentally recorded activation fronts. The free wall of swine RV has a thin epicardial layer with distinctly different fiber orientation, which can significantly affect propagation and give rise to unusually shaped activation fronts. This is important for understanding electrical propagation in the heart, and further refines the existing knowledge of myocardial fiber architecture.
Information Search in the Testing of Quantified Hypotheses: How “All,” “Most,” “Some,” “Few,” and “None” Hypotheses Are Tested
Authors: Sanbonmatsu David M. , Posavac Steven S. , Vanous Sam , Ho Edward A.
Published: December 2004

A series of experiments examined how the search for information in the testing of hypotheses is affected by quantifiers that specify the frequency of the test relation. The experiments showed that a positive search is used more in the testing of propositions in which some instances are predicted to have the test relation than in the testing of propositions in which most or few instances are predicted to have the test relation. In addition, the studies demonstrated that a negative or disconfirmatory search is more likely to characterize tests of absolute hypotheses than tests of hypotheses of the majority or minority form. Finally, the findings indicated that a negative search also is more common in tests of hypotheses predicting the absence rather than the presence of a phenomenon. Thus, as expected, participants generally engaged in a diagnostic search rather than the confirmatory search for information that has been so ubiquitous in previous research.
Advances in Violence and Trauma
Authors: Hughes Honore M. , Humphrey Natalie N. , Weaver Terri L.
Published: December 2004

The most important things learned about violence and trauma in the past 20 years are that interpersonal violence is prevalent, with different forms co-occurring, and that victims' reactions are complex. Researchers are called to consider models that include the ecological context within which victims experience violence and trauma to gain a better understanding of the variation seen in psychological outcomes. Multivariate data-analytic techniques such as structural equation modeling and cluster analysis are suggested as promising ways to explore questions framed by comprehensive models. These recommendations are predicted to provide comprehensive and individualized ways to intervene and prevent interpersonal violence.
Empirically Enhanced Reflections on 20 Years of Rape Research
Authors: Koss Mary P.
Published: December 2004

Using PsychInfo review of rape and sexual assault publications, the period of greatest fertility coincided with the establishment (1975) and demise (1987) of the National Center for the Prevention and Control of Rape. To document what has been learned and when, the era in which new rape concepts entered the literature is summarized and important developments highlighted. Then, new investigations that are urgently needed are elaborated. The author expresses concern that current federal investment is insufficient to sustain and expand a science workforce adequate to the tasks ahead. Since 1995, more than $1 billion have been awarded to prosecutors, law enforcement, and community agencies to assist victims of violence. In contrast, between 1996 and 2003, only 14 of 178 (7%) of investigator-initiated grants funded by the Department of Justice and the Centers for Disease Control and Prevention for violence against women had titles pairing the word sexual with assault, violence, abuse, or rape.
Preventing Violence and Trauma in the Next Generation
Authors: Ryan Gail
Published: December 2004

Research in recent times has clearly demonstrated that violence is predictable and preventable; however, the primary prevention of abusive and violent behavior will not occur without personal, interpersonal, and social change. This article reviews the empirical research supporting hypotheses for primary prevention of many risks associated with children becoming abusive.
Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro–transcribed MUC1 RNA
Authors: Dörfel Daniela , Appel Silke , Grünebach Frank , Weck Markus M. , Müller Martin R. , Heine Annkristin , Brossart Peter
Published: December 2004

RNA transfection of dendritic cells (DCs) was shown to be highly efficient in eliciting CD8+ and CD4+ T-cell responses. However, antigen presentation pathways involved in generation of human leukocyte antigen (HLA) class I and class II peptides have remained elusive. To analyze this we incubated mucin 1 (MUC1) RNA-transfected DCs with compounds known to inhibit HLA class I presentation and used these cells in chromium 51 (51Cr)–release assays. As effectors, we used cytotoxic T lymphocyte (CTL) lines specific for the MUC1 peptides M1.1 and M1.2. We observed that the presentation of HLA-A*02 epitopes is inhibited by brefeldin A and lactacystin. To determine the requirement of a functional transporter associated with antigen processing (TAP), we cotransfected DCs with MUC1 and infected cell peptide 47 (ICP47) RNA. ICP47 could only inhibit the presentation of the M1.1 but not the M1.2 peptide, indicating that this epitope derived from the signal sequence is presented independently of TAP. Cocultivation of MUC1 RNA-transfected DCs with MUC1-specific CD4+ T lymphocytes revealed that the presentation of HLA class II peptides is sensitive to proteasomal inhibitors and brefeldin A. Furthermore, the presentation pathway requires lysosomal and endosomal processing and is mediated by autophagy. Our results demonstrate that the efficient presentation of cytosolic proteins on major histocompatibility complex (MHC) class II combines the proteolytic and lysosomal pathways.
Differential Activation of the Connexin 43 Promoter by Dimers of Activator Protein-1 Transcription Factors in Myometrial Cells
Authors: Mitchell Jennifer A. , Lye Stephen J.
Published: December 2004

The expression of activator protein-1 (AP-1) transcription factors is increased in the myometrium at term and may therefore regulate the expression of genes, such as connexin 43 (Cx43), required for the onset of labor. The region upstream of the mouse, rat, and human Cx43 genes contains two consensus AP-1 binding sequences, a proximal AP-1, located close to the TATA box, and a distal AP-1, 1 kb upstream. A transient transfection system was developed in which Syrian hamster myometrial cells were transfected with Cx43 promoter-luciferase constructs in combination with expression vectors for the AP-1 family. Transfection with c-Jun or JunB had no effect on transcription from the Cx43 promoter, whereas transfection with JunD or combinations of Jun and Fos family members led to significant increases in transcription. Deletion of the distal AP-1 site did not abrogate transcription driven by Fos/Jun, whereas a 2-bp mutation in the proximal AP-1 site significantly reduced pCx43 transactivation by AP-1 dimers. Dimers comprising Fos/Jun proteins conferred greater transcriptional activity than Jun dimmers, with Fra-2/JunB combination conferring greatest activity. These data suggest that increased expression of Fos family members in the myometrium at term drives the increase in Cx43 transcription and expression during labor. Because expression of Fra-2 increases earlier than other Fos family members and confers the highest transcriptional drive to the Cx43 promoter, our data suggest that Fra-2 is a central component in the regulation of Cx43 expression during labor.
Chemiker(innen) am Öko‐Institut
Authors: Grießhammer Rainer
Published: December 2004

Das Öko‐Institut e. V. wurde am 5. November 1977 gegründet; Geburtsstunde der „alternativen”︁ Wissenschaft. Jeder Geburt geht freilich eine Zeugung voraus, und dieser Prozeß mag interessanter sein als die Erinnerung an den Geburtstermin. Allerorts entstanden zu Beginn der 70er Jahre Bürgerinitiativen, die sich gegen die hohe Belastung von Luft‐ und Wasser durch Chemikalien, gegen undichte und überbordende Müllkippen, gegen giftige Altlasten, gegen Emissionen aus Industrieanlagen und gegen problematische Produkte wehrten ‐ mit Öffentlichkeitsarbeit, Aktionen, in politischen Gremien und zum Teil vor Gericht.
Dipolmessungen an Benzhydroxamsäure‐ und Benzhydroximsäure‐Derivaten. Acylderivate des Hydroxylamins, XIV. Mitteilung [1]
Authors: Exner O. , Schindler O.
Published: December 2004

Der stereochemische Verlauf der Methylierung von Benzhydroxamsäureestern mit Diazomethan zu 3‐O‐Methyl‐benzhydroximsäureestern wurde mit Dipolmessungen abgeklärt. Die auf diesem Weg entstandenen Benzhydroximsäure‐Derivate IIa‐IId sowie VIII–X gehören zur syn‐Reihe. VIII–X liegen in einer Konformation vor, die angenähert dem Formelbild A1 (S. 580) entspricht. Die beträchtliche, in dieser Konformation auftretende sterische Wechselwirkung wird wahrscheinlich durch Abweichen vom planaren Bau ausgeglichen.
Die säurekatalysierte Isomerisierung von 7‐Oxabicyclo[2.2.1]‐heptadien‐ und Oxepin‐Derivaten [1]
Authors: Vogel P. , Willhalm B. , Prinzbach H.
Published: December 2004

The acid catalyzed isomerization of several substituted oxanorbornadienes 4 and oxepines 10 ‐ easily available from 4 by a photochemical and a consecutive thermal step ‐ allows the synthesis of several highly substituted phenols and 2,4‐cyclohexadienones in a straightforward manner and with good to excellent yields. The formation of the methoxycarbonyl‐hexadienes 18e and 18f upon photolysis of 9e and 17f in methanol supports the structure elucidation. The relative importance of the McLAFFERTY and EMERY effects in the mass spectral degradation of methoxycarbonyl and methyl substituted phenols are discussed.
Obtention de phosphore élémentaire et de phosphures de nickel par électrolyse de solutions de pentoxyde de phosphore dans des bains à base de cryolithe
Authors: Monnier R. , Tzanos D. , Tissot P.
Published: December 2004

By electrolysis of cryolitic solutions of P2O5, elementary pure phosphorus is obtained on carbon cathode and Ni phosphides on Ni cathode. The most probable mechanism of phosphorus formation in these conditions seems to be the final dissociation of P2O5 in P5+ and O2− and the primary electrodic discharge of these ions.
Dibenz [b, f]‐1, 4‐oxazepin‐11 (10 H)‐one und Dibenz [b, e]‐1, 4‐oxazepin‐11 (5 H)‐one. 12. Mitteilung über siebengliedrige Heterocyclen
Authors: Künzle F. , Schmutz J.
Published: December 2004

The syntheses of dibenzo [b, f]‐1, 4‐oxazepin‐11 (10 H)‐ones (I) with electron‐attracting substituents in position 2 by ring closure of the sodium salts of 2‐halogeno‐2′‐hydroxy‐benzanilides (II) are described. The reaction of II (R = SO2·N(CH3)2) in N‐methylpyrrolidone also led, by SMILES rearrangement, to the isomeric minor product dibenzo [b, e]‐1, 4‐oxazepin‐11 (5 H)‐one (III; R = SO2·N(CH3)2), whose constitution was proven by synthesis from VI. In the case of II (R = SO2·CH3), the 5‐methylsulfonyl‐2‐(2‐hydroxyanilino)‐benzoic acid (VI; R = SO2·CH3) was obtained directly after hydrolysis. The lactam I (R = NO2) was rearranged to the corresponding acid VI by heating with dilute caustic soda.
Die Struktur des Anhydro‐isocalebassin‐methyläthers; Säurekatalysierte Umlagerungen des Curare‐Alkaloids C‐Calebassin. 60. Mitteilung über Calebassen‐Alkaloide [1]
Authors: Gemmell K. W. , Robertson J. Monteath , Sim G. A. , Bernauer Karl , Guggisberg A. , Hesse M. , Schmid H. , Karrer P.
Published: December 2004

Treatment of the Calebash alkaloid C‐calebassine (1), C40H48N4O2++·2X−, with hot mineral acid yielded the anhydro‐isocalebassine acid adduct 3H, with the formula C40H47N4O+++·3X−.H2O. This was converted into anhydro‐isocalebassine methyl ether salts (4) C41H48N4O++·2X−·H2O with alkaline dimethyl sulphate. A total X‐ray analysis of the orthorhombic diiodide led to formula 4. The conversion of C‐calebassine (1) into 4 involves a radical change in the central part of the molecule.

The structure of the acid adduct 3H can be deduced from the structure of 4.

Treatment of 3 H with warm methanol or treatment of C‐calebassine (1) with acetic acid yielded a pale yellow compound 2, C40, H44N4++·2X−·H2O. The central part of the molecule 2 contains a pyrrole ring, and most probably this is an intermediate in the conversion of 1 into 3 H by mineral acid. The changes of 3 H and 2 in acidic, neutral and basic media can be shown by electronic spectroscopy.

Reaction of 3 H with 1 mole of oxygen at pH 4 converted it into a stable blood‐red oxidation product C40H44N4O2++·2X− containing a merocyanine system. The structure 7, proposed for this compound, is discussed.
Stereomere Muscarine kommen in der Natur vor. Gas‐chromatographische Trennung der Norbasen 30. Mitteilung über Inhaltsstoffe von Fliegenpilzen
Authors: Eugster C. H. , Schleusener E.
Published: December 2004

Im Fliegenpilz (Amanita muscaria (L. ex Fries) HOOKER) kommen neben Muscarin auch allo‐Muscarin, epi‐Muscarin und wahrscheinlich sogar epiallo‐Muscarin in geringer Menge vor. Dasselbe trifft für gewisse Inocybe‐Arten zu (J. patouillardi, fastigiata, rimosa s. cookei), in denen auch epiallo‐Muscarin aufgefunden werden konnte. Es ist möglich, dass in einzelnen Inocybe‐Arten Muscarin nicht das vorherrschende Isomere ist. Alle bisher zur Isolierung von Muscarin verwendeten Isolierungsverfahren sind zur Erkennung der Stereomeren ungeeignet. Wahrscheinlich haben sie auch zum Verlust einzelner Isomerer geführt.

Der analytische Nachweis gelingt durch Pyrolyse der quaternären Chloride im Vakuum bei 200–240° und anschliessede gas‐chromatographische Trennung der Norbasen an einer geeigneten Kapillarkolonne.

Unsere neuen Ergebnisse machen eine Überprüfung der bisherigen Untersuchungen an allen muscarinführenden Pilzen notwendig.
Fragmentierung einiger Azoverbindungen durch Pyrolyse und Elektronenstoss
Authors: Völlmin J. A. , Pachlatko P. , Simon W.
Published: December 2004

The structure of the products of the pyrolysis gas chromatography of some azobenzenes has been determined. The thermal fragmentation is compared with the fragmentation induced by electron impact.

The pyrolysis technique described gives information on the aromatic substitution not obtainable by mass spectrometry.
Zur Biosynthese des Strychnins. 135. Mitteilung über Alkaloide
Authors: Schlatter Ch. , Waldner E. E. , Schmid H. , Maier W. , Gröger D.
Published: December 2004

From the feeding of young plants of Strychnos nux‐vomica with [14C]‐1‐and [14C]‐2‐acetate it could be deduced that the C‐atoms 22 and 23 were derived from acetate. [14C]‐2‐mevalonate, [14C]‐2‐geraniol and [14C]‐2‐geranyl pyrophosphate were also incorporated into strychnine. The distribution of radioactivity in the «mevalonate‐strychnine» was in agreement with the monoterpenoid hypothesis. Feeding experiments especially with [14C]‐tryptophane showed that the main production centre of the alkaloid lay in the roots and that only a small part of it was carried to the leaves. Tritium labelled WIELAND GUMLICH aldehyde as well as N(a)‐[14C]‐1‐acetyl WIELAND GUMLICH aldehyde were not converted into strychnine by S. nux‐vomica.
α‐Caryopteron, ein neues Pyrano‐juglon aus Caryopteris clandonensis
Authors: Matsumoto T. , Mayer C. , Eugster C. H.
Published: December 2004

Caryopteris clandonsis BUNGE (Verbenaceae) enthält in der Wurzelrinde mehrere Farbstoffe, von denen einer, α‐Caryopteron, C15H12O4, kristallisiert und rein erhalten werden konnte. Er wurde als 9‐Hydroxy‐α‐dehydrolapachon (Ia) erkannt, wobei die Lage der Hydroxylgruppe unter Beiziehung der para‐ortho‐Chinonmlagerung nach PATERNÒ;‐HOOKER, am Dihydroderivat festgelegt wurde.
Indirekte Bestimmung von Sulfat neben Phosphat mit Hilfe der atomaren Absorptionsspektrometrie
Authors: Magyar B. , Santos F. Sanchez
Published: December 2004

The final equilibrium in the formation of solid BaSO4 is reached very slowly when solutions with Ba2+ and SO are mixed. The ion product Lp″ = [Ba2+] · [SO] of the concentrations remaining in solution however becomes rather constant after about 1/2 hour already, especially when the suspension is seeded with a specially prepared BaSO4. The apparent solubility product–somewhat larger than the theoretically expected value–varies with the composition of the solution (other solutes present than Ba2+ and SO) and the equilibration time, but it is independent of the Ba/SO4‐ratio. This allows a great improvement of the indirect determination of sulphate by adding barium and determining its excess by atomic absorption.
Zur Synthese von Aminocaprolactam
Authors: Kessler W. , Brenner M.
Published: December 2004

α‐Amino‐ϵ‐caprolactam (I), an intermediate for the synthesis of L‐lysine, has been synthesized by BECKMANN‐rearrangement of α‐amino‐cyclohexanoneoxime (XII) in concentrated sulfuric acid (13% yield) or oleum (34% yield). Cyclisation of α‐amino‐ϵ‐bromocaproamide hydrobromide (VIII) did not yield I but an isomer of I of unknown structure (compound X). Upon hydrolysis X gave a compound XI which was similar to lysine in its chromatographic and electrophoretic behavior.
Synthese von rac‐threo und rac‐erythro‐α‐(2, 2‐Dichloracetamido)‐β‐hydroxy‐p‐nitrohydrozimtaldehyd
Authors: Zanetti G. , Vogler K.
Published: December 2004

rac‐threo‐α‐(2, 2‐Dichloroacetamido)‐β‐hydroxy‐p‐nitrohydrocinnamaldehyde (3) and rac‐erythro‐α‐(2, 2‐dichloroacetamido)‐β‐hydroxy‐p‐nitrohydrocinnamaldehyde (4) were synthesized starting from α‐acetamido‐p‐nitroacetophenone (7), and their structures were proved bn− reduction to rac‐chloramphenicol (19) and rac‐erythro‐2‐(2, 2‐dichloroacetamido)‐1‐(p‐nitrophenyl)v 1, 3‐propanediol (14) respectively. 3 exhibited only low antibacterial activity compared to rac‐chloramphenicol (19).
Über ein neues Glykosidierungsverfahren II. Glykoside des 4′‐Demethylepipodophyllotoxins. 23. Mitteilung über mitosehemmende Naturstoffe [1]
Authors: Kuhn M. , von Wartburg A.
Published: December 2004

4′‐Demethylepipodophyllotoxin‐β‐D‐glucopyranoside (VIII) and 4′‐demethylepipodophyllotoxin‐β‐D‐galactopyranoside (X) have been synthesized by reaction of the aglycones III and IV with the corresponding tetra‐O‐acetyl‐β‐D‐hexopyranose in the presence of BF3‐etherate. The suggested configurations at C‐1 of the aglycone moiety in the new glycosides could be confirmed by NMR.‐spectra.