julilili42/papers huggingface dataset:
Binding and effect of KATP channel openers in the absence of Mg2+
2003-05-01

Openers of ATP‐sensitive K + channels (K ATP channels) are thought to act by enhancing the ATPase activity of sulphonylurea receptors (SURs), the regulatory channel subunits. At higher concentrations, some openers activate K ATP channels also in the absence of MgATP. Here, we describe binding and effect of structurally diverse openers in the absence of Mg 2+ and presence of EDTA. Binding of openers to SUR2B was measured using a mutant with high affinity for [ 3 H]glibenclamide ([ 3 H]GBC). In the absence of Mg 2+ , ‘typical' openers (benzopyrans, cyanoguanidines and aprikalim) inhibited [ 3 H]GBC binding with K i values ∼200 × higher than in the presence of MgATP. Minoxidil sulphate and nicorandil were inactive, whereas binding of diazoxide was unaffected by MgATP. In the absence/presence of MgATP, N ‐cyano‐ N ′‐(1,1‐dimethylpropyl)‐ N ′′‐3‐pyridylguanidine (P1075) activated the Kir6.2/SUR2B channel in inside–out patches with EC 50 =2000/67n M and E max =32/134%. In the absence of Mg 2+ , responses were variable with only a small part of the variability being explained by a decrease in channel responsiveness with time after patch excision and to differences in the ATP sensitivity between patches. The rank order of efficacy of the openers was P1075&gt;rilmakalim ∼nicorandil&gt;diazoxide&gt;minoxidil sulphate. The data show that structurally diverse openers are able to bind to, and to activate the Kir6.2/SUR2B channel by a pathway independent of ATP hydrolysis. These effects are observed at concentrations used to define the biochemical mechanism of the openers in the presence of MgATP and allow the openers to be classified into ‘typical’ and ‘atypical’ KCOs with diazoxide standing apart. British Journal of Pharmacology (2003) 139 , 368–380. doi: 10.1038/sj.bjp.0705238
Reactions of the Complexes ReNCl2(PMe2Ph)3, [ReNCl4]—, [OsO3N]—, and Cl3VNCl with Metal Halides
2003-05-01

Abstract The nitrido complexes ReNCl 2 (PMe 2 Ph) 3 and [OsO 3 N] — have strong basic terminal nitrido ligands which can react with Lewis acidic metal halides to form nitrido bridges. The synthesis and structure of complexes with ReNCl 2 (PMe 2 Ph) 3 and nitrido bridges Re≡N‐M (M = B, Ga, Sn, Ti, Zr, V, Nb, Ta, Mo, Re, Pd, Au, and Zn) as well as of complexes with [OsO 3 N] — and nitrido bridges Os≡N‐M (M = Pd and Pt) are reported. Strong Lewis acids can also remove phosphine or chloro ligands from ReNCl 2 (PMe 2 Ph) 3 . The resulting complex fragments subsequently combine to yield oligomeric complexes with nitrido bridges Re≡N‐Re. If the reaction with strong Lewis acids is carried out in a chlorinated solvent the solvent can be decomposed to form HCl which then protonates the nitrido ligand affording an imido complex. [ReNCl 4 ] — is able to form nitrido bridges to electrophilic halides if a donor ligand is coordinated in trans position to the nitrido ligand to enhance its basicity sufficiently. The synthesis and structure of examples with nitrido bridges Re≡N‐M (M = Pd, Pt, Ta) are reported. The chloro imido complex Cl 3 V≡N‐Cl can act as a nitride ion transfer reagent. Its reaction with MoCl 5 yields Mo 2 NCl 8 whereas with MoCl 3 the nitride chlorides Mo 3 N 2 Cl 11 and MoNCl 3 are obtained. Cl 3 VNCl can also act as an reactive intermediate by the reaction of VN with a halide as was shown by the reaction of MoCl 5 with VN yielding Mo 2 NCl 7 . The structures of these molybdenum nitride chlorides are discussed.
Synthesis and Structure of 1-{2,2-Dimethyl-4,6-dioxo-5-(1-pyridinio)-1,3- dioxan-5-yl}pyridinium Ylide: A New Route to Meldrum’s Acid Derivatives
2003-05-01

2-Bromo-5,5-dimethyl-4,6-dioxo-1,3-dioxine (3) reacts with pyridine and aqueous potassium carbonate to give 1-{2,2-dimethyl-4,6-dioxo-5-(1-pyridinio)-1,3-dioxan-5-yl}pyridinium ylide (5). The crystal structure analysis confirms the betaine nature of 5 consisting of two distored ring fragments [interplanar angle 58.0(4)°] connected by a C-N single bond [1.440(1) Å ].
The effect of retinal growth on the postnatal development and distribution of displaced retinal ganglion cells in the retina of the chameleon (squamata)
2003-05-01

Retinal ganglion cells (RGCs) usually increase their dendritic field area with postnatal retinal growth. The mechanisms that regulate the postnatal shape of dendritic arbors in the growing retina are not well understood. Quantitative studies suffer from the difficulty of labeling specific subpopulations of RGCs selectively including their dendritic processes. In this study, we labeled displaced retinal ganglion cells (DGC) that are known to project to the accessory optic system (AOS) in juvenile and adult chameleons by retrograde transport of dextran amines. The complete population of DGCs was quantitatively screened for the effects of postnatal retinal growth on cell morphology, dendritic field coverage, and dendritic arbor size. The adult eye contained 2000 DGCs/retina. This number was already present at birth. The smaller size of the hatchling eye (approximately 1/3 of the adult size) led to higher densities of DGCs. The greatest accumulation of juvenile DGCs (two-fold higher compared to the adult) was found in the periphery of the retina where the greatest surface expansion was observed. DGC dendritic field areas were adjusted proportionally to this expansion in order to maintain a constant dendritic coverage. The increase of dendritic fields was mediated by two putative passive mechanisms: First, an elongation of individual dendrites similar to previous reports of postnatal RGC development in the retina of goldfish and chicks. Second, and more prominent, we observed that neighboring dendrites were pulled apart from each other. This resulted in a looser spacing of the initially tightly packed dendrites of each dendritic arbor. This dispersal of dendrites over a larger area was, due to its passive nature, proportional to the increase of the retinal surface and preserved a constant dendritic coverage irrespective of the animal's age and eye size.
2-Amino-1,3-dimethylimidazolium 2,2-Dimethyl-4,6-dioxo-1,3-dioxanide. First Structural Characterisation of the Anion of Meldrum’s Acid [1]
2003-05-01

2-Amino-1,3-dimethylimidazolium 2,2-dimethyl- 4,6-dioxo-1,3-dioxanide (6) has been obtained from the reaction of 2,2-dimethyl-4,6-dioxo-1,3- dioxan (1, “Meldrum’s acid”) and 2-imino-1,3-dimethylimidazoline (5) in excellent yield. The unit cell of 6 contains two crystallographically independent anions lying on crystallographic mirror planes. The structure of the anion is compared with that of compound 1.
ABNORMAL LOW REGULAR HEART FREQUENCY IN A CYCLIST IN NEAR-MAXIMUM EXERCISE
2003-05-01

HISTORY A 39 year old man had noticed the low pulse on his pulse checker during strenuous biking. Being used to race bicycling for 15 years and knowing of a normal stress ECG 11 months earlier he thought the checker to be out of order when it showed a drop of the heart rate from about 120 • min-1 to between 80 and 90 • min-1 whenever he went up a steeper hill in the Alps. He felt somewhat less performing than usual, but had no other symptoms. PHYSICAL EXAMINATION The clinical examination revealed a normal cardiovascular status: regular heart beat 60/min, blood pressure 130/80 mm Hg, no murmur, normal auscultation of the lungs. DIFFERENTIAL DIAGNOSIS Sick sinus syndrome Exercise induced atrio-ventricular block Exercise induced His bundle blockade TEST AND RESULTS Resting ECG: regular sinus frequency 54 • min-1, atrio-ventricular block I°, right branch block, typical depolarization Bicycle ergometry setting out at 50 W, increment 50 W, step duration 3 min, maximum load 300 W 1 min = 3.1 W • kg-1 Heart frequency: 50 W 94, 100 W 120, 150 W 112, 200 W 82, 250 W 78, 300 W 88. 1 min after exercise 147 and 5 min after exercise 112 • min-1, maximum lactate 7.02 mmol • l-1 The ECG revealed regular sinus rhythm up to 100 W, then occasional blockade within the His bundle which was interrupted occasionally within 30 s after exercise and continued regular at 145 • min-1 1 min after exercise. Blood pressure increased from 120/95 to 170/60 mm Hg at 250 W. WORKING DIAGNOSIS Exercise induced 2: 1 block within the His bundle; atrio-ventricular block I ° and right branch block TREATMENT AND OUTCOMES Cardiac pacer planned Optional myocardial biopsy
DOPERS
2003-05-01

Doping substances are abused by an increasing number of hobby athletes. Unfortunately, the development of prevention programs is hampered by a controversially discussed abuser profile. According to one hypothesis, dopers are conceived as a socially disadvantaged group of multiple substance abusers. The alternative hypothesis holds that dopers want to improve body and performance and thus must be regarded as specific substance users. PURPOSE As a basis for future prevention and intervention programs, we examined the doping substance abuser profile among fitness center visitors as a heterogeneous group, which is known to represent 10% of western societies populations. METHODS 1802 standardized, anonymous questionnaires were distributed among the members of 113 fitness studios. Questions were raised concerning biometric parameters, social indicators, physical fitness and use of natural stimulants, illicit drugs and doping substances. RESULTS The scavenge was 34.5%. Of the participants 13.5% confessed intake of doping substances and 15.9% abuse of illicit drugs. Intake of doping substances were highly significantly correlated with abuse of illicit drugs (p<0.001). Detailed analysis of correlation by logistic regression models revealed substantial differences between illicit drug users and dopers. Doping was significantly positively correlated with cocaine abuse as the only illicit drug correlated with doping (p<0.005), training years (p<0.005), training frequency (p<0.01) and nationality (p<0.01) and negatively with high school graduation (p<0.05) and the frequency of alcohol intake (p<0.005). Illegal drug abuse however, was positively correlated with frequency of alcohol intake (p<0.05) and smoking (p<0.0001) and negatively with having children (p<0.05) and being older age (p<0.05). CONCLUSION These results indicate that dopers are a distinct group of substance abusers exhibiting a certain profile, which seems to be of high relevance for designing future prevention and intervention programs
DOPING IN FITNESS SPORTS IS STRONGLY SUPPORTED BY THE HEALTH-CARE SYSTEM
2003-05-01

In the past few years doping has become a remarkable problem in hobby fitness sports. Since almost 10% of the total population in western societies practice fitness sports, doping has rather become a matter of public health with economic impact than being of sport ethical or individual importance only. PURPOSE As a basis for future prevention and intervention, we examined the influence of the health care system on the use of doping substances. METHODS Using a standardized, anonymous questionnaire, 621 hobby athletes from 113 fitness studios, with a total of 90.100 members, were questioned about their use of doping substances. In the event of positive answers to drug use, we inquired further about the type, number and source of used substances, form of administration, as well as whether a physician was overseeing intake. RESULTS 19.2% of the men and 3.9% of the women answered positively to using doping substances. 83.5% reported taking AAS, and 40.3% reported using Beta-2-Recepor-Agonists. 51.5% of the AAS abusers took both oral and injected drugs, while 35.3% took oral forms only and 13.2% injected only. 39.7% of the athletes were found to use only one substance, 42.6% took two to four substances, and 17.7% used more than four substances. 16.7% of the athletes who doped obtained the substances exclusively from physicians or pharmacists, and another 29.8% used the black market in addition to these other two sources. 58.3% of the athletes who took more than four substances but only 34.5% of those who took two to four and only 11.1% of those using one substance reported their physician as source. In total 32.1% of the participants assured to be supervised by a physician. CONCLUSION Doping in fitness sports is strongly supported by the health-care system. Before introducing preventative programs, physicians and pharmacists should be intensively educated on the negative consequences of doping.
PROLONGED PERFORMANCE DEFICIENCY IN A PROFESSIONAL CYCLIST
2003-05-01

HISTORY A 24-year-old professional cyclist came to our out-patient department complaining of a prolonged performance deficiency, already lasting for at least 8 weeks. Due to his poor race performance, he had already cancelled the last races, in an attempt to recover from what he thought was a state of overtraining. Rest, compensatory work-outs and physical therapy, however, had failed to improve his condition. The initial detailed medical history and vegetative anamnesis were inconspicuous. Resting heart rate was within individual normal ranges and body weight was almost constant (normal variations +/- 1–2kg, weight loss of 1kg during last 6 months). No signs of infectious diseases or dyspnea were reported. He had a complete medical check-up three months before, which revealed no major abnormalities except for a slight eosinophilia of 6.7% (total eosinophils 436/μ l) which was put down to a suggested, yet unconfirmed, allergic predisposition. Typical symptoms, such as seasonal rhinitis or conjunctivitis, had not been present for years. PHYSICAL EXAMINATION The general examinations of the slim but powerful male (178cm, 66.5 kg, body fat 8.3%) were normal. DIFFERENTIAL DIAGNOSIS Overreaching due to training/competition intensity Infection Allergic reaction TESTS AND RESULTS ECG: inconspicuous Laboratory results: -mainly inconspicuous except for mild bilirubinaemia (30,4 μl/l) and relative eosinophilia of 4.1% with a normal eosinophilic count of 225/μ l, low triglycerides of 0,70 mmol/l and elevated available iron (47,4 μmol/l) SECOND HISTORY During the second examination, past laboratory examinations were presented which revealed a descending eosinophilia over time with the highest values 6 months before the investigation (eosinophilia of 11,8% total eosinophils 767/μl). Upon questioning, he remembered a case of mild diarrhea or irregular bowel movement about four months ago and occasional episodes of what he thought might be digestive irregularities due to his observation that after italian meals “spaghetti” were sometimes excreted in the stool. He had taken several journeys to subtropical and tropical destinations in Asia and Africa in the past fall. WORKING DIAGNOSIS Helminthiasis SECOND TESTS AND RESULTS stool examinations and faecal microscopy: - Taenia ova, probably Taenia saginata FINAL DIAGNOSIS Taeniasis, probably Taenia saginata TREATMENT AND OUTCOME After treatment with a single dose of praziquantel (10mg/kg) multiple stool examinations one, two and three months after treatment were negative. His subjective performance returned to normal levels within two weeks; racing performance was comparable to past achievements.
On the Landau–Ginzburg theory of MAG projected SU(2) lattice gauge theory
2003-05-01

Maximal Abelian gauge fixing and subsequent Abelian projection of SU(2) lattice gauge theory defines closed trajectories of magnetic monopoles. These trajectories can be interpreted in terms of an effective scalar field theory of the MAG monopoles using the worldline representation of the functional determinants. Employing the monopole worldlines detected in the numerical simulation, we show that a collective monopole anti-monopole excitation exists. The screening mass m of this state properly scales towards the continuum limit. We find m ~ 1.5 GeV when the string tension MeV is used as reference scale.
Chains of [RE6] Octahedra Coupled by (NCN) Links in the Network Structure of RE2Cl(CN2)N. Synthesis and Structure of Two Novel Rare Earth Chloride Carbodiimide Nitrides with Structures Related to the RE2Cl3 Type
2003-05-03

Solid state metathesis reactions between RECl(3) (RE = La, Ce) and Li(2)CN(2) at 800 degrees C have led to the discovery of the rare earth chloride carbodiimide nitrides La(2)Cl(CN(2))N (1) and Ce(2)Cl(CN(2))N (2), respectively. Single crystal X-ray diffraction analyses revealed that 1 and 2 crystallize isotypic in an orthorhombic system (Cmmm, Z = 4, a = 13.3914(8) A, b = 9.6345(7) A, c = 3.9568(2) A for 1 and a = 13.340(1) A, b = 9.5267(8) A, c = 3.9402(5) A for 2). The crystal structures of 1 and 2 contain linear chains of edge-sharing octahedra built from rare earth metal atoms. Similar to [M(6)X(8)] type clusters, the [RE(6)] octahedra are capped by eight nitrogen atoms above their faces, of which four are from N(3-) ions and the other four are from (CN(2))(2-) ions. The chains are interconnected by bridging (CN(2))(2-) to form a three-dimensional network with Cl(-) ions in linear channels. Compounds 1 and 2 are surprisingly stable toward air and water. They have been characterized by thermal analysis, infrared spectroscopy, and magnetic susceptibility studies.
Gene expression profiling of ciliary neurotrophic factor‐overexpressing rat striatal progenitor cells (ST14A) indicates improved stress response during the early stage of differentiation
2003-05-05

Abstract Neuronal progenitor cells delivering neurotrophic factors are a promising therapeutic tool for treatment of neurodegenerative diseases. Although several promising results have come from studies in different animal models, detailed knowledge of the action of neurotrophic factors in the CNS is still lacking. A clonally derived, immortalized rat striatal cell line (ST14A) expressing ciliary neurotrophic factor (CNTF) offers a stable and controlled background with which to analyze CNTF actions on the transcriptional level in CNS progenitor cells. To identify early transcriptional changes induced by CNTF expression, we transfected the CNTF gene into ST14A cells, which differentiate at the nonpermissive temperature of 39°C via suppression of the immortalizing SV40 large T antigen. This shows a CNTF‐dependent hypoxic/ischemic stress response during the earliest stage of differentiation, with expression of specific transcripts and evidence of translational repression leading to decreased protein synthesis in the transfected cells. This process is mediated by the Ras/MAP kinase pathway and is accompanied by impaired proliferation and metabolism as well as signs of neuronal differentiation. The stress‐like response in the early stage of differentiation improves the ability of the transfected cells to respond to and cope with a stressful environment in vivo. The present data indicate higher viability, longer life, and greater differentiation capacity of CNTF‐ST14A cells if they are used for transplantation. We conclude that the stress‐like response during the early stage of differentiation improves the ability of the CNTF‐ST14A cells to respond and adapt to a stressful environment, which renders them useful candidate cells for in vivo trials of treatment for neurodegenerative diseases in animal models, e.g., of Huntington's disease. © 2003 Wiley‐Liss, Inc.
Suppression of Coatomer Mutants by a New Protein Family with COPI and COPII Binding Motifs inSaccharomyces cerevisiae
2003-05-06

Protein trafficking is achieved by a bidirectional vesicle flow between the various compartments of the eukaryotic cell. COPII coated vesicles mediate anterograde protein transport from the endoplasmic reticulum to the Golgi apparatus, whereas retrograde Golgi-to-endoplasmic reticulum vesicles use the COPI coat. Inactivation of COPI vesicle formation in conditional sec21 (γ-COP) mutants rapidly blocks transport of certain proteins along the early secretory pathway. We have identified the integral membrane protein Mst27p as a strong suppressor of sec21-3 and ret1-1 mutants. A C-terminal KKXX motif of Mst27p that allows direct binding to the COPI complex is crucial for its suppression ability. Mst27p and its homolog Yar033w (Mst28p) are part of the same complex. Both proteins contain cytoplasmic exposed C termini that have the ability to interact directly with COPI and COPII coat complexes. Site-specific mutations of the COPI binding domain abolished suppression of the sec21 mutants. Our results indicate that overexpression of MST27 provides an increased number of coat binding sites on membranes of the early secretory pathway and thereby promotes vesicle formation. As a consequence, the amount of cargo that can bind COPI might be important for the regulation of the vesicle flow in the early secretory pathway.
Targeted ablation of CCAP neuropeptide-containing neurons ofDrosophilacauses specific defects in execution and circadian timing of ecdysis behavior
2003-05-07

Insect growth and metamorphosis is punctuated by molts, during which a new cuticle is produced. Every molt culminates in ecdysis, the shedding of the remains of the old cuticle. Both the timing of ecdysis relative to the molt and the actual execution of this vital insect behavior are under peptidergic neuronal control. Based on studies in the moth, Manduca sexta, it has been postulated that the neuropeptide Crustacean cardioactive peptide (CCAP)plays a key role in the initiation of the ecdysis motor program. We have used Drosophila bearing targeted ablations of CCAP neurons (CCAP KO animals) to investigate the role of CCAP in the execution and circadian regulation of ecdysis. CCAP KO animals showed specific defects at ecdysis, yet the severity and nature of the defects varied at different developmental stages. The majority of CCAP KO animals died at the pupal stage from the failure of pupal ecdysis, whereas larval ecdysis and adult eclosion behaviors showed only subtle defects. Interestingly, the most severe failure seen at eclosion appeared to be in a function required for abdominal inflation, which could be cardioactive in nature. Although CCAP KO populations exhibited circadian eclosion rhythms, the daily distribution of eclosion events (i.e.,gating) was abnormal. Effects on the execution of ecdysis and its circadian regulation indicate that CCAP is a key regulator of the behavior. Nevertheless, an unexpected finding of this work is that the primary functions of CCAP as well as its importance in the control of ecdysis behaviors may change during the postembryonic development of Drosophila.
Astroglial glutathione export and the supply of glutathione precursors to neurons
2003-05-08

Neurons rely on the availability of extracellular cysteine for their glutathione (GSH) synthesis. This amino acid is generated by processing of extracellular GSH. Astrocytes play an important role in the GSH metabolism of the brain, since of the different brain cell type investigated only astrocytes release substantial amounts of GSH. The multidrug resistance protein 1 (Mrp1) which is expressed in astrocytes in vitro and in vivo mediates about 60% of the GSH release from cultured astrocytes. Extracellular GSH serves as substrate for the astroglial ectoenzyme gamma‐glutamyl transpeptidase (gGT). Inhibition of this enzyme prevents the astroglia‐mediated increase in the GSH level of cocultured neurons. The dipeptide CysGly, which is produced by gGT, is hydrolysed by the neuronal aminopeptidase N to glycine and cysteine. By providing the glutamate‐precursor glutamine and the dipeptide CysGly astrocytes supply to neurons precursors for all three amino acids which are required for neuronal GSH synthesis.