Binding of radioactively labeled carboxyatractyloside, atractyloside and bongkrekic acid to the ADP translocator of potato mitochondria

1. The inhibition of the ADP-stimulated respiration of potato mitochondria by carboxyatractyloside is relieved by high concentration of ADP or by the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Atractyloside is a much less potent inhibitor than carboxyatractyloside. The inhibition of the ADP-stimulated respiration required about 60-times more atractyloside than carboxyatractyloside. 2. [35S]carboxyatractyloside and [3H]bongkrekic acid bind to potato mitochondria with high affinity (Kd = 10 to 20 nM, n=0.6-0.7 nmol per mg protein). Added ADP competes with carboxyatractyloside for binding; on the contrary ADP increases the amount of bound bongkrekic acid. [3H]atractyloside binds to potato mitochondria with a much lower affinity (Kd=0.45 muM) than carboxyatractyloside or bongkrekic acid. 3. Bound [3H]atractyloside is displaced by ADP, carboxyatractyloside and bongkrekic acid. The displacement of bound [35S]carboxyatractyloside by bongkrekic acid and of bound [3H]bongkrekic acid by carboxyatractyloside is markedly increased by ADP. 4. Bongkrekic acid competes with [35S]carboxyatractyloside for binding. Addition of a small concentration of ADP considerably enhances the inhibitory effect of bongkrekic acid on [35S]carboxyatractyloside binding. 5. The adenine nucleotide content of potato mitochondria is of the order of 1 nmol per mg protein. ADP transport in potato mitochondria is inhibited by atractyloside 30- to 40-times less efficiently than by carboxyatractyloside.     

New features of 23S ribosomal RNA folding: the long helix 41-42 makes a "U-turn" inside the ribosome

23S rRNA from Escherichia coli was cleaved at single internucleotide bonds using ribonuclease H in the presence of appropriate chimeric oligonucleotides; the individual cleavage sites were between residues 384 and 385, 867 and 868, 1045 and 1046, and 2510 and 2511, with an additional fortuitous cleavage at positions 1117 and 1118. In each case, the 3' terminus of the 5' fragment was ligated to radioactively labeled 4-thiouridine 5'-,3'-biphosphate ("psUp"), and the cleaved 23S rRNA carrying this label was reconstituted into 50S subunits. The 50S subunits were able to associate normally with 30S subunits to form 70S ribosomes. Intra-RNA crosslinks from the 4-thiouridine residues were induced by irradiation at 350 nm, and the crosslink sites within the 23S rRNA were analyzed. The rRNA molecules carrying psUp at positions 867 and 1117 showed crosslinks to nearby positions on the opposite strand of the same double helix where the cleavage was located, and no crosslinking was detected from position 2510. In contrast, the rRNA carrying psUp at position 384 showed crosslinking to nt 420 (and sometimes also to 416 and 425) in the neighboring helix in 23S rRNA, and the rRNA with psUp at position 1045 gave a crosslink to residue 993. The latter crosslink demonstrates that the long helix 41-42 of the 23S rRNA (which carries the region associated with GTPase activity) must double back on itself, forming a "U-turn" in the ribosome. This result is discussed in terms of the topography of the GTPase region in the 50S subunit, and its relation to the locations of the 5S rRNA and the peptidyl transferase center.     

Prevention of heart failure]

Heart failure is a major problem of public health, associated with poor outcome in the advanced stage, thus justifying its prevention. Primary prevention is based on the prevention and treatment of its principal etiologic factors, hypertension and coronary artery disease. Broad use of echocardiography or dosage of neurohormonal markers improve detection of asymptomatic left ventricular dysfunction. In ischemic heart disease, coronary recanalisation prevents or limits left ventricular remodeling and dysfunction, even if the "open artery" theory has not been entirely proved. Understanding the deleterous role of neurohormonal stimulation results in a large use of ACE-inhibitors, which beneficial effect has been demonstrated also in case of asymptomatic left ventricular dysfunction. Betablockers, already largely used after myocardial infarction, seem to have also a beneficial effect in heart failure: the same is probably also true for angiotensin II-antagonists. Double blocking of both the sympathetic nervous system and the angiotensin-aldosterone system seems to be recommended. More precisely understanding the pathways signaling the processes of ventricular remodeling and dysfunction points to new potential targets for a preventive treatment: endothelin receptors, apoptosis, oxidative stress, cytokines or even angiogenesis.     

Sidewall oxide effects on spin-torque- and magnetic-field-induced reversal characteristics of thin-film nanomagnets

The successful operation of spin-based data storage devices depends on thermally stable magnetic bits. At the same time, the data-processing speeds required by today's technology necessitate ultrafast switching in storage devices. Achieving both thermal stability and fast switching requires controlling the effective damping in magnetic nanoparticles. By carrying out a surface chemical analysis, we show that through exposure to ambient oxygen during processing, a nanomagnet can develop an antiferromagnetic sidewall oxide layer that has detrimental effects, which include a reduction in the thermal stability at room temperature and anomalously high magnetic damping at low temperatures. The in situ deposition of a thin Al metal layer, oxidized to completion in air, greatly reduces or eliminates these problems. This implies that the effective damping and the thermal stability of a nanomagnet can be tuned, leading to a variety of potential applications in spintronic devices such as spin-torque oscillators and patterned media.     

Sparing of striatal neurons coexpressing calretinin and substance P (NK1) receptor in Huntington's disease

Immunohistochemical studies of the striatum in normal human subjects with a double-antigen localization method have revealed the presence of large and medium-sized aspiny neurons displaying immunoreactivity for both the calcium-binding protein calretinin and substance P (neurokinin-1) receptor. These large and medium-sized cells from two distinct classes of striatal interneurons, which together represent less than 3% of the total neuronal population of the human striatum. Observations made in four cases of Huntington's disease revealed that such doubly labeled interneurons are still present in the striatum of these patients, despite the marked atrophy of the structure. This study provides the first evidence for the existence of interneurons containing calretinin and expressing tachykinin receptors in the human striatum. It also demonstrates the selective sparing of these chemospecific striatal neurons in Huntington's disease.     

The orthostatic resistance of the cerebral and peripheral circulations in patients with contusive brain lesions

Rat pancreatic islets were immunoisolated within alginate capsules with additional polyethyleneimine-protamine-heparin highly biocompatible membrane. Perifusion study in vitro demonstrated satisfactory similarities between the insulin release profiles of encapsulated and free islets. Concordant xenotransplantation of microencapsulated rat islets significantly prolonged mean time of restored normoglycemia (46 +/- 15 days) in streptozotocin-diabetic BALB/c mice recipients comparing to uncoated grafts (7 +/- 2 days).     

Ocular perforation during retrobulbar and peribulbar injections

BACKGROUND AND OBJECTIVE: To determine the ocular perforations during retrobulbar and peribulbar injections. PATIENTS AND METHODS: Twenty-five ocular perforations between 1976 and 1993 occurred after 13 retrobulbar and 12 peribulbar injections. Eighteen patients (72%) were women. Eighteen eyes were myopic (72%). Risk factors included high myopia in 11 cases (44%), use of Atkinson gaze in 21 cases (84%) and a sharp injection needle. RESULTS: Deep position of the posterior pole was common. Perforation signs comprised vitreous hemorrhage in 25 eyes (100%), subretinal hemorrhage in 19 eyes (76%), retinal breaks along the inferior vascular arcade in 19 eyes (76%), and retinal detachment in 14 eyes (56%). Proliferative vitreoretinopathy developed in 11 eyes (44%). CONCLUSION: Retinal detachment strongly correlated to poor visual outcome.