Neuronal Nsun2 deficiency produces tRNA epitranscriptomic alterations and proteomic shifts impacting synaptic signaling and behavior.

Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m5C levels, resulting in deficits in expression of 70% of tRNAGly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids.

Calorimeters for precision power dissipation measurements on controlled-temperature superconducting radiofrequency samples.

Two calorimeters, with stainless steel and Cu as the thermal path material for high precision and high power versions, respectively, have been designed and commissioned for the 7.5 GHz surface impedance characterization system at Jefferson Lab to provide low temperature control and measurement for CW power up to 22 W on a 5 cm diameter disk sample which is thermally isolated from the radiofrequency (RF) portion of the system. A power compensation method has been developed to measure the RF induced power on the sample. Simulation and experimental results show that with these two calorimeters, the whole thermal range of interest for superconducting radiofrequency materials has been covered. The power measurement error in the interested power range is within 1.2% and 2.7% for the high precision and high power versions, respectively. Temperature distributions on the sample surface for both versions have been simulated and the accuracy of sample temperature measurements have been analyzed. Both versions have the ability to accept bulk superconductors and thin film superconducting samples with a variety of substrate materials such as Al, Al(2)O(3), Cu, MgO, Nb, and Si.

Note: Radio frequency surface impedance characterization system for superconducting samples at 7.5 GHz.

A radio frequency (RF) surface impedance characterization (SIC) system that uses a novel sapphire-loaded niobium cavity operating at 7.5 GHz has been developed as a tool to measure the RF surface impedance of flat superconducting material samples. The SIC system can presently make direct calorimetric RF surface impedance measurements on the central 0.8 cm(2) area of 5 cm diameter disk samples from 2 to 20 K exposed to RF magnetic fields up to 14 mT. To illustrate system utility, we present first measurement results for a bulk niobium sample.

Stress as a diagnostic challenge for postconcussive symptoms: sequelae of mild traumatic brain injury or physiological stress response.

There is considerable controversy regarding whether persistent postconcussive symptoms (PCS) are injury-specific, in a subgroup of individuals after mild traumatic brain injury (TBI). The following findings have contributed to this controversy: (1) The base rate of PCS in mild TBI is comparable to uninjured controls; and (2) The severity of PCS covary with daily stress levels (Gouvier, Cubic, Jones, Brantley, & Cutlip, 1992). We examined this relationship further by evaluating the effects of experimental conditions of stress or relaxation on individuals with TBI and uninjured control subjects, with low and high PCS endorsement. We evaluated psychophysiological parameters, neuropsychological performance, and changes in PCS and stress perception. In our study, subjects with TBI increased PCS after engaging in cognitively challenging tasks, and demonstrated significant autonomic changes in the stress condition. Symptomatic TBI subjects exposed to high stress had increases in PCS complaints, decreased speed of information processing, and subtle memory deficits. Our results suggest that PCS are injury-specific and that individuals with a history of TBI are susceptible to the effects of stress. Relaxation training including breathing retraining may be an effective means of decreasing PCS and cognitive complaints in subjects with mild TBI.

A randomized controlled trial of the effects of three antihypertensive agents on blood pressure control and quality of life in older women.

We conducted a multicenter, randomized, double-blind, parallel group trial to compare the impact of titrated doses of atenolol (50 to 100 mg once a day), enalapril (5 to 20 mg once a day), and diltiazem (sustained release) (60 to 180 mg twice a day) on blood pressure and quality of life in older hypertensive women. Two hundred forty-two patients were randomized. Dose titration was completed by week 4 after randomization, and the maintenance phase was completed at week 16. Diltiazem (sustained release) demonstrated greater diastolic blood pressure lowering at both weeks 8 and 16 by an intent-to-treat analysis. At week 16, diltiazem changed diastolic blood pressure -13.7 +/- 0.7 mm Hg compared with -10.8 +/- 1.1 mm Hg for atenolol, and -10.5 +/- 0.9 mm Hg for enalapril. Diltiazem also demonstrated greater lowering of systolic blood pressure at week 3, but these differences in systolic blood pressure had decreased by week 16. More patients were classified as treatment failures during the 16 weeks of the trial for atenolol (15%) than for diltiazem (2.5%), while the treatment failure rate was intermediate with enalapril (8%). Total rates of adverse events were equivalent across the three treatment arms. There were few significant differences in the impact of the three treatments on mean scores of quality-of-life measures at week 16. There was a trend for atenolol to have somewhat worse quality-of-life scores, but none of these differences were statistically significant. In conclusion, all three treatment regimens were effective in lowering diastolic blood pressure without significant differences in rates of adverse events or deleterious effects on quality of life.

Efficacy of ciprofloxacin in the treatment of various bacterial infections.

The efficacy and safety of ciprofloxacin (500 mg administered every 12 hours) were evaluated in 62 patients enrolled in a prospective, open study. Fifty-three courses in the treatment of 56 infection sites suitable for evaluation were assessed. The infection sites involved were skin and skin structure (28), respiratory tract (21), urinary tract (5), and gastrointestinal tract (2). Bacterial isolates included 16 Pseudomonas aeruginosa, 13 Staphylococcus aureus, and 8 Escherichia coli. Signs and symptoms of infection completely resolved in 46 (82%) of the infection sites. Nine (16%) improved, and one (2%) failed to respond. Ciprofloxacin was well tolerated.

Comparison of aztreonam and tobramycin in the treatment of lower respiratory tract infections caused by gram-negative bacilli.

A comparison of aztreonam and tobramycin was carried out in 49 hospitalized patients with lower respiratory tract infections caused by gram-negative bacilli. Patients were randomly assigned to the treatment drug. Clindamycin was given concomitantly until the pathogen was identified and the presence of a gram-positive microorganism was ruled out. Samples of sputum were obtained for culture from the lung parenchyma by deep expectoration or transtracheal aspiration. A pathogen was defined as an organism that showed heavy growth and predominated in the culture. Pseudomonas aeruginosa was the most frequently isolated pathogen, followed by Haemophilus influenzae and Proteus mirabilis. A variety of less common pathogens were represented. Thirty-five patients were treated with intravenous aztreonam (1-2 g every 8 hr) and 14 with intravenous tobramycin (3-5 mg/kg per day) until they were afebrile and sputum cultures had been free of the pathogen for 48 hr. The minimum duration of treatment was five days. In the aztreonam group, only two (5%) of the 37 gram-negative pathogens--one P. aeruginosa and one Escherichia coli--persisted. In the tobramycin group, seven (50%) of the 14 pathogens persisted. Clinical response paralleled microbiologic response. Adverse effects in both treatment groups were minor and transient. In this trial aztreonam was effective and safe for treatment of lower respiratory tract infections caused by P. aeruginosa and a variety of other gram-negative bacilli.

Evaluation of the Directigen Group A Strep test kit.

The Directigen Group A Strep test kit (Hynson, Wescott, and Dunning, Baltimore, Md.) was tested for its ability to detect group A streptococci directly from 147 throat swabs. The results were compared with results from conventional culture and Lancefield serological grouping tests. The data showed that 121 of 124 culture-negative throat specimens were also Directigen negative (98%) and that 21 of 23 culture-positive specimens were Directigen positive (91%). If specimens that provided less than 10 colonies per plate of beta-hemolytic streptococci were eliminated, all of the culture-positive specimens were Directigen positive. Positive or negative results were available within 65 to 70 min of testing. The Directigen method is relatively simple to perform and easy to interpret and provides accurate assessment of the presence or absence of group A streptococci in throat swabs, with little or no cross-reactivity with other beta-hemolytic groups.

Clinical evaluation of cefotetan in the treatment of lower respiratory tract infections.

Cefotetan, a new cephamycin antibiotic, was evaluated for the treatment of lower respiratory tract infections. Intravenous cefotetan (2 g every 12 h) was administered for 4 to 8 days (mean, 5.8 days) to 56 hospitalized adult patients. Of the 41 evaluable patients, the clinical response was satisfactory in 38 (93%) and the bacteriological response was satisfactory in 36 (88%). The drug was well tolerated, and there were minimal complaints or changes in clinical laboratory values. From these preliminary results, cefotetan appears to be safe and effective for the treatment of lower respiratory tract infections.

Deoxyribonucleic Acid synthesis in root cap cells of cultured roots of convolvulus.

Isolated cultured roots of Convolvulus arvensis L. were incubated in 0.2 microcurie per milliliter methyl-(3)H-thymidine for 14 hours, for 64 hours, or for 14 hours followed by transfer to fresh nutrient medium without tritiated thymidine. Autoradiographs of serial, longitudinal sections of roots which were continuously incubated with tritiated thymidine showed that cells of the root cap columella did not undergo DNA synthesis after their formation from the root cap initials. In roots pulse-labeled with tritiated thymidine, the movement of labeled cells through the root cap columella was followed. Labeled cells were displaced at a constant rate of 72 microns per day over a period of 6 to 9 days before they were sloughed off from the root cap. The specialized role of the root cap cells in relation to their distinctive metabolism and longevity is discussed.