The occurrence of cyclic AMP in archaebacteria

Cyclic AMP was found in species representative of the three major groups of the archaebacteria. In Methanobacterium thermoautotrophicum starvation for H2 led to a significant increase in cellular cAMP. The findings suggest that the occurrence of cAMP antedates the divergence of the major kingdoms of biology; the observations also imply that cAMP constitutes a very early regulatory molecule.     

Autoradiographic localization of ornithine decarboxylase in mouse kidney by use of radiolabeled α-difluoromethylornithine

Summary Ornithine decarboxylase, a key enzyme in polyamine biosynthesis and cell growth, has been localized in mouse kidney by autoradiography after administration of radiolabeled -difluoromethylornithine. This drug is an enzyme-activated irreversible inhibitor of ornithine decarboxylase and forms a covalent bond with the enzyme. It was found that ornithine decarboxylase is present in all cell types studied but that the highest content occurs in the proximal convoluted tubules followed by the distal convoluted tubules and the collecting tubules. The majority of the enzyme is located in the cytoplasm but about 10–15% is present in the nuclei (often associated with nucleolus-like components) of the cells of the proximal and distal convoluted tubules. The labeled ornithine decarboxylase was lost rapidly from both nucleus and cytoplasm of all the cell types examined, and labeling by radioactive -difluoromethylornithine was greatly reduced if the mice were pretreated for 5 h with cycloheximide to block protein synthesis. These results indicate that ornithine decarboxylase turns over rapidly in all of the cells.     

Energy transfer in a model of the photosynthetic unit of green plants

A model array is set up to represent a photosynthetic unit of 344 chlorophyll molecules of seven different spectral varieties and in definite orientations. The array is provided with two traps, representing the reaction centers of photosystems I and II. The number of jumps required to obtain a high probability of trapping is lower than on a similar array of undifferentiated chlorophylls by a factor of 15. Most of the molecules fall into two groups which transfer their energy predominantly into one or the other trap, and which may be regarded as functional photosystems I and II. The rate of transfer between these two functional photosystems can be controlled by redirecting the orientation of only six of the molecules, which occupy a key position in the array. The effect on trapping rates of reorientation of these molecules is especially pronounced when one of the traps is closed. This constitutes a model for the control of energy distribution between the two photosystems, as indicated in recent years through fluorescence studies.     

THE COMPOSITION OF WATER COLLECTED FROM THE KUISEB RIVER,NAMIB DESERT,AT GOBABEB

SUMMARY

Water from the Kuiseb River at Gobabeb varied in ionic content. Various ionic dominance orders were recorded from flooding until the pools dried up. The quality was not suitable for irrigation, but would present no problems when used by stock or wildlife.     

Cellulose-bound Peptide Arrays: Preparation and Applications

Spatial organization of metabolic enzymes may represent a general cellular mechanism to regulate metabolic flux. One recent example of this type of cellular phenomenon is the purinosome, a newly discovered multi-enzyme metabolic assembly that includes all of the enzymes within the de novo purine biosynthetic pathway. Our understanding of the components and regulation of purinosomes has significantly grown in recent years. This paper reviews the purine de novo biosynthesis pathway and its regulation, and presents the evidence supporting the purinosome assembly and disassembly processes under the control of G-protein-coupled receptor (GPCR) signaling. This paper also discusses the implications of purinosome and GPCR regulation in drug discovery.     

Diurnal variation of milk fatty acids in early-lactation Holstein cows with and without hyperketonemia

Estimates of milk constituents by Fourier-transform mid-infrared (FTIR) analysis have been shown to be a useful tool in monitoring energy deficit in early-lactation dairy cows. Our objectives were to describe the diurnal variation in milk fatty acids (FAs) and estimate the association of hyperketonemia with concentrations and diurnal patterns of FTIR estimates of milk FA. Blood samples were collected via jugular catheters bihourly for 5 d from multiparous Holstein cows (n = 28) enrolled between 3 and 9 days in milk. Milk samples were collected thrice daily at 0600, 1400, and 2200 h for d 2, 3, and 4 of the study period. Cows were retrospectively classified as hyperketonemic (HYK; n = 13) or non-HYK (n = 15) based on blood beta-hydroxybutyrate (bBHB) concentrations analyzed during the study period. Cows were classified as HYK if bBHB was ≥ 1.2 mmol/l for ≥ 50% (22/44) of bihourly timepoints; cows were classified as non-HYK if bBHB was ≥ 1.2 mmol/l for < 50% of bihourly timepoints. The HYK cows had bBHB ≥ 1.2 mmol/l for 31.4 ± 6.8 timepoints while the non-HYK cows had bBHB ≥ 1.2 mmol/l for 8.0 ± 3.9 timepoints. We used generalized linear mixed models to analyze concentrations of milk FA over time and differences between HYK groups. The relative percentage of de novo, mixed, and preformed FAs all followed diurnal patterns, however only the yield of preformed FA diurnally cycled, reaching a nadir at 0600 h and peaking at 1400 h. The yield per milking of preformed FA was also greater in the HYK cows than in the non-HYK cows. Oleic acid in milk followed a similar diurnal pattern to the yield of preformed FA, likely driving the cyclical nature of preformed FA. Finally, stearic acid was greater in HYK cows. Our results suggest that FTIR estimates of milk FA offer the potential to provide insight on the energy status of early-lactation cows, and when interested in understanding the absolute concentrations and yields of milk FA, diurnal variation should be considered.     

From type 2 diabetes to antioxidant activity: a systematic review of the safety and efficacy of common and cassia cinnamon bark

Common (Cinnamomum verum, C. zeylanicum) and cassia (C. aromaticum) cinnamon have a long history of use as spices and flavouring agents. A number of pharmacological and clinical effects have been observed with their use. The objective of this study was to systematically review the scientific literature for preclinical and clinical evidence of safety, efficacy, and pharmacological activity of common and cassia cinnamon. Using the principles of evidence-based practice, we searched 9 electronic databases and compiled data according to the grade of evidence found. One pharmacological study on antioxidant activity and 7 clinical studies on various medical conditions were reported in the scientific literature including type 2 diabetes (3), Helicobacter pylori infection (1), activation of olfactory cortex of the brain (1), oral candidiasis in HIV (1), and chronic salmonellosis (1). Two of 3 randomized clinical trials on type 2 diabetes provided strong scientific evidence that cassia cinnamon demonstrates a therapeutic effect in reducing fasting blood glucose by 10.3%-29%; the third clinical trial did not observe this effect. Cassia cinnamon, however, did not have an effect at lowering glycosylated hemoglobin (HbA1c). One randomized clinical trial reported that cassia cinnamon lowered total cholesterol, low-density lipoprotein cholesterol, and triglycerides; the other 2 trials, however, did not observe this effect. There was good scientific evidence that a species of cinnamon was not effective at eradicating H. pylori infection. Common cinnamon showed weak to very weak evidence of efficacy in treating oral candidiasis in HIV patients and chronic salmonellosis.     

The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron loss, paralysis and death within 2-5 years of diagnosis. Currently, no effective pharmacological agents exist for the treatment of this devastating disease. Neuroinflammation may accelerate the progression of ALS. Cannabinoids produce anti-inflammatory actions via cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), and delay the progression of neuroinflammatory diseases. Additionally, CB2 receptors, which normally exist primarily in the periphery, are dramatically up-regulated in inflamed neural tissues associated with CNS disorders. In G93A-SOD1 mutant mice, the most well-characterized animal model of ALS, endogenous cannabinoids are elevated in spinal cords of symptomatic mice. Furthermore, treatment with non-selective cannabinoid partial agonists prior to, or upon, symptom appearance minimally delays disease onset and prolongs survival through undefined mechanisms. We demonstrate that mRNA, receptor binding and function of CB2, but not CB1, receptors are dramatically and selectively up-regulated in spinal cords of G93A-SOD1 mice in a temporal pattern paralleling disease progression. More importantly, daily injections of the selective CB2 agonist AM-1241, initiated at symptom onset, increase the survival interval after disease onset by 56%. Therefore, CB2 agonists may slow motor neuron degeneration and preserve motor function, and represent a novel therapeutic modality for treatment of ALS.     

Diurnal variation in heart rate variability before and after maximal exercise testing

As heart-rate variability (HRV) is under evaluation in clinical applications, the authors sought to better define the interdependent impact of age, maximal exercise, and diurnal variation under physiologic conditions. The authors evaluated the diurnal changes in HRV 24-h pre- and post-maximal aerobic exercise testing to exhaustion in young (19-25 yrs, n?=?12) and middle-aged (40-55 yrs, n?=?12) adults. Subjects wore a portable 5-lead electrocardiogram holter for 48?h (24?h prior to and following a maximal aerobic capacity test). Time-, frequency-, time-frequency-, and scale-invariant-domain measures of HRV were computed from RR-interval data analyzed using a 5-min window size and a 2.5-min step size, resulting in a different set of outputs every 2.5?min. Results were averaged (mean?±?SE) over four prespecified time periods during the morning, afternoon, evening, and night on Day 1 and Day 2. Diurnal changes in HRV in young and middle-aged adults were compared using a two-way, repeated-measures analysis of variance (ANOVA). Young adults demonstrated higher HRV compared to middle-aged adults during periods of wakefulness and sleep prior to maximal exercise stress testing (i.e., high-frequency power during Day 1: young adults: morning 1862?±?496?ms(2), afternoon 1797?±?384?ms(2), evening 1908?±?431?ms(2), and night 3202?±?728?ms(2); middle-aged adults: morning 341?±?53?ms(2), afternoon 405?±?68?ms(2), evening 469?±?80?ms(2), and night 836?±?136?ms(2)) (p < .05). Exercise resulted in reductions in HRV such that multiple measures of HRV were not significantly different between age groups during the afternoon and evening periods. All measures of HRV demonstrated between-group differences overnight on Day 2 (p < .05). Young adults are associated with higher baseline HRV during the daytime. Sleep increases variability equally and proportionally to daytime variability. Given the higher baseline awake HRV and equal rise in HRV during sleep, the change in HRV from sleep to morning with exercise is greater in younger subjects. These physiologic results have clinical significance in understanding the pathophysiology of altered variability in ill patients.     

Review and classification of variability analysis techniques with clinical applications

Background

Representation of independent biophysical sources using Fourier analysis can be inefficient because the basis is sinusoidal and general. When complex fractionated atrial electrograms (CFAE) are acquired during atrial fibrillation (AF), the electrogram morphology depends on the mix of distinct nonsinusoidal generators. Identification of these generators using efficient methods of representation and comparison would be useful for targeting catheter ablation sites to prevent arrhythmia reinduction.

Method

A data-driven basis and transform is described which utilizes the ensemble average of signal segments to identify and distinguish CFAE morphologic components and frequencies. Calculation of the dominant frequency (DF) of actual CFAE, and identification of simulated independent generator frequencies and morphologies embedded in CFAE, is done using a total of 216 recordings from 10 paroxysmal and 10 persistent AF patients. The transform is tested versus Fourier analysis to detect spectral components in the presence of phase noise and interference. Correspondence is shown between ensemble basis vectors of highest power and corresponding synthetic drivers embedded in CFAE.

Results

The ensemble basis is orthogonal, and efficient for representation of CFAE components as compared with Fourier analysis (p ≤ 0.002). When three synthetic drivers with additive phase noise and interference were decomposed, the top three peaks in the ensemble power spectrum corresponded to the driver frequencies more closely as compared with top Fourier power spectrum peaks (p ≤ 0.005). The synthesized drivers with phase noise and interference were extractable from their corresponding ensemble basis with a mean error of less than 10%.

Conclusions

The new transform is able to efficiently identify CFAE features using DF calculation and by discerning morphologic differences. Unlike the Fourier transform method, it does not distort CFAE signals prior to analysis, and is relatively robust to jitter in periodic events. Thus the ensemble method can provide a useful alternative for quantitative characterization of CFAE during clinical study.