CBS domains were originally identified as sequence motifs of approximately 60 amino acids that occur in CBS and several other proteins, in all organisms from archaea to humans (1). Although their functions were unknown, their importance was emphasized by findings that point mutations within them cause several hereditary diseases in humans. CBS domains are defined as sequence motifs that occur in several different proteins in all kingdoms of life. Although thought to be regulatory, their exact functions have been unknown. However, their importance was underlined by findings that mutations in conserved residues within them cause a variety of human hereditary diseases, including (with the gene mutated in parentheses): Wolff-Parkinson-White syndrome (γ2 subunit of AMP-activated protein kinase); retinitis pigmentosa (IMP dehydrogenase-1); congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members); and homocystinuria (cystathionine β-synthase). AMP-activated protein kinase is a sensor of cellular energy status that is activated by AMP and inhibited by ATP, but the location of the regulatory nucleotide-binding sites (which are prime targets for drugs to treat obesity and diabetes) was not characterized. We now show that tandem pairs of CBS domains from AMP-activated protein kinase, IMP dehydrogenase-2, the chloride channel CLC2, and cystathionine β-synthase bind AMP, ATP, or S-adenosyl methionine,while mutations that cause hereditary diseases impair this binding. This shows that tandem pairs of CBS domains act, in most cases, as sensors of cellular energy status and, as such, represent a newly identified class of binding domain for adenosine derivatives.

Neurotic syndromes are defined by characteristic patterns of symptoms, but the validity of the distinction between one syndrome and another depends on associations between the syndromes and clinical history, or treatment response factors that are independent of the defining phenomena. In both a group of twin volunteers and a group of patients with panic disorder/agoraphobia, the lifetime experience of more than one diagnosis of a neurotic syndrome was common but there was no evidence of patterns of co-occurrence of diagnoses being associated with particular syndromes. Receiving a diagnosis was associated with abnormal scores on measures of neuroticism and locus of control, the extent of the abnormality increasing with the number of different diagnoses satisfied. It is argued that the concept of a general neurotic syndrome depends in part on the presence of such predisposing personality factors, and that reduction in this predisposition to neurosis should be the focus of treatment.

Nitrogen fertilization is considered as an important source of atmospheric N 2 O emission. A seven site-year on-farm field experiment was conducted at Ottawa and Guelph, ON and Saint-Valentin, QC, Canada to characterize the affect of the amount and timing of N fertilizer on N 2 O emission in corn (Zea mays L.) production. Using the static chamber method, gas samples were collected for 28-days after preplant and 28-days after sidedress fertilization at the seven site-year, resulting in 14 monitoring periods. For both methods of fertilization, peak N 2 O flux and cumulative emission increased with the amount of N applied, with rates ranging from 30 to 900 lg N m À2 h À1 . Depending on N amount and time of application, cumulative emission varied from 0.05 to 2.42 kg N ha À1 , equivalent to 0.03% to 1.45% of the N fertilizer applied. Differences in N 2 O emission peaks among fertilizer treatments were clearly separated in 13 out of 14 monitoring periods. Total N 2 O emissions may have been underestimated compared with annual monitoring in 10 out of the 49 cases because the monitoring period ended before N 2 O efflux returned to the baseline level. The flux of N 2 O was negligible when soil mineral N in the 0-15 cm layer was o20 mg N kg À1 . While rainfall stimulated emission, soil temperature 415 1C was likely the driving force responsible for the higher levels of N 2 O found for sidedress than preplant application methods. However, caution must be taken when interpreting these later results as preplant fertilization may have continuously stimulated N 2 O emissions after the 28-days monitoring period, especially in situations where N 2 O effluxes have not fallen back to their baseline levels. Increasing fertilizer rates from 90 to 150 kg N ha À1 resulted in slight increases in yields, but doubled cumulative N 2 O emissions.

To investigate whether this could be due to sex-specific regulation of hormone-sensitive lipase (HSL) and to use sex comparison as a model to gain further insight into HSL regulation, nine women and eight men performed bicycle exercise (90 min, 60% V O2 peak), and skeletal muscle HSL expression, phosphorylation, and activity were determined. Supporting previous findings, basal IMTG content (P Ͻ 0.001) and net IMTG decrease during exercise (P Ͻ 0.01) were higher in women than in men and correlated significantly (r ϭ 0.72, P ϭ 0.001). Muscle HSL mRNA (80%, P ϭ 0.11) and protein content (50%, P Ͻ 0.05) were higher in women than in men. HSL total activity increased during exercise (47%, P Ͻ 0.05) but did not differ between sexes. Accordingly, HSL specific activity (HSL activity per HSL protein content) increased during exercise (62%, P Ͻ 0.05) and was generally higher in men than in women (82%, P Ͻ 0.05). A similar pattern was observed for HSL Ser 659 phosphorylation, suggesting a role in regulation of HSL activity. Likewise, plasma epinephrine increased during exercise (P Ͻ 0.05) and was higher in men than in women during the end of the exercise bout (P Ͻ 0.05). We conclude that, although HSL expression and Ser 659 phosphorylation in skeletal muscle during exercise is sex specific, total muscle HSL activity measured in vitro was similar between sexes. The higher basal IMTG content in women compared with men is therefore the best candidate to explain the higher IMTG net hydrolysis during exercise in women. intramuscular triacylglycerol; epinephrine; extracellular signal-regulated kinase TRIACYLGLYCEROL STORED IN skeletal muscle fibers (intramuscular triacylglycerol, IMTG) represents a large source of energy that may be used for muscle contraction during exercise. In men, it is still controversial to what extent IMTG is utilized during exercise (18,29,40). This is probably so because methodological limitations in measuring IMTG content have made it difficult to detect the relatively small net hydrolysis of IMTG that appears to occur during submaximal exercise in men (13,29,40,46). On the other hand, in women it has been shown that IMTG content is reduced by ϳ25% during 90-min bicycle exercise at 60% peak oxygen uptake (V O 2 peak ) (33), and it can be estimated that IMTG covers a large fraction (ϳ25%) of oxidative energy production in such an exercise bout in women (27). Therefore, the degree of IMTG hydrolysis during submaximal exercise appears to depend on sex, being higher in women than in men. It is presently unknown what may be the cause underlying this sex difference in IMTG hydrolysis during exercise.Hormone-sensitive lipase (HSL) is thought to catalyze the hydrolysis of IMTG in skeletal muscle as it does in adipose tissue (14,21). In rodent as well as in human skeletal muscle, neutral lipase activity increases during contraction (22,28,41), and it has been shown that the increase in neutral lipase activity elicited by contraction is completely accounted for by HSL activation both in rats and in man (22,28,45)...

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To investigate pyruvate dehydrogenase (PDH)-E1␣ subunit phosphorylation and whether free fatty acids (FFAs) regulate PDH activity, seven subjects completed two trials: saline (control) and intralipid/heparin (intralipid). Each infusion trial consisted of a 4-h rest followed by a 3-h two-legged knee extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1␣ site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion. Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1␣ phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1␣ phosphorylation, but exercise overrules this effect of FFA on PDH-E1␣ phosphorylation leading to even greater dephosphorylation during exercise with intralipid infusion than with saline. Diabetes 55:3020 -3027, 2006

Ammonia (NH3) volatilization is one of the main pathways through which applied N enters the environment undesirably. A seven site‐year on‐farm field experiment was performed for 3 yr at Ottawa, ON, and 2 yr at Guelph, ON, and Saint‐Valentin, QC, Canada. Our objectives were to (i) quantify the flux and the amount of NH3 volatilization as affected by the rate and time of N fertilizer; (ii) assess the impact of rainfall and soil temperatures on NH3 volatilization; and (iii) determine the threshold level of N fertilizer at which large NH3 volatilization losses occur. Using the static chamber method, NH3 volatilization was monitored after preplant or sidedress N application. Rate of NH3 volatilization peaked at 3 to 7 d and then dropped sharply within next 7 d before leveling off in the following weeks. The amount of NH3 volatilization increased with increasing N levels applied preplant or sidedress at all site‐years. Peak NH3 volatilization ranged from 40 to 8000 g N ha−1 d−1 after preplant fertilization and from about 100 to 2100 g N ha−1 d−1 after sidedress, resulting in NH3 losses of 0.1 to 47 kg N ha−1 and 0.6 to 20 kg N ha−1, respectively, equivalent to 0.1 to 38% and 0.3 to 13% of fertilizer‐induced emission (FIE) within 28 d after preplant or sidedress N fertilization. Our data clearly indicate that sidedress applications enable reduction in N fertilizer for economic crop yields, and may reduce losses simply due to lower total N rates.

Elucidating the molecular pathways linking electrical activity to gene expression is necessary for understanding the effects of exercise on muscle. Fast muscles express higher levels of MyoD and lower levels of myogenin than slow muscles, and we have previously linked myogenin to expression of oxidative enzymes. We here report that in slow muscles, compared with fast, 6 times as much of the MyoD is in an inactive form phosphorylated at T115. In fast muscles, 10 h of slow electrical stimulation had no effect on the total MyoD protein level, but the fraction of phosphorylated MyoD was increased 4-fold. Longer stimulation also decreased the total level of MyoD mRNA and protein, while the level of myogenin protein was increased. Fast patterned stimulation did not have any of these effects. Overexpression of wild type MyoD had variable effects in active slow muscles, but increased expression of fast myosin heavy chain in denervated muscles. In normally active soleus muscles, MyoD mutated at T115 (but not at S200) increased the number of fibres containing fast myosin from 50% to 85% in mice and from 13% to 62% in rats. These data establish de-phosphorylated active MyoD as a link between the pattern of electrical activity and fast fibre type in adult muscles.