Metabolic Reconfiguration in C. elegans Suggests a Pathway for Widespread Sterol Auxotrophy in the Animal Kingdom

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The role of lipid second messengers in aldosterone synthesis and secretion

Second messengers are small rapidly diffusing molecules or ions that relay signals between receptors and effector proteins to produce a physiological effect. Lipid messengers constitute one of the four major classes of second messengers. The hydrolysis of two main classes of lipids, glycerophospholipids and sphingolipids, generate parallel profiles of lipid second messengers: phosphatidic acid (PA), diacylglycerol (DAG), and lysophosphatidic acid versus ceramide, ceramide-1-phosphate, sphingosine, and sphingosine-1-phosphate, respectively. In this review, we examine the mechanisms by which these lipid second messengers modulate aldosterone production at multiple levels. Aldosterone is a mineralocorticoid hormone responsible for maintaining fluid volume, electrolyte balance, and blood pressure homeostasis. Primary aldosteronism is a frequent endocrine cause of secondary hypertension. A thorough understanding of the signaling events regulating aldosterone biosynthesis may lead to the identification of novel therapeutic targets. The cumulative evidence in this literature emphasizes the critical roles of PA, DAG, and sphingolipid metabolites in aldosterone synthesis and secretion. However, it also highlights the gaps in our knowledge, such as the preference for phospholipase D-generated PA or DAG, as well as the need for further investigation to elucidate the precise mechanisms by which these lipid second messengers regulate optimal aldosterone production.     

Statistical Evaluation of the Effect of Gemfibrosil,a Cholesterol Reducing Drug,on Some Biochemical Coronary Heart Disease Risk Variables

The evaluation is based on the clinic trial with gemfibrosil (“Gevilon”, Parke-Davis) carried out in a group of 48 patients, to whom the drug was administered in the single dose of 900 mg daily during the period of 3 months. In this paper we show the results of the treatment on five biochemical Coronary Heart Disease (CHD) risk variables: Cholesterol (CHOL), High Density Lipoprotein (HDL), Triglyccrides (TGL), Uric Acid (UA) and Glucose (GL). We are concerned with a statistical model allowing to predict which and how large changes in the considered variable can be expected in a patient taking the drug. This is done considering the “regression to the mean” effect.     

Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500–1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = ?55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = ?41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated.     

Effect of soil water stress on soil respiration and its temperature sensitivity in an 18-year-old temperate Douglas-fir stand

We analyzed 17 months (August 2005 to December 2006) of continuous measurements of soil CO₂ efflux or soil respiration (R_S) in an 18‐year‐old west‐coast temperate Douglas‐fir stand that experienced somewhat greater than normal summertime water deficit. For soil water content at the 4 cm depth (θ) > 0.11 m³ m^?3 (corresponding to a soil water matric potential of ?2 MPa), R_S was positively correlated to soil temperature at the 2 cm depth (T_S). Below this value of θ, however, R_S was largely decoupled from T_S, and evapotranspiration, ecosystem respiration and gross primary productivity (GPP) began to decrease, dropping to about half of their maximum values when θ reached 0.07 m³ m^?3. Soil water deficit substantially reduced R_S sensitivity to temperature resulting in a Q₁₀ significantly < 2. The absolute temperature sensitivity of R_S (i.e. dR_S/dT_S) increased with θ up to 0.15 m³ m^?3, above which it slowly declined. The value of dR_S/dT_S was nearly 0 for θ < 0.08 m³ m^?3, thereby confirming that R_S was largely unaffected by temperature under soil water stress conditions. Despite the possible effects of seasonality of photosynthesis, root activity and litterfall on R_S, the observed decrease in its temperature sensitivity at low θ was consistent with the reduction in substrate availability due to a decrease in (a) microbial mobility, and diffusion of substrates and extracellular enzymes, and (b) the fraction of substrate that can react at high T_S, which is associated with low θ. We found that an exponential (van't Hoff type) model with Q₁₀ and R₁₀ dependent on only θ explained 92% of the variance in half‐hourly values of R_S, including the period with soil water stress conditions. We hypothesize that relating Q₁₀ and R₁₀ to θ not only accounted for the effects of T_S on R_S and its temperature sensitivity but also accounted for the seasonality of biotic (photosynthesis, root activity, and litterfall) and abiotic (soil moisture and temperature) controls and their interactions.     

Gradients in maize roots: local elongation and pH

The elongation rate, the gradient of the local elongation rate and the surface pH of maize roots were measured over 12 h. A data bank was constituted by storing these values. By sorting these results on the basis of different elongation rates, different classes of root were obtained. Two classes were chosen: the low-growth roots and the high-growth roots. The mean growth of these two root classes was stable with time and differed significantly from one another. The surface pH of the elongation zone was the same for the roots of these two classes, but the roots selected for their higher growth rate had a larger acid efflux in this zone.