Achieving bilateral symmetry during vertebrate limb development

While the various internal organs of vertebrates display many obvious left–right asymmetries in their location and/or morphology, external features exhibit a high degree of bilateral symmetry. How this external bilateral symmetry is established during development is largely unknown. In this review, we explore several mechanisms, in place during development, that regulate the final size of the limb. These mechanisms rely on the presence of positive signaling feedback loops during limb bud growth. Through the activity of these signaling loops and their eventual breakdown when the limb bud has reached a certain size, bilateral symmetry can be achieved.     

Ablation of LKB1 in the heart leads to energy deprivation and impaired cardiac function

Energy deprivation in the myocardium is associated with impaired heart function and increased morbidity. LKB1 is a kinase that is required for activation of AMP-activated protein kinase (AMPK) as well as 13 AMPK-related protein kinases. AMPK stimulates ATP production during ischemia and prevents post-ischemic dysfunction. We used the Cre–Lox system to generate mice where LKB1 was selectively knocked out in cardiomyocytes and muscle cells (LKB1-KO) to assess the role of LKB1 on cardiac function in these mice.Heart rates of LKB1-KO mice were reduced and ventricle diameter was increased. Ex vivo, cardiac function was impaired during aerobic perfusion of isolated working hearts, and recovery of function after ischemia was reduced. Although oxidative metabolism and mitochondrial function were normal, the AMP/ATP ratio was increased in LKB1-KO hearts. This was associated with a complete ablation of AMPKα2 activity, and a stimulation of signaling through the mammalian target of rapamycin. Our results establish a critical role for LKB1 for normal cardiac function under both aerobic conditions and during recovery after ischemia. Ablation of LKB1 leads to a decreased cardiac efficiency despite normal mitochondrial oxidative metabolism.     

Deactivation of isoamylase and β-amylase in the agitated reactor under supercritical carbon dioxide

The current research examines the impact of agitation on deactivation of isoamylase and β-amylase under supercritical carbon dioxide (SC-CO₂). Our experimental results showed that the activity of either enzyme decreased with increasing pressure or speed of agitation. The degree of enzymatic deactivation caused by pressure became more prominent in the presence of agitation, suggesting that the agitation plays an important role in enzymatic deactivation in SC-CO₂ environment. Moreover, the enzymatic deactivation behavior associated with agitation and pressure was further quantitatively analyzed using a proposed inactivation kinetic model. Our analysis indicated that isoamylase and β-amylase exhibited significantly different relationships between the inverse of percentage residual activity and the product of number of revolution per time and time elapsed under pressurized carbon dioxide. We believe that the outcome from this work may provide a better understanding of the effects of agitation and pressure in enzyme deactivation behavior under SC-CO₂.     

Nasogastric intubation technique for bile sampling in the baboon (Papio ursinus).

A duodenal tube was introduced into the duodenum of the fasted baboon via the nasal passage. After the application of vacuum for several minutes, the baboon received an intravenous injection of pancreozymin and cholecystokinin which caused contraction of the gall bladder. Aspiration of the bile sample was carried out via the duodenal tube.     

Correlation between loss of pro-chiral hydrogen and E,Z geometry in isoprenoid biosynthesis

Biosynthesis of several mono- and sesqui-terpenes that possess E or Z double bonds, or which are generally considered to be derived from precursors possessing such geometries, involved loss of the pro-4S hydrogen of mevalonate in the construction of the double bond. These results confirm and extend previous observations. A recent claim to have newly discovered such a stereochemical correlation is rejected.     

Effect of carnitine on greening barley leaves

Carnitine increases chlorophyll production in greening barley leaves. [Methyl-¹⁴C]carnitine fed to greening leaves was not utilized as a carbon sou     

Augmented cocaine conditioned place preference in rats pretreated with systemic ghrelin

The physiological mechanism through which food restriction (FR) enhances the biobehavioral actions of psychostimulants is unknown but may involve the gut peptide ghrelin. Plasma levels of ghrelin are increased by FR and reduced by eating. Moreover, systemically administered ghrelin crosses into the brain and is known to augment the locomotor-stimulating effects of cocaine [COC: Wellman et al., 2005]. This study sought to determine whether pretreatment with ghrelin (5 nmol) would enhance the rewarding properties of COC (0.0, 0.312, 0.625, or 1.25 mg/kg i.p.) as measured by conditioned place preference (CPP). Adult male Sprague–Dawley rats were given free access to both sides of a CPP chamber to determine initial side preference. The rats were then confined for 30 min to either their preferred side or non-preferred side on 8 consecutive days. When rats were confined to the least preferred side, each was injected with 0.5 ml (i.p.) of either ghrelin (5 nmol) or saline 1 h before the conditioning trial and then injected (i.p.) with one of the COC doses immediately prior to the conditioning trial. On alternate days, rats were injected with vehicle one hour before and again immediately before the conditioning trial. Place preference scores were computed as the differences in time (min) spent on the least preferred side of the chamber for the pre-test and the postconditioning test, covaried by the initial degree of preference (% time spent on the black side during the pre-test). These analyses indicated a significant interaction between ghrelin pretreatment and COC dose on changes in preference scores. Significantly higher place preference scores were noted for rats treated with either 0.312 or 0.625 mg/kg COC doses, but only when these COC doses were preceded by administration of 5 nmol ghrelin. In contrast, saline pretreated rats exhibited significant CPP at the 1.25 mg/kg COC dose, but the ghrelin pretreated group did not. These results provide partial support for the contention that ghrelin pretreatment can augment the rewarding effects of sub-threshold doses of COC in a CPP procedure. Moreover, these findings are consistent with the view that ghrelin may play a role in the capacity of FR to augment psychostimulant action.