Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation

Phospholipase A(2)(PLA(2)) enzymes are considered the primary source of arachidonic acid for cyclooxygenase (COX)-mediated biosynthesis of prostaglandins. Here, we show that a distinct pathway exists in brain, where monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to generate a major arachidonate precursor pool for neuroinflammatory prostaglandins. MAGL-disrupted animals show neuroprotection in a parkinsonian mouse model. These animals are spared the hemorrhaging caused by COX inhibitors in the gut, where prostaglandins are instead regulated by cytosolic PLA(2). These findings identify MAGL as a distinct metabolic node that couples endocannabinoid to prostaglandin signaling networks in the nervous system and suggest that inhibition of this enzyme may be a new and potentially safer way to suppress the proinflammatory cascades that underlie neurodegenerative disorders.     

Kinetics of morphogen gradient formation

In the developing fly wing, secreted morphogens such as Decapentaplegic (Dpp) and Wingless (Wg) form gradients of concentration providing positional information. Dpp forms a longer-range gradient than Wg. To understand how the range is controlled, we measured the four key kinetic parameters governing morphogen spreading: the production rate, the effective diffusion coefficient, the degradation rate, and the immobile fraction. The four parameters had different values for Dpp versus Wg. In addition, Dynamin-dependent endocytosis was required for spreading of Dpp, but not Wg. Thus, the cellular mechanisms of Dpp and Wingless spreading are different: Dpp spreading requires endocytic, intracellular trafficking.     

Assisted colonization: Integrating conservation strategies in the face of climate change

Global climate change poses an immense challenge for conservation biologists seeking to mitigate impacts to species and ecosystems. Species persistence will depend on geographic range shifts or adaptation in response to warming patterns as novel climates and community assemblages arise. Assisted colonization has been proposed as a method for addressing these challenges. This technique, which consists of transporting species to a new range that is predicted to be favorable for persistence under future climate scenarios, has become the subject of controversy and discussion in the conservation community due to its highly manipulative nature, questions about widespread feasibility, and uncertainty associated with the likelihood of translocated species becoming invasive. We reviewed the discussion and criticism associated with assisted colonization and sought to identify other conservation techniques that also display potential to promote the colonization and adaptation of species in response to climate change. We propose an integrated conservation strategy that includes management for habitat connectivity, conservation genetics, and when necessary, assisted colonization of species that are still unable to shift their ranges even given implementation of the above standard conservation approaches. We argue that this integrated approach will facilitate persistence for a larger proportion of species than is possible by solely using assisted colonization. Furthermore, a multi-faceted approach will likely reduce the uncertainty of conservation outcomes and will become increasingly necessary for conservation of biodiversity in a changing climate.     

Bioactivity-guided fractionation for the butyrylcholinesterase inhibitory activity of furanocoumarins from Angelica archangelica L. roots and fruits

Isolation and identification of the inhibitors of butyrylcholinesterase (BChE), obtained from the extracts of roots and fruits of Angelica archangelica L., are reported. Our results confirmed the weak inhibitory effect of Angelica roots on acetylcholinesterase activity. BChE inhibition was much more pronounced at a concentration of 100 μg/mL for hexane extracts and attained a higher rate than 50%. The TLC bioautography guided fractionation and spectroscopic analysis led to the isolation and identification of imperatorin from the fruit's hexane extract and of heraclenol-2'-O-angelate from the root's hexane extract. Both compounds showed significant BChE inhibition activity with IC(50) = 14.4 ± 3.2 μM and IC(50) = 7.5 ± 1.8 μM, respectively. Only C8-substituted and C5-unsubstituted furanocoumarins were active, which could supply information about the initial structures of specific BChE inhibitors.     

Clinical management of a western lowland gorilla (Gorilla gorilla gorilla) with a cardiac resynchronization therapy device

A 24-yr-old, male western lowland gorilla (Gorilla gorilla gorilla) was diagnosed with congestive heart failure using transesophageal and transthoracic echocardiology. New York Heart Association (NYHA) Class III was assigned to the severity of the condition. Over 16 mo, this progressed to NYHA Class IV despite increasing medical therapy. Repeated evaluations suggested that implantation of a cardiac resynchronization therapy device with a defibrillator (CRT-D) could benefit this animal based on clinical signs and underlying evidence of dyssynchrony and suspected fibrotic myocardial disease. Surgical implantation of leads into the right atrium, right ventricle, and left ventricle was accomplished. The CRT-D device was placed under the thoracic pectoral muscles during an initial surgical procedure. Improvement in the gorilla's clinical condition after implantation of the CRT-D device was immediate and dramatic. Subsequent scanning of the device was accomplished through operant conditioning. The data from these device interrogations included stored and real-time cardiac data, which were used to minimize recognized environmental stressors and change device settings. Over 4 yr, case management was critical to successful device use in treatment of the clinical disease. This involved medications, training for device interrogation, exercise to increase activity and improve body condition, and phlebotomy attempts. Dietary management was necessary to manipulate caloric and sodium intake and encourage medication compliance. Cardiac resynchronization therapy device implantation, although requiring specialized equipment and surgical skill, appears to be a viable option for treatment of fibrosing cardiomyopathy with systolic dysfunction in gorillas refractory to medical management. In addition to treatment, this device provides cardiovascular data at rest that could allow for early diagnosis and treatment of gorillas with this and other cardiac conditions in the future. This describes the comprehensive medical, husbandry, and training techniques necessary to successfully manage this intense clinical case in conjunction with intracardiac device therapy.     

Short-term effects of olive mill waste water (OMW) on chemical and biochemical properties of a semiarid Mediterranean soil

Olive mill waste water (OMW), a by-product of the olive mill industry, is produced in large amounts in Mediterranean countries. Olive mill waste water contains a high organic load, substantial amounts of plant nutrients but also several compounds with recognized toxicity towards living organisms. Moreover, OMW may represent a low cost source of water. Thus, the use of OMW for soil fertigation is a valuable option for its disposal, provided that its impact on soil chemical and biochemical properties is established. Investigations were performed on the short-term influence of OMW on several chemical and biochemical properties of a soil from a continental semi-arid Mediterranean region (Morocco). The soil was amended with 0, 18 and 36 ml 100 g⁻¹ soil of OMW (corresponding to a field rate of 0, 40 and 80 m³ ha⁻¹, respectively) and changes in various functionally related properties such as microbial biomass, basal respiration, extractable C and N, and soil hydrolases and oxido-reductases activities were measured over time. The variations of the main physical and chemical properties as well as the residual phytotoxicity of OMW amended and non-amended soils as assessed by tomato seed germination tests were also monitored. Temporary and permanent changes in several chemical and biochemical soil properties occurred following OMW application, thus being these properties varied in sensitivity to the applied disturbance. A sudden increase of total organic C, extractable N and C, available P and extractable Mn and Fe contents were measured. Simultaneously, a rapid increase of soil respiration, dehydrogenase and urease activities and microbial biomass (at 14 day incubation) of OMW amended soils occurred. In contrast, the activities of phosphatase, β-glucosidase, nitrate reductase and diphenol oxidase decreased markedly. The soil became highly phytotoxic after OMW addition (large decline of soil germination capability), mainly at 80 m³ ha⁻¹ OMW. After 42 days' incubation, however, a complete recovery of the soil germination capability and a residual phytotoxicity of about 30% were observed with 40 and 80 m³ ha⁻¹ OMW, respectively. These findings indicate that the impact of OMW on soil properties was the result of opposite effects, depending on the relative amounts of beneficial and toxic organic and inorganic compounds present. The toxic compounds contained in OMW most likely counteracted the beneficial effect of organic substrates provided, which promoted the growth and activity of indigenous microorganisms.     

Isozyme analysis of genetic diversity in wild Sicilian populations of Brassica sect. Brassica in view of genetic resources management

In Sicily and in the small surrounding islands the section Brassica of the genus Brassica comprises five species, B. insularis Moris, B. incana Ten., B. macrocarpa Guss., B. rupestris Raf. and B. villosa Biv. These taxa represent a genetic resource as relatives of kale crops but some populations are endangered or threatened, thus isozyme analyses were performed to assess the genetic diversity degree at population and species levels in order to assist the design of conservation management programs.Eleven loci from five enzyme systems (aconitase, leucine aminopeptidase, 6-phosphogluconate dehydrogenase, phosphoglucoisomerase phosphoglucomutase) were analyzed in sixteen natural population (fifteen from Sicily, one from Calabria). Mean within-population genetic diversity was moderate (P = 41%, A = 1.54, H = 0.16). In some cases a great number of heterozygous individuals were detected, in other cases fixation index (F) deviated significantly from Hardy-Weinberg genotypic expectations.A total of 37 alleles was recognized, six of which resulted exclusive to single populations. The among-population component of the total genetic diversity (Gst mean values) for each species was 0.30–0.37, indicating genetic differentiation among populations.Among B. villosa and B. rupestris populations genetic distance values resulted rather low and they resulted high with B. incana and B. macrocarpa populations.The results are discussed with regard to the distribution of the genetic diversity level and the genetic resources management.     

Isoflavonoids isolated from Cuban propolis

Chemical investigation of a red-type Cuban propolis sample has led to the isolation of 11 isoflavonoids (2 isoflavones, 3 isoflavans, and 6 pterocarpans), together with gallic acid, isoliquiritigenin, and (-)-liquiritigenin. Structural determination, including the absolute stereochemistry, was accomplished by spectroscopic analysis, particularly CD and 2D NMR techniques. The fragmentation behavior of pterocarpans was studied by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) using an ion-trap analyzer, and a generalized fragmentation pathway, useful in the identification and structural characterization of pterocarpans, is proposed. Isoflavonoids are reported for the first time from propolis samples.