Dietary fatty acids and chylomicron synthesis and secretion

There is currently considerable interest in potential atherogenic and thrombogenic consequences of elevated concentrations of triacylglycerols, especially in the post-prandial state. Despite this, there is limited information on the effects of dietary fatty acids on the synthesis, secretion and metabolism of chylomicrons, the large triacylglycerol-rich lipoproteins synthesized in the enterocyte following the digestion and absorption of dietary fat. This brief review considers current approaches to the investigation of chylomicron synthesis and summarizes some of the human, cell and animal studies that have investigated effects of different fatty acids on these pathways. Potential sites for modulatory effects of dietary fatty acids on the molecular events of chylomicron synthesis are proposed in the light of the recent model that has been developed from cell and animal studies and observations based on abnormalities in chylomicron formation in human inherited autosomal recessive diseases.

The symbolic value of grafting in ancient Rome

Some scholars have read Virgil’s grafted tree (G. 2.78–82) as a sinister image, symptomatic of man’s perversion of nature. However, when it is placed within the long tradition of Roman accounts of grafting (in both prose and verse), it seems to reinforce a consistently positive view of the technique, its results, and its possibilities. Virgil’s treatment does represent a significant change from Republican to Imperial literature, whereby grafting went from mundane reality to utopian fantasy. This is reflected in responses to Virgil from Ovid, Columella, Calpurnius, Pliny the Elder, and Palladius (with Republican context from Cato, Varro, and Lucretius), and even in the postclassical transformation of Virgil’s biography into a magical folktale.

Synthesis of a systolic array genetic algorithm

The paper presents a design for a hardware genetic algorithm which uses a pipeline of systolic arrays. These arrays have been designed using systolic synthesis techniques which involve expressing the algorithm as a set of uniform recurrence relations. The final design divorces the fitness function evaluation from the hardware and can process chromosomes of different lengths, giving the design a generic quality. The paper demonstrates the design methodology by progressively re-writing a simple genetic algorithm, expressed in C code, into a form from which systolic structures can be deduced. This paper extends previous work by introducing a simplification to a previous systolic design for the genetic algorithm. The simplification results in the removal of 2N 2 + 4N cells and reduces the time complexity by 3N + 1 cycles.

Rapid synthesis of carbohydrate derivatives, including mimetics of c-linked disaccharides and c-Linked aza disaccharides, using the Hetero-Diels−Alder Reaction

In this work we demonstrate the value of performing a Hetero Diels-Alder reaction (HDAR) between Danishefsky’s diene and a range of aldehydes or imines, under microwave irradiation. By using a range of aldehydes and imines, including those derived from carbohydrates, access to functionalised 2,3-dihydro-4H-pyran-4-ones or 2,3-dihydro-4-pyridinones in good to excellent synthetic yields is possible. A particular strength of the methodology is its ability to access mimetics of C-linked disaccharides and C-linked aza disaccharides, targets of current therapeutic interest, in a rapid, convenient and diastereoselective manner. The effect of high pressure on the HDARs involving carbohydrate derived aldehydes and imines is also explored, with enhancement in yields occurring for the aldehyde substrates. Finally, HDARs using carbohydrate derived ketones, enones and enals are described under a range of conditions. Optimum results were obtained under high pressure conditions, with highly functionalized carbohydrate derivatives being afforded, in good yields, in this way.

The impact of harvesting on a formerly endangered tropical bird: insights from life-history theory

1. Life-history theory assumes that trade-offs exist between an individual's life-history components, such that an increased allocation of a resource to one fitness trait might be expected to result in a cost for a conflicting fitness trait. Recent evidence from experimental manipulations of wild individuals supports this assumption. 2. The management of many bird populations involves harvesting for both commercial and conservation purposes. One frequently harvested life-history stage is the egg, but the consequences of repeated egg harvesting for the individual and the long-term dynamics of the population remain poorly understood. 3. We used a well-documented restored population of the Mauritius kestrel Falco punctatus as a model system to explore the consequences of egg harvesting (and associated management practices) for an individual within the context of life-history theory. 4. Our analysis indicated that management practices enhanced both the size and number of clutches laid by managed females, and improved mid-life male and female adult survival relative to unmanaged adult kestrels. 5. Although management resulted in an increased effort in egg production, it reduced parental effort during incubation and the rearing of offspring, which could account for these observed changes. 6. Synthesis and applications. This study demonstrates how a commonly applied harvesting strategy, when examined within the context of life-history theory, can identify improvements in particular fitness traits that might alleviate some of the perceived negative impact of harvesting on the long-term dynamics of a managed population.

Splanchnic metabolism of dairy cows during the transition from late gestation through early lactation

Blood flow and net nutrient fluxes for portal-drained viscera (PDV) and liver ( total splanchnic tissues) were measured at 19 and 9 d prepartum and at 11, 21, 33, and 83 d in milk ( DIM) in 5 multiparous Holstein-Friesian cows. Cows were fed a grass silage-based gestation ration initially and a corn silage-based lactation ration peripartum and postpartum. Meals were fed at 8-h intervals and hourly (n = 8) measures of splanchnic metabolism were started before ( 0730 h and 0830 h) feeding at 0830 h. Dry matter intakes (DMI) at 19 and 9 d prepartum were not different. Metabolism changes measured from 19 to 9 d prepartum were lower arterial insulin and acetate, higher arterial nonesterified fatty acids and increased net liver removal of glycerol. After calving, PDV and liver blood flow and oxygen consumption more than doubled as DMI and milk yield increased, but 85 and 93% of the respective increases in PDV and liver blood flow at 83 DIM had occurred by 11 DIM. Therefore, factors additional to DMI must also contribute to increased blood flow in early lactation. Most postpartum changes in net PDV and liver metabolism could be attributed to increases in DMI and digestion or increased milk yield and tissue energy loss. Glucose release was increasingly greater than calculated requirements as DIM increased, presumably as tissue energy balance increased. Potential contributions of lactate, alanine, and glycerol to liver glucose synthesis were greatest at 11 DIM but decreased by 83 DIM. Excluding alanine, there was no evidence of an increased contribution of amino acids to liver glucose synthesis is required in early lactation. Increased net liver removal of propionate (69%), lactate (20%), alanine (8%), and glycerol (4%) can account for increased liver glucose release in transition cows from 9 d before to 11 d after calving.

Effect of plasma insulin and branched-chain amino acids on skeletal muscle protein synthesis in fasted lambs

The increase in fractional rate of protein synthesis (K-s) in the skeletal muscle of growing rats during the transition from fasted to fed state has been explained by the synergistic action of a rise in plasma insulin and branched-chain amino acids (BCAA). Since growing lambs Also exhibit an increase in K-s with level of feed intake, the objective of the present study was to determine if this synergistic relationship between insulin and BCAA also occurs in ruminant animals. Six 30 kg fasted (72 h) lambs (8 months of age) received each of four treatments, which were based on continuous infusion into the jugular vein for 6 h of: (1) saline (155 mmol NaCl/l); (2) a mixture of BCAA (0.778 mumol leucine, 0.640 mumol isoleucine and 0.693 mumol valine/min.kg); (3) 18.7 mumol glucose/min.kg (to induce endogenous insulin secretion): (4) co-infusion of BCAA and glucose. Within each period all animals received the same isotope of phenylalanine, (Phe) as follows: (1) L-[1-C-13]Phe; (2) L-phenyl-[ring H-2(5)]-alanine; (3) L-[N-15]Phe; (4) L-[ring 2,6-H-3]Phe. Blood was sampled serially during infusions to measure plasma concentrations of insulin, glucose and amino acids, and plasma free Phe isotopic activity; biopsies were taken 6 h after the beginning of infusions to determine K-s in in. longissimus dorsi and vastus muscle. Compared with control (saline-infused) lambs, K-s was increased by an average of 40% at the end of glucose infusion, but this effect was not statistically significant in either of the muscles sampled. BCAA infusion, alone or in combination with glucose, also had no significant effect on K-s compared with control sheep. K-s was approximately 60% greater for vastus muscle than for m. longissimus dorsi (P<0.01), regardless of treatment. It is concluded that there are signals other than insulin and BCAA that are responsible for the feed-induced increase in K-s in muscle of growing ruminant animals.

Immunogenetics of drug-induced skin blistering disorders. Part II: Synthesis

The overall immunopathogenesis relevant to a large series of disorders caused by a drug or its associated hyperimmune condition is discussed based upon examining the genetics of severe drug-induced bullous skin problems (sporadic idiosyncratic adverse events including Stevens-Johnson syndrome and Toxic epidermal necrolysis). New results from an exemplar study on shared precipitating and perpetuating inner causes with other related disease phenotypes including aphtous stomatitis, Behcets, erythema multiforme, Hashimoto's thyroiditis, pemphigus, periodic fevers, Sweet's syndrome and drug-induced multisystem hypersensitivity are presented. A call for a collaborative, wider demographic profiling and deeper immunotyping in suggested future work is made.

De novo alanine synthesis by bacteroids of Mesorhizobium loti is not required for nitrogen transfer in the determinate nodules of Lotus corniculatus

Deletion of both alanine dehydrogenase genes (aldA) in Mesorhizobium loti resulted in the loss of AldA enzyme activity from cultured bacteria and bacteroids but had no effect on the symbiotic performance of Lotus corniculatus plants. Thus, neither indeterminate pea nodules nor determinate L. corniculatus nodules export alanine as the sole nitrogen secretion product.

A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone (PZ-S), benign prostatic hyperplasia (BPH-S), and cancer (CA-S) to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone, or BPH-1 epithelial cells alone produced no visible grafts. Recombining PZ-S with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized and sharply demarcated grafts approximately 3-4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining CA-S with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye stained specimens is an efficient method to generate high quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo which mimics the natural history of these diseases.

The role of satellite image-processing for national-scale estimates of gene flow from genetically modified crops: rapeseed in the UK as a model

1.There is concern over the possibility of unwanted environmental change following transgene movement from genetically modified (GM) rapeseed Brassica napus to its wild and weedy relatives. 2. The aim of this research was to develop a remote sensing-assisted methodology to help quantify gene flow from crops to their wild relatives over wide areas. Emphasis was placed on locating sites of sympatry, where the frequency of gene flow is likely to be highest, and on measuring the size of rapeseed fields to allow spatially explicit modelling of wind-mediated pollen-dispersal patterns. 3. Remote sensing was used as a tool to locate rapeseed fields, and a variety of image-processing techniques was adopted to facilitate the compilation of a spatially explicit profile of sympatry between the crop and Brassica rapa. 4. Classified satellite images containing rapeseed fields were first used to infer the spatial relationship between donor rapeseed fields and recipient riverside B. rapa populations. Such images also have utility for improving the efficiency of ground surveys by identifying probable sites of sympatry. The same data were then also used for the calculation of mean field size. 5. This paper forms a companion paper to Wilkinson et al. (2003), in which these elements were combined to produce a spatially explicit profile of hybrid formation over the UK. The current paper demonstrates the value of remote sensing and image processing for large-scale studies of gene flow, and describes a generic method that could be applied to a variety of crops in many countries. 6.Synthesis and applications. The decision to approve or prevent the release of a GM cultivar is made at a national rather than regional level. It is highly desirable that data relating to the decision-making process are collected at the same scale, rather than relying on extrapolation from smaller experiments designed at the plot, field or even regional scale. It would be extremely difficult and labour intensive to attempt to carry out such large-scale investigations without the use of remote-sensing technology. This study used rapeseed in the UK as a model to demonstrate the value of remote sensing in assembling empirical information at a national level.

The structure and mechanism of serine acetyltransferase from Escherichia coli

Serine acetyltransferase (SAT) catalyzes the first step of cysteine synthesis in microorganisms and higher plants. Here we present the 2.2 Angstrom crystal structure of SAT from Escherichia coli, which is a dimer of trimers, in complex with cysteine. The SAT monomer consists of an amino-terminal alpha-helical domain and a carboxyl- terminal left-handed beta-helix. We identify His(158) and Asp(143) as essential residues that form a catalytic triad with the substrate for acetyl transfer. This structure shows the mechanism by which cysteine inhibits SAT activity and thus controls its own synthesis. Cysteine is found to bind at the serine substrate site and not the acetyl-CoA site that had been reported previously. On the basis of the geometry around the cysteine binding site, we are able to suggest a mechanism for the O-acetylation of serine by SAT. We also compare the structure of SAT with other left-handed beta-helical structures.

Synthesis and characterization of fluorescent poly(aromatic amide) dendrimers

The synthesis of a series of poly(aromatic amide) dendrimers up to the second generation is described herein. The AB, building block used throughout the synthesis of the dendrimers was the allyl ester of 3,5-diaminocinnamic acid, which has been synthesized from 3,5-dinitrobenzoic acid in good yield with use of a four-step procedure. Dendron synthesis was achieved via a convergent approach with use of a sequence of deprotection/coupling steps. Two commercially available alcohols, L-menthol and citronellol, were coupled to the AB(2) monomer by using an alkyl diacid spacer and two core units; 1,7-diaminoheptane and tris(2-aminoethyl)amine have been used to produce the final dendrimers. Characterization was carried out by NMR and IR spectroscopies, MALDI-TOF mass spectrometry, GPC, and DSC. The novel monomer and dendritic derivatives exhibited a strong fluorescence emission in the visible region (lambda approximate to 500 nm) of the spectrum and a weak emission in the near-infrared (lambda approximate to 850 nm) upon excitation in the near-UV region. The fluorescence emission characteristics were found to be solvent and dendrimer generation dependent.

Fragrance release from the surface of branched poly(amide)s

Enzymes are powerful tools in organic synthesis that are able to catalyse a wide variety of selective chemical transformations under mild and environmentally friendly conditions. Enzymes such as the lipases have also found applications in the synthesis and degradation of polymeric materials. However, the use of these natural catalysts in the synthesis and the post-synthetic modification of dendrimers and hyperbranched molecules is an application of chemistry yet to be explored extensively. In this study the use of two hydrolytic enzymes, a lipase from Candida cylindracea and a cutinase from Fusarium solani pisii, were investigated in the selective cleavage of ester groups situated on the peripheral layer of two families of branched polyamides. These branched polyamides were conjugated to simple fragrances citronellol and L-menthol via ester linkages. Hydrolysis of the ester linkage between the fragrances and the branched polyamide support was carried out in aqueous buffered systems at slightly basic pH values under the optimum operative conditions for the enzymes used. These preliminary qualitative investigations revealed that partial cleavage of the ester functionalities from the branched polyamide support had occurred. However, the ability of the enzymes to interact with the substrates decreased considerably as the branching density, the rigidity of the structure and the bulkiness of the polyamide-fragrance conjugates increased.

Dinuclear complexes of M-II thiocyanate (M = Ni and Cu) containing a tridentate Schiff-base ligand: synthesis, structural diversity and magnetic properties

A dinuclear Ni-II complex, [Ni-2(L)(2)(H2O)(NCS)(2)]center dot 3H(2)O (1) in which the metal atoms are bridged by one water molecule and two mu(2)-phenolate ions, and a thiocyanato-bridged dimeric Cull complex, [Cu(L)NCS](2) (2) [L = tridentate Schiff-base ligand, N-(3-aminopropyl)salicylaldimine, derived from 1:1 condensation of salicylaldehyde and 1,3-diaminopropane], have been synthesized and characterized by IR and UV/Vis spectroscopy, cyclic voltammetry and single-crystal X-ray diffraction studies. The structure of 1 consists of dinuclear units with crystallographic C-2 symmetry in which each Ni-II atom is in a distorted octahedral environment. The Ni-O distance and the Ni-O-Ni angle, through the bridged water molecule, are 2.240(11) angstrom and 82.5(5)degrees, respectively. The structure of 2 consists of dinuclear units bridged asymmetrically by di-mu(1,3)-NCS ions; each Cull ion is in a square-pyramidal environment with tau = 0.25. Variable-temperature magnetic susceptibility studies indicate the presence of dominant ferromagnetic exchange coupling in complex 1 with J = 3.1 cm(-1), whereas complex 2 exhibits weak antiferromagnetic coupling between the Cu-II centers with J = -1.7 cm(-1). ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)