Lipids are a fundamental class of organic molecules implicated in a wide range of biological processes related to their structural diversity, and based on this can be broadly classified into five categories; fatty acids, triacylglycerols (TAGs), phospholipids, sterol lipids and sphingolipids. Different lipid classes play major roles in neuronal cell populations; they can be used as energy substrates, act as building blocks for cellular structural machinery, serve as bioactive molecules, or a combination of each. In amyotrophic lateral sclerosis (ALS), dysfunctions in lipid metabolism and function have been identified as potential drivers of pathogenesis. In particular, aberrant lipid metabolism is proposed to underlie denervation of neuromuscular junctions, mitochondrial dysfunction, excitotoxicity, impaired neuronal transport, cytoskeletal defects, inflammation and reduced neurotransmitter release. Here we review current knowledge of the roles of lipid metabolism and function in the CNS and discuss how modulating these pathways may offer novel therapeutic options for treating ALS.

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Neuronal Lipid Metabolism: Multiple Pathways Driving Functional Outcomes in Health and Disease.

Penicillins and cephalosporins are β-lactam antibiotics widely used in human medicine. The biosynthesis of these compounds starts by the condensation of the amino acids L-α-aminoadipic acid, L-cysteine and L-valine to form the tripeptide δ-L-α-aminoadipyl-l-cysteinyl-D-valine catalysed by the non-ribosomal peptide 'ACV synthetase'. Subsequently, this tripeptide is cyclized to isopenicillin N that in Penicillium is converted to hydrophobic penicillins, e.g. benzylpenicillin. In Acremonium and in streptomycetes, isopenicillin N is later isomerized to penicillin N and finally converted to cephalosporin. Expression of genes of the penicillin (pcbAB, pcbC, pendDE) and cephalosporin clusters (pcbAB, pcbC, cefD1, cefD2, cefEF, cefG) is controlled by pleitropic regulators including LaeA, a methylase involved in heterochromatin rearrangement. The enzymes catalysing the last two steps of penicillin biosynthesis (phenylacetyl-CoA ligase and isopenicillin N acyltransferase) are located in microbodies, as shown by immunoelectron microscopy and microbodies proteome analyses. Similarly, the Acremonium two-component CefD1-CefD2 epimerization system is also located in microbodies. This compartmentalization implies intracellular transport of isopenicillin N (in the penicillin pathway) or isopenicillin N and penicillin N in the cephalosporin route. Two transporters of the MFS family cefT and cefM are involved in transport of intermediates and/or secretion of cephalosporins. However, there is no known transporter of benzylpenicillin despite its large production in industrial strains.

https://sfamjournals.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-7915.2009.00123.x

Regulation and compartmentalization of β‐lactam biosynthesis

The author would like to thank H. H. Sheikh Zayed Bin Sultan Al Nahyan, President of the United Arab Emirates, and H. H. Sheikh Tahnoon Bin Zayed Al Nahyan, Chairman of the Private Department, for the great support they extended to this paper. The author also thanks Mr A. Pohl for help with sampling the birds, Mrs M. Ibrahim for the laboratory work, and Mr A. Azeez, Mr A. Rasheed, Mr Yousuf and Mr Noushat for feeding and observing the falcons. Special thanks are due to N. Harcourt-Brown for proofreading the manuscript and all his advice.

Relative resistance of pigs to infection by natural aerosols of FMD virus

Clinical implication Persistent remnants of vitelline arteries and veins should be considered in the differential diagnosis of colic in foals. In the present case, the recurrent signs of colic were probably due to the strangulation of an intestinal segment and the fibrinous peritonitis. The foal died of septicaemia. Exploratory laparotomy is the most obvious way to diagnose such congenital anomalies. During the curative resection of the strangulating band, the viability of the affected intestine should always be thoroughly evaluated (Kleinhaus and others 1974).

Possibility of sexual transmission of foot-and-mouth disease from African buffalo to cattle.

The single-module non-ribosomal peptide synthetase BpsA from Streptomyces lavendulae has the unique ability to autonomously synthesize a coloured product (indigoidine) from a single substrate (l-glutamine), conditional upon activation by a 4'-phosphopantetheinyl transferase (PPTase) partner. We show that bpsA can be expressed in an entD PPTase gene deleted mutant of Escherichia coli to yield a sensitive reporter strain for recovery of PPTase genes from metagenome libraries. We also show that recombinant bpsA constructs, generated by substitution of the native peptidyl carrier protein domain followed by directed evolution to restore function, can be used to increase the diversity of PPTase genes recovered from a sample. As PPTases are essential for activation of non-ribosomal peptide synthetase and polyketide synthase enzymes, they are frequently associated with secondary metabolite gene clusters. Nearly half of the PPTases recovered in our screening of two small-insert soil metagenome libraries were genetically linked to recognizable secondary metabolite biosynthetic genes, demonstrating that PPTase-targeting functional screens can be used for efficient recovery of natural product gene clusters from metagenome libraries. The plasticity and portability of bpsA reporter genes can potentially be exploited to maximize recovery and expression of PPTase-bearing clones in a wide range of hosts.

Питер Джон Уайт (Gb)

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The new enzyme