SEQ-ED: an interactive computer program for editing, analysis and storage of long DNA sequences

The rapidly growing body of sequenced DNA demands efficientcomputer programs for its analysis and storage. The programdescribed in this paper, SEQ-ED, has been designed to handlea large number of DNA sequences up to 200 kilobases [kb] longstored in a sequence library. In order to minimize the requiredstorage space, the sequences are stored in a compressed formatusing three binary digits per base. In the development of thisprogram, special care has been given to make it easy to usefor molecular biologists without any previous computer experience. Received on September 10, 1984; accepted on October 30, 1984     

Metabolic adaptations for isopod specialization in three species of Dysdera spiders from the Canary Islands

The spider genus Dysdera is considered to comprise specialist isopod feeders, although the degree of specialization varies between species, depending on morphological (shape of chelicerae), behavioural (attack tactics) and metabolic (food quality of prey) adaptations. Dysdera has radiated extensively in the Canary Islands (currently 47 endemic species are described) and codistributed species have different cheliceral shapes and body sizes indicating different feeding niches. In the present study, we investigate the existence of metabolic adaptations to feeding on isopods by three endemic species (Dysdera insulana Simon, Dysdera macra Simon and Dysdera verneaui Simon) from Tenerife. We hypothesize that there is enhanced extraction efficiency of fundamental macronutrients from isopods compared with control prey in species with special morphological and behavioural adaptations for this prey type. We measure quantitatively spider growth, dry mass consumption, lipid and nitrogen consumption, and calculate growth efficiency and efficiency of utilization of dry mass, lipid and nitrogen. The results show that all three species are able to utilize both prey types, indicating that none of them are strict isopod specialist. Dysdera insulana shows enhanced growth efficiency and D. macra shows enhanced nitrogen extraction efficiency compared with D. verneaui when feeding on Porcellio rather than on Musca. Both traits indicate likely adaptations for the utilization of isopods. Spider species, sex and prey type all affect lipid and nitrogen extraction efficiencies, indicating that spiders do not simply extract nutrients in the proportions available. The results support the hypothesis that adaptations for enhanced digestion of focal prey evolve in species that already have adaptations for enhanced capture success.     

Impact of Histone H4 Lysine 20 Methylation on 53BP1 Responses to Chromosomal Double Strand Breaks

Recruitment of 53BP1 to chromatin flanking double strand breaks (DSBs) requires γH2AX/MDC1/RNF8-dependent ubiquitination of chromatin and interaction of 53BP1 with histone H4 methylated on lysine 20 (H4K20me). Several histone methyltransferases have been implicated in 53BP1 recruitment, but their quantitative contributions to the 53BP1 response are unclear. We have developed a multi-photon laser (MPL) system to target DSBs to subfemtoliter nuclear volumes and used this to mathematically model DSB response kinetics of MDC1 and of 53BP1. In contrast to MDC1, which revealed first order kinetics, the 53BP1 MPL-DSB response is best fitted by a Gompertz growth function. The 53BP1 MPL response shows the expected dependency on MDC1 and RNF8. We determined the impact of altered H4K20 methylation on 53BP1 MPL response kinetics in mouse embryonic fibroblasts (MEFs) lacking key H4K20 histone methyltransferases. This revealed no major requirement for the known H4K20 dimethylases Suv4-20h1 and Suv4-20h2 in 53BP1 recruitment or DSB repair function, but a key role for the H4K20 monomethylase, PR-SET7. The histone methyltransferase MMSET/WHSC1 has recently been implicated in 53BP1 DSB recruitment. We found that WHSC1 homozygous mutant MEFs reveal an alteration in balance of H4K20 methylation patterns; however, 53BP1 DSB responses in these cells appear normal.     

Opinion Formation Models on a Gradient

Statistical physicists have become interested in models of collective social behavior such as opinion formation, where individuals change their inherently preferred opinion if their friends disagree. Real preferences often depend on regional cultural differences, which we model here as a spatial gradient g in the initial opinion. The gradient does not only add reality to the model. It can also reveal that opinion clusters in two dimensions are typically in the standard (i.e., independent) percolation universality class, thus settling a recent controversy about a non-consensus model. However, using analytical and numerical tools, we also present a model where the width of the transition between opinions scales , not as in independent percolation, and the cluster size distribution is consistent with first-order percolation.     

Acidic Nonsteroidal Anti-inflammatory Drugs Inhibit Rat Brain Fatty Acid Amide Hydrolase in a pH-dependent Manner

Previous studies have demonstrated that fatty acid amide hydrolase, the enzyme responsible for the metabolism of anandamide, is inhibited by the acidic non-steroidal anti-inflammatory drug (NSAID) ibuprofen with a potency that increases as the assay pH is reduced. Here we show that (R) -, (S) - and (R, S) -flurbiprofen, indomethacin and niflumic acid show similar pH-dependent shifts in potency to that seen with ibuprofen. Thus, (S) -flurbiprofen inhibited 2 μM [3 H]anandamide metabolism with IC 50 values of 13 and 50 μM at assay pH values of 6 and 8, respectively. In contrast, the neutral compound celecoxib was a weak fatty acid amide hydrolase inhibitor and showed no pH dependency (IC 50 values ~300 μM at both assay pH). The cyclooxygenase-2-selective inhibitors nimesulide and SC-58125 did not inhibit fatty acid amide hydrolase activity at either pH. The data are consistent with the conclusion that the non-ionised forms of the acidic NSAIDs are responsible for the inhibition of fatty acid amide hydrolase.     

Inhibition of Fatty Acid Amidohydrolase,the Enzyme Responsible for the Metabolism of the Endocannabinoid Anandamide,by Analogues of Arachidonoyl-serotonin

Arachidonoyl-serotonin inhibits in a mixed-type manner the metabolism of the endocannabinoid anandamide by the enzyme fatty acid amidohydrolase. In the present study, compounds related to arachidonoyl-serotonin have been synthesised and investigated for their ability to inhibit anandamide hydrolysis by this enzyme in rat brain homogenates. Removal of the 5-hydroxy from the serotonin head group of arachidonoyl-serotonin produced a compound (N-arachidonoyltryptamine) that was a 2.3-fold weaker inhibitor of anandamide hydrolysis, but which also produced its inhibition by a mixed-type manner (K_i(slope) 1.3 µM; K_i(intercept) 44 µM). Replacement of the amide linkage in this compound by an ester group further reduced the potency. In contrast, replacement of the arachidonoyl side chain by a linolenoyl side chain did not affect the observed potency. N-(Fur-3-ylmethyl) arachidonamide (UCM707), N-(fur-3-ylmethyl)linolenamide and N-(fur-3-ylmethyl)oleamide inhibited anandamide hydrolysis with pI50 values of 4.53, 5.36 and 5.25, respectively. The linolenamide derivative was also found to be a mixed-type inhibitor. It is concluded that the 5-hydroxy group of arachidonoyl-serotonin contributes to, but is not essential for, inhibitory potency at fatty acid amidohydrolase.