On finite pp-groups whose automorphisms are all central

An automorphism $\alpha$ of a group $G$ is said to be central if $\alpha$ commutes with every inner automorphism of $G$. We construct a family of non-special finite $p$-groups having abelian automorphism groups. These groups provide counter examples to a conjecture of A. Mahalanobis [Israel J. Math., {\bf 165} (2008), 161 - 187]. We also construct a family of finite $p$-groups having non-abelian automorphism groups and all automorphisms central. This solves a problem of I. Malinowska [Advances in group theory, Aracne Editrice, Rome 2002, 111-127].Comment: 11 pages, Counter examples to a conjecture from [Israel J. Math., {\bf 165} (2008), 161 - 187]; This paper will appear in Israel J. Math. in 201

Orthonasal and retronasal detection thresholds of 26 aroma compounds in a model alcohol-free beer: effect of threshold calculation method

Detection thresholds are used routinely to determine the odour-active compounds in foods. The composition of a food matrix, such as hydrophobicity or solids content, has an impact on the release of flavour compounds, and thus on thresholds. In the case of beer, thresholds determined in alcoholic beer may not be the same for alcohol-free beer (AFB). Therefore, the aim of this study was to determine detection thresholds for aroma compounds typically found in beer within a model AFB. The model was designed to match the sugar concentration and pH of an AFB brewed by a cold contact process. Thresholds were measured using a 3-AFC procedure and calculated using either Best Estimate Threshold (BET) method or by logistic regression. Moreover, an algorithm for the removal of false positives was applied to adjust the assessors’ raw responses. Retronasal thresholds were generally lower than orthonasal. Those calculated by BET were significantly higher (p < 0.05) than those from logistic regression, and removal of false positives also produced significantly higher thresholds than those from raw data. The use of logistic regression has the advantage of providing the mathematical model describing the behaviour of the group. The results from this study can be used to better understand the role of flavour compounds in AFB and the effect of the calculation method to prevent under- or overestimated results

The interaction site of Flap Endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA

Werner and Bloom syndromes are genetic RecQ helicase disorders characterized by genomic instability. Biochemical and genetic data indicate that an important protein interaction of WRN and Bloom syndrome (BLM) helicases is with the structure-specific nuclease Flap Endonuclease 1 (FEN-1), an enzyme that is implicated in the processing of DNA intermediates that arise during cellular DNA replication, repair and recombination. To acquire a better understanding of the interaction of WRN and BLM with FEN-1, we have mapped the FEN-1 binding site on the two RecQ helicases. Both WRN and BLM bind to the extreme C-terminal 18 amino acid tail of FEN-1 that is adjacent to the PCNA binding site of FEN-1. The importance of the WRN/BLM physical interaction with the FEN-1 C-terminal tail was confirmed by functional interaction studies with catalytically active purified recombinant FEN-1 deletion mutant proteins that lack either the WRN/BLM binding site or the PCNA interaction site. The distinct binding sites of WRN and PCNA and their combined effect on FEN-1 nuclease activity suggest that they may coordinately act with FEN-1. WRN was shown to facilitate FEN-1 binding to its preferred double-flap substrate through its protein interaction with the FEN-1 C-terminal binding site. WRN retained its ability to physically bind and stimulate acetylated FEN-1 cleavage activity to the same extent as unacetylated FEN-1. These studies provide new insights to the interaction of WRN and BLM helicases with FEN-1, and how these interactions might be regulated with the PCNA-FEN-1 interaction during DNA replication and repair

A conserved loop-wedge motif moderates reaction site search and recognition by FEN1

DNA replication and repair frequently involve intermediate two-way junction structures with overhangs, or flaps, that must be promptly removed; a task performed by the essential enzyme flap endonuclease 1 (FEN1). We demonstrate a functional relationship between two intrinsically disordered regions of the FEN1 protein, which recognise opposing sides of the junction and order in response to the requisite substrate. Our results inform a model in which short-range translocation of FEN1 on DNA facilitates search for the annealed 3′‑terminus of a primer strand, which is recognised by breaking the terminal base pair to generate a substrate with a single nucleotide 3′‑flap. This recognition event allosterically signals hydrolytic removal of the 5′-flap through reaction in the opposing junction duplex, by controlling access of the scissile phosphate diester to the active site. The recognition process relies on a highly-conserved ‘wedge’ residue located on a mobile loop that orders to bind the newly-unpaired base. The unanticipated ‘loop–wedge’ mechanism exerts control over substrate selection, rate of reaction and reaction site precision, and shares features with other enzymes that recognise irregular DNA structures. These new findings reveal how FEN1 precisely couples 3′-flap verification to function

Prefactorized subgroups in pairwise mutually permutable products

The final publication is available at Springer via http://dx.doi.org/10.1007/s10231-012-0257-yWe continue here our study of pairwise mutually and pairwise totally permutable products. We are looking for subgroups of the product in which the given factorization induces a factorization of the subgroup. In the case of soluble groups, it is shown that a prefactorized Carter subgroup and a prefactorized system normalizer exist.Aless stringent property have F-residual, F-projector and F-normalizer for any saturated formation F including the supersoluble groups.The first and fourth authors have been supported by the grant MTM2010-19938-C03-01 from MICINN (Spain).Ballester-Bolinches, A.; Beidleman, J.; Heineken, H.; Pedraza Aguilera, MC. (2013). Prefactorized subgroups in pairwise mutually permutable products. Annali di Matematica Pura ed Applicata. 192(6):1043-1057. https://doi.org/10.1007/s10231-012-0257-yS104310571926Amberg B., Franciosi S., de Giovanni F.: Products of Groups. Clarendon Press, Oxford (1992)Ballester-Bolinches, A., Pedraza-Aguilera, M.C., Pérez-Ramos, M.D.: Totally and Mutually Permutable Products of Finite Groups, Groups St. Andrews 1997 in Bath I. London Math. Soc. Lecture Note Ser. 260, 65–68. Cambridge University Press, Cambridge (1999)Ballester-Bolinches A., Pedraza-Aguilera M.C., Pérez-Ramos M.D.: On finite products of totally permutable groups. Bull. Aust. Math. Soc. 53, 441–445 (1996)Ballester-Bolinches A., Pedraza-Aguilera M.C., Pérez-Ramos M.D.: Finite groups which are products of pairwise totally permutable subgroups. Proc. Edinb. Math. Soc. 41, 567–572 (1998)Ballester-Bolinches A., Beidleman J.C., Heineken H., Pedraza-Aguilera M.C.: On pairwise mutually permutable products. Forum Math. 21, 1081–1090 (2009)Ballester-Bolinches A., Beidleman J.C., Heineken H., Pedraza-Aguilera M.C.: Local classes and pairwise mutually permutable products of finite groups. Documenta Math. 15, 255–265 (2010)Beidleman J.C., Heineken H.: Mutually permutable subgroups and group classes. Arch. Math. 85, 18–30 (2005)Beidleman J.C., Heineken H.: Group classes and mutually permutable products. J. Algebra 297, 409–416 (2006)Carocca A.: p-supersolvability of factorized groups. Hokkaido Math. J. 21, 395–403 (1992)Carocca, A., Maier, R.: Theorems of Kegel-Wielandt Type Groups St. Andrews 1997 in Bath I. London Math. Soc. Lecture Note Ser. 260, 195–201. Cambridge University Press, Cambridge, (1999)Doerk K., Hawkes T.: Finite Soluble Groups. Walter De Gruyter, Berlin (1992)Maier R., Schmid P.: The embedding of quasinormal subgroups in finite groups. Math. Z. 131, 269–272 (1973

Dynamic Disorder in Quasi-Equilibrium Enzymatic Systems

Conformations and catalytic rates of enzymes fluctuate over a wide range of timescales. Despite these fluctuations, there exist some limiting cases in which the enzymatic catalytic rate follows the macroscopic rate equation such as the Michaelis-Menten law. In this paper we investigate the applicability of macroscopic rate laws for fluctuating enzyme systems in which catalytic transitions are slower than ligand binding-dissociation reactions. In this quasi-equilibrium limit, for an arbitrary reaction scheme we show that the catalytic rate has the same dependence on ligand concentrations as obtained from mass-action kinetics even in the presence of slow conformational fluctuations. These results indicate that the timescale of conformational dynamics – no matter how slow – will not affect the enzymatic rate in quasi-equilibrium limit. Our numerical results for two enzyme-catalyzed reaction schemes involving multiple substrates and inhibitors further support our general theory

Functional regulation of FEN1 nuclease and its link to cancer

Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. FEN1 possesses FEN, 5′-exonuclease and gap-endonuclease activities. The multiple nuclease activities of FEN1 allow it to participate in numerous DNA metabolic pathways, including Okazaki fragment maturation, stalled replication fork rescue, telomere maintenance, long-patch base excision repair and apoptotic DNA fragmentation. Here, we summarize the distinct roles of the different nuclease activities of FEN1 in these pathways. Recent biochemical and genetic studies indicate that FEN1 interacts with more than 30 proteins and undergoes post-translational modifications. We discuss how FEN1 is regulated via these mechanisms. Moreover, FEN1 interacts with five distinct groups of DNA metabolic proteins, allowing the nuclease to be recruited to a specific DNA metabolic complex, such as the DNA replication machinery for RNA primer removal or the DNA degradosome for apoptotic DNA fragmentation. Some FEN1 interaction partners also stimulate FEN1 nuclease activities to further ensure efficient action in processing of different DNA structures. Post-translational modifications, on the other hand, may be critical to regulate protein–protein interactions and cellular localizations of FEN1. Lastly, we also review the biological significance of FEN1 as a tumor suppressor, with an emphasis on studies of human mutations and mouse models

Complementary non-radioactive assays for investigation of human flap endonuclease 1 activity

FEN1, a key participant in DNA replication and repair, is the major human flap endonuclease that recognizes and cleaves flap DNA structures. Deficiencies in FEN1 function or deletion of the fen1 gene have profound biological effects, including the suppression of repair of DNA damage incurred from the action of various genotoxic agents. Given the importance of FEN1 in resolving abnormal DNA structures, inhibitors of the enzyme carry a potential as enhancers of DNA-interactive anticancer drugs. To facilitate the studies of FEN1 activity and the search for novel inhibitors, we developed a pair of complementary-readout homogeneous assays utilizing fluorogenic donor/quencher and AlphaScreen chemiluminescence strategies. A previously reported FEN1 inhibitor 3-hydroxy-5-methyl-1-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione displayed equal potency in the new assays, in agreement with its published IC50. The assays were optimized to a low 4 µl volume and used to investigate a set of small molecules, leading to the identification of previously-unreported FEN1 inhibitors, among which aurintricarboxylic acid and NSC-13755 (an arylstibonic derivative) displayed submicromolar potency (average IC50 of 0.59 and 0.93 µM, respectively). The availability of these simple complementary assays obviates the need for undesirable radiotracer-based assays and should facilitate efforts to develop novel inhibitors for this key biological target

The wonders of flap endonucleases: structure, function, mechanism and regulation.

Processing of Okazaki fragments to complete lagging strand DNA synthesis requires coordination among several proteins. RNA primers and DNA synthesised by DNA polymerase α are displaced by DNA polymerase δ to create bifurcated nucleic acid structures known as 5'-flaps. These 5'-flaps are removed by Flap Endonuclease 1 (FEN), a structure-specific nuclease whose divalent metal ion-dependent phosphodiesterase activity cleaves 5'-flaps with exquisite specificity. FENs are paradigms for the 5' nuclease superfamily, whose members perform a wide variety of roles in nucleic acid metabolism using a similar nuclease core domain that displays common biochemical properties and structural features. A detailed review of FEN structure is undertaken to show how DNA substrate recognition occurs and how FEN achieves cleavage at a single phosphate diester. A proposed double nucleotide unpairing trap (DoNUT) is discussed with regards to FEN and has relevance to the wider 5' nuclease superfamily. The homotrimeric proliferating cell nuclear antigen protein (PCNA) coordinates the actions of DNA polymerase, FEN and DNA ligase by facilitating the hand-off intermediates between each protein during Okazaki fragment maturation to maximise through-put and minimise consequences of intermediates being released into the wider cellular environment. FEN has numerous partner proteins that modulate and control its action during DNA replication and is also controlled by several post-translational modification events, all acting in concert to maintain precise and appropriate cleavage of Okazaki fragment intermediates during DNA replication