Letters

Out of focus; Keith Leech

No more projects?; Judith Tborley

Nuffield Advanced Biology; Tim Turvey

AIDS information for schools; Dana Schmidt Hopfeld, Avi Hofstein and David Samuel     

Research in Context

Using newspapers in your science classroom;Ruth Jarman and Billy Mclune

Conventional or computer-based rat dissection?;Martin Predavec

Development of knowledge frameworks and higher order cognitive operations;Paul J Bischoff and O Roger Anderson     

Research in context

Do young people understand cellular genetics?; Colin Wood-Robinson, Jenny Lewis, and John Leach

Do young people understand cellular genetics?; Din Yan Yip

Improve your students' understanding of ecology; Kathleen Hogan     

Biotransformation of heterocyclic dinitriles by Rhodococcus erythropolis and fungal nitrilases

2,6-Pyridinedicarbonitrile (1a) and 2,4-pyridinedicarbonitrile (2a) were hydrated by Rhodococcus erythropolis A4 to 6-cyanopyridine-2-carboxamide (1b; 83% yield) and 2-cyanopyridine-4-carboxamide (2b; 97% yield), respectively, after 10 min. After 118 h, the intermediates 1b or 2b were transformed into 2,6-pyridinedicarboxamide (1c; 35% yield) and 2,6-pyridinedicarboxylic acid (1d; 60% yield) or 2-cyanopyridine-4-carboxylic acid (2c; 64% yield), respectively. The nitrilase from Fusarium solani afforded cyanocarboxylic acids 1e and 2c after 118 h (yields 95 and 62%, respectively). 3,4-Pyridinedicarbonitrile (3a) and 2,3-pyrazinedicarbonitrile (4a) were inferior substrates of nitrile hydratase and nitrilase.     

Dragma Hippomanicum II: Astragali Novi Peninsulares Moraniani

Three new species are described from Estado Baja California, Mexico:A. (sect. Trichopodi)oxyphysopsis;A. (sect. Inflati)sanctorum; andA. (sect. Inflati)moranii.     

Letters

No more projects?; D. R. Holdford

SA/V ratios and gaseous exchange; Michael Reiss     

Synthesis,antitumour and antioxidant activities of novel α,β-unsaturated ketones and related heterocyclic analogues: EGFR inhibition and molecular modelling study

New α,β-unsaturated ketones 4a,b; 5a–c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxazoline 9; pyridine 10–11; and quinoline-4-carboxylic acid 12a,b derivatives were synthesized and evaluated for in vitro antitumour activity against HepG2, MCF-7, HeLa, and PC-3 cancer cell lines. Antioxidant activity was investigated by the ability of these compounds to scavenge the 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS^?+). Compounds 6a, 6b, 7, and 8b exhibited potent antitumour activities against all tested cell lines with [IC₅₀] ?5.5–18.1 µΜ), in addition to significantly high ABTS^?+ scavenging activities. In vitro EGFR kinase assay for 6a, 6b, 7, and 8b as the most potent antitumour compounds showed that; compounds 6b, and 7 exhibited worthy EGFR inhibition activity with IC₅₀ values of 0.56 and 1.6?µM, respectively, while compounds 6a and 8b showed good inhibition activity with IC₅₀ values of 4.66 and 2.16?µM, respectively, compared with sorafenib reference drug (IC₅₀?=?1.28?µM). Molecular modelling studies for compounds 6b, 7, and 8b were conducted to exhibit the binding mode towards EGFR kinase, which showed similar interaction with erlotinib.     

New species and other nomenclatural changes for ferns from Bolivia

We describe 11 new pteridophyte species belonging to various families from Bolivia: Dennstaedtiaceae:Hypolepis, scandens, Hypolepis minima; Pteridaceae:Cheilanthes glutinosa, Eriosorus angustus, E. ascendens, E. madidiensis; Tectariaceae:Tectaria jimenezii; and Woodsiaceae:Athyrium latinervatum. Diplazium bipinnatum, D. bolivianum, D. yuyoense. The following new combinations are proposed:Anemia australis, Diplazium andicola, D. andinum, andD. petiolulatum.Polystichum maximum is proposed as a new name forPolystichum giganteum.     

Cancer models,genomic instability and somatic cellular Darwinian evolution

   

The biology of cancer is critically reviewed and evidence adduced that its development can be modelled as a somatic cellular Darwinian evolutionary process. The evidence for involvement of genomic instability (GI) is also reviewed. A variety of quasi-mechanistic models of carcinogenesis are reviewed, all based on this somatic Darwinian evolutionary hypothesis; in particular, the multi-stage model of Armitage and Doll (Br. J. Cancer 1954:8;1-12), the two-mutation model of Moolgavkar, Venzon, and Knudson (MVK) (Math. Biosci. 1979:47;55-77), the generalized MVK model of Little (Biometrics 1995:51;1278-1291) and various generalizations of these incorporating effects of GI (Little and Wright Math. Biosci. 2003:183;111-134; Little et al. J. Theoret. Biol. 2008:254;229-238).     

Grassflies of the genus <Emphasis Type="Italic">Polyodaspis</Emphasis> Duda (Diptera,Chloropidae) in the fauna of southeast Asia

Over 200 specimens of Polyodaspis from Vietnam and Thailand (project TIGER) were studied. Variations in the color of the body and, especially, of the setae and setulae of the head, scutellum, and abdomen are demonstrated. The following new synonymy is established: Polyodaspis ruficornis (Macquart, 1835) = P. ruficornis var. tarsalis Frey, 1923, syn. n.; = P. flavipila Duda, 1934, syn. n.; = P. endogena de Meijere, 1938, syn. n.; = P. flavisetosa Nartshuk, 1991, syn. n.; = P. similis Nartshuk, 1991, syn. n.     

Increments to the genus Mimosa (Mimosaceae) from South America

Four new species are described and discussed: from BoliviaM. (sect.Habbasia ser.Setosae)huanchacae; from SE brazilM. (sect.Habbasia ser.Pachycarpae)chiliomera andM. (sect.Mimosa)murex; and from EcuadorM. (sect.Mimosa subser.Polycarpae)Loxensis. The two Brazilian species are illustrated.     

Synthesis and potential antitumor activity of 7-(4-substituted piperazin-1-yl)-4-oxoquinolines based on ciprofloxacin and norfloxacin scaffolds: in silico studies

The potential antitumor activities of a series of 7-(4-substituted piperazin-1-yl)fluoroquinolone derivatives (1–14a,b) using ciprofloxacin and norfloxacin as scaffolds are described. These compounds exhibit potent and broad spectrum antitumor activities using 60 human cell lines in addition to the inherent antibacterial activity. Compounds 1a, 2a, 3b, 6b and 7a were found to be the most potent, while 2b, 5b, and 6a were found to have an average activity. The results of this study demonstrated that compounds 1a, 2a, 3b, 6b and 7a (mean GI₅₀; 2.63–3.09?µM) are nearly 7-fold more potent compared with the positive control 5-fluorouracil (mean GI₅₀; 22.60?µM). More interestingly, compounds 1a, 2a, 3b, 6b and 7a have an almost antitumor activity similar to gefitinib (mean GI₅₀; 3.24?µM) and are nearly 2-fold more potent compared to erlotinib (mean GI₅₀; 7.29?µM). In silico study and ADME-Tox prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.     

Disaccharide Pyrimidine Nucleosides and Their Derivatives: A Novel Group of Cell-Penetrating Inhibitors of Poly(ADP-Ribose) Polymerase 1

Nearly 30 synthetic nucleosides were tested with human recombinant poly(ADP-ribose) polymerase 1 as potential inhibitors of this enzyme. The most active compounds were some disaccharide analogues of thymidine: 3′-O-β-D-ribofuranosyl-5-iodo-dUrd (2d; IC₅₀ = 45 μM), 3′-O-β-D-ribofuranosyl-2′-deoxythymidine (2e; IC₅₀ = 38 μM), and 3′-O-β-D-ribofuranosyl-2′-deoxythymidine oxidized (4; IC₅₀ = 25 μM). These compounds also reduced H₂O₂-induced synthesis of poly(ADP-ribose) in cultured human ovarian carcinoma (SKOV-3) cells in a dose-dependent manner. Furthermore, compounds 2d or 2e until a concentration of 1 mM did not affect growth of SKOV-3 cells, whereas dialdehyde compound 4, as well as thymidine, exhibited a significant cytotoxicity.     

News

Schools affiliation scheme

BES expedition grants

Fermenters for schools project; Jonathan Bach

Case studies in evolution     

The psychosocial impact of bilateral prophylactic mastectomy: prospective study using questionnaires and semistructured interviews

ObjectivesTo investigate the psychosocial impact of bilateral prophylactic mastectomy for women with increased risk of breast cancer and to identify, preoperatively, risk factors for postoperative distress.DesignProspective study using interviews and questionnaire assessments.SettingParticipants'' homes throughout the United Kingdom.Participants143 women with increased risk of developing breast cancer who were offered bilateral prophylactic mastectomy and who accepted or declined the surgery; a further 11 were offered surgery but deferred making a decision.ResultsPsychological morbidity decreased significantly over time for the 79 women who chose to have surgery (accepters): 58% (41/71) preoperatively v 41% (29/71) 6 months postoperatively (difference in percentages 17%, 95% confidence interval 2% to 32%; P=0.04) and 60% (39/65) preoperatively v 29% (19/65) 18 months postoperatively (31%, 15% to 47%; P<0.001). Psychological morbidity in the 64 women who declined surgery (decliners) did not decrease significantly: 57% (31/54) at baseline v 43% (23/54) at 6 months (14%, 0% to 29%; P=0.08) and 57% (29/52) at baseline v 41% (21/52) at 18 months (16%; −2% to 33%; P=0.11). Greater than normal proneness to anxiety was more common in the decliners than in the accepters: 78% (45/58) v 56% (41/73) (22%, 6% to 38%; P=0.006). Accepters were more likely than decliners to believe it inevitable that they would develop breast cancer (32% (24/74) v 10% (6/58) (difference in percentages 22%, 9% to 35%; P=0.003)), and decliners were more likely to believe that screening could help (92% (55/60) v 74% (55/74) (18%, 5% to 31%; P=0.007)). Level of sexual discomfort and degree of sexual pleasure did not change significantly over time in either of the two groups.ConclusionsBilateral prophylactic mastectomy may provide psychological benefits in women with a high risk of developing breast cancer.     

Plants recently discovered in Scotland

Summary

Saxifraga rosacea is recorded and Poa scotica described new to Scotland. The position of segregate taxa or breeding units within several species complexes is clarified within Scotland: (a) the hexaploid cytotype within the mostly tetraploid Campanula rotundifolia; (b) diploid Hedera helix and tetraploid H. hibernica;, (c) diploid and tetraploid Deschampsia cespitosa, D. alpina and D. parviflora; (d) octoploid sub-species scotica within usually hexaploid Festuca rubra; (e) an octoploid mountain Agrostis; (f) fertile hexaploid Potentilla anserina; (g) an approximately triploid aneuploid Vaccinium uliginosum ssp. microphyllum.     

Heterometallic coordination polymers constructed by linear ligands

Eight lanthanide–copper coordination polymers of linear rigid 4-(4-pyridyl)benzoate(L¹) and isonicotinate(L²), [LnCuI(L¹)₂(OAc) (H₂O)]_n (Ln = Pr, 1; Nd, 2; Sm, 3; Eu, 4; Gd, 5), [Ln₂Cu₄I₃(L²)₇ (H₂O)]_n (Ln = La, 6; Pr, 7), and [Nd₂Cu₇I₆(L²)₇ (H₂O)₆]_n·2.5nH₂O (8), were hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction. The three-dimensional frameworks of 1–5 can be described as wave-like layer modules of [Ln(L¹)₂(OAc)(H₂O)]_n linking with each other through dimeric units of Cu₂I₂, whereas that of compounds 6 and 7 are constructed by layer modules of and Cu₄I₃ clusters. As for 8, dimeric units of Nd₂(L²)₇(H₂O)₆ connect layered polymeric forming a 3D framework.     

Notes on some rare Dicranaceae

Abstract

Dicranella riparia is shown to be more appropriately treated as Kiaeria riparia comb. nov.; Kiaeria glacialis is shown to be a misfit in Dicranum; Oncophorus sardous is placed in synonymy of O. wahlenbergii; Arctoa anderssonii is shown to be a distinct species.     

Conformational Aspects of Differences in Requirements for Oxytocin and Vasopressin Receptors

Abstract

Conformational energy calculations were carried out on three non-peptide antagonists of oxytocin and vasopressin: penicilide (compound 1; selective for oxytocin receptors), 1- {1-[4-(3-acetylaminopropoxy (benzoyl]-4-piperidyl}-3,4-dihydro-2(1H)-quinoline (compound 2; selective for vasopressin V₁ receptors) and 5-dimethylamino-1-{(2-methylbenzylamino)-benzoyl}-2,3,4,5–tetrahydro-1H-benzapine (compound 3; selective for vasopressin V₂ receptors). The obtained low-energy conformations of compound 1 were compared with low-energy conformations of oxytocin (OT) and low-energy conformations of compounds 2 and 3 were compared with low-energy conformations of arginine vasopressin (AVP). It was found that the affinity of the non-peptide antagonists and their selectivity for vasopressin and oxytocin receptors is probably connected with mimicking the aromatic rings of the Tyr² and the Phe³ residues of AVP in the case of compounds 2 and 3 and with mimicking the Tyr² residue and the Ile³ or Leu⁸ residues of OT by the outer benzene ring and the isobutyl group of compound 1. Application of the results in the design of more potent non-peptide antagonists of OT and VP is also discussed.