Organization of the nervous system of physonectid siphonophores

Summary An antiserum to the sequence Arg-Phe-amide (RFamide) was used to stain the nervous systems of various physonectid siphonophores. In the stem of Nanomia bijuga, this antiserum stained an ectodermal nerve net, which was interrupted, at regular intervals, by transverse collars of neurons. Injection of Lucifer yellow into the giant axon of the stem showed that this axon was dye-coupled to an ectodermal nerve net that resembled the RFamide-positive network. Ectodermal nets of neurons were also found in the pneumatophore, gastrozooids, tentacles and tentilla. At the junctions of the pneumatophore, the gastrozooids, the dactylozooids and the gonozooids with the stem, and at the junctions of tentacles and tentilla, collars or rings of neurons occurred. The stem was connected to the phyllozooids and nectophores by muscular lamellae, which were bordered by chains of neurons. At the margin of the nectophores, an immunoreactive nerve ring was found. Connected to this ring and located in theseitliche Zapfen (sidely-located patche), were two agglomerations of nerve cells. On the upper side of the bell margin, positioned at 90° relative to the seitliche Zapfen, a delta-shaped neuronal structure was found. This structure was connected to the nerve ring and was associated with a muscle, which ran a short distance along the exumbrellar surface.The nervous systems of Agalma elegans, Forskalia edwardsi, Forskalia leuckarti and Halistemma rubrum resembled that of Nanomia bijuga in all major respects.     

Polymorphism of the HLA DR1 haplotype in the Israeli population investigated at the serological,cellular, and genomic levels

In the present report, we used serological, cellular, and restriction fragment length polymorphism (RFLP) to investigate the DR1 haplotype in the Israeli population. We describe an Israeli homozygous typing cell (HTC), HLA-DwLVA, which defines a new lymphocyte-activating determinant associated with Bw65, DR1 and distinct from Dwl. The parents of this donor, non-Ashkenazi Algerian Jews, are first cousins and share HLA-Cw8, Bw65, BfS, DR1, DQw1, DPw4. No specificity could be assigned to HLA-DwLVA using the 91 Ninth Workshop HTCs. Two families and forty unrelated DR1 individuals were studied with DwLVA and a panel of DR1/Dw1 HTCs. HLA-DwLVA showed segregation as a single determinant within families. This new specificity was present in 24 out of 40 (60%) unrelated DR1 individuals, indicating that in the Israeli population DwLVA is the main lymphocyte-defined determinant associated with the serologically defined DRI specificity, in contrast to non-Jewish Caucasoids where DR1 is significantly associated with Dw1. The vast majority of DwLVA-positive carriers were also Bw65 carriers, indicating that Bw65, DR1, DwLVA may represent a typical allele combination in the Israeli population. The RFLP analysis established the correlation of certain RFLPs with Dw1 and DwLVA. In addition, we describe a cluster of RFLPs that may correspond to a new Dw subtype associated with DR1, for which no serological and cellular reagents have been described so far.     

Comparative study of the antitumor effect of two types of murine recombinant interferons, (β) and (γ), against B16-F10 melanoma

Summary A comparative study of the antitumor effect of murine recombinant interferon() Mu-rIFN() and murine recombinant interferon() Mu-rIFN() on B16-F10 melanoma was conducted. Administration of Mu-rIFN() i.p. into C57BL/6 mice on days 1 to 7 produced a higher suppressive effect than Mu-rIFN() both on the growth of s.c. implanted tumor and on the formation of artificial pulmonary metastasis. Pharmacokinetic study of Mu-rIFN() demonstrated that high plasma levels were retained for a long time. In clonogenic assay, Mu-rIFN() at 1000 units/ml showed about 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN() hardly inhibited the colonies, even at 1000 units/ml. Augmentation of natural killer (NK) cytotoxicity was much greater with Mu-rIFN() than Mu-rIFN(), whereas Mu-rIFN() enhanced the cytotoxicity of peritoneal macrophages more strongly than Mu-rIFN(). Injection of Mu-rIFN() i.p. 1 day before tumor challenge also inhibited the formation of pulmonary metastasis of B16-F10 melanoma. However, pretreatment of mice with carrageenan significantly suppressed the inhibitory effect of Mu-rIFN(). From these results, it is suggested that the inhibitory effect of Mu-rIFN() on the tumor growth and metastases of B16-F10 melanoma is mediated partly by direct antitumor effect and partly by the activation of macrophages, and that the augmentation of NK activity contributes mainly to the antitumor effect of Mu-rIFN().     

Interaction of cycloalkanoprogesterones with mammalian progesterone receptor: binding of pregna-D'-pentaranes in the calf uterine cytosol

Pregna-D'-pentaranes (pentaranes) are modified progesterones with demonstrable progestational activity and contraceptive effect. We have examined the steroid binding characteristics of the two newly synthesized progesterone analogs, Pentarane A (16, 17-cyclohexanoprogesterone) and Pentarane B (6-methyl, 16, 17-cyclohexanoprogesterone), and studied the nature of their interaction with progesterone receptor (PR) from the chicken oviduct and the calf uterine cytosols. Pregna-D'-pentaranes exhibited no affinity for the chick PR but interacted with the calf uterine PR as did R5020. The pentaranes, however, bound PR less tightly. R5020- or pentarane-bound PR sedimented as an 8S moiety in 8–30% linear glycerol gradients. Thermal transformation of receptor resulted in the reduction of the 8S form, and caused an increase in the binding of R5020-and progesterone-bound PR complexes to DNA-cellulose. The pentarane-bound PR bound poorly, if at all, to DNA-cellulose. Our data suggest that pentaranes exhibit both similarities and differences with natural and synthetic progestins with respect to their interaction with calf uterine PR. The lack of pentarane binding to chicken PR is reminiscent of the general phenomenon that antiprogestins (RU486, ZK98299, and Org 31710 and Org 31806) do not interact with chicken PR. Pentaranes, therefore, represent unique steroid analogs to investigate the molecular mechanism of steroid hormone action.Abbreviations DMSO Dimethyl sulfoxide - DTT Dithiothreitol - E Estradiol - EDTA Ethylene-diaminetetraacetate - F Cortisol - IA Iodoacetamide - MER -mercaptoethanol - MTG Monothioglycerol - NEM N-ethylmaleimide - Org 31710 (6, 11, 17)-11-(4-dimethylaminophenyl)-6 methyl-4, 5-dihydro[estra-4, 9-diene-17, 2(3H')-furna]-3-one - Org 31806 (7, 11, 17)-11-(4-dimethyl-aminophenyl)-7 methyl-4, 5-dihydro[estra-4, 9-diene-17, 2(3H)-furan]-3-one - P Progesterone - Pentarane A 16, 17-cyclohexanoprogesterone - Pentarane B 6-methyl, 16, 17-cyclohexanoprogesterone - PMSF Phenylmethylsulfonyl Fluoride - PR Progesterone Receptor - R5020 17, 21-dimethylpregna-4, 9(10)-diene-3     

A structural model for elongation factor 1 (EF-1) and phosphorylation by protein kinase CKII

EF-1a binds aminoacyl-tRNA to the ribosome with the hydrolysis of GTP; the complex facilitates the exchange of GDP for GTP to initiate another round of elongation. To examine the subunit structure of EF-1 and phosphorylation by protein kinase CKII, recombinant , , and subunits from rabbit were expressed in E. coli and the subunits were reconstituted into partial and complete complexes and analyzed by gel filtration. To determine the availability of the and subunits for phosphorylation by CKII, the subunits and the reconstituted complexes were examined as substrates for CKII. Formation of the nucleotide exchange complex increased the rate of phosphorylation of the subunit and reduced the Km, while addition of to or the complex inhibited phosphorylation by CKII. However, a had little effect on phosphorylation of . Thus, the and subunits in EF-1 were differentially phosphorylated by CKII, in that phosphorylation of was altered by association with other subunits, while the site on was always available for phosphorylation by CKII. From the availability of the subunits for phosphorylation by CKII and the composition of the reconstituted partial and complete complexes, a model for the subunit structure of EF-1 consisting of (22)2 is proposed and discussed.     

Genetic characterization of a new splice variant of the β2 subunit of the voltage-dependent calcium channel

This study reports a novel splice variant form of the voltage-dependent calcium channel ₂ subunit (_2g). This variant is composed of the conserved amino-terminal sequences of the _2a subunit, but lacks the -subunit interaction domain (BID), which is thought essential for interactions with the ₁ subunit. Gene structure analysis revealed that this gene was composed of 13 translated exons spread over 107 kb of the genome. The gene structure of the ₂ subunit was similar in exon-intron organization to the murine ₃ and human ₄ subunits. Electrophysiological evaluation revealed that _2a and _2g affected channel properties in different ways. The _2a subunit increased the peak amplitude, but failed to increase channel inactivation, while _2g had no significant effects on either the peak current amplitude or channel inactivation. Other subunits, such as ₃ and ₄, significantly increased the peak current and accelerated current inactivation.     

Charles Darwin's theory of evolution: A review of our present understanding

The paper characterizes Darwin's theory, providing a synthesis of recent historical investigations in this area. Darwin's reading of Malthus led him to appreciate the importance of population pressures, and subsequently of natural selection, with the help of the wedge metaphor. But, in itself, natural selection did not furnish an adequate account of the origin of species, for which a principle of divergence was needed. Initially, Darwin attributed this to geographical isolation, but later, following his work on barnacles which underscored the significance of variation, and arising from his work on botanical arithmetic, he supposed that diversity allowed more places to be occupied in a given region. So isolation was not regarded as essential. Large regions with intense competition, and with ample variation spread by blending, would facilitate speciation. The notion of place was different from niche, and it is questioned whether Darwin's views on ecology were as modern as is commonly supposed. Two notions of struggle are found in Darwin's theory; and three notions of variation. Criticisms of his theory led him to emphasize the importance of variation over a range of forms. Hence the theory was populational rather than typological. The theory required a Lamarckian notion of inheritable changes initiated by the environment as a source of variation. Also, Darwin deployed a use/habit theory; and the notion of sexual selection. Selection normally acted at the level of the individual, though kin selection was possible. Group selection was hinted at for man. Darwin's thinking (and also the exposition of his theory) was generally guided by the domestic-organism analogy, which satisfied his methodological requirement of a vera causa principle.     

α-and β-Glycosidases in maize roots

Four glycosidases were analyzed in 10 mm apical segments prepared from growing roots (15 mm) of Zea mays L. The pH optima were found to be 5.8 for -glucosidase, 4.4 for -galactosidase, 6.4 for -glucosidase and 6.0 for -galactosidase. The -glucosidase showed 4-fold higher activity than the -galactosidase. The distribution of the -glucosidase activity was signifcantly different from that of the -galactosidase, -glucosidase and -galactosidase.Abbreviations -Glu -glucosidase - -Gal -galactosidase - -Glu -glucosidase - -Gal -galactosidase     

Travelling waves and dominance of ESS's

We consider a simple two strategy game in which each pure strategy is an evolutionarily stable strategy (ESS). Under the usual dynamical equations, the large-time behaviour of the system will depend upon the initial conditions and the pay-off matrix. If spatial effects are included to give a reaction-diffusion system, we prove that travelling wavefronts can occur which in effect replace one ESS by another. The strength or dominance of each ESS which decides the winner in a precisely defined sense is determined by its pay-off and by its diffusion rate. Good strategies have large pay-offs and small diffusion rates.     

Einige Bemerkungen über die Ersatzgeschlechtstiere vonReticulitermes

Zusammenfassung An Laboratoriumszuchten vonReticulitermes lucifugus Rossi undReticulitermes flavipes Kollar (aus den Hamburger Befallsgebieten) werden Beobachtungen zur Biologie der Ersatzgeschlechtstiere mitgeteilt. Für die Durchführung dieser Beobachtungen wurden besondere Schaunester eingerichtet. Folgende Punkte der beobachteten Verhaltensweisen werden hier hervorgehoben: Die Nymphen der Ersatzgeschlechtstiere sammeln sich stets in Herden von 80–100 Einzeltieren und werden von einer Gruppe Arbeiter (als Hütehunde) bewacht. Die Arbeiter halten die Nymphen auf einem engen Raum zusammen und versuchen andere Nestgenossen von den Nymphen fernzuhalten. Alle ein bis zwei Tage wechseln die Herden ihren Standort. Das Weiterziehen geschieht gleichfalls in Form von Herden.Die Ernährung der Nymphen geschieht auf stomodealem Wege durch die Arbeiter. *** DIRECT SUPPORT *** A0180089 00007     

Characterization of human chromosomal unit fibers

A structural component of mitotic chromosomes that partially explains the compaction of DNA within mitotic chromosomes is suggested on the basis of the occurrence of long, regular cylindrical structures in preparations of isolated human chromosomes. These structures, unit fibers, of a rather constant diameter of about 4,000 Å have been postulated to be formed by coiling of the 250T2–300 Å solenoid chromatin fiber that itself is formed by coiling of the 100 Å string of nucleosome fiber. The human chromatid would thus be composed by a hierarchy of helices with contraction ratios for DNA at each level of coiling of 7 (string of nucleosomes), 5 (solenoid) and 40 (4,000 Å unit fiber or super-solenoid) which results in an overall contraction ratio for DNA in the unit fiber structures of about 1,400, which is approximately 5-fold less than the final contraction of DNA in intact chromatids of condensed metaphase chromosomes. The present report concerns more detailed studies with respect to the dimensions and cytochemical properties of the unit fiber structures observed in preparations of isolated human mitotic chromosomes that provide direct and indirect evidence in support of their super-solenoid structure and relate to known properties of human mitotic chromosomes.     

Testis-specific β2 tubulins are identical in Drosophila melanogaster and D. hydei but differ from the ubiquitous β1 tubulin

In Drosophila as in many organisms tubulins are encoded by a gene family. We have determined the complete nucleotide sequences coding for the 1 and 2 tubulins of Drosophila melanogaster and the 2 tubulin of D. hydei, and found these insect tubulins to be highly conserved and like tubulins of other organisms. This is discussed with reference to the possible functional domains of these proteins. — The 1 tubulin gene of Drosophila is constitutively expressed, whereas the 2 tubulin is expressed specifically in the testes. In D. melanogaster the amino acid sequences of these proteins are 95% homologous, differing at only 25 positions. In the testes the 2 tubulin participates in different microtubules as shown by genetic analysis (Kemphues et al. 1982). Interestingly, all of the amino acids characteristic of the testis-specific 2 tubulin are also present in the corresponding gene of D. hydei. Of special interest is the high degree of conservation of the carboxy-terminal domain in these functionally equivalent tubulins.     

Chromophore assignment in phycoerythrocyanin from Mastigocladus laminosus

The component spectra (maxima of absorption, circular and linear dichroism) of individual chromophores have been assigned for phycoerythrocyanin (PEC) trimer, monomer(s), and its subunits (-PEC and -PEC) by titration with p-chloromercury-benzene-sulfonate (PCMS), linear dichroism and photochemical transformations, as well as by deconvolution using a bilin line-shape spectrum based on the -84 phycoviolobilin-chromophore in the -subunit. The level ordering PVB--84 PCB--155 PCB--84 is the same irrespective of aggregation. Two different monomers () were observed. In 4 M urea, the spectra are appropriately weighted sums of the subunit spectra, whereas in the monomer obtained in 1 M KSCN, both -chromophores are red-shifted by 4–5 nm. Formation of trimer ()_{_3}gives considerable spectral changes: (1) the absorption is narrowed, which has been rationalized by excitonic coupling between neighbouring monomers, (2) the short wavelength part in the CD spectrum is missing and (3) a fourth band (+) at 528 in the LD spectrum appears. A deconvolution of the trimeric aggregation state using only the bilin line-shape model is not possible.     

Characterization of the effectors required for stable inheritance of Streptococcus pyogenes pSM19035-derived plasmids in Bacillus subtilis

The low-copy-number and broad-host-range pSM19035-derived plasmid pBT233 is stably inherited in Bacillus subtilis cells. Two distinct regions, segA and segB, enhance the segregational stability of the plasmid. Both regions function in a replicon-independent manner. The maximization of random plasmid segregation is accomplished by the recombination proficiency of the host or the presence of the pBT233 segA region. The segA region contains two open reading frames (or) [ and ]. Inactivation or deletion of or results in SegA^– plasmids. Better than random segregation requires an active segB region. The segB region contains two ors (or and or). Inactivation of either of the orfs does not lead to an increase in cell death, but or^– plasmids are randomly segregated. These results suggest that pBT233 stabilization relies on a complex system involving resolution of plasmid oligomers (segA) and on the function(s) encoded by the segB region.     

Conservation status of parrot populations in an Atlantic rainforest area of southeastern Brazil

A census of four species of syntopic parrots was carried out using distance sampling methods on São Sebastião island, SE Brazil. Most of the 33593 ha island is covered by mature and secondary Atlantic rainforest. Almost 80% of these forests are within the Ilhabela Park. Although the species counted have marked differences in size and weight, density (individuals/km²) and estimated population size in 23500 ha of well-preserved forests were similar: Amazona farinosa (13.82±5.94; 3247±1395), Pionus maximiliani (15.79±7.04; 3712±1654), Brotogeris tirica (15.05±4.87; 3537±1143) and Pyrrhura frontalis (13.06±5.53; 3068±1298). Encounter rates of Forpus crassirostris and Pionopsitta pileata were very low, which suggests that there is only a small population of these species on the island. The São Sebastião forests still support healthy populations of parrots. Although woodpecker population estimates on the island are large enough to provide nesting sites for parrots, competition for holes with other secondary cavity nesters such as toucans, flycatchers and tytiras, and the selective cutting of dead trees for canoe construction, which is a common practice on the island, may limit hole availability for parrots.     

Synthesis of Aminoethyl Glycosides of the Ganglioside GM1 and Asialo-GM1 Oligosaccharide Chains

4-O-Glycosylation of 2-azidoethyl 2,3,6-tri-O-benzyl-4-O-(2,3-di-O-benzyl-6-O-benzoyl--D-galactopyranosyl)--D-glucopyranoside with a disaccharide donor, 4-trichloroacetamidophenyl 4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl--D-galactopyranosyl)-1-thio-2-trichloroacetamido--D-galactopyranoside, in dichloromethane in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid resulted in a tetrasaccharide, 2-azidoethyl (2,3,4,6-tetra-O-acetyl--D-galactopyranosyl)-(1 3)-(4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido--D-galactopyranosyl)-(1 4)-(2,3-di-O-benzyl-6-O-benzoyl--D-galactopyranosyl)-(1 4)-2,3,6-tri-O-benzyl--D-glucopyranoside, in 69% yield. The complete removal of O-protecting groups in the tetrasaccharide, the replacement of N-trichloroacetyl by N-acetyl group, and the reduction of the aglycone azide group to amine led to the target aminoethyl glycoside of -D-Gal-(1 3)--D-GalNAc-(1 4)--D-Gal-(1 4)--D-Glc-OCH₂CH₂NH₂ containing the oligosaccharide chain of asialo-GM₁ ganglioside in 72% overall yield. Selective 3-O-glycosylation of 2-azidoethyl 2,3,6-tri-O-benzyl-4-O-(2,6-di-O-benzyl--D-galactopyranosyl)--D-glucopyranoside with thioglycoside methyl (ethyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero--D-galacto-2-nonulopyranosyl)oate in acetonitrile in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid afforded 2-azidoethyl [methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero--D-galacto-2-nonulopyranosyl)oate]-(2 3)-(2,6-di-O-benzyl--D-galactopyranosyl)-(1 4)-2,3,6-tri-O-benzyl--D-glucopyranoside, the selectively protected derivative of the oligosaccharide chain of GM₃ ganglioside, in 79% yield. Its 4-O-glycosylation with a disaccharide glycosyl donor, (4-trichloroacetophenyl-4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl--D-galactopyranosyl) 1-thio-2-trichloroacetamido--D-galactopyranoside in dichloromethane in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid gave 2-azidoethyl (2,3,4,6-tetra-O-acetyl--D-galactopyranosyl)-(1 3)-(4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido--D-galactopyranosyl)-(1 4)-{[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero--D-galacto-2-nonulopyranosyl)onate]-(2 3)}-(2,6-di-O-benzyl--D-galactopyranosyl)-(1 4)-2,3,6-tri-O-benzyl--D-glucopyranoside in 85% yield. The resulting pentasaccharide was O-deprotected, its N-trichloroacetyl group was replaced by N-acetyl group, and the aglycone azide group was reduced to afford in 85% overall yield aminoethyl glycoside of -D-Gal-(1 3)--D-GalNAc-(1 4)-[-D-Neu5Ac-(2 3)]--D-Gal-(1 4)--D-Glc-OCH₂CH₂NH₂ containing the oligosaccharide chain of GM₁ ganglioside.     

Biometeorological comfort index

The paper aims to represent and scale biometeorological sensations through a thermal index which comprises the effects of temperature, humidity and wind. The cooling power of a measured combination of wind speed and air temperature is equated with that due to the combination of a reference wind speed (related to the air movement experienced by a person walking in still air), and a derived aerodynamic temperature. A biometeorological temperature which is the average of such an aerodynamic temperature and a conventionally measured wet bulb temperature is shown to afford a better measure of comfort in Spain than some other, alternative indices.     

“Searching time aggregation” and density dependent parasitism in a laboratory host-parasitoid interaction

Summary Assuming random search by parasitoids within host-containing patches, and a constant search rate, current host-parasitoid models suggest that searching time aggregation by parasitoids in patches of high host density should tend to produce spatially density dependent parasitism at the patch level. It is not clear, however, that statistically significant searching time aggregation necessarily implies that significant density dependent parasitism will occur. In actual host-parasitoid systems the amounts of searching time allocated to patches of equal host density may vary a great deal from patch to patch. Such behavioral variability may be capable of obscuring an underlying density dependent trend, producing density independent parasitism at the patch level despite significant searching time aggregation in patches of high host density. This possibility is tested using data from an earlier laboratory study (Morrison and Lewis; Ent. exp. et appl. 30:31–39 [1981]) of the foraging behavior of Trichogramma pretiosum Riley, a generalist parasitoid of lepidopteran eggs. Searching time allocation is found to be highly variable among patches of equal host density, and significant density dependent parasitism does not occur despite significant searching time aggregation in patches of high host density. This suggests that in cases in which density independent or density vague patterns of parasitism are observed in field samples, direct field measurements of searching time allocation in patches of different host density may be necessary to demonstrate the presence or absence of significant searching time aggregation by foraging parasitoids.     

β2-Adrenoceptor activation by zinterol causes protein phosphorylation,contractile effects and relaxant effects through a cAMP pathway in human atrium

Evidence from ventricular preparations of cat, sheep, rat and dog suggests that both ₁-adrenoceptors (₁AR) and ₂-adrenoceptors (₂AR) mediate positive inotropic effects but that only ₁AR do it through activation of a cAMP pathway. On the other hand, our evidence has shown that both ₁ AR and ₂ AR hasten relaxation of isolated human myocardium consistent with a common cAMP pathway. We have now investigated in the isolated human right atrial appendage, a tissue whose -AR comprise around 2/3 of ₁AR and 1/3 of ₂AR, whether or not ₂AR-mediated effects occur via activation of a cAMP pathway. We carried out experiments on atria obtained from patients without advanced heart failure undergoing open heart surgery. To activate ₂AR, we used the ₂AR-selective ligand zinterol. Experiments were carried out on paced atrial strips (1 Hz) and tissue homogenates and membrane particles. Zinterol caused positive inotropic and lusitropic (i.e. reduction of t_1:2 of relaxation) effects with EC₅₀ values of 3 and 2 nM, respectively. The zinterol-evoked effects were unaffected by the AR-selective antagonist CGP 20712A (300 nM) but blocked surmountably by the ₂AR-selective antagonist ICI 118551 (50 nM) which reduced both EC₅₀ values to 1 M. Zinterol stimulated adenylyl cyclase activity with an EC₅₀ of 30 nM and intrinsic activity of 0.75 with respect to (–)-isoprenaline (600 M); the effects were resistant to blockade by CGP 20712A (300 nM) but antagonised surmountably by ICI 118551 (50 nM). Zinterol bound to membrane PAR labelled with (–)-[¹²⁵I] cyanopindolol with higher affinity for ₂AR than for - 1 AR; the binding to ₂AR but not to - BAR was reduced by GTPyS (10 M). In the presence of CGP 20712A (300 nM) (–)-isoprenaline (400 M); (to activate both ₁AR and ₂AR maximally) and zinterol (10 M); increased contractile force 3.4-fold and 2.5-fold respectively and reduced relaxation tut by 32% and 18% respectively. These effects of (–)-isoprenaline and zinterol were associated (5 min incubation) with phosphorylation (pmol P/mg supernatant protein) of troponin I and C-protein to values of 8.4 ± 2.0 vs 12.4 ± 2.3 and 10.1 ± 2.5 vs 8.6 ± 1.6 respectively. (–)-Isoprenaline and zinterol also caused phosphorylation of phospholamban (1.8 ± 0.3 vs 0.4 ± 0.1 pmol P/mg respectively) specifically at serine residues. We conclude that in human atrial myocardium activation of both ₁AR and ₂AR leads to cAMP-dependent phosphorylation of proteins involved in augmenting both contractility and relaxation.     

Methodological problems in evolutionary biology VIII. Biology and culture

Biology cannot accommodate all aspects of culture. Aspects of culture that a biological approach can take into account can be covered by the biological categories of phenotype and environment. There is no need to treat culture as a separate category. Attempts to elaborate biological explanations of cultural variation will meet with success only if biologists expand theories of development, and integrate them in evolutionary biology. The alternative — elaborating the idea of so-called cultural inheritance — makes little sense from a biological point of view.